P. 1
Internal Medicine and Neurolog

Internal Medicine and Neurolog

|Views: 838|Likes:

More info:

Published by: Pedro Henrique Sales Pontes on Jan 23, 2011
Copyright:Attribution Non-commercial

Availability:

Read on Scribd mobile: iPhone, iPad and Android.
download as PDF, TXT or read online from Scribd
See more
See less

04/30/2014

pdf

text

original

e

3

lint:ernal m.edilc:i'ne Be neulr1ollogy

- - - ---- - - ------

Volume 1

lneClical

*USMLE is a Joint program of the Federation of State Medical Boards of the United States, Inc. and the National Board of Medical Examiners.

Not for resale.

©2004 Kaplan, Inc.

All rights reserved. No part of this book may be reproduced in any form, by photostat, rnicrofilm, xerography or any other means, or incorporated into any information

retrieval system, electronic or mechanical, without the written permission of Kaplan, Inc.

AUTHORS

Internal Medicine Conrad Fischer, M.D.

Residency Program Director Flushing Hospital

Director of Faculty Development Jamaica, Flushing, Brookdale Hospitals

Charles J. Faselis, M.D.

Assistant Professor of Medicine Associate Program Director, Internal Medicine George Washington University Washington, D.C.

Neurology Scot Hines, M.D.

Southeast Georgia Regional Medical Center Brunswick, Georgia

Content Editor in Chief Elissa Levy, M.D.

Director of Clinical Curriculum Kaplan Medical

Faculty Editor in Chief

Elmar Peter Sakala, M.D., M.A., M.P.H., EA.C.O.G.

Executive Director of Curriculum Richard Friedland, D.P.M.

Director of Publishing and Media Michelle Covello

Managing Editor Kathlyn McGreevy

Production Artist Michael Wolff

Cover Design J.oanna Myllo

Contents

Preface vii

Author's Note ; .. ix

Section I. Internal Medicine

Chapter 1. Gastroenterology Cases 1

Gastroenterology Bonus Cases 37

Chapter 2. Endocrinology Cases 49

Endocrinology Bonus Cases 75

Chapter 3. Rheumatology Cases 83

Chapter 4. Emergency Medicine Cases 113

Emergency Medicine Bonus Cases 147

Chapter 5. Cardiology Cases 161

Cardiology Bonus Case .............................• 203

Chapter 6. Hematology Cases 205

Hematology Bonus Cases 245

Chapter 7. Oncology Cases 253

Oncology Bonus Cases 274

Chapter 8. Infectious Diseases Cases 291

Infectious Diseases Bonus Cases 339

IAPLA~. I meulca

v

vi _leal

Chapter 9. Nephrology Cases ..•....•.•..•.•...•.•.•..•........ 379

Chapter 10. Pulmonology Cases 411

Pulmonology Bonus Case 440

Section II. Neurology

Neurology Cases 445

Neurology Bonus Cases 488

Preface

These two volumes of Lecture Notes represent a yearlong effort on the part of the Kaplan Medical faculty to update the curriculum to reflect the most-likely-be-tested material on the current USMLE Step 3. To maximize the effectiveness of these Notes, annotate them as you listen to the lectures. To facilitate this process, we've created wide, blank margins.

Within these pages you will find cases that are divided by specialty. They begin with a chief complaint, history, and physical exam and then follow the patient through the diagnosis and management process. Many of the cases contain Case Review sections, which are designed to review some major points of related differential diagnoses. Finally, a majority of the sections also include bonus cases. These cases are designed as self-study supplements to the covered material and do not contain live or video lecture review.

Many students find that previewing the Notes prior to attending or viewing the lecture is a very effective way to prepare. This allows you to anticipate the areas where you'll need to pay particular attention. It also affords you the opportunity to map out how the information is going to be presented and what sort of study aids (charts, diagrams, etc.) you might want to add. This strategy works regardless of whether you're attending a live lecture or watching one on video.

Finally, we want to hear what you think. What do you like about the notes? What do you think could be improved? Please share your feedback with us at medfeedback@kaplan.com.

Thank you for joining Kaplan Medical, and best of luck on your Step 3 exam!

Kaplan Medical

IIIPL. l"iI-. . I me 1C8 .... '

Author's Note

Here you will find all of the content and material that you need for your journey to master the material necessary to pass and excel on the Step 3 USMLE.

This journey will involve much work, struggle, and at times pain. Aristotle said "The greatest part of courage is endurance:' What can we offer you as an analgesic for this pain?

If your highest goal is simply the exam, you may still succeed but the journey will be fraught with more anguish. If you can remember that someday you can relieve the suffering of one individual or save the life of even a single person from what you will learn as you study for Step 3, then all of your efforts will take on a new meaning and purpose. Make your goal the eternal quest to perfect the Art of Medicine in service of Humanity.

Hold fast to this goal and several extraordinary things will happen:

1. You will help people.

2. You will exchange bliss, relaxation, and a sense of joy for much of the hardship.

3. You will get an even higher grade.

Many years from now, when you have achieved all you desire professionally, much of the information you learn today will have faded. But if you see yourself as serving the ideals of goodness and beauty through medicine, then this simple but crucial purpose will not be forgotten with the rest. Medicine is more than just applying scientific facts to treat people. Learn to love what you do, and this will enrich not only your patients' lives, but yours as well. As the thirteenth century poet Rumi said, "Let the Beauty that we love be what we do, there are hundreds of ways to kneel and kiss the ground:'

Conrad Fischer, M.D.

UP~!.. I m.nllC8

ix

SECl'lON I

Internal Medicine

l

t

t

I'

t ~ ,

I

I Gastroenterology

~ CASE 1

!

r Chief complaint

Ie

I "My belly is swollen, and it hurts:'

I'

History and physical examination

A 48-year-old woman comes to the emergency department with fever, abdominal pain, and abdominal distention. In the last several months, she has developed ascites, anorexia, and progressive wasting. She also complains of severe itching. She is on no medications. She is a former intravenous drug user who was discharged several months ago from an alcohol-detoxification unit.

She is disheveled appearing and cachectic with a grossly distended abdomen. Her temperature is 38.3 C (101.0 F), blood pressure is 110/70 mrn Hg, pulse is 107/min, and respirations are 22/rnin. Physical examination shows poor dentition, parotid gland enlargement, and scleral icterus. Her lungs are clear, and her heart has a regular rate and rhythm. Her abdomen is distended, tympanic, tender, and with shifting dullness. A liver edge is not palpable, but the spleen is palpable 3 cm below the left costal margin. She has bilateral palmar erythema. Multiple spider angiomata and excoriations are also present.

Differential diagnosis

• Alcoholic cirrhosis and hepatitis

• Chronic viral hepatitis or acute hepatitis superimposed on chronic liver disease

• Complications associated with chronic liver disease

• Spontaneous bacterial peritonitis

• Hepatoma

• Peritoneal carcinomatosis

• Tuberculous ascites

KAPLAlril- I me 1C8

1

USMLE Step 3: Internal Medicine

2

Initial diagnostic plan

1. Prothrombin and partial thromboplastin times, INR

2. Complete blood count, peripheral smear

3. BUN/creatinine

4. Aspartate amino transferase

5. Alanine aminotransferase

6. Alkaline phosphatase

7. Total and fractionated bilirubin

8. Albumin

9. Total protein

Results

1. PT 16 seconds (normal: <13 seconds), PTT 38 seconds, INR 1.4

2. White blood count 4,800/mm3, hemoglobin 11 mgldL, platelets 120,000/mm3, MCV 102 f,Lm3;

acanthocytosis on peripheral smear

3. 30 mgldL, 1.0 mg/dL

4. 200 U/L

5. 100 U/L (normal: .8-20 U/L)

6. 150 U/L (normal: 20---70 U/L)

7. Total bilirubin 3.4 mg/dl, (normal: 0.1-1.0 mgldL)

8. 2.8 gldL (normal: 3.5-5.5 gldL)

9. 6.5.gldL (normal: 6-7.8 g/dL)

Assessment

This patient has evidence of chronic liver disease. Signs of chronic liver disease on physical examination include ascites, spider angiomata, asterixis, splenomegaly, and palmar erythema.

This patient has a history of alcoholism, and the increase in aspartate aminotransferase when compared with alanine aminotransferase points to alcohol-related liver disease. Chronic viral hepatitis should be ruled out in this patient given her history of intravenous drug use. Serologies for hepatitis Band C should be performed. Hepatitis A does not give chronic liver disease.

In a patient with or without a history of alcohol abuse with ascites, you should always consider cancer and tuberculosis as a potential etiology of the ascites. The MCV is elevated from liver disease.

Vascular causes of ascites are less likely in this case but may be ruled out through the use of Doppler ultrasound or CT of the abdomen with contrast. Other improbable causes of cirrhosis are primary biliary cirrhosis, hemochromatosis, Wilson disease, and Alpha I-antitrypsin deficiency. These diseases should be ruled out in this patient given that they may be reversible. A thorough history should be obtained to rule out drug-related hepatotoxicity secondary to isoniazid, methotrexate, or acetaminophen.

Liver-generated ascites is a sign of advanced disease and usually results from portal hypertension, which leads to vasodilatation. The vasodilatation that occurs triggers renal sodium retention and results in high intravascular volume and ascites formation. The volume/pressor sensors in the cirrhotic patient are limited in the face of volume overload. Consequently, these volume/pressure

Gastroenterology

sensors sense volume depletion in the face of volume overload and paradoxically stimulate release of renin/aldosterone, which leads to more increased sodium retention and increased fluid volume.

Other causes of progressive ascites include malignant ascites (e.g., ovarian carcinoma), rightsided heart failure, and vascular obstruction due to hepatic vein thrombosis (Budd-Chiari) or inferior vena cava clot.

The etiology of ascites can be distinguished by obtaining a serum ascites:albumin gradient. This is a gradient obtained by taking the difference between the serum albumin and the albumin in the ascitic fluid. A serum ascites albumin difference of > 1.1 is indicative of portal hypertension and is seen in cirrhosis, cardiovascular ascites (congestive heart failure), or hepatic/portal vein thrombosis syndromes. If the serum ascites albumin gradient is <1.1, portal hypertension is absent; this can be seen in peritoneal carcinomatosis, peritonitis in the absence of cirrhosis (i.e., tuberculosis), nephrotic syndrome, or pancreatic or biliary ascites. Basically, if the ascitic fluid albumin level is much lower (> 1.1) than the serum albumin level, it is from a hydrostatic problem like portal hypertension.

A patient with cirrhosis and ascites is at high risk for the development of spontaneous bacterial peritonitis. In a febrile patient with ascites, a diagnostic paracentesis should be performed to exclude this. Peritoneal fluid with absolute polymorphonuclear leukocytes >250 mm suggests the presence of infection.

Sudden worsening of ascites in a patient with known cirrhosis raises the concern for the development of hepatoma. This can be evaluated through diagnostic imaging, such as ultrasonography or CT scan, as well as serum alpha-fetoprotein, which is elevated in patients with hepatoma.

The liver has a large role in synthesis of albumin and proteins involved in coagulation. Laboratory abnormalities of cirrhosis include evidence of poor synthetic function demonstrated by low serum albumin levels and elevated prothrombin and partial thromboplastin times. Elevation of the prothrombin and partial thromboplastin times is caused by deficient production of clotting factors, which results from loss of liver parenchymal cell function. Vitamin K serves as a cofactor used by liver parenchymal cells in the production of these clotting factors. Other hematologic abnormalities seen in cirrhosis include anemia and thrombocytopenia from hypersplenism, marrow suppression, or the anemia of chronic disease.

Liver failure is often associated with an elevation in the direct bilirubin, transaminases, lactate dehydrogenase, and alkaline phosphatase. However, patients with a cirrhotic liver that becomes progressively more fibrotic may lose their ability to produce these enzymes, and, consequently, their levels can be decreased.

Further diagnostic plan

1. Hepatitis Band C serologies

2. Paracentesis

3. Fe studies

4. Ceruloplasmin levels

5. Alpha-l antitrypsin levels

6. Antimitochondrial antibodies

7. Liver ultrasound

Ni~ical 3

;\JSMLEStep 3: Internal Medicine

i'J

n

4

IAPLAlril- I me lea

Results

i. Negative

2. Total WBCs: 50 mm; Gram stain and culture are negative; albumin: 1.2.

3. Normal

4. Normal

5. Normal

6. Negative

7. Shrunken nodular fatty liver, normal bile ducts, no evidence of mass

Treatment plan

1. Salt restriction, diuretics (spironolactone and furosemide)

2. Counsel against further alcohol ingestion and encourage enrollment in alcohol treatment program

3. Balanced diet with adequate protein ingestion, possible use of diet-enriched branched chain amino acids as protective for development of hepatic encephalopathy

4. Follow patient closely and watch for signs of gastrointestinal bleeding and encephalopathy.

Given that she has portal hypertension and ascites, she will need an upper endoscopy to exclude esophageal varices.

Discussion

This patient presents with several classic findings of cirrhosis secondary to alcoholic liver disease. The other disease entities in the differential have been ruled out by negative testing.

Alcoholic hepatitis may present with acute symptoms of fever, hepatosplenomegaly, and elevated transaminases. In alcoholic cirrhosis, patients usually present with anorexia, loss of muscle mass, and fatigue. The liver may be enlarged and fatty, but as the disease progresses cirrhosis ensues and the liver becomes hard, nodular, shrunken, and scarred. Fibrous bands connecting portal triads and central veins as well as regenerative parenchyma forming micronodules characterize liver histology in cirrhosis. Men often present with gynecomastia and testicular atrophy caused by decreased hepatic clearance of androstenedione that is converted to estrogen and leads to increased estrogen levels. Patients with alcoholic cirrhosis usually have signs of portal hypertension, which include ascites, hemorrhoids, splenomegaly, and esophageal varices. Transaminase elevations are usually mild and do not exceed 300 U/L. The transaminase elevation is characterized by an AST that is. approximately 2 to 3x ALT, as is seen in this patient. Bilirubin elevations are often modest but progress as the disease worsens. Patients have decreased albumin levels and oncotic pressure, which increase the risk of ascites formation. Splenomegaly can be associated with pancytopenia. Coagulopathy is another sign of liver dysfunction. Hepatic encephalopathy is seen in end-stage disease (to be discussed in a later case).

Patients with alcoholic fatty liver have a good prognosis, and the problem may resolve after cessation of drinking. Patients with alcoholic hepatitis who stop drinking rarely develop cirrhosis. Of those who continue drinking, the incidence of cirrhosis is 45 to 80%. Hyperbilirubinemia, prolongation of clotting times, ascites, and encephalopathy are associated with a mortality, which may exceed 50%.

The prognosis is largely affected by whether the patient continues to drink. In a large study from Copenhagen, the 5-year survival for nondrinkers without jaundice was 85%, whereas it was only 60% for those who drank. Once jaundice occurs, survival falls to 50% in nondrinkers and 30% in drinkers. Gastrointestinal bleeding carries the worst prognosis. Treatment is largely supportive.

Gastroenterology

Corticosteroids may be used in treatment of acute alcoholic hepatitis in patients who are very coagulopathic, but corticosteroids do not have a role in the treatment once cirrhosis occurs. Advanced disease can be treated with liver transplantation if the patient discontinues drinking.

case Review

Ascites Related to Cirrhosis

• History of alcohol abuse or chronic hepatitis

• Stigmata of chronic liver disease

• Serum ascites albumin gradient >1.1

Ascites Related to Peritoneal Carcinomatosis

• No prior history of liver disease

• No stigmata of chronic liver disease Serum ascites albumin gradient <1.1

• Paracentesis fluid analysis may reveal cancer cells

Tuberculous Ascites

• No prior history of liver disease

• No stigmata of chronic liver disease

• Serum ascites albumin gradient <1.1

• Paracentesis fluid analysis may reveal stain-positive organisms, and cultures may grow mycobacteria.

IIlP~!.. I mgulC8

5

USMLE step 3: Internal Medicine

6 KAPLArril· I

me lea

eASE 2

Chief complaint ''I'm vomiting blood:'

History and physical examination

A 72-year-old man comes to the emergency department vomiting blood. The patient has a known history of ethanol abuse and has had a couple of episodes of upper gastrointestinal bleeding in the past. He was on a drinking binge earlier today, and 1 hour ago he was found by the emergency workers in a pool of blood on the sidewalk. He denies any pain at this time.

He is afebrile, his blood pressure is 80 mm Hg/palpation, and pulse is 125/min. He is stuporous and reeks of alcohol. Physical examination shows scleral icterus, gynecomastia, and spider angiomata. Cardiovascular examination is normal except for tachycardia. His chest is clear to auscultation. His abdomen is soft, nontender, and nondistended; splenomegaly is evident. Rectal examination is significant for melena, but no masses are seen.

Differential diagnosis

• Bleeding esophageal varices

• Mallory-Weiss tear

• Erosive gastritis

• Peptic ulcer bleeding

Initial diagnostic plan

The initial management plan in the case of an upper gastrointestinal bleed is the same for all causes. It always focuses on stabilizing the patient.

1. Insert two large-bore intravenous lines and start fluids (normal saline or crystalloid).

2. Saline infusion until systolic blood pressure is >90 mm Hg

3. Insert a nasogastric tube for gastric lavage.

4. Obtain a complete blood count, biochemical profile, and prothrombin and partial throm-

boplastin times.

5. Transfusions of packed red blood cells as needed

6. Fresh frozen plasma in patients with coagulopathy

7. Upper endoscopy with therapeutic intervention

Results of initial diagnostic plan

1. Blood clots and coffee grounds with nasogastric tube saline lavage. No evidence of active bleeding.

2. Hemoglobin 10 mg/dL (normal: 13-16 mg/dl.), platelets 80,000/mm3 (normal: 140,000- 340,000/mm3)

Gastroenterology

3. Sodium 150 mEq/L (normal: 135-150 mEq/L), BUN 30 mg/dl, (normal: 8-18 mg/dl.), creatinine 1.4 mg/dl, (normal: 0.6-l.3 mg/dl.), bilirubin 3.5 mg/dL (normal: 0.1-1.0 mg/dL), AST 240 U/L, ALT 80 U/L (normal: 8-20 U/L), alkaline phosphatase 160 U/L

4. Prothrombin/partial thromboplastin times: 17 seconds/45 seconds (elevated)

Assessment

The patient presents with evidence of vomiting bright red blood and with melena in the rectal vault. The presence of melena suggests a bleed greater than 100 mL, originating from a source proximal to the ligament of Treitz. Placement of the nasogastric tube is not necessary to confirm the presence of an upper gastrointestinal source of bleeding.

An upper gastrointestinal bleed in an alcoholic patient has several possible etiologies. Massive blood loss is often caused by esophageal varices resulting from progressive portal hypertension. However, even alcoholics with known esophageal varices often suffer upper gastrointestinal bleeding from other causes. Other possibilities include peptic ulcer disease or severe gastritis. Recurrent retching can result in a Mallory-Weiss tear and subsequent bleeding.

This patient also has evidence of cirrhosis and alcoholic liver disease on physical examination (gynecomastia, spider angiomatas, icteric sclera) and laboratory findings (elevated bilirubin, elevated AST/ALT ratio 3:1, elevated PT/PTT, low albumin).

In assessing this patient, primary attention is given to determining the extent of blood loss and stabilizing intravascular volume with crystalloids and packed REC transfusions. Given the history of alcoholism, evidence for an underlying coagulation defect should also be explored and corrected. Emergent endoscopy should be performed to determine the source of bleeding once the patient is stabilized.

Further diagnostic plan

Obtain an emergent upper endoscopy once patient is stabilized.

Results of further diagnostic plan

Upper endoscopy reveals esophageal varices with cherry red spots and a varix with a clot but no active bleeding. There are normal gastric mucosae, and there is no evidence of peptic ulcers. The patient undergoes banding of the esophageal varices to control the bleeding.

Further management

Admit the patient to the intensive care unit for continued observation and blood transfusion as appropriate.

Additional treatment

1. Somatostatin/octreotide intravenously

2. Monitor for signs of recurrent bleeding

3. Beta-blockade once blood pressure is stable

4. Monitor for signs of delirium tremens

Discussion

This patient has bleeding esophageal varices as a result of portal hypertension secondary to alcohol-induced cirrhosis. Varices are portosystemic collaterals that can develop in the esophagus, stomach, or rectum in patients with portal hypertension. Varices in the esophagus and

mellical 7

USMLE Step 3: Internal Medicine

8 meClical

stomach can be seen in up to 60% of cirrhotic patients and have a 30% chance of bleeding. Factors that increase the likelihood of variceal bleeding include size and presence of cherry red spots or red streaks on varices. This patient had cherry red spots as well as a clot on a varix that had recently bled. Sixty percent of upper gastrointestinal bleeds in cirrhotics result from esophageal varices; gastric varices account for 7%. Variceal bleeding carries a high mortality rate of up to 70%.

Upper endoscopy is the mainstay of both diagnosis and treatment of varices. Octreotide should be used immediately in all patients with variceal bleeding. Variceal rubber band ligation and sclerotherapy are treatment options to control bleeding, but they do not treat portal hypertension. Sclerotherapy has more complications, such as stricture formation and scarring. It is important to stabilize the patient before any procedure and to try to correct coagulopathy as well. The risk of recurrent bleeding from varices is very high and ranges from 40 to 80%. Risk of recurrent variceal bleeding can be reduced with the use of nonselective beta-blockers (e.g., propanolol) once the patient is stable.

If bleeding cannot be controlled with banding, the next line of treatment includes TIPS, or transjugular intrahepatic portosystemic shunting. Somatostatin/octreotide causes splanchnic vasoconstriction and should be used as adjuncts to endoscopic therapy to control bleeding and prevent further bleeding. If the above measures fail, shunt operations can be considered to decrease portal hypertension. A Blakemore tube is rarely used and only as a bridge to surgery.

Platelet transfusions are used as needed if the platelet count drops. Fresh frozen plasma is used to correct the elevation in PT/PTT. This elevation is common in alcoholics and can be secondary to nutritional deficiency or liver disease with poor synthetic function.

Given the history of recent alcohol use and severe bleeding, this patient should also be monitored in an intensive care setting for signs of delirium tremens, which has a mortality rate of 5%. Gastric varices can regress in alcoholic patients who abstain from alcohol. Once this patient recovers, he should be advised to stop alcohol consumption and seek professional treatment regarding this.

Vasopressin is no longer used with variceal bleeding. It has no additional efficacy when compared with octreotide and has more potential cardiac adverse effects.

Gastroenterology

Case Review

Bleeding Esophageal Varices

• History of alcohol abuse or chronic liver disease

• Hematemesis with or without melena

• Stabilize patient first. Somatostatin (odreotide) should be used with all initial treatment plans

with variceal bleeding.

• Endoscopy is the mainstay of diagnosis and treatment.

• Treatment options include banding, sclerotherapy, and shunting.

• Nonselective beta-blockers (propranolol) can reduce the risk of recurrent variceal bleeding.

Mallory-Weiss Tear

• Mucosal tear at gastroesophageal junction from retching or vomiting

• Hematemesis with or without melena, typically sell-limited

• Stabilize patient first.

• Endoscopy establishes diagnosis.

Erosive Gastritis

• History of alcohol abuse, use of nonsteroidal antiinflammatory agents, or medical/surgical stress

• Hematemesis with or without melena may occur; typically asymptomatic

• Stabilize patient first.

• Endoscopy establishes diagnosis.

Peptic Ulcer Bleeding

• Hematemesis with or without melena or hematochezia

• Patients typically have history of dull, achy, gnawing epigastric pain; however, up to 20% may have no antecedent symptoms.

• Stabilize patient first.

• Endoscopy establishes diagnosis.

KAPLAICiI·· I me 1C8

9

USMLE Step 3: Internal Medicine

10 ffieClical

CASE 3

Chief complaint

"My gut hurts, but it feels better after I eat:'

History and physical examination

A 52-year-old man comes to the emergency department with a 2-month history of epigastric pain. The pain wakes him up from his sleep. Eating and over-the-counter antacids relieve it. He has no significant weight loss and no nausea or vomiting. He has no known history of pancreatic or ulcer disease. He does not drink alcohol. He occasionally smokes and takes aspirin for back pain.

He is a healthy-appearing man in very mild distress. His vital signs are stable. Examination of his heart and lungs is within normal limits. His abdomen is soft, nontender, nondistended, and there are no palpable masses. Rectal examination is without any masses and is guaiac negative.

Differential diagnosis

• Duodenal ulcer

• Gastric ulcer

• Gastritis

• Esophagitis

• Gastric cancer

• Cholelithiasis

Initial diagnostic plan

1. Complete blood count

2. Liver function tests

3. Ultrasound of the gall bladder

Results

1. Normal

2. Normal

3. Normal amylase and lipase

Assessment

The patient presents with epigastric pain relieved partially with antacids. This is suggestive of peptic ulcer disease, specifically duodenal ulceration. Pain is classically described as burning or gnawing and is most severe in early morning and 2 to 3 hours after eating. Gastric ulceration can be associated with a worsening. pain on eating. Complications of peptic ulcer disease include bleeding, perforation, and gastric outlet obstruction, which may present as protracted vomiting immediately after eating.

Gastroenterology

Cholelithiasis may also present with postprandial epigastric pain and may be excluded with an ultrasound of the gall bladder.

Initial diagnostic assessment should exclude evidence of chronic blood loss. A young patient with classic presentation for peptic ulcer disease can be treated empirically with H2-blockers or proton pump inhibitors. If symptoms persist, then an evaluation should be pursued. An underlying disorder, such as Zollinger Ellison syndrome, should be excluded if ulcers recur. A patient over age 50 is at greater risk for a malignant ulcer and should be evaluated initially with endoscopy.

Further diagnostic plan

1. Upper endoscopy

2. Campylobacter-like organism urease test

3. Helicobacter pylori antibodies in serum

Results

1. Nondilated stomach, I-em ulceration in the first portion of the duodenum with no bleeding and no evidence of gastric outlet obstruction

2. Positive

3. Positive for H. pylori antibodies

Treatment plan

H. pylori therapy for 2 weeks with an oral proton pump inhibitor (such as omeprazole, pantoprazole, or rabeprazole) combined with amoxicillin/clarithromycin, or metronidazole/clarithromycin. Alternatives include: tetracycline/metronidazole/bismuth subsalicylate or tetracycline/ clarithromycin/bismuth subsalicylate.

Discussion

This patient has a duodenal ulcer secondary to H. pylori. The initial medical management of peptic ulcer disease is antisecretory therapy with H2 receptor antagonists (e.g., cimetidine, ranitidine, nizatidine, famotidine) or proton pump inhibitors (e.g., omeprazole, lanzoprazole). There is no difference between the different medications within a class; however, the proton pump inhibitors produce more rapid healing of duodenal ulcers because of their sustained antiacid secretory effect. Sucralfate is an inert orally ingested medicine that topically coats the ulcer, forming a protective layer. Sucralfate is equal in ulcer-healing efficacy to H2 blockers. Antacids are composed of aluminum and magnesium hydroxide and act by neutralizing gastric acid and protecting gastric mucosa. Antacids at high doses also demonstrate healing rates comparable with H2 blockers.

H. pylori infection is associated with 90% of duodenal ulcers and 70% of gastric ulcers. Therapy for H. pylori dramatically reduces the recurrence of ulcer disease (75 to 90% reduction in peptic ulcer). Almost 50 to 60% of patients will have a recurrence after treatment with H2 blockers alone if H. pylori is not eradicated with antibiotics. Unfortunately, the therapeutic regimen for H. pylori has not been sufficiently standardized to offer a single recommendation. A combination therapy with a proton pump inhibitor and two of four antibiotics (clarithromycin, amoxicillin, tetracycline, or metronidazole) is most commonly used. Other therapeutic regimens include bismuth subsalicylate combined with two antibiotics. The urease test, breath test, and H. pylori serum antibody all have a sensitivity of over 96% and a specificity of 99%. When duodenal ulcers occur in young patients with typical features, an upper endoscopy is not always necessary to confirm the diagnosis.

IlAPLAlril· I me 1C8

11

USMLE Step 3: Internal Medicine

12 Hi.ilical

Lifestyle modifications, such as cessation of smoking, alcohol, and nonsteroidal antiinflammatory agents, help healing and prevent recurrence. Bland (nonspicy) diets do not help.

Surgery is indicated for severe complications such as severe bleeding not responsive to local therapy, perforation, or obstruction. Although duodenal ulcers are not associated with malignancy, refractory cases may occasionally require surgery.

Case Review

Duodenal Ulcer

o Pain occurs a few hours after food intake.

o Pain is relieved with food and antacids.

o No vomiting or weight loss

Gastric Ulcer

o Pain occurs sometimes within 30 minutes after food intake.

o Pain is worsened with food; antacids commonly do not relieve pain.

o It is common to have vomiting and weight loss.

Gastroesophageal Reflux

o Abdominal and chest discomfort that occurs after heavy meals, especially at night

o Antacids relieve pain as well as lifting the head of the bead and avoiding late meals, alcohol, cigarettes, and fatty and citrus foods.

o No vomiting or weight loss

Gastric Cancer

o Pain is continuous and occurs after food intake.

o Pain is worsened with food; antacids do not relieve pain.

o Marked vomiting and weight loss

o Supraclavicular lymphadenopathy

Ciastroenterology

CASE 4

Chief complaint

"My stomach hurts, and I'm vomiting dark stuff."

History and physical examination

A 65-year-old man comes to the emergency department complaining of upper abdominal pain and vomitus resembling coffee grounds. The patient was in his usual state of health until about 2 months ago when he began noticing upper abdominal pain, which is worsened by food. This pain has progressed over the last few weeks to be a little more frequent in nature. In addition, yesterday the patient vomited and noticed what appeared to be coffee grounds in the vomit. He denies any significant weight loss and only occasionally uses nonsteroidal antiinflammatory agents for back pain. He is a smoker for the past 25 years, and he does not drink alcohol. There is no significant past medical history.

He is a well appearing man in no distress. His blood pressure is 120/80 mm Hg, and his pulse is 80/min with no orthostatic changes. His abdomen is soft with very mild .epigastnc tenderness. There are normoactive bowel sounds, but no visible veins or ascites. Rectal examination shows brown, guaiac-positive stool; no hemorrhoids are seen.

Differential diagnosis

• Gastric ulcer disease

• Gastritis

• Peptic ulcer disease

• Reflux esophagitis

• Gastric cancer

• Cholelithiasis

• Pancreatitis

Initial diagnostic plan

1. Complete blood count

2. Prothrombin and partial thromboplastin times

3. Serum electrolytes

4. Amylase/lipase

5. Ultrasound of the abdomen

meCtlcal 13"

USMLE Step 3: Internal Medicine

14 n;~ilical

Results

1. Hemoglobin 11 mg/dl, (normal: 13-18mg/dL)

2. Normal

3. Normal

4. Normal

5. No evidence of cholelithiasis

Assessment

It is impossible to tell solely by symptoms the exact cause of this patient's nausea, abdominal pain, and coffee ground emesis. All of the conditions in the differential could produce these complaints.

Generally, duodenal ulcer pain is relieved by ingestion of food, whereas the pain of gastric ulcers is generally worsened or unchanged by the ingestion of food, as is seen in this patient. Barium radiologic studies can be diagnostic in many of cases, but accuracy is dependent on size and location of the ulcer and on the technique used. Barium radiography is also limited because it does not allow for biopsies to exclude malignancy. This is more important with gastric ulcers than duodenal because gastric ulcers are associated with malignancy.

The use of nonsteroidal antiinflammatory agents and stress (such as burns) are risks for peptic ulcer disease. Nonsteroidal antiinflammatory agents work in general by inhibiting prostaglandins. Prostaglandins protect the gastric mucosa by increasing the secretion of its protective mucous and bicarbonate covering. The prevalence of ulcer formation in patients who take nonsteroidal antiinflammatory agents is 20 to 30% for gastric ulcers and 4 to 10% for duodenal ulcers. The risk of bleeding is higher in patients who are older, have a previous history of peptic ulcer disease, take high doses of nonsteroidal antiinflammatory agents, have cardiac disease, and take concurrent steroids.

Alcohol can damage gastric mucosa and promote acid secretion but is not itself ulcerogenic. However, alcohol taken in large doses impairs ulcer healing.

Tobacco also decreases the healing rate, increases persistence and recurrence rates of ulcers, and is associated with higher mortality rates.

Greater than 90% of duodenal and 70% of gastric ulcers are caused by H. pylori infection. Colonization increases with age so that above age 60 the risk is approximately equal to age.

Further diagnostic plan

1. Upper endoscopy (Note: Upper endoscopy has to be obtained in all patients with presumed upper gastrointestinal bleeding. This procedure allows accurate diagnosis, prognosis, and treatment of the condition.)

2. Biopsy

Results

1. Gastric ulcer approximately 2 cm in size in the body of the stomach with no active bleeding

2. No cancer

Treatment plan

1. H2-blockers, sucralfate, or proton pump inhibitors

2. Treatment of Helicobacter pylori if it is present

Gastroenterology

This patient has a bleeding gastric ulcer related to tobacco and nonsteroidal antiinflammatory agents use.

The treatment plan includes H2-blockers or proton pump inhibitors for 6 to 8 weeks. Alternatively, sucralfate can be given, 1 g qid. All aspirin and aspirin-like products and non-steroidal antiinflammatory agents should be avoided, and the patient has to be advised not to smoke or drink alcohol. The patient should undergo follow-up upper endoscopy in approximately 8 weeks to document healing. Biopsies of the ulcer should be obtained to rule out gastric cancer. Biopsy is relatively contraindicated with recent active bleeding because it may worsen the bleeding.

If active bleeding is seen, the ulcer can be treated endoscopically with bipolar cautery, heater probe, or epinephrine injection. Gastric ulcers rebleed three times more frequently than duodenal ulcers,

Approximately 5% of patients with bleeding peptic ulcers requiring transfusions need to have surgical intervention. The indications for surgery include multiple recurrent ulcerations or complications such as hemorrhage, obstruction, or perforation. Surgery is also considered for those who do not respond to prolonged medical therapy.

The healing of gastric ulcers is related more to the duration of acid suppression therapy than to the level of acid suppression. H2-blockers like cimetidine and ranitidine may be used. All agents in this group have similar clinical efficacy. Sucralfate offers equivalent efficacy as well. These drugs have largely supplanted the long-term use of magnesium and calcium carbonate-containing liquid antacids that have comparable efficiency as the H2-blockers. The proton-pump inhibitors omeprazole or lansoprazole produce more rapid healing of duodenal ulcers, but this effect is less pronounced with gastric ulcers.

me&lcal 15

USMLE Step 3: Internal Medicine

16 KAPLA~. I

meulC8

case Review

Duodenal Ulcer

o Pain occurs a few hours after food intake.

o Pain is relieved with food and antacids.

o No vomiting or weight loss

Gastric Ulcer

o Pain occurs sometimes within 30 minutes after food intake.

o Pain is worsened with food; antacids commonly do not relieve pain.

o It is common to have vomiting and weight loss.

Gastroesophageal Reflux

o Abdominal and chest discomfort that occurs after heavy meals, especially at night

o Antacids relieve pain as well as lifting the head of the bead and avoiding late meals, alcohol, cigarettes, and fatty and citrus foods.

o No vomiting or weight loss

Gastric Cancer

o Pain is continuous and occurs after food intake.

o Pain is worsened with food; antacids do not relieve pain.

o Marked vomiting and weight loss

o Supraclavicular lymphadenopathy

Gastroenterology

CASE 5

Chief complaint Confusion

History and physical examination

A 45-year-old man was admitted 2 days ago for an acute upper gastrointestinal bleed. The patient is an alcoholic with a long history of alcoholic liver disease. He underwent endoscopy on admission and was found to have a bleeding duodenal ulcer that responded to treatment with ranitidine. The patient appeared to be stabilizing, but his nurse noted that he was becoming increasingly confused this . morning. He appeared agitated and was oriented to his name but thought it was 1972 and that Nixon was president. The patient has become increasingly lethargic over the last few hours. He has been on thiamine since admission.

He is afebrile; his blood pressure is 130/80 mm Hg, pulse is 80/min, and respirations are 16/min. His neck is supple, lungs are clear, and his heart has a regular rate and rhythm. His abdomen is soft, nontender, liver edge not palpated, splenic tip 3 cm below the left costal margin. He is lethargic and uncooperative, withdraws to pain, is hyperreflexic bilaterally, and asterixis is present. Nystagmus is not present. Cranial nerve examination reveals no overt opthalmoplegia.

Differential diagnosis

• Hepatic encephalopathy

• Alcohol withdrawal/delirium tremens

• Wernicke encephalopathy

• Hepatorenal syndrome

• Infection: meningitis, bacterial peritonitis if the patient has ascites

Initial diagnostic plan

1. Complete blood count

2. BUN/creatinine

3. AST/ALT

4. Lactate dehydrogenase

5. Bilirubin

6. Glucose

7. Ammonia

KAPLANii' . I me lea

17

USMLE Step 3: Internal Medicine

18 R;e&ical

Results

1. White blood count 5,000/mm3 (normal: 4,000-11,000/mm3), hemoglobin 10 mg/dL (normal:

13-17 mg/dL), platelets 1l0,000/mm3 (normal: 150,00G-350,000/mm3); MCV 92 f.Lm3•

2. 20 mg/dL; l.lmg/dL

3. 60 U/L (normal: 8-30 U/L); 48 U/L (normal: 8-30 U/L)

4. 250 U/L (normal: 100-300 U/L)

5. 1.5 mg/dl, (normal: 0.1-1.0 mg/dl.)

6. 110 mg/dl, (normal: 80-120 mg/dl.)

7. 180 (normal: 47-65)

Assessment

A stressor such as gastrointestinal bleeding or infection often precipitates hepatic encephalopathy. An elevated ammonia level roughly correlates with this diagnosis. Ammonia levels by themselves do not adequately diagnose hepatic encephalopathy. Confusion and agitation several days into hospitalization is suggestive of delirium tremens, but this patient appears more confused than agitated and does not appear to be in a hypersympathetic state. Wernicke encephalopathy is possible, particularly in a patient receiving intravenous glucose solution who has underlying thiamine depletion, but this patient has been on thiamine replacement.

Further plan

1. Correct precipitating factors (e.g., gastrointestinal bleeding or infections)

2. Airway protection including intubation if necessary

3. Lactulose or neomycin to prevent ammonia absorption and facilitate excretion. The dose of lactulose should be titrated to produce 2 to 4 stools a day.

4. Limit dietary protein.

5. Neomycin to decrease intestinal flora if unresponsive to lactulose

Discussion

This patient has hepatic encephalopathy precipitated by recent gastrointestinal bleeding. Hepatic encephalopathy is a reversible change or decrease in neurologic status that is secondary to liver disease. The etiology of hepatic encephalopathy is not fully understood. It is associated with severe hepatocellular dysfunction, portal hypertension, shunting of blood away from portal circulation, and ingestion of high-protein meals. Toxic nitrogenous by-products of proteins absorbed from the intestine are not detoxified by the liver and gain access to the systemic circulation, leading to encephalopathy. Encephalopathy is often associated with high ammonia levels in 60 to 80% of cirrhotics.

Gastrointestinal bleeding or an increase in dietary protein often precipitates hepatic encephalopathy, which is associated with increased nitrogenous substances generated by colonic bacteria. Aggressive use of diuretics and associated electrolyte disturbances may also precipitate an event. This is associated with a contraction alkalosis that increases the proportion of circulating uncharged ammonia that can penetrate the blood-brain barrier.

Patients usually present with progressive confusion that may lead to stupor and coma. Focal signs may transiently develop. Hyperreflexia, rigidity, and asterixis are present. Fetor hepaticus refers to a musty smell related to the presence of mercaptans in the blood associated with encephalopathy. Cerebral edema may be present. The diagnosis of hepatic encephalopathy is one of exclusion.

Gastroenterology

Encephalopathy is treated by identifying and eliminating precipitating causes, such as protein sources in the gut (e.g., blood or food). Therefore, patients should be assessed for gastrointestinal bleeding, and dietary protein intake should be minimized. Sedatives or tranquilizers should be eliminated. Ammonia-lowering therapy with Iactulose should be initiated. Lactulose is an osmotic diuretic that acidifies colonic contents, which trap ammonia in the lumen and prevent its absorption. Lactulose also decreases ammonia production by colonic bacteria. Antibiotics such as neomycin, ampicillin, and rifampin can reduce ammonia levels by killing urease-producing colonic bacteria.

Case Review

Hepatic Encephalopathy

• History of liver disease

• Precipitating factor: gastrointestinal bleed, infection, overdiuresis, benzodiazepines, etc.

• Confusion and reverse of the sleep-wake cycle

• Elevated ammonia levels

• Treat with lactulose and antibiotics

Alcohol Withdrawal/Delirium Tremens

• Usually, but not always, occurs in known alcoholics

• Occurs after 24 to 48 hours of alcohol cessation

• Hypersympathetic state: elevated blood pressure, tachycardia

• Visual and auditory hallucinations; combative patient

• laboratory results normal

• Treat with benzodiazepines

Wernicke Encephalopathy

• History of malnutrition

• Recently given glucose

• Opthalmoplegia

• Ataxia

• Treat with thiamine

IlAPLAN'... I me lea,

USMLE Step 3: Internal Medicine

20 G;~cal

CASE 6

"I've had diarrhea, weight loss, and abdominal distension:'

History and physical examination

A 27-year-old woman comes to the office with 8 months of diarrhea, weight loss, and a pruritic skin rash. There is no blood or mucus in the diarrhea. She is a very anxious person and has been recently more depressed. She is very frustrated because she cannot identify a cause of the diarrhea and has become obsessive about eating only food that she is sure cannot be contaminated with any possible form of food poisoning. She denies fevers, abdominal pain, or bleeding, and her appetite is excellent.

Her temperature is 37.0 C (98.6 F), blood pressure is 130/80 mm Hg, pulse is 70/min, and respirations are 14/min. Examination of her eyes, ears, nose, throat, and neck is normal. Her abdomen is soft, nontender, and somewhat distended with hyperactive bowel sounds. Rectal examination shows guaiac-negative, brown stool. She has a diffuse, papulovesicular rash over her elbows, knees, buttocks, and back.

Differential diagnosis

• Inflammatory bowel disease

• Celiac disease

• Lactulose intolerence

• Whipple disease

• Irritable bowel syndrome

• Infectious diarrhea/parasitic infection (e.g., Giardia; cryptosporidiosis)

Initial diagnostic plan

1. Complete blood count, serum iron, calcium, B12

2. Stool culture

3. Stool examination for ova and parasites

4. Smear for fecal leukocytes

5. Stool for fat determination (Sudan stain)

Results

1. Mild macrocytic anemia; Bl2, folate, serum iron, calcium, and magnesium all mildly

decreased

2. Negative for enteric pathogens

3. Negative x3

4. No fecalleucocytes noted

5. Multiple fat globules seen

Gastroenterology

Assessment

The differential diagnosis of chronic diarrhea includes infectious etiologies, inflammatory bowel disease, and malabsorption syndromes. Bacterial gastroenteritis would present acutely and often resolves spontaneously over several days. Giardia may cause a chronic diarrheal syndrome associated with bloating and dyspepsia. In immunocompromised patients (e.g., AIDS patients), cryptosporidia, microsporidia, giardia, and Mycobacterium avium intracellular are common causes of chronic diarrhea.

Malabsorption syndromes are characterized by steatorrhea and weight loss. Pancreatic insufficiency-induced malabsorption is caused by chronic pancreatitis or cystic fibrosis. Injury to the small bowel surface is seen with celiac sprue, Whipple disease, or tropical sprue.

Finally, lactase deficiency results in bloating and diarrhea after ingesting milk products. It is documented by history and the impact of cessation of milk products in the diet.

Once infectious etiologies are excluded, malabsorption is documented with fecal fat examination and D-xylose absorption test.

Further diagnostic plan

1. Urinary D-xylose

2. Antiendomysial antitransglutaminase and antigliadin antibodies

3. Small bowel biopsy if D-xylose test is abnormal

Results

1. Abnormal, low ( <5 g in 5 hours)

2. Ptesent

3. Abnormal, with total villous atrophy

Treatment plan

1. Gluten-free diet (no wheat, rye, oats, bran)

2. Use of rice and corn-containing products 3: Folate and iron supplementation as needed

Discussion

Celiac sprue is suggested here, given laboratory and endoscopic findings. Celiac disease or gluten-sensitive enteropathy results from damage to the mucosa of the proximal small intestine from an unknown mechanism. There seems to be an immunologic reaction that results in the development of an immune response against the intestinal mucosa that is stimulated by digestion of gluten, which is a protein contained in grains. The disease seems to be somewhat genetically predisposed, because there are certain HLA haplotypes that are more common in these patients and their relatives. Celiac disease can first present in childhood and resolve spontaneously, only to recur as an adult usually in the fourth and fifth decades. Other patients may not manifest symptoms until middle or old age. These patients may have asymptotic disease in childhood or may develop the disease in adulthood, as may be the case with this patient.

Patients with celiac disease present with diarrhea, weight loss, abdominal distention, fatigue, and skin lesions. The skin lesions are characteristically vesiculopapular and intensely pruritic and are known as dermatitis herpetiformis.

III P LA Ir .. _ .•

me lea··

21'

USMLE Step 3: Internal Medicine

22 iilec.ical

The three features of celiac sprue that establish diagnosis include (1) evidence of malabsorption, (2) characteristic duodenal mucosal changes seen on biopsy (as discussed below), and (3) symptomatic improvement on gluten-free diet. Diarrhea occurs secondary to malabsorption, and hence steatorrhea occurs. Diagnosis is based on confirming steatorrhea by fecal fat examination with Sudan black staining. Serum iron, vitamin' B12, zinc, magnesium, and calcium can also be decreased because of the malabsorption, given that these elements are absorbed in the small intestine. Iron deficiency anemia is most common among these because of impaired absorption in the duodenum.

The D-xylose test helps to differentiate malabsorption from pancreatic insufficiency from sprue because sprue is caused by an intestinal mucosal defect and not an enzyme secretory defect. D-xylose is a five-carbon sugar that should be absorbed in the proximal small intestine and excreted in the urine easily as long as the small bowel mucosa is intact. Because metabolism of the sugar is not necessary for absorption, pancreatic and other enzyme deficiencies do not affect it. In this patient, the D-xylose level in the urine was low, indicating that the defect lies at the level of the intestinal mucosa and that D-xylose was not absorbed.

The small bowel duodenal biopsy is essential in the diagnosis of this disease because it identifies the total villous atrophy that is seen in 80% of patients and mononuclear infiltrate in the lamina propria. Celiac sprue patients should respond to the gluten-free diet. Diagnosis can be confirmed with resolution of symptoms while on a gluten free diet. Antibody tests, including antiendomysial antibody and antigliadin, can also assist in diagnosis. Antiendomysial antibody is more useful with a specificity and sensitivity of 90%.

Lymphoma can occur in 10 to 15% of cases of celiac disease. It is unclear whether therapy with a gluten-free diet decreases the incidence oflymphoma.

The mainstay of therapy is placement on a gluten-free diet (diet free of wheat, rye, and barley gluten), which is difficult for most patients to comply with because the standard western diet is high in gluten content. With compliance with therapy, the small intestinal mucosa normalizes. Patients with anemia and electrolyte abnormalities may require supplemental therapy.

Gastroenterology

Case Review

Malabsorption Syndromes Caused by

Bowel Inflammation

• Voluminous foul-smelling stool; no blood in the stool

• Weight loss and malnutrition

,

• Whipple disease: arthritis and central nervous system symptoms

• Laboratory evidence of vitamin deficiencies and anemia

• Fat in the stool

• D-xylose is abnormal.

• Antiendomysial, antigliadinantibodies may be positive.

• Small bowel biopsy shows inflammation.

Malabsorption Syndromes Caused by Pancreatic Insufficiency

• Voluminous foul-smelling stool; no blood in the stool

• History of chronic pancreatitis or cvsticfibrosis

• Weight loss and malnutrition

• Fat in the stool

• D-xylose is normal.

• Pancreatic enzymes decreased

Inflammatory Bowel Disease

• Bloody diarrhea

• Family history of inflammatory bowel disease

• Weight loss and low-grade fever

• Arthritis and erythema nodosum

• Flexible sigmoidoscopy is diagnostic

Irritable Bowel Syndrome

• Alternating constipation and diarrhea

• Normal laboratory tests

• Normal flexible sigmoidoscopy

iii~&ical 23.

USMLE Step 3: Internal Medicine

24 a;~ical

eASE 7

Chief complaint

"Food gets stuck in when I eat:'

History and physical examination

A 55-year-old man comes to the office complaining of progressive difficulty swallowing food over the last 3 months. The patient states that he initially noted that meat was difficult to swallow and that it appeared to be getting "stuck" in his midchest. He was able to avoid these symptoms by careful chewing. Over the last 2 months, he began to have difficulty with all solid food and notes that last week he began to regurgitate liquid. He notes a weight loss of 25 Ib over this period. He has a history of smoking two packs of cigarettes per day and drinks "socially." He states that he has had blackouts in the past associated with drinking.

He is disheveled and cachetic appearing. He is afebrile; blood pressure is 120/72 mm Hg, pulse is 72/min, and respirations are 16/min. He has poor dentition but no lymphadenopathy. His chest is clear, and his heart has a regular rate and rhythm with normal 51 and 52. His abdomen is soft, nontender, and with no hepatosplenomegaly. Rectal examination shows guaiac-positive brown stool. His extremities are normal with no edema.

Differential diagnosis

• Esophageal carcinoma

• Achalasia

• Esophageal stricture

• Schatzki's ring

Initial diagnostic plan

1. Barium swallow

2. Complete blood count

Results

1. Circumferential mass in the midesophagus

2. WBC 5,000/mm3 (normal: 4,000-1l,000/mm3), hemoglobin 10.2 mg/dl, (normal: 13-17 mg/dl.), MCV 78 f.Lm3

Assessment

The differential diagnosis of dysphagia is diverse and includes obstructive lesions of the esophagus and motility disorders. Achalasia is associated with swallowing difficulties and regurgitation often provoked by liquids and solids. It is confirmed by abnormal manometry studies and barium studies showing disordered esophageal contractions.

Gastroenterology

Esophageal strictures are seen with chronic gastroesophageal reflux. Stricture formation can also be secondary to ingestion of caustic substances, such as lye, which injure the mucosa.

In a patient with progressive dysphagia and weight loss, mechanical obstruction caused by an intrinsic or extrinsic mass should be suspected. Extrinsic compression may be caused by mass lesions like lymphoma, whereas intrinsic compression is most likely caused by esophageal carcinoma. Diagnosis is established by endoscopy and biopsy.

Further dagnostic.plan

1. Endoscopy and biopsy of the mass

2. Endoscopic ultrasound

3. Abdominal CT scan and chest x-ray

Results

1. Squamous cell carcinoma

2. Mass penetrates through esophageal wall

3. Negative

Treatment plan

1. Surgical resection

2. Radiation therapy combined with neoadjuvant chemotherapy

Discussion

Esophageal carcinoma is uncommon in the United States but is common in areas of China, Iran, Afghanistan, and Iceland. Squamous cell carcinoma and adenocarcinoma account for 95% of esophageal cancers. Squamous cell carcinoma is seen predominantly in black men who are in their sixth or seventh decade. Smoking and alcohol abuse account for almost 90% of cases in the United States; there is a greater association with hard liquor. It is also associated with history of chronic strictures (lye or radiation), chronic achalasia, and the presence of esophageal webs with iron deficiency (Plummer-Vinson syndrome).

Most of the disease involves the midesophagus where 85% of the carcinomas are squamous cell. Adenocarcinoma, which is derived from the distal esophagus, has become increasingly more cornmono Since the 1980s, the incidence of adenocarcinoma of the esophagus has been increasing because of reflux disease. Adenocarcinomas are seen most frequently in white men in their sixth decade. These tumors are associated with chronic reflux and Barrett esophagus.

Esophageal carcinoma presents with progressive dysphagia to solids followed by liquids, weight loss, and sometimes aspiration pneumonia. The disease spreads locally to adjacent lymph nodes, lungs, and pleura. Hematogenous spread to the liver is common.

Laboratory abnormalities seen in patients with esophageal squamous cell carcinoma include microcytic anemia (secondary to bleeding from mass) and low albumin and cholesterol caused by poor nutritional status. Patients may have guaiac-positive stools if blood loss is occurring from the mass, as seen in this case. Elevated calcium levels can be present with bone metastasis or with parathyroid-like molecule secretion from squamous cell cancer.

The disease is diagnosed by endoscopic biopsy. Concurrent tumors of the head, neck, and lung should be investigated. CT scan, MRI, and endoscopic ultrasonography can assist in staging. Bronchoscopy, thoracoscopy, and laporoscopy can be useful in determining metastases that are

USMLE Step 3: Internal Medicine

,i

26 me'lieal

smaller than 1 cm and may not be seen on imaging studies. A tumor that invades through the esophageal wall has a dismal prognosis: The 5-year survival rate is less than 5%.

Surgical resection is feasible in only 40% of cases and has a significant associated tnorbidity. Radiation therapy is the mainstay of treatment of squamous cell carcinoma and is Used alone or in conjunction with surgery and/or chemotherapy.

Endoscopic dilation of an obstructing mass can be done for palliative care in unresectable tumors and provides symptomatic relief of dysphagia. An esophageal stent can be placed endoscopically if needed.

--,-.~.----

'-------'",

CIse Review

Esophageal Carcinoma

• History of progressive dysphagia to solids and then liquids

• Weight loss

• History of heavy alcohol consumption and/or smoking

• Barium swallow shows evidence of tumor.

Achalasia

• History of dysphagia that occurs slowly, sometimes over years

• With or without weight loss

• If associated with Chagas disease: travel to endemic areas

• Barium swallow shows smooth tapering of the esophagus

Esophageal Stricture

• Dysphagia to solids and rarely to liquids

• Usually no weight loss

• Prior history of gastroesophageal reflux

• Barium swallow shows evidence of stricture.

Schatzki Ring

• Episodic dysphagia to solids and liquids that comes and goes

• No weight loss

• Occurs in middle-aged men

• Barium swallow shows evidence of ring in the lower esophagus.

Gastroenterology ,

CASE 8

Chief complaint "Left-sided abdominal pain"

History and physical examination

A 78-year-old African American woman comes to an unscheduled office visit complaining of left-sided abdominal pain for the past 24 hours. She had a similar episode approximately 3 months ago, which seemed to go away on its own. Yesterday, she noted some mild abdominal pain on the left lower abdomen, which has steadily worsened over the course of the day in association with low-grade fevers. She denies nausea or vomiting. She denies a change in her bowel habits or blood per rectum. She denies any change in her urinary habits or any weight loss. Her appetite is good.

Her temperature is 38.3 ( (101.0 F), blood pressure is 130/80 mm Hg, pulse is gO/min, and respirations are 18/min. Examination of her heart and lungs is normal. Her abdomen is soft, nondistended, and there is mild rebound noted in the left lower quadrant. There is no evidence of diffuse peritonitis or costovertebral angle tenderness. Rectal examination shows guaiac-negative stool with no masses.

Differential diagnosis

• Diverticulitis

• Colonic perforation

• Pyelonephritis

• Left lower lobe pneumonia

• Appendicitis

• Colon cancer

Initial diagnostic plan

1. Complete blood count

2. Biochemical profile

3. Chest x-ray

4. Abdominal x-ray

5. Urinalysis

Results

1. WBC count lS,OOO/mm3 (normal: 4,OOO-ll,OOO/mm3), normal hemoglobin

2. Normal

3. Normal

4. Air-filled small bowel in the lower pelvis. No evidence of intestinal obstruction, no free air.

5. No pyuria or blood

HI.&leal 27

USMLE Step 3: Internal Medicine

Ii Ii

28 ~&ical

i'

.

Assessment

Fever and lower abdominal pain are worrisome findings that could be consistent with appendicitis. Pain and tenderness exclusively on the left is inconsisterit with appendicitis. A good appetite and the absence of tenderness on rectal examination are also inconsistent with appendicitis. Colitis is unlikely without diarrhea or blood in the stool.

Further diagnostic plan

CT scan of abdomen and pelvis

Results

CT scan of abdomen and pelvis shows localized inflammatory changes along the sigmoid colon with no evidence of free air or abscess. The bowel loops and diverticula are visible.

Treatment plan

1. Nothing by mouth

2. Intravenous hydration

3. Intravenous antibiotics, such as ciprofloxacin and metronidazole

4. Surgical exploration if the patient worsens

Discussion

This patient has findings consistent with diverticulitis. Diverticulitis results from inflammation and microperforation of colonic diverticulum. The microperforation is thought to occur secondary to a fecalith, which becomes trapped in the diverticulum and causes inflammation. Diverticulitis is seen in up to 25% of patients with diverticula. It most commonly occurs on the left side of the colon. Patients commonly present with fever, leukocytosis, and left lower quadrant abdominal pain, as seen in this patient.

Complications of diverticulitis include abscess formation, colovesical fistula formation (causing recurrent urinary tract infections or pneumaturia), or perforation leading to peritonitis.

Physical examination reveals left lower quadrant tenderness. Occasionally, an inflammatory phlegmonous mass can be felt on palpation.

Diagnosis can be suspected from the clinical findings listed above. CT scan confirms diagnosis and often reveals a thickened (inflamed) colon with a possible abscess or fistula.

Patients with minimal symptoms can be treated on an outpatient basis with oral antibiotics. Patients who demonstrate more significant signs of inflammation, such as this patient, should be admitted to the hospital and receive nothing by mouth, started on intravenous hydration, and given broad-spectrum antibiotics to cover Gram-negative and anaerobic colonic flora. If the patient's clinical condition improves on this regimen with normalization of physical findings, the patient can be slowly started on oral intake, and the diet can be advanced as tolerated. Once resolution occurs, 7 to 10 days of oral antibiotics should be given. Most patients display symptomatic improvement within 72 hours.

If the patient's clinical condition continues to worsen while on intravenous antibiotics, or if the patient develops peritonitis of a more diffuse nature, surgical intervention and an exploratory laparotomy are indicated. Resection of the involved area would be necessary, in addition to creating a colostomy. Surgery can also be considered on an elective basis in patients with recurrent episodes of diverticulitis. Abscess drainage and fistula repair may also be needed.

Gastroenterology

Colonoscopy and barium enemas are contraindicated in active diverticulitis because of the potential for perforation. However, colonoscopy should be performed once inflammation resolves in all patients over 50 years of age to rule out a microperforation from a sigmoid colon carcinoma, which can present the same way.

Case Review

Diverticulitis

• Left lower quadrant abdominal pain, fever, leukocytosis, and possibly diarrhea and/or constipation

• Diagnosis established with CT scan.

• Admit to hospital for intravenous antibiotics, hydration, and nothing by mouth for severe

disease.

• Outpatient treatment with oral antibiotics for milder disease

• No colonoscopy or barium enema during acute episode

• Surgery may be necessary if there is no improvement or if complications such as peritonitis develop

• Recommend high-fiber diet after episode

Colonic Perforation

• Acute abdominal pain with signs of peritonitis (rebound tenderness and rigidity)

• Fever and marked leukocytosis

• Free air under diaphragm on upright chest x-ray

• Treat with volume resuscitation, intravenous antibiotics, and surgery

Pyelonephritis

• Flank pain, fever, chills, urgency, dysuria, and frequency

• Leukocytosis, pyuria, bacteriuria, and hematuria typically present

• Urine culture positive

• Antibiotic therapy

• Renal ultrasound is indicated if the patient fails to respond to therapy or if a complication, such as hydronephrosis, is suspected.

• Follow-up urine culture is indicated after treatment.

Left Lower Lobe Pneumonia

• Cough, fever, and dyspnea

• Altered breath sounds with or without rales

• Typically abnormal chest x-ray

• Antibiotic therapy

(Continued)

KAPUN' .. _ I me 1C8

29

USMLE Step 3: Internal Medicine

1:1

'i.!

I:

11 ,~ '!

l'

!

30 IAPLAJr... I me 1C8

case Review (continued)

Appendicitis

• Initially, periumbilical pain that typically localizes in the right lower quadrant, fever, anorexia,

nausea, and vomiting

• Leukocytosis is common; pyuria and microscopic hematuria may be present.

• Pain on passive flexion and internal rotation of right hip (obturator sign)

• Pain on passive extension of right hip (psoas sign)

• Tenderness on rectal examination

• Imaging studies typically not necessary; ultrasound and CT scan may be helpful

• Surgical treatment is necessary.

Gastroenterology

CASE9

Chief complaint

"Red blood mixed with loose stools"

History and physical examination

A 17-year-old white woman comes to the office because of bright red blood per rectum and loose stools for the past 2 weeks. She associated the rectal bleeding with 5 to 6 soft/loose stools per day and lower abdominal discomfort. There is no history of antibiotic use, no fever, no unusual travel, and no joint discomfort.

She is afebrile, and vital signs are stable. Cardiovascular and pulmonary examinations are within normal limits. Her abdomen is non distended, with normal bowel sounds. There is tenderness in the left lower quadrant. Rectal examination shows bright red blood in rectal ampulla. Nothing abnormal is palpated.

Differential diagnosis Infectious enterocolitis

• Inflammatory bowel disease

• Hemorrhoidal bleeding

Initial diagnostic plan

1. Stool for culture

2. Examine stool for ova and parasite

3. Examine stool for fecal leukocytes

4. Abdominal x-ray

5. Complete blood count and erythrocyte sedimentation rate

Results

1. Negative

2. Negative x3

3. Positive

4. Normal

5. Elevated white count and erythrocyte sedimentation rate

Assessment

Inflammatory bowel disease is a good consideration in this case and is divided into ulcerative colitis and Crohn disease. The predominant symptom of ulcerative colitis is bloody diarrhea, given rectal involvement in almost 100% of cases. Infection is unlikely, given negative stool studies. Hemorrhoids can occur at any age but should be palpable on examination.

32 IlAPLAIf... I

me .ca

Further diagnostic plan Unprepped flexible sigmoidoscopy

Results

Continuous petechial hemorrhage, mild exudate, edema, and hyperemia are seen in the rectosigmoid colon. A few superficial ulcerations are noted.

Treatment plan

1. Mesalamine

2. Corticosteroids are used in severe disease.

3. Supportive antidiarrheal agents

4. Total colectomy should be considered in severe cases refractory to steroids.

Discussion

This patient has ulcerative colitis. Ulcerative colitis is seen predominantly in young adults, but it has a second peak of incidences in the elderly population. There is a genetic predisposition to ulcerative colitis, with up to 20% of patients having a family member with the disease. The etiology of ulcerative colitis is unknown but is thought to possibly be immune-mediated or to result from food allergy or infection.

Patients with ulcerative colitis initially present with bloody diarrhea and abdominal pain for several weeks duration. The disease course can vary from mild proctitis to fulminant pancolitis. There is an increased risk of cancer in ulcerative colitis patients with disease> 1 0 years duration. These patients need to have a colonoscopy with biopsy to rule out dysplasia.

It is important to rule out infectious causes of diarrhea, which can present in a similar fashion in these patients. Stool studies should be checked. Sigmoidoscopy is useful in diagnosis and is best performed in an unprepped bowel. Colonic findings may reveal mucosal inflammation extending from the rectum proximally. The inflammation is continous (unlike Crohn disease, which has skip lesions). Biopsy sample can be obtained to assist in diagnosis. It is important to rule out toxic megacolon, which is a complication of ulcerative colitis, by abdominal films.

In an acute flare, patients can have elevated complete blood count and sedimentation rate. If significant blood loss occurs, anemia can be seen.

Patients with ulcerative colitis and Crohn disease may have extra-intestinal manifestations, which include arthritis, erythema nodosum, episcleritis, iritis, and sclerosing cholangitis.

Salicylates, such as mesalamine, should be used for initial therapy. Corticosteroids are used in the treatment of severe cases. Immunosuppressive agents (azathioprine and 6MP) can be used in chronic active disease where they have a steroid-sparring effect in patients who are steroid dependent. Enemas can be used for proctosigmoiditis. Surgery is occasionally needed for those patients with severe disease refractory to steroid therapy.

Gastroenterology

Case Review

Inflammatory Bowel Disease

• Bloody diarrhea

• Family history of inflammatory bowel disease

• Weight loss and low-grade fever

• Arthritis and erythema nodosum

• Flexible sigmoidoscopy is diagnostic.

• Increased risk of colon cancer

Infectious Enterocolitis

• Bloody diarrhea

• Positive stool cultures

Hemorrhoids

• Rectal bleeding, pain, and discomfort

• Associated with constipation, straining, low-fiber diet, pregnancy, and obesity

• Visual inspection, palpation, and anoscopy typically establish diagnosis.

• Conservative management with increased fiber in diet and increased fluid intake

• Surgery treatment with injection sclerotherapy, rubber band ligation, and surgical excision is sometimes necessary.

KAPUl[iI· ..•

me lea

USMLE Step :5: Internal Mediane

34 ~cal

CASE 10

Chief complaint

"Severe, dull abdominal pain"

History and physical examination

A 32-year-old man with a history of alcohol abuse comes to the emergency department with a 2-day history of increasing, constant dull epigastric pain that radiates to the back. He has had two episodes of emesis without any blood or coffee grounds. The patient admits to an alcoholic binge yesterday. He denies prior history of similar episodes. He denies any history of trauma or medication use.

His temperature is 37.7 ( (99.9 F). His supine blood pressure is 110/70 mm Hg, and pulse is 100/min; standing blood pressure is 90/60 mm Hg, and pulse is 120/min. His heart is tachycardic, and his lungs are within normal limits. His abdomen has decreased bowel sounds, tenderness to palpation in the epigastric region, but no guarding or rebound tenderness. Rectal examination shows guaiac-negative stool.'

Differenti~1 diagnosis

• Pancreatitis

• Peptic ulcer disease with possible perforation

Initial diagnostic plan

1. Stabilize patient

2. Complete blood count

3. Biochemical profile

4. Amylase and lipase

5. Abdominal x-ray

Results

1. Place large bore catheters and start fluids

2. WBC count 15,000/mm3 (normal: 4,000-11,000 rnml)

3. Glucose 204 mg/dL (normal: 80-120 mg/dL) and calcium 7.2 mg/dL (normal: 8.5-10.5 mg/dL)

4. Amylase 460 U/L (normal: 60-180 U/L);lipase 1,000 U/L (elevated 3x normal)

5. No evidence of free air

Assessment

People with a history of alcohol abuse are at risk for acute pancreatitis" which classically presents with abdominal pain that radiates to the back. This patient is orthostatic from fluid sequestration and vomiting. There is no rebound tenderness Of guarding, arguing against a perforated peptic ulcer. Patients with pancreatitis can have low-grade fevers, increased whiteblood-cell count, and electrolytic abnormalities, especially hypocalcemia. An elevated amylase

Gastroenterology

and lipase support the diagnosis. There are no features that localize the source of the problem to the gall bladder, although gallstone pancreatitis must be considered.

Further diagnosti, plan CT scan of the abdomen

Results of further diagnostic plan

Abdominal CT scan shows diffuse pancreatic edema with extension to the pancreatic fat.

Further treatment plan

1. Nothing by mouth

2. Analgesics (e.g., meperidine or morphine) 3 .. Intravenous hydration

Discussion

This patient has alcohol-induced pancreatitis. In acute pancreatitis, there is pancreatic inflammation, and autodigestion occurs within. acinar cells by activated pancreatic enzymes. In the United States, alcohol abuse accounts for 30% of cases of acute pancreatitis, followed by gallstones. The exact mechanism of alcoholic injury to the pancreas is unknown. Other causes of pancreatitis include hyperlipidemia, hypercalcemia/hyperparathyroidism, pancreatic divisum, medications, and pancreatic trauma.

Most patients present with abdominal pain in the upper abdomen or epigastric region that usually radiates tothe back. The pain is often dull in nature. Patients may have nausea and vomiting accompanied by severe abdominal pain. Patients usually have upper abdominal tenderness on physical examination. Abdominal ecchymosis can be seen in severe cases of pancreatic necrosis where exudate accumulates in the periumbilical region (Cullen sign) or flank region (GreyTurner sign).

Pancreatic enzymes amylase and lipase are elevated at least to 3 times their normal limit. Amylase increases first, followed by the lipase, which is more specific for pancreatic injury. Increase glucose levels are seen secondary to decreased levels of glucagon. A decrease in calcium occurs secondary to sequestration and does not mandate treatment.

Abnormalities that are indicative of a poor prognosis are also known as Ranson's criteria and are divided into those seen at admission and at 48 hours. Some of these criteria are WBC >16,000/mm3, glucose >200 mgldL; SGOT (AST) >250 U/L, calcium <8 mg/dl., BUN increase, and dehydration (> 10% fall in HCT with hydration). They help determine which patients will develop serious complications and may need to have surgical intervention.

Abdominal CT is helpful in confirming diagnosis and detecting the progression of disease. Pancreatic inflammation can be seen on CT as well as phlegmonous changes, pseudocysts formation, and pancreatic necrosis.

Other complications of pancreatitis include phlegmonous changes (early in disease), abscess formation (4 to 6 weeks), formation of pseudocyst (collection of pancreatic fluid surrounded by fibrous or granulation tissue occurring at 1 to 4 weeks), necrosis (2 weeks), and acute respiratory distress syndrome. The mortality rate for acute pancreatitis is 10% and is related to the presence and severity of pancreatic necrosis.

m8CIlcal 31

USMLE Step 3: Internal Medicine

36 iC;.Clical

The mainstay of treatment for pancreatitis is supportive, and 90% patients with pancreatitis spontaneously resolve. Support consists of putting the pancreas at rest by stopping all oral intake and correcting all of the fluid sequestration by providing intravenous fluids and analgesic therapy. This patient should be encouraged to stop alcohol ingestion and be monitored for delirium tremens. Patients can be started on oral intake once abdominal pain resolves and narcotic analgesics are not needed. Normalization of amylase or lipase is not needed to initiate oral intake. There is no evidence that antibiotics help resolve uncomplicated episodes of pancreatitis. Antibiotics (imipenem or cefuroxime) are used in the setting of severe pancreatitis with organ failure or necrosis. Surgical therapy may be needed for pseudocyst removal or necrotic debridement.

Case Review

Pancreatitis

• Severe epigastric pain radiating to the back, anorexia, nausea, vomiting

• Associated with history of alcohol abuse or gallstones

• Elevated serum amylase and lipase, hypocalcemia

• Ultrasound of gallbladder and CT scan of abdomen

• Supportive treatment with nothing by mouth, nasogastric tube, intravenous fluids, and analgesics

Peptic Ulcer Disease With Possible Perforation

• Sudden onset of severe abdominal pain

• Patients typically have history of dull, achy, gnawing epigastric pain; however, up to 20% may

have no antecedent symptoms.

• Rebound tenderness and guarding, hypotension when peritonitis develops

• Leukocytosis and mildly elevated serum amylase

• Free intraperitoneal air seen on upright and decubitus abdominal x-rays

• Fluid resuscitation, nasogastric tube suction, intravenous antibiotics

• Surgery usually indicated

Gastroenterology

BONUS CASE A

Chief complaint

"I passed some blood."

History and physical examination

A sa-veer-old man is brought to the emergency department complaining of painless blood per rectum. He was doing we" until yesterday when, after getting up from the toilet, he noticed some maroon blood in the bowl. He felt a little lightheaded and sat down, and the symptoms passed. This morning he had a similar episode. He denies any fever or current abdominal pain. Bowel habits have generally been otherwise normal. He denies hematemesis or any history of epigastric ulcers, weight loss, or cardiac disease.

He is well appearing. His pulse is 8S/min lying down, lOS/min standing; his blood pressure is 124/84 mm Hg lying down, 104/70 mm Hg standing. Examination of his heart and lungs is significant only for tachycardia. His abdomen is soft, nontender, and nondistended. Rectal examination shows gross maroon clotted blood but no masses.

Differential diagnosis

• Diverticular bleeding

• Arteriovenous malformation

• Colon cancer/polyps

• Hemorrhoids

• Upper gastrointestinal bleeding source (rarely)

• Peptic ulcer

• Esophageal varices

Initial diagnostic plan

1. Placement of large-bore intravenous line

2. Fluid administration of normal saline

3. Obtain a complete blood count

4. Blood transfusion (packed RBC) as needed

5. Electrolytes; prothrombin and partial thromboplastin times (PT/PTT)

6. Flexible sigmoidoscopy and anoscopy in the emergency room, nasogastric tube

7. Repeat complete blood count every 2 hours until stable

8. Nasogastric lavage if considering upper gastrointestinal source

IAP!!!._ I m ... lC8

37

USMLE Step 3: Internal Medicine

38 lii8C1ical

Results of initial diagnostic plan

1. Hemoglobin 12 gldL (normal: 13.5-17.5 g/dl.)

2. Normal electrolytes

3. Normal PT/PTT

4. Flexible sigmoidoscopy and anoscopy reveal no evidence of site of bleeding

5. No blood in nasogastric tube lavage

Assessment

The patient presents with evidence of acute significant blood loss demonstrated by the presence of orthostatic changes on examination. Orthostatic changes are defined as an increase of pulse of > 10 beats/min and/or a drop in systolic blood pressure >20 mm Hg when the patient changes from a recumbent to an erect position. The relatively mild drop in the patient's hemoglobin reflects the lack of time for equilibration of blood volume after the acute episode. Once the patient is hydrated, the hemoglobin falls to a level more consistent with the volume of blood loss.

The presence of maroon stool or bright red blood per rectum (hematochezia) is most commonly associated with a lower gastrointestinal bleeding source. Massive bleeding from an upper source can also result in this presentation. Nasogastric tube placement with lavage can exclude this possibility. The nasogastric tube lavage is 90% sensitive on localizing an active upper gastrointestinal bleed. The negative predictive value in a lavage is elevated when there is nonbloody bilious drainage from the nasogastric tube that indicates placement of the tube has passed the pylorus and is in the duodenum. Etiologies of lower gastrointestinal bleeding include diverticular disease, colon polyp, colon carcinoma, hemorrhoids, arteriovenous malformations/angiodysplasia of the large intestine, and colonic ischemia. Inflammatory bowel disease and infectious colitis may result in gross gastrointestinal bleeding and is often associated with fever and mucus in the stool. Given the patient's age and history of painless rectal bleeding, lack of weight loss, and lack of cardiac disease, diverticular bleeding is most likely.

The assessment of the bleeding source is determined by the rapidity and volume of blood loss. Attention is initially given to stabilizing blood volume with crystalloids and packed RBCs as needed. Anoscopy may reveal a hemorrhoidal source. Flexible sigmoidoscopy/colonoscopy may also be useful acutely; however, fiberoptic examination may be limited by ongoing blood loss. If the patient stops bleeding, an appropriate oral colonic lavage can be given, followed by a colonoscopy. Colonoscopy can identify bleeding sites in up to 85% of patients.

If the patient continues to bleed aggressively obscuring fiberoptic examination, a tagged RBC or sulfur colloid bleeding scan or angiography can be attempted to identify the bleeding source. A slow rate of bleeding (0.1 mUmin) can be detected by a bleeding scan and is a sensitive test in patients with intermittent bleeding. Angiography is best at detecting faster rates of bleeding (0.5 to 1 mL blood/min) and can be useful in treatment with the use of intraarterial infusion of embolizing agents (e.g., Gelfoam) or vasospastic agents (e.g., vasopressin).

Further diagnostic plan

Complete colonoscopy after stabilization and adequate bowel preparation

Results of further diagnostic plan

Colonoscopy reveals diverticular disease of the sigmoid and ascending colon, with no active bleeding at this time. No evidence of any arteriovenous malformations is seen.

Gastroenterology

Final treatment plan

1. Monitor for further signs of bleeding.

2. High fiber diet once patient is stable

3. Consider surgery in the future if patient continues to have bleeding episodes that require transfusion.

Discussion

The primary objective in the management of any form of acute bleeding is maintenance of adequate fluid volume. Severe, intractable bleeding is managed with surgical resection of the site of bleeding if supportive measures are not effective. It is difficult to give concrete numerical values for hematocrits that would indicate the need for transfusion. A hematocrit as low as 25% may be well tolerated in a healthy, younger person. An older person or a person with a history of coronary disease should be maintained at a hematocrit above 30. Again, these numbers are approximations only. The rate of fall of the hematocrit is as important as the absolute number.

This patient has had a diverticular colonic bleed. Diverticular bleeding is the most common cause of lower gastrointestinal bleeding in patients over 50 years of age. It is usually painless and insignificant in terms of blood loss. However, a small percentage (5%) of patients may experience massive bleeding. Diverticular bleeding is seen in older patients and tends to be secondary to diverticula in the right colon; however, diverticular bleeding from the left colon can occur as well. A diverticulum is a herniation in the colonic mucosa, submucosa, and muscularis. The arterial supply via the vasarecta penetrates the circular muscle and submucosa and becomes chronically injured in the lumen of the diverticulum, which leads to bleeding. The diverticulum of the right colon has a larger lumen that allows for more vasa rectal injury and subsequent bleeding.

The recurrence of diverticular bleeding after an initial episode is estimated at 20 to 30%. Once the patient has a second diverticular bleed, the likelihood of a third bleeding episode increases to 50%. Elective surgical intervention should be considered if patients have had two or more bleeding episodes requiring transfusions and are good operative candidates.

Case Review

Diverticular Bleeding

• Painless rectal bleeding

• Stabilize patient first.

• Evaluate with nasogastric tube lavage, flexible sigmoidoscopy, anoscopy, and colonoscopy.

• Bleeding scan or angiography may be necessary to identify bleeding source.

• Recommend high-fiber diet once stabilized.

• Surgery may be indicated if there are recurrent episodes of diverticular bleeding.

Arteriovenous Malformation

• Painless rectal bleeding

• Stabilize patient first.

• Evaluate with nasogastric tube lavage, flexible sigmoidoscopy, anoscopy, and colonoscopy. """"",n" scan or angiography may be necessary to identify bleeding source.

(Continued)

KAPUlril'· , '. me 1C8

39

USMLEStep 3: Internal Medicine

40 ~I

Bleeding Esophageal Varices

• History of alcohol abuse or chronic liver disease

• Hematemesis with or without melena

• Stabilize patient first.

• Upper endoscopy is the mainstay of diagnosis and treatment.

• Treatment options include banding, sclerotherapy, vasopressin, sornatostann/ooreofide, and shunting.

• Nonselective beta-blockers (propranolol) can reduce the risk of recurrent variceal bleeding.

Case Review (continued)

Colon cancer/Polys

• Abdominal pain, change in bowel habits, frank or occult blood in stool, fatigue, weight loss,

anemia

• Colonoscopy with biopsy establishes diagnosis.

• Polypectomy typically curative for polyps

• Surgery typically indicated for colon cancer

Hemorrhoids

• Rectal bleeding, pain, and discomfort

• Associated with constipation, straining, low-fiber diet, pregnancy, and obesity

• Visual inspection and anoscopy typically establishes diagnosis.

• Conservative management with increased fiber in diet and increased fluid intake

• Surgery treatment with injection sclerotherapy, rubber band ligation, and surgical excision is sometimes necessary.

Peptic Ulcer Bleeding

• Hematemesis with or without melena or hematochezia

• Patients typically have history of dull, achy, gnawing epigastric pain; however, up to 20% may have no antecedent symptoms.

• Stabilize patient first.

• Upper endoscopy establishes diagnosis.

BONUS CASE B

Chief complaint

C4I've had diarrhea for one year:'

History and physical examination

A 52-year-old man complains of diarrhea for 1 year. He states that he has had several bowel movements each day; his diarrhea occurs with every bowel movement, and each episode is similar in nature. He denies any blood, mucus, or tenesmus. He has a history of recurrent peptic ulcers, despite treatment for Helicobader pylori. His weight is stable. There is no other significant past medical history.

He is a thin man in no distress. Cardiovascular and pulmonary examinations are within normal limits. Abdominal examination shows hyperactive bowel sounds, minimal epigastric pain, no masses, and no hepatosplenomegaly. StooUs yellowish

brown and guaiac negative. '. ~:"':.:

Differential diagnosis

• Zollinger-Ellison syndrome

• Hyperthyroidism

• Inflammatory bowel disease

• Irritable bowel syndrome

• Malabsorption

Initial diagnostic plan

1. Complete blood count

2. Stool culture

3. Ova/parasites

4. Fecalleukocytes

5. Serum electrolytes

6. Thyroid function tests

7. Upper gastrointestinal series

Results

1. Normal

2. Negative

3. Negative

4. No fecal leukocytes

5. Normal

6. Normal

7. Large mucosal folds

Gastroenterology

mMic81 4.1

USMLE Step 3: Internal Medicine

42 n;~ilical

Assessment

Chronic diarrhea seen in office practice is caused most often by functional disorders (irritable bowel), diseases of the colon (Crohn disease, ulcerative colitis), diseases of the small intestine (malabsorption syndromes-sprue, bacterial overgrowth) or carbohydrate intolerance (e.g., lactose, sorbitol, fructose) secondary to laxative abuse, and more rarely Zollinger-Ellison syndrome (gastrinoma) or carcinoid diarrhea.

History is most important in the diagnosis of chronic diarrhea. For example, age of onset may help narrow the likelihood of a disease process. Inflammatory bowel disease has a bimodal distribution and is seen in patients in their twenties and thirties and in patients who are 60 to 70 years of age.

Important tests to remember in chronic diarrhea evaluation are:

• Complete blood count with eosinophil count

• Stool ova/parasites

• Thyroid

• Postprandial glucose evaluation Serum folate and vitamin B12levels

Other important tests in chronic diarrhea are vitamin BIZ and Schilling test (pernicious anemia), 72-hour fecal fat (malabsorption syndrome), D-xylose test (jejunal mucosal disease), lactose tolerance test, and small bowel biopsy. If the preceding tests are unrevealing, procedures such as upper gastrointestinal series, endoscopy, and colonoscopy are part of further evaluation.

In this case, gastric acid output, serum gastrin, and gastrin response to secretin should be checked to rule out gastrinoma. Zollinger-Ellison syndrome or gastrinoma should be suspected when chronic diarrhea is associated with chronic peptic ulcer disease. The chronicity (> 1 year) of this patient's disease .points away from an infectious etiology. The absence of stool blood/mucus and weight loss point away from inflammatory bowel disease.

Further diagnostic plan

1. Basal gastric acid output

2. Serum gastrin

3. Gastrin response to intravenous secretin

4. Parathyroid hormone level

Results

1. > 15 mg/hour (high)

2. > 1 ,000 pg/mL (high)

3. >200 pglmL (high)

4. Normal

Treatment plan

1. High-dose omeprazole

2. Tumor localization with CT scan or MRI

3. Somatostatin-receptor scintigraphy

4. Endoscopic ultrasound

5. Surgical consult for possible laparotomy and resection of primary tumor

Gastroenterology

Discussion

Zollinger-Ellison syndrome should be considered in this patient given his history of recurrent peptic ulcer disease. Zollinger-Ellison syndrome occurs secondary to a gastrinoma that hypersecretes gastrin and leads to refractory recurrent duodenal bulb or stomach ulcers. A gastrinoma is a nonbeta islet cell tumor found most frequently in the duodenum (50%) and pancreas (25%); other sites include the spleen, stomach, and lymph nodes. Ninety percent of gastrinomas are found in the anatomic region known as the gastrinoma triangle, which includes midduodenum, porta hepatis, and the head of the pancreas. Zollinger-Ellison syndrome is more common in male patients 30 to 50 years of age.

Gastrinomas are biologically malignant in 60% of cases, and most malignant tumors involve the pancreas. These tumors are often multiple and slow growing. Ulcers are seen in the duodenal bulb or stomach. Pain from the peptic ulcer is common. The ulcer is duodenal in 75% of the cases. Diarrhea is noted in about 50% of cases and is caused by gastric hypersecretion. The high acid level may damage the small intestinal mucosa, inactivate pancreatic lipase, and precipitate bile acids, causing steatorrhea. The high gastrin levels cause incomplete sodium and water absorption, which increases intestinal motility. Gastrinomas are associated with multiple endocrine neoplasia type I (MENI).

These patients show elevated gastrin levels in the basal state. Basal or unstimulated gastric acid output is > 15 mEq/h. Serum gastrin levels are the most sensitive and specific way to identify patients with gastrinomas. Patients with gastrinomas have gastrin levels> 150 pg/mL (normal: <60 pg/mL). A patient with a marked increase in fasting gastrin level> 1,000 pg/mL along with the above clinical features is pathognomonic for Zollinger-Ellison syndrome. However, it is important to note that other entities can cause an elevated gastrin level, such as pernicious anemia, chronic gastritis, and the use of proton pump inhibitors. Provocative testing with intravenous secretin is useful in patients without striking elevations of fasting gastrin (> 1 ,000 pglmL) but with clinical features suggestive of Zollinger-Ellison syndrome. In patients with Zollinger- Ellison syndrome, intravenous infusion of secretin produces a marked increase in serum gastrin level by at least 200 pg/mL. In this case, the serum gastrin levels were >1,000 pg/mL, which, with the clinical history, establishes the diagnosis of Zollinger-Ellison syndrome. This is further confirmed with the elevated level of gastrin after infusion of secretin. At times, the upper gastrointestinal series shows large gastric mucosal folds, large amounts of gastric fluid thickened, and dilated small bowel, which may be suggestive of Zollinger-Ellison syndrome.

Treatment of Zollinger-Ellison syndrome is acid suppression with high-dose proton pump inhibitors and surgical removal of the tumor. It is important to attempt to locate the gastrinoma before surgery because it can occur in various locations. This can be a challenge for the physician because gastrinomas are difficult to locate in up to 20% of patients. Imaging studies such as arteriography, CT scan, MRI, or endoscopic ultrasound can be used. Arteriography and abdominal CT can identify 80% of tumors before surgery. Upper endoscopy may assist diagnosis as well, given the high incidence of tumor location in the duodenum. Surgery is thought to provide complete resection of gastrinomas and subsequent cure in 40% of patients with Zollinger-Ellison syndrome.

IlAP~!.. I mvulC8

43

USMLE Step 3: Internal Medicine

44 ~cal

case Review

Zollinger-Ellison Syndrome

• Diarrhea in a patient with peptic ulcer disease

• Elevated gastrin levels

Hyperthyroidism

• Significant weight loss

• Evidence of tremor, tachycardia, and enlarged thyroid

• Low thyroid-stimulating hormone and elevated free T4

Inflammatory Bowel Disease

• Bloody diarrhea

• Family history of inflammatory bowel disease

• Weight loss and low-grade fever

• Arthritis and erythema nodosum

• Flexible sigmoidoscopy is diagnostic.

Irritable Bowel Syndrome

• Alternating constipation and diarrhea

• Normal laboratory tests

• Normal flexible sigmoidoscopy

Malabsorption

• Voluminous foul-smelling stool

• Possible history of chronic pancreatitis or cystic fibrosis

• Weight loss and malnutrition

• Laboratory evidence of vitamin deficiencies and anemia

BONUS CASE C

Chief complaint

"Difficulty swallowing and weight loss"

History and physical examination

A 40-year-old woman presents with a 2-year history of progressive dysphagia to solids and liquids and weight loss of 15 pounds. She describes frequent regurgitation of food particles after meals. She is otherwise in good health and does not take medications. She has no recent travel history and no recent alcohol or tobacco use.

Her temperature is 37.0 ( (98.6 F), blood pressure is 120/80 mm Hg, pulse is 80/min, and respirations are 16/min. She appears thin and chronically ill. Examination of the eyes, ears, nose, and throat is unremarkable. Her chest is clear to auscultation, her heart has a regular rate and rhythm, and her abdomen is benign. Extremities are normal with no edema.

Differential diagnosis

• Achalasia

• Esophageal cancer

• Esophageal web

• Esophageal stricture

• Diffuse esophageal spasm

Initial diagnostic plan Barium esophagram

Results

Esophageal dilatation with smooth tapering of the distal esophagus ("bird beak sign")

Assessment

The complaint of dysphagia to solids and liquids that is progressive over 2 years and associated with regurgitation and recurrent aspiration is characteristic of achalasia. A malignancy would be expected to be seen in an older patient (>60 years) and would produce severe symptoms over a shorter duration of time «6 months). Idiopathic achalasia is the most common type in the United States. Chagas disease (achalasia, cardiomyopathy, and megacolon) should be considered as a cause in patients from South America. The smooth tapering of the distal esophagus on barium swallow is suggestive of a benign process.

a;;.1 I .. caJ

45

USMLE Step 3: Internal Medicine

46 KAPLAWiI- I me lea

Further diagnostic plan

1. Esophageal manometry

2. Esophageal endoscopy to exclude lower esophageal sphincter malignancy

Results

1. Aperistalsis, elevated lower esophageal sphincter pressure

2. Upper endoscopy-dilated esophagus with closed lower esophageal sphincter

Treatment plan

Pneumatic dilation or botulin toxin

Discussion

Achalasia is a disorder of the esophagus characterized by an abnormally high resting pressure of the lower esophageal sphincter with incomplete relaxation of the lower esophageal sphincter after swallowing and aperistalsis of the esophageal body. The result is esophageal dilatation and retention of swallowed food and secretions. The cause of achalasia is unknown. Achalasia is seen in males and females equally and has its highest frequency of occurrence in the third and fifth decades.

The diagnosis should be suspected by the classic presentation of progressive dysphagia, regurgitation of food hours after eating, and recurrent aspiration. Up to one third of patients mayexperience chest pain with food ingestion. Significant weight loss can be seen in advanced stages. Chest x-ray may reveal esophageal dilatation, which is confirmed by barium esophagram and shows the distinctive smooth tapering or "bird-beaking" of the distal esophagus. All patients with achalasia should undergo esophageal endoscopy to rule out gastric esophageal malignancy. The upper endoscopy in patients with achalasia can reveal a dilated esophagus and a closed lower esophageal sphincter. The endoscopy may be normal in some patients with less advanced disease states. Esophageal manometry establishes the diagnosis and reveals the characteristic high lower esophageal sphincter pressures with incomplete lower esophageal sphincter relaxation, and aperistalsis of esophageal body.

Treatment is directed at lowering the lower esophageal sphincter pressure. Medical pharmacotherapy uses smooth muscle relaxants, such as calcium channel blockers and nitroglycerin, which offer temporary relief. Botulinum toxin can be injected endoscopically to reduce lower esophageal sphincter pressures, but repeat injections are usually needed within a year. Mechanical interventions include pneumatic dilatation, in which a balloon is placed endoscopically in the lower esophageal sphincter and insufflated, thereby causing dilation of the sphincter. Pneumatic dilation offers a 60% response rate. The long-term solution involves surgical myotomy.

Gastroenterology

Case Review

Esophageal Carcinoma

• History of progressive dysphagia to solids and then liquids

• Weight loss

• History of heavy alcohol consumption and/or smoking

• Barium swallow shows evidence of tumor.

Achalasia

• History of dysphagia that occurs slowly sometimes over years

• With or without weight loss

• If associated with Chagas disease: travel to endemic areas

• Barium swallow shows smooth tapering of the esophagus

Esophageal Stricture

• Dysphagia to solids and rarely to liquids

• Usually no weight loss

• Prior history of gastroesophageal reflux

• Barium swallow shows evidence of stricture.

Schatzki Ring

• Episodic dysphagia to solids and liquids that comes and goes

• No weight loss

• Occurs in middle-aged men

• Barium swallow shows evidence of ring in the lower esophagus.

Endocrinology

CASE 1

Chief complaint

Lower abdominal pain, dysuria, weakness, and lethargy for two days

History and physical examination

A 17-year-old girl comes to the emergency department with lower abdominal pain, increasing weakness, and lethargy for 2 days. Her family has noticed a decreased appetite, nausea, and vomiting. For the last month they have also noticed that the patient has been complaining of being thirsty and going to the bathroom to urinate constantly.

Her temperature is 37.8 C (100.0 F), blood pressure is 100/70 mm Hg, pulse is 130/min, and respirations are 32/min. She is ill appearing and lethargic. She answers questions with difficulty but appropriately. Physical examination shows dry oral mucosa, a supple neck, no jugular venous distension, equally round and reactive pupils, and clear lungs. Her heart has a regular rhythm and is tachycardic. Her abdomen is tender to deep palpation. Neurologic examination shows no obvious focal deficits.

Differential diagnosis

Note: A good mnemonic to remember for the differential diagnosis of altered mental status with no focal neurologic deficits is DIM (a person presenting with a DIM mind):

Urugs Infections

Metabolic causes (sodium, glucose, calcium, renal abnormalities)

This is not only a good mnemonic but gives us the causes in order of frequency (i.e., the most common cause of altered mental status with nonfocal neurologic exam is drug side effects or overdose, etc.).

• Encephalitis/meningitis

• Urosepsis

• Diabetes

• Renal failure

• Drug overdose

KAPLA,.. .. _ I me 1C8

49

USMLE Step 3: Internal Medicine

50 "",lIical

Initial diagnostic plan

1. Biochemical profile

2. Complete blood count

3. Urinalysis

4. Lumbar puncture

5. Toxicology screen

Results

1. Sodium 130 mEq/L (normal: 135-145 mEq/L), potassium 6.5 mEq/L (normal: 3.5-5.2 mEq/L), chloride 100 mEq/L (normal: 96--108 mEq/L), bicarbonate 8 mEq/L (normal: 20-24 mEq/L), BUN/creatinine 65 mg/dl, / 2.5 mg/dl, (normal: 10-20 mg/dl, / 0.6--1.2 mg/dl.), glucose 580 mg/dl, (normal: 80-120 mg/dl.)

2. Normal

3. 60 white blood cells, ketones

4. 0 white blood cells, normal glucose and protein

5. Negative

Assessment

In this patient, the elevated glucose accompanied by a low bicarbonate and an elevated anion gap point to the diagnosis of diabetic ketoacidosis.

Diabetic ketoacidosis is a complication of diabetes mellitus. It may result from failure to take an adequate amount of insulin, or it may occur as the first manifestation of diabetes in a previously undiagnosed diabetic. Ketoacidosis is precipitated by conditions that increase the patient's requirement for insulin, such as infections and trauma. Thus, history of disease or infection is most important.

When dehydration occurs secondary to osmotic diuresis, impaired renal blood flow reduces the ability of the kidney to excrete glucose, worsening hyperosmolarity. Severe hyperosmolarity correlates closely with central nervous system depression and coma. Prolonged acidosis can compromise cardiac output and reduce vascular tone, thereby contributing to circulatory collapse in the dehydrated patient.

A common finding in acidosis is hyperkalemia, which results as potassium shifts into the extracellular space. In diabetic ketoacidosis, hyperkalemia is also a result of insulin deficiency. The hyperkalemia resolves with insulin treatment. A concern should be raised in the patient with diabetic ketoacidosis who presents with normal potassium levels. This patient has "masked hypokalemia" and should be treated with potassium supplements.

Treatment plan

1. Admit to intensive care unit.

2. Insulin coverage: intravenously first, then subcutaneous

3. Aggressive intravenous hydration with 0.9 normal saline

4. Blood and urine cultures

5. Confirm ketones in the blood

6. Start antibiotics for presumed urosepsis

Endocrin~ogy

Discussion

In diabetic ketoacidosis, obtunded patients without a gag reflex should be positioned so that aspiration does not occur. Isotonic fluids should be administered aggressively with at least I liter in the first I to 2 hours. Continue aggressive hydration until glucose is approximately 250 mg/dl., and continue with D5W 1I2NS. Give an initial intravenous bolus of 0.3 U/kg of insulin and while continuing intravenous fluid administration. Any pH over 7.2 is well tolerated and usually is quickly corrected with fluids and insulin.

Patients with moderately severe diabetic ketoacidosis have a plasma glucose of 350 to 900 mg/dL and positive acetoacetate. Acidosis is associated with hyperventilation. Serum potassium is usually normal or slightly elevated because of acidosis that shifts potassium from the cells into plasma. Severe volume depletion, azotemia, elevated hematocrit, and an elevated creatinine are also found in ketoacidosis.

Further into the hospital course

Two hours into her treatment this patient answers questions adequately and tells you that she feels much better. The accucheck shows a sugar of 350 mg/dL.

You are paged by the nurse about 3 hours later, and he informs you that the patient's accucheck is now 220 rng/dl., The patient now feels great. Her repeat basic metabolic panel comes back showing the bicarbonate to be 14 mEq/L.

What is your next step? Change the fluids to glucose and half normal saline.

The patient's next scheduled visit is in 6 months. You receive a call 5 weeks after her hospital discharge that her sugars are constantly running low when she takes the insulin; in fact she informs you that, although she has stopped insulin, her sugars are normal.

What is your next step? This is likely the honeymoon period, and a small amount of insulin should be continued.

Additional concepts in diabetic management

The "honeymoon" period (in insulin-dependent diabetes mellitus patients) is an initial episode of ketoacidosis followed by a symptom-free interval, during which no treatment is required. Presumably, stress-induced epinephrine release blocks insulin secretion, causing the syndrome. In normal individuals, insulin reserve is such that hormone release is adequate even in the face of stress.

The Somogyi effect is rebound hyperglycemia in the morning caused by counter- regulatory hormone release following an episode of hypoglycemia in the middle of the night.

The Dawn phenomenon is an early morning rise in plasma glucose requiring increased amounts of insulin to maintain euglycemia.

Glycosylated hemoglobin Ai is produced by non-enzymatic condensation of glucose molecules with free amino groups on the globin component of hemoglobin. It is not used for diagnosis but is used to follow compliance of the treatment and glucose control in diabetic patients. Glycosylated hemoglobin Al is high in diabetics with chronic hyperglycemia during the preceding 8 to 12 weeks.

UPLA!.. I"

meUlIC8 '

51

USMLE Step 3: Internal Medicine

52 IlAPLAlfil· I me lea

Final diagnosis Diabetic ketoacidosis

case Review

Diabetic Ketoacidosis

• Altered mental status

• With 'or without fever if precipitating factor is infection

• Anion gap acidosis

• Ketones in the blood and urine

Meningoencephalitis

• Altered mental status

• Fever, vomiting

• No acidosis

• I~o ketones in blood and urine

• Positive lumbar puncture

Urosepsis

• Altered mental status only in elderly patients

• Fever

• Anion gap acidosis only with hypotension

• No ketones in blood and urine

• Urinalysis shows pyuria; urine culture positive

Drug Overdose

• Altered mental status

• R,arely fever

• No anion gap acidosis (except w~h methanol, ethylene glycol, and salicylates)

• No ketones in blood and urine

• Urine tox positive

Endocrinology

eASE 2

Chief complaint

A diabetic patient complains of "low glucose readings at suppertime."

History and physical examination

A 28-year-old man with insulin-dependent diabetes mellitus Type I since age 12 has been on the same dose of insulin (22 NPH and 18 regular in morning, and 18 NPH and 8 regular in the evening, both before meals) for the last 8 months. He started a new exercise program a week ago when he joined a health club as part of his company's health promotion program. He goes to the health club around 5:30 PM. Since starting the exercise program, he has noticed symptoms of hypoglycemia, namely headaches, tremors, diaphoresis, and palpitations.

Home glucose monitoring results from the last few days are (in rng/dl): AM: 112, 104, 98, 103; noon: 85, 92, 87, 91; PM: 62, 40, 35, 37; bedtime: 88, 82, 89, 93. His vital signs are stable. Physical examination is within normal limits.

Differential diagnosis

• Hypoglycemia secondary to insulin overdose

• Hypoglycemia secondary to renal failure

Assessment

Hypoglycemia is defined as plasma glucose of less than 60 mg/dl, To establish a diagnosis, the following criteria should be filled: symptoms consistent with hypoglycemia should occur (adrenergic signs such as anxiety, diaphoresis, tremors, fatigue, or syncope with visual or behavioral changes), low plasma glucose, and relief of symptoms following ingestion of carbohydrates.

In a normal person, when plasma glucose level is low, so is the insulin level. For any hypoglycemic episode in a nondiabetic patient, a plasma insulin level should be drawn. Insulin antibodies, plasma, and urine sulfonylurea levels and C-peptide should be investigated. Plasma insulin level is increased following exogenous insulin injection. Insulin antibodies are produced after chronic insulin injection. C-peptide is not a part of exogenous insulin, so a level is very helpful to differentiate exogenous from naturally occurring insulin. Some miscellaneous causes of hypoglycemia are liver failure, chronic renal failure, deficiency of counter-regulatory hormones, and non-islet neoplasm.

Treatment plan

1. Decrease insulin (NPH A.M.)

2. Continue exercise program

3. Basic metabolic panel shows no evidence of renal impairment

IlPLllI'iI· I me·lC8

53

USMLE Step 3: Internal Medicine

54 KA PU Nil· • I me 1C8

Discussion

Hypoglycemia may be precipitated in diabetics receiving insulin when food intake is inadequate or delayed, when the insulin dose is too high, or when physical activity is excessive. A common problem is from increasing the activity level without adjusting the insulin level.

Spontaneous recovery from insulin-induced hypoglycemia largely depends on an outpouring of counter-regulatory hormones. Deficiencies in the release or action of these hormones may contribute to the hypoglycemia seen in some cases of Brittle Diabetes. Heavy alcohol use and poor food intake can cause hypoglycemia by suppressing hepatic gluconeogenesis.

Final diagnosis

Diabetes mellitus: hypoglycemia

Case Review

Hypoglycemia Associated with Excessive Insulin in the Diabetic Patient

• Symptoms of hypoglycemia and low serum glucose

• Elevated insulin

• Low C peptide

• Recent increase in exercise or renal insufficiency

Hypoglycemia Associated with Exogenous Insulin Use in the Nondiabetic Patient

• Symptoms of hypoglycemia and low serum glucose

• Elevated insulin

• Low C peptide

• Positive insulin antibodies

Hypoglycemia Associated with Insulinoma

• Symptoms of hypoglycemia and low serum glucose

• Elevated insulin

• High C peptide

• Negative insulin antibodies

Hypoglycemia Associated with Surreptitious Sulfonylurea Use

• Symptoms of hypoglycemia and low serum glucose

• Elevated insulin

• High C peptide

• Negative insulin antibodies

• Positive sulfonylurea in the urine

Hypoglycemia Associated with Prolonged Fasting

• Symptoms of hypoglycemia and low serum glucose

• Low insulin

• Low C peptide

Endocrinology

CASE 3

Chief complaint Confusion

History and physical examination

A 49-year-old obese man is brought to the emergency department by his wife because he is "not himself." He was very drowsy and 110t eating much for the last 4 days. He was making urine every hour and was drinking water because he felt thirsty. His wife had not noticed any fever, chills, nausea, or vomiting. He was known to be hypertensive for 10 years and takes hydrochlorothiazide. About 2 years ago, he was told by his doctor that he had borderline diabetes mellitus and was started on a diet. No medications were prescribed at that time.

He appears very lethargic. He is arousable but responds incoherently to questions. He only orients to his name and does not know where he is, and he does not recognize his wife. His temperature is 37.7 C (99.9 F), blood pressure is 100/60 mm Hg, pulse is 11O/min with orthostasis, and respirations are 20/min. His lung examination is normal with good air entry. His heart shows a normal rhythm without a murmur. There are no focal neurologic signs, and the rest of his physical examination is unremarkable.

Differential diagnosis

• Nonketotic hyperosmolar state

• Other metabolic causes (renal failure, hyper- or hyponatremia, hypercalcemia)

• Infection (urosepsis, pneumonia, meningitis)

• Cerebrovascular accident (stroke)

Initial diagnostic plan

1. Biochemical profile

2. Complete blood count

3. Urinalysis

4. Chest x-ray

5. Lumbar puncture

6. Toxicology screen

KAPLA.... • I me 1C8

55

USMLE Step 3: Intemal Medicine

56 lA'iiilLA.. . I m lea

Results

1. Sodium 130 mEq/L, potassium 5.2 mEq/L, chloride 95 mEq/L, bicarbonate 24 mEq/L,

BUN/creatinine 58 mgldL /2.2 mg/dL, glucose 998 mg/dl,

2. WBCs: 15,000/mm3

3. No WBCs, negative for ketones

4. Normal

5. Normal

6. Negative

Assessment

Both diabetic ketoacidosis and hyperosmolar nonketotic state may be associated with altered mental status and dehydration. Patients with diabetic ketoacidosis have ketones in urine, and the anion gap is elevated, whereas the plasma pH is decreased (acidotic). In hyperosmolar nonketotic state, there is no acidosis or ketone formation.

Patients with hyperosmolar nonketotic state have very high blood sugars, often above 500 mg/mL. They are also very dehydrated. Often, hydration alone is enough to lower the blood sugar. In dehydrated patients, 0.9% NaCl is the ideal intravenous fluid of choice because most of the normal saline remains intravascularly and quickly replenishes the intravascular volume and rapidly stabilizes the hemodynamic status. Insulin requirements in patients with hyperosmolar nonketotic state are small; large doses should be avoided.

Further diagnostic plan

Always look for a precipitating cause: electrocardiogram, blood, and urine cultures.

Treatment plan

1. Large volumes of intravenous 0.9% NaCI

2. Small doses (0.1 U /kg/h) of intravenous regular insulin

Discussion

Hyperosmolar nonketotic coma is a syndrome that occurs predominantly in patients with Type II diabetes and is characterized by severe hyperglycemia in the absence of significant ketosis. Precipitating factors include noncompliance with treatment and the inability to drink sufficient water to keep up with urinary losses. This is common in elderly diabetic patients living in nursing homes. Infections, strokes, use of phenytoin, steroids, immunosuppressant agents, and diuretics are other precipitating factors. Hyperosmolar nonketotic coma can occur after therapeutic procedures, such as peritoneal or hemodialysis, tube-feeding of high-protein formulas, and high-carbohydrate infusion. The pathophysiology involved is profound dehydration resulting from a sustained hyperglycemic diuresis. The clinical findings are weakness, polyuria, polydipsia, lethargy, confusion, convulsions, and coma.

The diagnosis of hyperosmolar nonketotic coma is suggested by elevated blood glucose (1,000 mg/dl.), extremely high serum osmolality (serum osmolality in mOsmoVkg Hp = 2 [sodium] + BUN/2.8 + serum glucose/18). A high BUN (prerenal azotemia) and mild metabolic acidosis (bicarbonate around 20 mEq/L) is also seen without ketosis.

Chronic complications of diabetes involve the micro- and macrovasculature.

Endocrinology

In microvascular complications, various organs are involved. Diabetic retinopathy is the leading cause of blindness in middle-aged patients in the United States. The retina is affected, and simple, background, or proliferative (microaneurysms, hemorrhages, exudates, retinal edema) damage can occur.

Nephropathy affects 30 to 40% of Type I and 20 to 30% of Type II diabetics. Hyperproliferation, proteinuria, and end-stage renal disease can develop. The pathology can be diffuse, which is more common, and lead to widening of glomerular basement membrane and mesangial thickening. Nodular pathology can occur and results in hyalinization of afferent glomerular arterioles (Kimmelstiel-Wilson). Management of nephropathy involves strict control of diabetes, angiotensin-converting enzyme (ACE) inhibitors, dialysis, and renal transplantation.

There are various types of diabetic neuropathy. Peripheral neuropathy is the most common. It is symmetrical, with symptoms of numbness, paresthesia, and pain being prevalent; physical examination in these patients reveals absent reflexes and loss of vibratory sense. Mononeuropathy affects a single nerve or nerve trunk (mononeuritis multiplex) and is vascular in origin. Patients with mononeuropathy have sudden foot drop, wrist drop, or paralysis of the third, fourth, or sixth cranial nerve. Autonomic neuropathy is usually devastating for the patient. Patients with this type of neuropathy have orthostatic hypotension and syncope as the main manifestations. Gastrointestinally, there may be difficulty swallowing, delayed gastric emptying (gastroparesis), constipation, or diarrhea. Bladder dysfunction or paralysis can lead to urinary retention in patients with autonomic neuropathy. Impotence and retrograde ejaculation are seen in men with this type of neuropathy.

Management of neuropathy depends on type. For peripheral neuropathy, analgesics, amitriptyline, and carbamazepine are used. For gastroparesis, metoclopramide or erythromycin can be used.

Macrovascular complications include increased risk of strokes, myocardial infarction, and peripheral vascular disease.

Final diagnosis

Nonketotic hyperosmolar state

IlAPUlril· I . .• IRe ca

51

USMLE Step 3: Internal Medicine

58 me&ical

CASE 4

Chief complaint

Increased serum calcium on routine medical evaluation

History and physical examination

A 30-year-old man comes to your office for the evaluation of hypercalcemia, noted on routine tests performed at his workplace. He denies any specific complaints and is not taking any medications. His past medical history is significant for several episodes of renal stones 2 to 3 years ago. Physical examination is unremarkable.

Differential diagnosis

• Primary hyperparathyroidism

• Malignancy

• Sarcoidosis

• Familial hypocalciuric hypercalcemia

Initial diagnostic plan

1. Basic metabolic panel (sodium, potassium chloride, bicarbonate)

2. Serum calcium

3. Chest x-ray

Results

1. Within normal limits

2. 11.3 mg/dL (normal: 8.5-10.3 mg/dl.)

3. Normal

Assessment

Most cases of asymptomatic hypercalcemia in young ambulatory patients are caused by primary hyperparathyroidism. Given the history of renal stones 2 years ago, the patient probably has had increased serum calcium for a long time without any other problems. The age of the patient and the benign course of his hypercalcemia make a diagnosis of malignancy less likely, but malignancy should always be ruled out in cases where history and physical examination suggest it.

Malignant diseases can lead to hypercalcemia via parathyroid hormone-related proteins (1-25 [OH] vitamin D), interleukins, tumor necrosis factor, and osteoclastic activating factor. Other causes of hypercalcemia include acute or chronic renal failure, drugs (thiazides, lithium), granulomatous diseases (sarcoidosis), thyrotoxicosis, and immobilization.

Familial hypocalciuric hypercalcemia is a benign condition that can be diagnosed by checking urinary calcium levels «200 mg/24 h) combined with a family history of similar conditions and normal parathyroid hormone levels.

Endocrinology

Further diagnostic plan

L Immunoassay for serum parathyroid hormone

Results

1. 22 mEq/mL (normal: 4--9 mEq/mL)

Treatment plan

1. Parathyroidectomy because of the history of kidney stones

Discussion

The higher level of parathyroid hormone is in favor of primary hyperparathyroidism. About 85% of cases are caused by adenoma of a single gland, 15% are caused by hyperplasia of all four glands, and <1 % are caused by parathyroid carcinoma.

In this asymptomatic patient with serum calcium levels less than 12 mgldL, no other management is required. The only effective treatment for primary hyperparathyroidism is parathyroidectomy. Many patients have a benign course over the years, but a major concern is the possibility of progressive bone loss, increased risk of fractures, and recurrent nephrolithiasis.

Because this patient has a history of nephrolithiasis and persistently high calcium, surgery is indicated. Surgery has high success rate with low morbidity and mortality.

Acute management of hypercalcemia is warranted when serum calcium levels are >12 mg/dl, or when severe symptoms are present. The goal is to alleviate symptoms; it is not necessary to achieve normal serum calcium levels. These measures allow time to complete diagnostic studies and begin treatment of underlying conditions. Initial management of a patient with very high serum calcium levels is to replace extracellular fluid volume with 0.9% saline (3 to 6 Lid in the first 24 hours), to restore the glomerular filtration rate, and to promote calcium excretion.

After extracellular fluid volume is restored, furosemide 20 to 40 mg intravenously 2 to 4 times per day can be given if evidence of fluid overload or heart failure develops. Close monitoring of fluid balance and electrolytes should be done. Thiazides should be avoided because they impair calcium excretion and increase serum calcium. Alternative therapy used in emergency treatment if hypercalcemia does not improve with fluids is calcitonin and pamidronate.

One week later the patient is admitted to the hospital and has successful removal of a single parathyroid adenoma. He is doing well after the surgery and is transferred to the surgical wards. The nurse contacts you 12 hours after the surgery and tells you that the patient has developed facial spasm. You immediately order a calcium level and find it to be 6.4 mgldL.

What is the likely diagnosis in this case, and what would you do next?

The likely diagnosis is hungry bones syndrome. The treatment of hypocalcemia is to give intravenous calcium.

Final diagnosis Hypercalcemia

USMLE Step·3: Internal Medicine

Case Review

Primary Hyperparathyroidism

• Mild serum calcium elevation

• With or without symptoms

• Elevated parathyroid hormone

Malignancy

• Severe serum calcium elevation

• Severe symptoms

• Low parathyroid hormone

Sarcoidosis

• Mild serum calcium elevation

• With or without symptoms

• Low parathyroid hormone

• Elevated vitamin D levels

Familial Hypocalciuric Hypercalcemia

• Mild serum calcium elevation

• No symptoms

• Normal parathyroid hormone

• Low urine calcium

60 HieClical

-----------,~-,,--------

Endocrinology

CASES

Chief complaint

"I feel tired all the time."

History and physical examination

A 64-year-old woman complains of feeling tired all the time for the past 6 months. She was planning to visit you, her primary care physician, for a while but has put it off until now. She has gained about 8 pounds in the last 6 months. She does not feel like doing much of anything. She complains of feeling cold and has been using heavy blankets even in the summer. She is constipated, gets frequent headaches, and is experiencing severe muscle cramps. The only good thing she had to report was that her anginal chest pains are not as frequent as they used to be. She only had two episodes of chest pains in the last 6 months and none in the last 4 months. For her angina, she was taking isosorbide dinitrate and a beta-blocker. Her cardiologist had recommended coronary artery bypass graft after cardiac catheterization showed more than 70% obstruction of the left main artery.

Her blood pressure is 150/100 rnm Hg, and pulse is SO/min. Her skin is dry. There is no thyromegaly. The deep tendon reflexes have a delayed relaxation phase. The rest of the physical examination is unremarkable.

Differential diagnosis Hypothyroidism

Initial diagnostic plan

1. Thyroid-stimulating hormone

2. Free T4

Results

1. High: 49 J.LU/mL (normal: 0.1-5 J.LU/mL)

2. Low: 1.5 ug/ml, (normal: 5-12 ug/ml.)

Assessment

This elderly patient has typical symptoms of hypothyroidism. The weight gain, cold intolerance, and the complaint of feeling tired all the time are highly suggestive of hypothyroidism. The seemingly improving anginal history is not uncommon in hypothyroidism. As the demand for oxygen by the myocardium is diminished, the angina "improves." Dry skin and a puffy face are signs of long-standing hypothyroidism. The diastolic hypertension and the delayed relaxation phase are classical signs of hypothyroidism. The laboratory tests are diagnostic of primary hypothyroidism.

In the elderly patient, cognitive deficits are sometimes seen with hypothyroidism.

melilcal 61

USMLE Step 3: Internal Medicine

62 Hi.Clical

Primary hypothyroidism is the cause of hypothyroidism in over 950/0 of cases and is usually a result of chronic thyroiditis (Hashimoto disease). This is the most common cause of goitrous hypothyroidism and is associated with antimicrosomal antibodies. Post-ablative surgery or radioactive iodine, heritable biosynthetic defects, and iodine deficiency can also lead to primary hypothyroidism. Drugs such as lithium and acetylsalicylic acid can elicit primary hypothyroidism.

Suprathyroid causes of hypothyroidism include pituitary-induced hypothyroidism (secondary hypothyroidism) or hypothalamic-induced hypothyroidism (tertiary hypothyroidism).

Treatment plan

1. Consider bypass surgery before correcting the thyroid dysfunction.

2. Thyroxine replacement

Discussion

In patients with hypothyroidism, it is preferable to get coronary artery bypass graft done before correcting the thyroid dysfunction with levothyroxine. Retrospective studies have shown that there is no need to correct hypothyroidism before coronary artery bypass graft. Correcting the thyroid dysfunction with levothyroxine is not only unnecessary, but it is potentially dangerous. T3 is not any safer in patients with coronary artery disease. Theoretically, it is more dangerous than levothyroxine.

If patient had no history of angina, we would have simply started her on 25 ug of levothyroxine and would have gradually increased the dose over several weeks until she became euthyroid. The presence of coronary artery disease makes this situation more complex. Retrospective studies have documented that hypothyroidism is not a contraindication for major cardiac surgery because these patients have comparable complication rates to euthyroid patients. Therefore, it is strongly recommended that hypothyroid patients that require coronary artery bypass graft do undergo the surgery before starting levothyroxine. This is compounded by the apprehension that starting levothyroxine in these patients is going to increase their heart rate and may actually aggravate their angina and precipitate myocardial infarction.

Generalities

The normal function of the thyroid gland is directed toward the secretion of L-thyroxine (T4) and 3,5,5' triode-L-thyroxine (T3), which regulate metabolic processes. The main secretory hormone of the thyroid is T4, and it is only the free, nonbound-to-protein fraction of T4 and T3 that affects metabolism. This free hormone is less than 0.01% of the total. Over 99% of the total hormones are bound to thyroid-binding globulin.

Laboratory tests to measure free T4 and free T3 are now more accessible and give a direct measurement of the metabolic active percentage of the hormone. These are the measurements to look for when assessing thyroid function.

Free T4 index (free T4 index = RT3 x T4 [total]) is an indirect way to measure free T4 and is now rarely used because free T4 has become more available. Resin T3 uptake is the inverse measure of thyroid-binding globulin and does not measure T3.

Total T4 or T3 is not always accurate because they measure protein bound and unbound thyroid hormones. Increased thyroid-binding globulin levels, and thus total T4levels, are seen in pregnancy and with the use of oral contraceptives (but free or active T4 level is normal). Decreased thyroid-binding globulin levels, and thus total T4 levels, are also seen in nephrotic syndrome and cirrhosis (but free or active T4level is normal with the patient being euthyroid).

, Endocrinology

Thyroid-stimulating hormone is probably the most useful test in the diagnosis of hypothyroidism. It is the best screening test for both hyper- and hypothyroidism. Overall, if the thyroid-stimulating hormone is normal then likely the patient is euthyroid. (Note: Always look at the thyroidstimulating hormone first when assessing thyroid hormonal function.) It is also the besttest to

do when following treatment of thyroid diseases. .

Final diagnosis Hypothyroidism

Hi~lcal 63

USMLE Step 3: Internal Medicine

64 KAPLA .. N" • I me 1C8

CASE 6

Chief complaint Neck swelling

History and physical examination

A 43-year-old woman noticed neck swelling 1 week ago and decided to come to your office for evaluation. She does not know how long it was there. There is no history of swallowing or breathing problems. She had no hoarseness. She denies any symptoms of hypothyroidism or hyperthyroidism.

She has an enlarged (4x the normal size) thyroid with multiple nodules in both lobes of the thyroid. There is one nodule that is much bigger than the rest of the nodules in the lower pole of the right lobe of the thyroid. On palpation, this nodule is very firm and nontender. There was no associated lymphadenopathy. The rest of her physical examination is unremarkable. (

Differential diagnosis

• Nontoxic multinodular goiter

• Toxic multinodular goiter

• Thyroid cancer

• Graves disease

Initial diagnostic plan

Serum thyroid-stimulating hormone

Results

1.2 j.LU/mL (normal: 0.5-12 j.LU/mL)

Assessment

This is a middle-aged woman who presents with multinodular goiter. It was causing neither local pressure symptoms nor symptoms of hyperthyroidism. She appeared euthyroid on physical examination, and the biochemical tests have also confirmed this.

The concern with thyroid nodules is the possibility of thyroid cancer. This is a concern only in the nontoxic!nonfunctioning noduleis). Thus, if the patient is clinically and biochemically euthyroid, then cancer should be ruled out with a fine needle aspiration of the nodule.

Toxic multinodular goiter and the very rare nodular Graves disease present with thyrotoxicosis, which is not present in this patient.

Further diagnostic plan

Fine-needle aspiration of the large nodule

Endocrinology

Results

1. Benign cytology

Treatment plan

1. Because patient is euthyroid and has no local pressure symptoms, this goiter may simply be observed, unless the patient wants it removed for cosmetic purposes.

Discussion

The presence of the large nodule in any multinodular goiter should raise the possibility of underlying malignancy, and this needs to be further evaluated. A large nodule (sometimes called a "dominant nodule") has to be evaluated exactly like a solitary thyroid nodule. The only diagnostic test that answers the question "Is this nodule malignant?" is fine-needle aspiration of the nodule. Suppression of the nodule with large doses oflevothyroxine should not be attempted before malignancyis excluded. Some malignant nodules have been documented to shrink on suppressive doses of levothyroxine. Large multinodular goiters do not usually respond to suppression.

When to Suspect a Thyroid Carcinoma. Suspect a thyroid carcinoma when there is recent growth of thyroid or mass with no tenderness or hoarseness. Patients with a history of radiation therapy of the head, neck, and upper mediastinum in childhood average 30 years to develop thyroid cancer. Male and the elderly patients have a higher incidence of thyroid malignancy than female patients. The presence of a solitary nodule or the production of calcitonin are also clues to malignancy. Calcifications on x-rays, such as psammoma bodies, suggest papillary carcinoma.

Diagnostic Approach to Solitary Nodule. Fine-needle aspiration for cytology is the initial procedure of choice in the evaluation of most patients.

Thyroid Carcinomas. Papillary carcinoma is the most common thyroid cancer. It is associated with history of radiation exposure. Sixty to 70% of all thyroid cancers are papillary. Females are affected by papillary carcinoma 2 to 3 times more than males. There is a bimodal frequency, and peaks occur in the second and third decades and again later in life. This tumor is slow growing and spreads via lymphatics after many years. The treatment is surgery when the tumor is small and limited to a single area of the thyroid. Thyroid-stimulating hormone suppression therapy is also used. With large tumors, radiation therapy is used with surgery.

Follicular Carcinoma. Follicular carcinoma accounts for 15% of all thyroid cancers. It is more common in elderly patients and in females. This tumor is more malignant than papillary.carcinoma. Follicular carcinoma spreads hematogenously with distant metastasis to the lung and bone. Treatment requires near total thyroidectomy with post-operative radioiodine ablation.

Anaplastic Carcinoma. Anaplastic carcinoma accounts for 10% of all thyroid cancer. It occurs mostly in elderly patients. Females are affected more than males with this tumor. Anaplastic carcinoma is highly malignant with rapid and painful enlargement. Eighty percent of patients die within 1 year of diagnosis.

Medullary Carcinoma, Medullary carcinoma accounts for 5% of all thyroid cancers. It occurs as a sporadic form or familial form. This tumor arises from parafollicular cells of the thyroid and is more malignant than follicular carcinoma. The tumor often produces calcitonin. Medullary carcinoma is the component of two types of multiple endocrine neoplasia. In Type IIa (Sipple syndrome), pheochromocytoma, medullary thyroid carcinoma, and (in one-half of cases) parathyroid hyperplasia occur. In multiple endocrine neoplasia Type IIb, pheochromocytoma, medullary carcinoma, and neuromas occur. Medullary carcinoma may also occur in families without other associated endocrine dysfunctions. The only effective therapy is thyroidectomy.

KAPLAlfil· I me lea

USMLE Step ~: Internal Medicine

66 ",~&Ical

Final diagnosis

Nontoxic multinodular goiter

Further concepts

Consider that the fine-needle aspiration cytology results showed follicular elements. What would be your next step in this case? Excisional biopsy.

case Review

Nontoxic Multinodular Goiter

• Multiple thyroid nodules

• Euthyroid clinically and biochemically

• Thyroid scan: multiple "cold" nodules

• Fine-needle aspiration: benign cytology

Toxic Multinodular Goiter

• Multiple thyroid nodules

• Hyperthyroid clinically and biochemically

• Thyroid scan: multiple "hot" nodules

• Fine-needle aspiration: not needed

I Thyroid Cancer

• Single thyroid nodule (rarely multiple)

• Euthyroid clinically and biochemically

• Thyroid scan: single "cold" nodule

• Fine-needle aspiration: papillary cancer or other thyroid malignancy

Graves Disease

• Diffuse thyroid enlargement

• Hyperthyroid clinically and biochemically

• Thyroid scan: diffuse uptake (the entire thyroid is "hot")

• Fine-needle aspiration: not done

Endocrinology

Chief complaint Weight loss

History and physical examination

A 44-year-old woman comes to the office complaining of 15-lb, weight loss over 3 months, She gives a history of feeling hot and sweaty and of difficulty sleeping and easy arousability, She also complains of muscle weakness, especially when she tries to climb stairs, She admits to moving her bowels 2 to 3 times per day for the last 4 months and has noticed that her hands are trembling all the time and that her heart is racing.

She is afebrile, her blood pressure is 150/90 mm Hg, pulse is 112/min, and respirations are 16/min. She is thin and is very restless and fidgety. She has a pronounced stare. There is a diffusely enlarged thyroid without any bruit. There is a very fine tremor of both of her hands. She is unable to get up from a squatting position without assistance.

Differential diagnosis

• Graves disease

• Toxic multinodular or nodular goiter

• Subacute thyroiditis

Initial diagnostic plan

1. Serum free T 4

2. Serum thyroid-stimulating hormone

3. 24-hour radioactive iodine uptake scan

Results

1. 6 ng/dL (normal 0.8-2 ngldL)

2. <0.1 f.LU/mL (normal: 0.5-5 f.LU/mL)

3. 68% (normal: 25-35%) with diffuse uptake

Assessment

This patient has all the symptoms and signs of primary hyperthyroidism due to Graves disease.

Treatment plan

1. Beta-blocker and antithyroid drugs (propylthiouracil or methimazole) initially to suppress the hyperactive thyroid

2. After the patient is euthyroid, radioactive iodine ablation for permanent treatment

USMLE Step 3: Internal Medicine

Discussion

The treatment of choice during acute thyrotoxicosis like this patient is having is antithyroid medications and beta-blockers to make the patient clinically more stable. Once the patient is less toxic, radioactive iodine can be used for permanent resolution of hyperthyroidism. If radioactive iodine is given during severe hyperthyroidism, there is the possibility of inducing radiation thyroiditis and releasing more thyroxine in to the circulation, worsening her condition. Surgery is not an option initially in the treatment of Graves disease.

The most common cause of hyperthyroidism in young people in the United States is Graves disease. Patients with Graves disease have diffuse thyromegaly and may also have vascular bruit on auscultation because of increased blood supply to the gland. Up to 70% of patients with Graves disease have exophthalmos, which is not a feature of any other thyroid disease. The presence of exophthalmos makes the diagnosis certain.

The myopathy described in the patient is proximal myopathy, which is the most common myopathy not just in Graves disease but in all thyroid disease.

Plummer disease patients have long-standing multinodular goiters that become thyrotoxic later.

Toxic multinodular goiter patients have a hyperfunctioning solitary nodule, which is not present in this patient. Subacute thyroiditis patients have diffuse thyromegaly like our patient, but the thyroid is tender. The thyroiditis patients are differentiated by their short duration of symptoms and low 24-hour radioactive iodine uptake (usually <5%).

Final Diagnosis Graves disease

Endocrinology

Case Review

Graves Disease

• Diffuse thyroid enlargement

• Proptosis

• Thyroid scan: diffuse increased uptake (the entire thyroid is "hot")

• Positive thyroid-stimulating immunoglobulin

Toxic Multinodular Goiter

• Multiple thyroid nodules

• No proptosis

• Thyroid scan: multiple "hot" nodules

• History of prior nontoxic goiter

Subacute Thyroiditis

• Painful thyroid

• No proptosis

Thyroid scan: low uptake

Erythrocyte sedimentation rate is elevated Low antithyroid antibodies

UPeII- . I m .. lea

69

USMLE Step 3: Internal Medicine

CASE 8

Chief complaint

"I feel thirsty, and I'm urinating aloe'

History and physical examination

A 56-year-old woman with a 15-year history of Cushing disease and pituitary adenoma comes to your office complaining of polyuria and polydipsia of 4 days' duration. She denies any burning sensation on micturition and has no fever or chills. However, she says she had gained approximately 131b over the last 4 months and feels depressed and tired.

She is afebrile. Her blood pressure is 160/98 mm Hg, pulse is 78/min, and respirations are 14/min. On physical examination she is 140% of her ideal body weight, and her face is remarkably round and ruddy. Her abdomen is very obese, and there are several purple striae over the abdomen and the thighs. Her heart and lung examinations are within normal limits. Neurologic examination is nonfocal. There is mild edema of the extremities.

Differential diagnosis

• Obesity, diabetes, hypertension

• Cushing syndrome

Initial diagnostic plan

L plasma cortisol after overnight dexamethasone

2. Blood sugar

3. 24-hour urine free cortisol

Results

1. 28 J-Lg/dL (normal: <5 J-Lg/dL)

2. 213 rng/dl,

3. 650 J-Lg/24 hour (normal: <200 IJ.g/24 hour)

Assessment

The patient has features of Cushing syndrome. Obesity and diabetes mellitus may be the presenting diagnoses in Cushing syndrome. Depression is also a frequent finding among Cushing patients. The physical examination with obesity and the presence of purple striae are also very suggestive of Cushing syndrome. Whereas a large number of obese people may have striae, they are usually white and not very broad. The striae of Cushing syndrome are characteristically very wide and appear purplish because of the thinning of the skin.

The easiest and the best screening test is overnight dexamethasone suppression test. In this test, 1 mg of dexamethasone is given at 11 PM before the patient goes to sleep. If the next morning serum cortisol is <5 /Lg/dL, Cushing syndrome is ruled out. If this screening test is positive, a more

zcumoersome test, like the 24-hour urine free cortisol, can be done to confirm the presence of hypercortisolism. Other manifestations of Cushing syndrome are hirsutism, amenorrhea, osteoporosis, and ecchymosis. The dermatologic manifestations are caused by the weakening effects of steroids on collagen fibers.

Further diagnostic plan

Focus on finding the cause of Cushing syndrome.

1. High-dose dexamethasone suppression test

2. Magnetic resonance imaging of the pituitary

Results

1. 4 ug/dl, (suppressed)

2. Pituitary adenoma

Treatment plan

1. Surgical resection

Discussion

The high-dose dexamethasone suppression test will differentiate pituitary Cushing disease from extra-pituitary Cushing syndrome. In pituitary-dependent Cushing disease, 8 mg of dexamethasone causes the plasma cortisol level to get suppressed to less than 50% of the previous day's value. In all other causes of Cushing syndrome, this level does not get suppressed.

The result in our patient is suggestive of pituitary Cushing syndrome. If there were no suppression of cortisol by the high-dose dexamethasone suppression test, that would suggest extra-pituitary Cushing syndrome, either from the adrenal Or an ectopic tumor secreting adrenocorticotropic hormone (ACTH). Because adrenal tumors secreting cortisol are associated with suppressed ACTH levels secondary to negative feedback. and because ectopic ACTH secreting tumors have very high levels of ACTH, measuring the ACTH is very useful at this stage.

Postoperatively, the patient had lost weight, her blood pressure was easily controlled by a diuretic, and her blood sugar was well controlled by diet alone.

Final diagnosis Cushing syndrome

IIP~!.. I m ... lC8

7T

USMLE Step 3: Internal Medicine

{Osteoporosis Central adiposity

Clinical suspicion Diabetes mellitus

~ Hirsutism amenorrhea

r-------------~------~=-~

Screening test

Overnight dexamethasone suppression test

-- Normal

No Cushing

~

Abnormal

(Can be seen in obese, alcoholics or depressed individuals [false 0])

~

24-hour urine-free cortisol

Abnormal test

~

Normal

test ~

Dexamethasone suppression test (high dose)

L... s_u_p_p_r~es_s_io_n_t_o ~~IL... ~ ~

<50% Control . No response

! +

I

Pituitary adenoma (Cushing disease)

• ACTH-producing tumor

• Adrenal neoplasia

I ACTH level I

Adrenal ~ '------,I..------(-=-=:L~

neoplaSia - ~ _------L..-----..... ~_/

t

Urinary 17KS DHEA-S abdominal CT

Adrenal hyperplasia due

to ACTH-producing tumor (lung)

CT (chest)

Figure 1. Evaluating a Patient With Presumed Cushing Syndrome

72 IAPUIIN" • I

me 1C8

Endocrinology

CASE 9

Chief complaint Headache and palpitations

History and physical examination

A 33-year-old woman comes to the office for evaluation of several hours of severe headache, flushing, and palpitations. She recalls several similar episodes in the past, but her symptoms were less severe and of shorter duration. Each of these episodes occurred after going to the bathroom. Her past medical history is significant only for a long history of migraine headaches, which are difficult to control.

She is diaphoretic and anxious appearing. Her temperature is 37.0 C (98.6 F), blood pressure is 195/110 mm Hg, respirations are 20/min, and pulse is 138/min. Orthostasis is elicited. Her head, eyes, ears, nose, and throat are unremarkable. Her heart is tachycardiac with normal heart sounds. Her lungs are clear to auscultation, abdomen is benign, and extremities are unremarkable.

Differential diagnosis

• Pheochromocytoma

• Primary aldosteronism

• Renal artery stenosis

• Essential hypertension

Initial diagnostic plan

1. 24-hour urine collection for vanillylmandelic acid, metanephrine, and unconjugated free catecholarnines

Results

1. Increased vanillylmandelic acid, metanephrine, and free catecholamines

Assessment

The clinical presentation of paroxysms of headache, sweating, palpitations, and anxiety attacks in association with labile hypertension is classic for pheochromocytoma. Such patients most commonly seek medical attention in the setting of a hypertensive crisis. Signs and symptoms of an increased metabolic rate may include profuse sweating, tachycardia, and weight loss. Supraventricular arrhythmias are commonly seen. Measurement of 24-hour urine vanillylmandelic acid levels is diagnostic in 95% of cases of pheochromocytoma. CT scan is used to try to identify the exact location of the tumor. Remember, 10% of pheochromocytomas are extraadrenal.

Further diagnostic plan 1. Abdominal CT scan

me&ical 73

USMLE Step 3: Internal Medicine

74 Ki~cal

Results

L Left adrenal mass present

Treatment plan

1. Alpha-adrenergic antagonist (phentolamine or phenoxybenzamine) until the blood pressure is well controlled. Remember: Besides alpha-blockers, no other antihypertensives should be used initially in the management.

2. Fluid replacement

3. Surgical consultation for resection of the tumor

Discussion

Less than 0.1 % of patients with hypertension have an underlying pheochromocytoma. However, in the appropriate clinical setting, this diagnosis should be aggressively pursued because it is a potentially reversible cause of hypertension. Approximately 80% of lesions are unilateral and localized to the adrenals; 10% bilateral, and 10% occur extraadrenally. Approximately 5% of cases are associated with the familial multiple endocrine neoplasia II and III syndromes.

Once the diagnosis is established, surgical excision is the treatment of choice. Preoperative management focuses on establishing alpha-adrenergic blockade. Beta-blockers should be given only once alpha-blockade is achieved.

Final diagnosis Pheochromocytoma

case Review

Pheochromocytoma

• Episodic hypertension

• Orthostasis

• Elevated urine catecholamines

Primary Aldosteronism

• Diastolic hypertension; males affected more than females

• Fatigue and weakness

• Hypokalemia

• Elevated aldosterone and decreased renin

Renal Artery Stenosis

• Young women (fibromuscular dysplasia) or older men (atherosclerosis)

• Abdominal bruit in 30% of cases

• Positive captopril scan

Endocrinology:,

BONUS CASE A

Chief complaint

"I have frequent headaches and feel weak and tired:'

History and physical examination

A 36-year-old man with no significant past medical history comes to the clinic complaining of frequent headaches and feeling weak and tiring very easily. He used to go for 5-mile jogs on a routine basis but now he feels tired even after a walk around the block. Getting through the day at his office has become a major accomplishment each day. He was asked by his boss to seek medical help. The headaches are generalized and come at any time; they usually last 30 to 45 minutes. The patient is not taking any medications and has no significant past medical history.

His temperature is 37.0 C (98.6 F), blood pressure is 200/110 mm Hg, respirations are 14/min, and pulse is 82/min with no orthostasis. Funduscopic examination reveals no papilledema or hemorrhages. The rest of the examination is normal except for a mild proximal weakness on both legs.

Differential diagnosis

• Hyperaldosteronism

• Pheochromocytoma

• Renal artery stenosis

• Essential hypertension

Initial diagnostic plan

Biochemical profile and treat as hypertensive urgency

Results

Sodium 143 mEq/L (normal: 135-145 mEq/L), potassium 2.1 mEq/L (normal: 3.5-5.2mEq/L), chloride 100 mEq/L (normal: 95-105 mEq/L), bicarbonate 32 mEq/L (normal: 22-26 mEq/L), glucose 198 mgldL (normal: 80-120 mgldL)

Assessment

This young man had no significant past history. He has very high blood pressure. Pheochromocytoma is possible, but he has no associated beta-adrenergic symptomatology. Renal artery stenosis is usually associated with an abdominal bruit.

Hyperaldosteronism is a frequent cause of severe hypertension, especially in young individuals. The presence of unprovoked (by diuretics) hypokalemia makes this diagnosis very likely. Potassium is needed for the release of insulin, and hypokalemia can cause insulin deficiency, leading to glucose intolerance or frank diabetes mellitus. Replacement of potassium often corrects the diabetes without any additional treatment. Hypokalemia can also cause muscle weakness.

In primary hyperaldosteronism, the plasma aldosterone is grossly elevated without anyelevation of plasma renin activity. The plasma aldosterone (ng/dL) to plasma renin activity (ng/mU/hr) ratio is a simple test that is often used as a screening test. Confirmation is usually obtained by 24-hour urine aldosterone. Remember that primary aldosteronism is renin independent aldosteronism, i.e., aldosterone is elevated independent of a low renin level.

USMLE Step 3: Internal Medicine

76 ~ical

Further diagnostic plan

1. Plasma aldosterone to plasma renin activity ratio

2. CT scan of the adrenal glands

3. Admit the patient and replace potassium.

Results

1. 43 (normal: <20)

2. 3-cm right adrenal tumor

Treatment plan Surgical removal of mass

Discussion

Right adrenalectomy is scheduled. In the meantime, patient is placed on KCI replacement and starts fosinopril for his hypertension (this latter is an angiotensin-converting enzyme inhibitor), with very good results.

Patient underwent right adrenalectomy. Following surgery, his potassium returned to normal, but his blood pressure was still elevated, although not as high as it was preoperatively, and was easily managed by a small dose of fosinopril.

The most common cause of primary hyperaldosteronism is aldosterone-producing adenoma. A CT of the adrenals is a valuable tool to look for these tumors. If an adenoma is identified, surgery is the best treatment available and should be offered to all the patients.

Final diagnosis Primary aldosteronism

Case Review

Primary Aldosteronism

• Diastolic hypertension; males affected more than females

• Fatigue and weakness

• Hypokalemia

• Elevated aldosterone and decreased renin

Pheochromocytoma

• Episodic hypertension

• Orthostasis

• Hypertension worsens with the use of non-alpha blocker antihypertensives

• Elevated urine catecholamines

Renal Artery Stenosis

• Young women (fibromuscular dysplasia) or older men (atherosclerosis)

• Abdominal bruit in 30% of cases

• Positive captopril scan

USMLE Step 3: Internal Medicine

~~. 78 meCtical

l

BONUS CASE B

Chief complaint

Routine physical examination

History and physical examination

A 32-year-old white man comes to your office for a yearly routine physical. He has no significant past medical history or complaints. He exercises routinely. His family history is significant for Type 2 diabetes. Physical examination and vital signs are unremarkable.

Initial diagnostic plan

You explain to the patient that the routine laboratory tests, given his age, consist of a fasting lipid profile. Given his family history you also want to check a fasting glucose.

1. Fasting lipids

2. Fasting glucose

Results

1. Low-density lipoprotein 172 mg/dl., high-density lipoprotein 52 mg/dl., triglycerides 126 mg/dL

2. 102 mg/dL

Discussion

The basis for cholesterol screening stems out of two basic observations:

• There is a direct relation between the plasma levels of total and low-density lipoprotein plasma cholesterol and the risk of coronary heart disease.

• Low-density lipoprotein cholesterol lowering in patients leads to reduction in cardiovascular events.

A meta -analysis of 38 primary and secondary prevention trials found that for every 10% reduction in serum cholesterol, coronary heart disease mortality was reduced by 15%, and total mortality risk was reduced by 11%.

The Third Report of the Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (ATP III) has presented guidelines that are based upon epidemiologic observations showing relationship between the total cholesterol concentration and coronary risk. They are influenced by the absence (primary prevention) or presence (secondary prevention) of preexisting coronary heart disease.

Men and women with coronary heart disease have a risk of myocardial infarction 20 times higher than those without coronary heart disease. Elevations in serum cholesterol, even when modest, increase the risk of a cardiac event in patients with coronary heart disease or in those with a recent myocardial infarction.

The ATP III recommendations for the treatment of hypercholesterolemia are based upon the low-density lipoprotein cholesterol fraction and are influenced by the coexistence of coronary heart disease and the number of cardiac risk factors.

Endocrinology

There is a new recommendation to screen adults with hypertension or hyperlipidemia for type 2 diabetes.

There are five major steps to determining an individual's risk category; these steps serve as the basis for the treatment guidelines.

Step 1. The first step in determining patient risk is to obtain a fasting lipid profile.

Step 2. Coronary heart disease equivalents, that is, risk factors that place the patient at similar risk for coronary heart disease events as a history of coronary heart disease itself, are identified:

• Diabetes mellitus

• Symptomatic carotid artery disease

• Peripheral arterial disease

• Abdominal aortic aneurysm

• Multiple risk factors that confer a lO-year risk of coronary heart disease >20% (see Step 4).

Step 3. Major coronary heart disease factors other than low-density lipoprotein are identified:

• Cigarette smoking

• Hypertension (blood pressure 2140/90 or antihypertensive medication)

• Low high-density lipoprotein cholesterol «40 mg/dL [1.03 mmol/LJ)

• Family history of premature coronary heart disease (in male first-degree relatives <55 years, in female first-degree relative <65 years)

• Age (men 245 years, women 25,5 years)

• High-density lipoprotein cholesterol 260 mg/dL (1.55 mmol/L) counts as a "negative" risk factor; its presence removes one risk factor from the total count.

Step 4. If two or more risk factors other than low-density lipoprotein (as defined in Step 3) are present in a patient without coronary heart disease or a coronary heart disease equivalent (as defined in Step 2), the lO-year risk of coronary heart disease is assessed using Framingham risk tables. Risk does not need to be assessed in people without coronary heart disease who have 0 to 1 risk factors because individuals in this category have a 10-year risk of coronary heart disease that is <10%.

Step 5. The last step in risk assessment is to determine the risk category that establishes the lowdensity lipoprotein goal, when to initiate therapeutic lifestyle changes, and when to consider drug therapy.

Summary and recommendations

Cardiovascular benefits of cholesterol lowering with statin drugs have now been demonstrated in the following groups:

• Patients with coronary heart disease, with or without hyperlipidemia

• Men with hyperlipidemia but no known coronary heart disease

• Men and women with average total and low-density lipoprotein cholesterol levels and no known coronary heart disease

Secondary Prevention. Taken together, these findings suggest that patients who already have coronary heart disease merit aggressive lipid management. The ATP III report recommended a goal low-density lipoprotein cholesterol value of less than 100 mg/dL (2.6 mmol/L) for secondary prevention, suggesting that dietary modification be employed in any patient with a low-density

KAPurril· I me 1C8

79

USMLE Step 3: Internal Medicine

80 iileClical

lipoprotein cholesterol exceeding 100 mg/dl, (2.6 rnmol/L) and that drug therapy be considered if the low-density lipoprotein cholesterol remains above 130 mg/dL (3.4 mmol/L), However, the consistent and early benefit of statin therapy in patients with coronary heart disease demonstrated in numerous studies suggests that drug therapy should not be postponed if the target for lowdensity lipoprotein cholesterol lowering «100 mg/dl, or 2.6 mmol/L) is unlikely to be achieved in the near term by nonpharmaceutic approaches.

The ATP. II report recommended that hormone replacement therapy be used as first-line therapy in women with coronary heart disease. This recommendation was omitted in ATP III as a result of clinical trials that failed to show any benefit of hormone replacement for secondary prevention

Primary Prevention. It is apparent that the patients most likely to benefit from cholesterol-lowering therapy as primary prevention are those with baseline hyperlipidemia. Subgroups with other cardiac risk factors derive the greatest benefit from cholesterol-lowering therapy. The serum low-density lipoprotein cholesterol concentration and risk factor status determine the suggested approach: Individuals with desirable serum low-density lipoprotein cholesterol values may be reevaluated in 5 years, whereas those with borderline high-risk values and fewer than two cardiac risk factors should be reevaluated in 1 year (one risk factor is subtracted if the serum high-density lipoprotein is ~60 mg/dL [1.6 mmol/L]).

A cholesterol-lowering diet is indicated in patients with a high-risk serum low-density lipoprotein cholesterol concentration and in those with borderline high-risk values plus two or more cardiac risk factors.

Drug therapy with a statin should be considered if, after an adequate trial of dietary modification, serum low-density lipoprotein cholesterol remains above 190 mg/dL (4.9 mmol/L) in any patient or above 160 mg/dl, (4.1 mmol/L) in a patient with two or more risk factors for coronary heart disease.

The goal serum low-density lipoprotein cholesterol concentration should be below 160 mg/dL (4.1. mmol/L) in patients with fewer than two risk factors for coronary heart disease. A lower value of 130 mg/dL (3.4 rnmol/L) is recommended in patients with two or more risk factors for coronary heart disease.

Patients with low high-density lipoprotein. Therapy aimed at raising high-density lipoprotein levels into the normal range has been advocated by some investigators in patients with overt coronary heart disease and in patients at high risk because of a strong family history. In ATP III, low high-density lipoprotein cholesterol is defined as <40 mg/dl, (1.03 mmollL), a change from the level of 35 mg/dL (0.91 mmol/L) in ATP II.

Treatment

All patients with high low-density lipoprotein cholesterol should undergo lifestyle modifications to reduce the serum cholesterol. Many will not reach the goal level of cholesterol with these measures and will require drug therapy.

Lifestyle Modifications. All patients with high low-density lipoprotein cholesterol should undergo lifestyle modifications (therapeutic lifestyle changes as stated in ATP III), such as reductions in dietary total and saturated fat, weight loss in overweight patients, aerobic exercise, and plant stanols/sterols.

Drug Therapy. Lipid-altering agents encompass several classes of drugs that include statins, fibric acid derivatives, bile acid sequestrants, nicotinic acid, and probucol. These drugs differ with respect to mechanism of action and to the degree and type of lipid lowering. Thus, the indications for a particular drug are influenced by the underlying lipid abnormality.

Endocrinology

The statins are commonly used in the treatment of hypercholesterolemia. They are the most powerful drugs for lowering low-density lipoprotein cholesterol, with reductions in the range of 20 to 60%. Atorvastatin is the most potent, reducing LDL levels by 29 to 61 % over the dosing range of 5 to 80 mg/d. An additional benefit of atorvastatin is more effective triglyceride lowering in patients with hypercholesterolemia that ranges from 14 to 33%. Adverse reactions occur less frequently with the statins than with the other classes of lipid-lowering agents, but myositis is an important concern.

The major effects of the fibrates are to lower plasma triglyceride and raise high-density lipoprotein levels.

Monitoring Therapy. There are no reliable data on the optimal method of monitoring the effects of lipid-lowering therapy. ATP III recommends that the low-density lipoprotein cholesterol be monitored every 6 weeks after the initiation of treatment. Measurement every 4 to 6 months is reasonable once the goal low-density lipoprotein cholesterol is achieved.

The optimal value for low-density lipoprotein cholesterol in both men and women is <100 mg/dL.

A standard serum lipid profile consists of total cholesterol, triglycerides, and high-density lipoprotein cholesterol. Lipoprotein analysis should be performed after 12 to 14 hours of fasting to minimize the influence of postprandial hyperlipidemia. The primary effect of eating is to increase plasma triglyceride levels. The LDL-cholesterol concentration can be estimated from:

low-density lipoprotein cholesterol = total cholesterol - very low-density lipoprotein - cholesterol - high-density lipoprotein cholesterol

where VLDL-cholesterol is assumed to be one-fifth of the total triglyceride concentration. The formula is valid only if the total triglyceride concentration is <400 mg/dL.

ATP III screening guidelines for lipid abnormalities published in 2001 recommended that screening be performed at least once every 5 years for all persons age 20 and over. In a change from previous guidelines, a fasting lipid profile is recommended for screening.

Individuals without known coronary heart disease who have a desirable serum low-density lipoprotein cholesterol concentration «160 mg/dL or <3.4 mmol/L for zero to one risk factor and <130 mg/dL for two or more risk factors) can be re-screened in 5 years. Patients with borderlinehigh cholesterol and fewer than two risk factors should be re-screened within 1 to 2 years.

The desirable low-density lipoprotein cholesterol level for those with coronary heart disease or coronary heart disease equivalent is <100 mg/dL «2.6 mmo1!L). Coronary heart disease equivalents include:

• Symptomatic carotid artery disease

• Peripheral arterial disease

• Abdominal aortic aneurysm

• Diabetes mellitus

KULA ... iI- .. I me 1C8

81

Rheumatology

CASE 1

Chief complaint

Joint pain, weakness, and fatigue for year

History and physical examination

A 35-year-old woman has had joint pain and swelling for one year. The pain began in her right knee, left elbow, and right wrist and now has become bilateral and involves the metacarpophalangeal joints. She has not had any pain or swelling that involved the distal interphalangeal joints. She has morning stiffness that lasts for approximately two hours. The patient also notes generalized fatigue and weakness. She has no rashes, hair loss, or back pain and no history of fever, weight loss, or diarrhea.

Her temperature is 37.0 C (98.6 F).There is active synovitis consisting of warmth, swelling, and tenderness of the knees, wrists, elbows, metacarpophalangeal joints, proximal interphalangeal joints, and ankles symmetrically. Distal interphalangeal joints are spared. There is a flexion contracture of the right elbow. There is no hair loss, oral ulcers, or rash. Her lungs are clear, and heart has no murmurs, rubs, or gallops. Her abdomen is soft and nontender with no hepatosplenomegaly.

Differential diagnosis

• Rheumatoid arthritis

• Systemic lupus erythmatosus

• Viral syndromes, e.g., hepatitis B, Epstein-Barr virus, parvovirus B-19

Initial diagnostic plan

1. Antinuclear antibodies

2. Rheumatoid factor

3. C-reactive protein and erythrocyte sedimentation rate

4. Complete blood count

5. Creatinine

6. Hepatitis panel, IgM parvovirus titers, Epstein-Barr virus titers

IlAPLAN'iI· I me 1C8

83

USMLE Step 3: Internal Medicine

Results

1. Negative

2. Positive IgM (1:3,200, considered very high)

3. Both are elevated

4. Normochromic normocytic anemia

5. Normal

6. Negative

84 KAPLAN"iI· I

me lea

Assessment

Rheumatoid arthritis classically presents with symmetrical arthritis. It spares the distal interphalangeal joints and the lower back.

Systemic lupus also presents with symmetrical arthropathy, but there are usually other organs involved, e.g., kidney (renal insufficiency), skin (malar rash), lungs (pleural effusions). However, the antinuclear antibody test is not specific for systemic lupus, but it is positive in 97% of cases. A negative antinuclear antibody test rules out lupus.

Viral syndromes, e.g., hepatitis B, Epstein-Barr, parvovirus B-19, are a possibility, but these are usually of short duration. Our patient had the symptoms for a year, which makes one of these diseases unlikely. Hepatitis B sometimes will present with arthropathy in the early phase, when there is absence of jaundice. Parvovirus usually is seen in children presenting with the classic "slapped cheek" appearance; in adults the rash is seen in only 30% of cases, the rest presenting with symmetrical arthropathy. Think of parvovirus infections in patients who come into contact with small children (e.g., teachers) and especially if the erythrocyte sedimentation rate and C-reactive protein levels are within normal limits. The IgM antibodies will be elevated in patients that have an acute parvovirus infection.

Further diagnostic plan 1. X-rays of hands

Results

1. Bony erosions at second and third metacarpophalangeal joints

Treatment plan

1. Nonsteroidal antiinflammatory medications to relieve inflammation

2. Disease-modifying therapy (e.g. methotrexate) should be considered early in this patient because she has early joint erosions and a high rheumatoid factor. Both of these findings are bad prognostic indicators.

Discussion

Rheumatoid arthritis is a chronic, inflammatory, systemic disease with the main focus of inflammation being the synovium. The hallmark of rheumatoid arthritis is inflammatory synovitis that presents in a symmetric distribution. The intense joint inflammation that occurs has the potential to destroy cartilage and cause bone erosions, eventually deforming the joint.

The cause of rheumatoid arthritis is unknown. It may be triggered as a reaction to an infectious agent (Mycoplasma, parvovirus) in a susceptible host. Of the environmental factors, only cigarette smoking seems to be associated. Women are affected three times more than men, and in 80% of the cases, the age of onset is between 35 to 50 years.

Rheumatology

An initiation phase of nonspecific inflammation occurs, followed by an amplification phase resulting from T-cell activation. The last stage involves chronic inflammation and tissue injury.

The predominant infiltrating cell is the T lymphocyte. Diseases like HIV, in which T cells are decreased, will characteristically improve pre-existing rheumatoid arthritis; this is also the reason why RA is very rare in patients with HIY.

You need four of the diagnostic criteria listed in Table 1.

Table 1. Diagnostic Criteria for Rheumatoid Arthritis

1 Morning stiffness (> 1 h) for 6 wk
2 Swelling of wrists, MCPs, PIPs for 6 wk
3 Swelling of 3 joints for 6 wk
4 Symmetric joint swelling for 6 wk
5 Joint erosions on x-rays
6 Positive rheumatoid factor
7 Rheumatoid nodules MCP = metacarpophalangeal joint, PIP = proximal interphalangeal joint.

Memorizing the above table is unnecessary. The criteria can be summarized as follows: (1) Rheumatoid arthritis is q chronic, inflammatory, symmetric arthropathy, and (2) there needs to be involvement of multiple joints-vbut some joints are never involved: the distal interphalangeal joints and the lower back.

Because rheumatoid arthritis is a systemic disease, two-thirds of the patients present with constitutional symptoms: fatigue, anorexia, weight loss, and generalized weakness before the onset of the arthritis.

Extra-articular manifestations include:

• Damage to the ligaments and tendons=-Radial deviation of the wrist with ulnar deviation of the digits, Boutonniere deformity, Swan neck deformity

• Rheumatoid nodules=-Initial event due to focal vasculitis; occurs in 20 to 30% of patients with rheumatoid arthritis, usually in areas of mechanical stress (olecranon, occiput, Achilles tendon). Methotrexate may flare this process.

• Felty syndrome

• Caplan syndrome

The diagnosis is on the basis of the clinical criteria. There is no single test or finding that will diagnose rheumatoid arthritis.

Treatment plan

1. None of the nonsteroidal antiinflammatory medications has better antiinflammatory effects than aspirin, but they do have less gastrointestinal side effects.

There is no single nonsteroidal antiinflammatory medication superior to other agents, and the newer agents have not been shown to have a decreased incidence in toxicity (gastrointestinal, renal, etc.).

ufl. LAlI'iI· • ••

me lea

85

USMLE Step 3: Internal Medicine

2. COX-2 inhibitors (celobix, rofecoxib) inhibit only this specific enzyme and seem to be associated with less toxicity. It seems that COX-l is the enzyme that accounts for most of the side effects seen with the nonspecific inhibitors (ibuprofen, indomethacin, naproxen, etc.).

Although good studies have not determined if these drugs are side-effect free; at this time, the patient with increased risk for these (advanced age, comorbid conditions) should be placed on COX-2 inhibitors.

Other drugs used for rheumatoid arthritis are glucocorticoids and disease-modifying agents (antimalarials, gold, sulfasalazine, methotrexate, and tumor-necrosis-factor inhibitors.

86 G;eclical

Table 2. Disease-Modifying Agents

-, """"--,",~"~...,......",,,"
Drug Profile/Side Effects Screening Tests for Toxicity
Hydroxychloroquine Retinopathy Regular eye examinations
i Gold Rash, mild decrease in WBCs, Renal function, urine
1 nephritic syndrome analysis, CBC
I
I Stop usage with pruritic rash
or proteinuria
I
MTX Rapid onset of action; CBC and liver enzymes
(Most utilized agent) hepatitis and hepatic fibrosis; every 4-8 weeks
pneumonitis; may flare
rheumatoid nodules Aggressive disease is likely to occur with the following features: high titers of rheumatoid factor, diffuse rheumatoid nodules, early joint erosions, late age of onset, and certain subtypes of the HLA-DR4. Atlanto-axial subluxation may present when rheumatoid arthritis involves Cl and C2. If there is hyperextension of the neck, there may be permanent damage to the spinal cord. All patients with rheumatoid arthritis before anesthesia or intubation is done must be screened for this with a plain x-ray (lateral neck and open mouth view). If there is evidence of subluxation, then stabilize the spine before the procedure. This syndrome may also present with occipital headaches.

If a patient with rheumatoid arthritis presents with a swollen, painful calf, consider a ruptured Baker cyst, which is the extension of inflamed synovium into the popliteal space.

Final diagnosis Rheumatoid arthritis

Rheumatology

case Review

Rheumatoid Arthritis

• Symmetrical arthropathy

• Significant inflammation

• No rash or renal failure

• Rare pulmonary involvement

• Rheumatoid factor positive

Systemic lupus Erythmatosus

• Symmetrical arthropathy

• Significant inflammation

• Rash and renal involvement

• Lung involvement common

• Positive for antinuclear antibody with decreased complement levels

Viral Arthropathy

• Symmetrical arthropathy

• No significant inflammation

• No rash or renal failure

• No pulmonary involvement

• IgM titers high for specific virus

KA .. PLAlril·caI· me I ,

87

USMLE Step 3: Internal Medicine

88 meClical

eASE 2

Chief complaint

Pain and swelling in the left ankle for one day

History and physical examination

A 50-year-old man, seen in the clinic two days ago for community-acquired pneumonia, comes to your clinic today with swelling of his left ankle joint. The swelling and pain of the ankle joint developed overnight. He denies any trauma. He has had similar attacks 6 months ago, for which he took some over-the-counter painkillers. He never sought medical help, and the symptoms resolved spontaneously after a week or so. He denies any other significant past medical history and has not had recent sexual contact or trauma to the area.

His temperature is 37.3 C (99.1 C), blood pressure is 120/85 mm Hg, and pulse is 88/min. The left ankle is swollen, warm, tender, and erythematous. A small effusion is present, and movement of the ankle is very painful. The other joints are normal. No skin rash is noted.

Differential diagnosis

• Acute monoarthropathy

• Crystal-associated arthritis, such as gout or pseudogout

• Septic or gonococcal arthritis

• Gonococcal or staphylococcal septic arthritis

• Osteoarthritis

Initial diagnostic plan

1. Joint aspiration and x-ray ofIeft ankle

Results

1. There is soft tissue swelling with minimal effusion in the left ankle but no dislocation or fracture. The arthrocentesis of the left ankle shows WBC as 37,OOO/mm3 and a negative Gram stain. Needle-shaped, negatively birefringent crystals are present.

Assessment

Joint aspiration is the single most important test to get in this patient. It is reasonable to get an x-ray of the ankle to rule out any fracture, dislocation, or bony abnormality, but it is not always needed.

Acute monoarthropathy is due to septic arthritis or crystal-induced arthropathy. In this case, a similar history of arthropathy that resolved in the past makes the most likely cause a crystalassociated arthritis such as gout or pseudogout. Both of these conditions can be precipitated by an acute illness, such as pneumonia.

Rheumatology

Septic arthritis and gonococcal arthritis are other possible diagnoses, which may be associated with fever and leukocytosis. The only way to differentiate between these conditions is to do an arthrocentesis. Gonococcal arthritis is the most common cause of septic arthritis. Staphylococcal septic arthritis is more commonly seen in older patients and in those with preexisting rheumatic diseases. Septic arthritis is diagnosed by a WBC count of over 50,000/mm3 in the synovial fluid and the absence of crystals. The culture and Gram stain is usually negative.

Osteoarthritis may present as a chronic monoarthropathy without any evidence of inflammation.

Treatment plan

1. Nonsteroidal antiinflammatory medications (indomethacin) or colchicine is the treatment of choice for acute gout and is continued until the pain goes away. Indomethacin is preferred because it has fewer side effects when compared to colcichine.

2. If the patient cannot take the above, glucocorticoids can be given orally or as an intra-articular injection.

Remember: Do not give allopurinol for acute gout because it can increase the severity of an acute attack.

Discussion

The crystal-induced arthropathies (monosodium urate, calcium pyrophosphate, calcium oxalate, and calcium hydroxyapatite) are due to microcrystal deposition in the joints. Despite differences in crystal morphology, they have identical clinical presentations and can only be distinguished by synovial fluid analysis.

Gout is a disease that affects middle-aged men and presents most commonly with acute monoarthritis. (Women represent only about 5 to 15% of all patients with gout; premenopausal women make up 17% of all women with gout). As gout becomes chronic, multiple joints may be involved, and deposition of urate crystals in connective tissue (tophi) and the kidneys may occur.

The metatarsophalangeal joint of the first toe is commonly affected (podagra), but other joints like the knee, ankle, PIPs, or distal interphalangeal joints may be initially involved. The first episode commonly occurs at night with severe joint pain that wakes the patient from sleep. The joint rapidly becomes warm, red, and tender (it looks exactly like cellulitis). Without treatment, the joint pain goes away spontaneously within 3 to 14 days.

Certain events that precipitate gout sometimes precede the attack: excessive alcohol ingestion, trauma, surgery, infection, steroid withdrawal, drugs (diuretics [hyrdochlorothiazide and furosemide 1, antituberculosis medications [pyrazinamide and ethambutol]), and serious medical illnesses.

The serum uric acid during the acute attack may be normal or low. On the other hand, many people have elevated serum-uric acid levels and never develop gout. Thus, the serum uric acid level is of no value in the diagnosis of acute urate arthropathy. This is why the diagnosis is made by the analysis of synovial fluid.

In treating acute gouty arthritis, the goal is to decrease inflammation and thus prevent erosions and joint destruction. Also in this stage, it is very important to avoid any fluctuations in serum uric-acid levels. Treatment options include:

• Nonsteroidal antiinflammatory medications, e.g., indomethacin 50 mg TID

• Colchicine 0.6 mg every hour until symptoms resolve or gastrointestinal upset occurs

• Intra-articular or oral steroids in the elderly who cannot tolerate nonsteroidal antiinflammatory medication or colchicine

IlAP~!.. I m~lca

89

USMLE Step 3: Internal Medicine

90 m.&ical

For chronic hypouricemic therapy, the goal is to decrease uric-acid levels, and this treatment is usually required for life. It is initiated on patients who have had recurrent gouty attacks that cannot be corrected by a low-purine diet, limitation of alcohol, avoiding diuretics, etc. Unlike acute gout, the uric-acid level may be helpful in following the effect of hypourecemic treatment. Treatment options include:

• Probenecid for the "undersecretors" (>80% of adults)

• Allopurinol for "overproducers" or for patients with renal failure and/or kidney stones

Final diagnosis Gout

Case Review

Crystal-Induced Arthritis

• Acute rnonoarthropalhv

• Severe inflammation

• Crystals found in the joint aspiration

• WBCs in the synovial fluid <50,OOO/I-LL

Septic Arthritis

• Acute monoarthropathy

• Severe inflammation

• No crystals found in the joint fluid

• WBCs in the synovial fluid >50,OOO/I-LL

Osteoarthritis

• Chronic monoarthropathy

• No evidence of inflammation

• Minimal effusion with WBCs q,OOO/I-LL

Rheumatology

CASEl

Chief complaint

Joint pain for several months

History and physical examination

A 28-year-old woman comes to the office and states that for several months she has had intermittent joint pain but only had discrete swelling of the joints recently. She points to her wrists and metacarpophalangeal and proximal interphalangeal joints. She has also suffered from intermittent fevers, morning stiffness for longer than 1 hour, and a weight loss of 15 Ibs. She noted a rash on her face several months ago after being at the beach, which took one month to resolve. She expresses the concern that "maybe it is all in my head. I feel like I am going crazy." She denies a history of diarrhea. There is no history of known insect bites. Her prior medical history is significant for two spontaneous abortions. She is afebrile.

Her blood pressure is 145/90 mm Hg, pulse is 70/min, and respirations are 14/min. Examination of the head, eyes, ears, nose, and throat is normal. There is no cervical adenopathy noted. There is good air entry in both lungs. The heart has a regular rate and rhythm, with no murmurs or rubs appreciated. There is no splenomegaly, but her liver is mildly enlarged. There are no rashes. Neurologic examination is nonfocal.

Differential diagnosis

• Systemic lupus erythematosus

• Rheumatoid arthritis

• Hepatitis or other viral polyarthropathies

Initial diagnostic plan

1. Antinuclear antibodies (ANA)

2. Complement levels (C3, C4, or CH50)

3. Complete blood count

4. Chest x-ray

5. BUN/Creatinine'

6. Urinalysis

7. Rheumatoid factor

8. Erythrocyte sedimentation rate and C-reactive protein

9. Liver function tests and viral titers

10. Lyme titers

KAPUIr .. _. me 1C8

91

USMLE Step 3: Internal Medicine

Results

1. Positive 1:640

2. Depressed

3. White blood cells 3,000/mm3; hemoglobin 11 mg/dL; platelets 120,000/mm3

4. No effusions or infiltrates

5. Creatinine 2.1 mgldL

6. Mild proteinuria

7. Negative

8. Moderate elevations of both

9. Within normal limits

10. Both negative

Assessment

This patient has a nonspecific history of joint pain and rash, but laboratory results show renal insufficiency with proteinuria, leukopenia, anemia, and mild thrombocytopenia. This picture is most consistent with systemic lupus, although another collagen vascular disease, such as rheumatoid arthritis, is possible.

A positive ANA is a sensitive test for lupus; <3% of patients with systemic lupus are ANA negative if the HEP-2 substrate is used. However, it is relatively nonspecific, particularly at a low titer. A positive ANA may be seen in other autoimmune diseases or in 10% of the normal population.

In general, in rheumatoid arthritis the physical findings for joint disease are more prominent. Hepatitis can present with arthropathy, but in this case the titers were negative, and in fact there are multiple other organs involved.

Further diagnostic plan

1. 24-hour urine protein measurement

2. Double-stranded DNA antibodies

Results

1. 4 gm/24 hours

2. Positive

Treatment plan

1. Prednisone should be started immediately at 1 rug/kg/day

2. A kidney biopsy should be performed to diagnose the type of lupus nephritis

3. Consider immunosuppressants, like azathioprine or cyclophosphamide

Discussion

Systemic lupus erythematosus is a systemic disease in which tissues and multiple organs are damaged by pathogenic autoantibodies and immune complexes. Systemic lupus erythematosus is of unknown etiology. Ninety percent of cases are women. The abnormal immune response probably depends upon interactions between a susceptible host and environmental factors. Ultraviolet B light is the only environmental factor known to cause flares.

Individuals need to meet four of the 11 criteria (Table 3).

Rheumatology "

Table 3. Diagnostic Criteria for Systemic Lupus Erythematosus

r---
1 Malar rash
2 Discoid rash
3 Photosensitivity
4 Oral ulcers
5 Arthritis"
6 Serositis (pleuritis or pericarditis)
7 Renal involvement
8 Neurologic disorder (seizures or psychosis)
9 Hematologic disorder (hemolytic-anemia)
10 Immunologic disorder (anti-dsDNA, anti-Smith)
11 Positive ANA • Arthritis is identical to that of rheumatoid arthritis, except that it is nonerosive.

Both the malar rash and photosensitivity rash (diffuse, maculopapular) flare with exposure to ultraviolet- Blight (thus, patients are considered photosensitive) and resolve with no scarring of the skin. Discoid lupus isa circular rash with a raised rim that occurs over the scalp and face; it can be disfiguring because of central atrophy and scarring. Only 5% of patients with discoid lupus will go on to develop systemic lupus erythematosus.

The dsDNA and anti-Smith antibodies are specific for lupus. These only occur with lupus, so if found, think lupus only. Complement levels (C3, C4, or the more sensitive CH50) are depressed in patients with active lupus. Remember, when dsDNA antibody levels are elevated, this is very specific for the diagnosis of lupus; they also increase the likelihood of lupus nephritis. Also, a change of personality and psychosis may be manifestations of central nervous system lupus.

An associated syndrome often seen with systemic lupus is the antiphospholipid syndrome. This is a syndrome of recurrent arterial and venous thrombosis, spontaneous abortions, thrombocytopenia, and a false-positive venereal disease research laboratory test. It is also associated with an elevated prothrombin time. However, Libman-Saks endocarditis is a noninfectious endocarditis rarely seen in lupus patients.

All patients with renal involvement must undergo renal biopsy before treatment is initiated.

Drug-Induced Lupus. This is usually a limited form of lupus that occurs with exposure to certain drugs. Procainamide, hydralazine, isoniazid, and methyldopa are the most common. There is no major organ involvement (no kidney or central nervous system) with drug-induced lupus. It presents only with a rash and antihistone antibodies and resolves after the offending agent is removed. There is also no hypocomplementemia with drug-induced lupus.

Pregnancy and Systemic Lupus Erythematosus. Fertility rates are normal in patients with systemic lupus erythematosus, but spontaneous abortions and stillbirths are more common. One reason for the spontaneous abortions in these patients may be the antiphospholipid antibodies causing placental infarcts. This is treated with low molecular weight heparin. It is unclear if lupus worsens with pregnancy; in the case of a flare during this time, steroids may be used safely to suppress the disease.

You're Reading a Free Preview

Download
scribd
/*********** DO NOT ALTER ANYTHING BELOW THIS LINE ! ************/ var s_code=s.t();if(s_code)document.write(s_code)//-->