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INVOLUNTARY WEIGHT LOSS

an approach to diagnosis

Gatot Sugiharto, MD, Internist

Internal Medicine Department
Faculty of Medicine, Wijaya Kusuma University Surabaya
 Introduction
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 Involuntary weight loss is a challenging problem

 This has serious health implications, with the risk of
patient morbidity and mortality
 The key to the diagnosis of involuntary weght loss is a
careful and complete history and physical
examination.
 The approach begins broadly and then quickly
focuses on specifics derived from the initial
evaluation.
 Definition
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 Significant weight loss: loss of 5% body weight

in 30 days, 7.5% in 60 days, or 10% in 180
days
 Severe weight loss: loss of more than 5% body
weight in 30 days, more than 7.5% in 60 days,
or more than 10% in 180 days.
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 Initial Evaluation (1)
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A. Quantify loss. A loss of 5% of the baseline body

weight (not ideal body weight) is significant
• 1. Can the weight loss be verified? Serial
measurements are best, but other markers include
numerical estimates and changes in clothing or belt
size.
• 2. Up to 25% of cases with documented weight loss
and thorough evaluation, no cause is ever found
• 3. Is there a physical cause? One-third of cases will
be caused by depression, dementia, or social factors
 Initial Evaluation (2)
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B. Categories of weight loss can be divided into four major

categories: decreased intake, increased nutrient loss,
increased metabolic demand, and impaired absorption
C. Special considerations
1. A tailored approach in the elderly
2. The approach in human immunodeficiency virus infection and acquired
immunodeficiency syndrome is more comprehensive
3. Special attention is given to disease-specific infections, nutritional
changes, and neoplasia.
 History: Initial data
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A. Is the loss intentional ? Consider dieting, diuretics, and eating disorders.

B. What is the patient’s average daily or weekly intake ? Consider frequency

of meals, appetite changes, and difficulty with food preparation.

C. Tobacco, alcohol, and drug histories are very important and frequently
lead to other concerns.

D. Chronic conditions? Medical, surgical, psychiatric, and family histories are

always pertinent.

E. Social factors include stress, isolation, and the cost and effort required to
eat.
 History taking (1)
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 Is there fever?
 Suggest an infectious disease, such as tuberculosis, AIDS,
brucellosis, and typhoid fever
 Collagen diseases and neoplasms should not be forgotten

 Is there anorexia?
 Anorexia may be related to a febrile process, but if there is
no fever one should consider the possibility of Addison's
disease, anorexia nervosa, Simmonds' disease, drug abuse,
poisoning such as arsenic poisoning, scurvy, malabsorption
syndrome, uremia, and liver failure, neoplasm.
 History taking (2)
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 Is there lymphadenopathy?
 Generalized lymphadenopathy should suggest leukemia, sarcoidosis,
and lymphoma, as well as infectious disease processes.
 Is there an abdominal mass?
 An abdominal mass may be an enlarged spleen, a pancreatic
carcinoma, an enlarged liver, or renal mass. These masses would suggest
disease of those organs.
 Mass also may be a carcinoma of the stomach or intestine.
 Is there hyperpigmentation?
 Hyperpigmentation would suggest Addison's disease.
 History taking (3)
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 Is the appetite normal or increased?

 A normal or increased appetite in the presence of weight
loss should suggest hyperthyroidism and diabetes mellitus.
 May be taking thyroid hormone medication in increased
quantities.
 Is the thyroid gland enlarged?
 Enlarged thyroid would suggest hyperthyroidism
 A focal thyroid mass which might be a toxic adenoma.
 Is the chest x-ray abnormal?
 CXR abnormality which may induce weight loss are
carcinoma of the lung, tuberculosis, congestive heart failure,
pulmonary emphysema, and fibrosis.
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 Basic physical examination
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Relevant physical findings will be present in 66% of cases

Quantify loss by serial weight measurements.

Check the vital signs: temperature, blood pressure, and

respiratory and heart rates. Consider determining oxygen
saturation.

Perform a physical examination, with emphasis on areas

suggested by clues from the history.
 Basic laboratory tests
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Useful tests include:

 Complete blood count, sedimentation rate, urinalysis, and fecal
occult blood testing.
 Comprehensive chemistry panel : albumin, BS, thyroid panel, serum
amylase and lipase, febrile agglutinins, tuberculin test, ANA titer,
serum protein electrophoresis, serum B 12 and folic acid,
transaminases, blood urea nitrogen, creatinine, and electrolytes—
calcium, magnesium, phosphorus, sodium, and potassium
 Chest radiograph, ECG, BOF are often useful
 An HIV antibody titer needs to be done in selected clinical
circumstances
 Comprehensive analysis
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Further testing : (should be done only as directed by the initial

findings)
 Endoscopy, and colonoscopy, esophagogram, a small
bowel series, barium enema, and a sigmoidoscopic
examination.
 Computed tomography and other expensive

investigations seldom beneficial in the absence of a

specific (often guideline-based) indication
 Useful Tests
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 Tuberculin test (tuberculosis)
 Glucose tolerance test (diabetes
mellitus)
 Serum amylase and lipase levels
(chronic pancreatitis, pancreatic
neoplasm)
 Drug screen (drug abuse)
 HIV antibody titer (AIDS)
 Stool for fat and trypsin (malabsorption
syndrome)
 Stool for ova and parasites (parasites
infestation)
 d-Xylose absorption test
(malabsorption syndrome)
 Urine 5-HIAA (carcinoid syndrome,
malabsorption syndrome)
 Bone scan (metastatic malignancy)
 CT scan of the abdomen (malignancy
abscess)
 Lymphangiogram (Hodgkin disease,
metastatic malignancy)
 CT scan of the brain (pituitary tumor)
 Lymph node biopsy (lymphoma,
malignancy)
 Serum ADH level (diabetes insipidus)
 Serum cortisol level (Addison disease,
hypopituitarism)
 Serum growth hormone, LH or FSH
(Simmonds disease)
 Diagnostic assessment.
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The integration of history, examination, and laboratory data usually reveals

the cause for involuntary weight loss.
 Cancer, including gastrointestinal malignancies, accounts for 16% to 36% of
cases, and other gastrointestinal diseases account for another 14% to 23%
 If the initial steps are not conclusive  careful observation. Follow-up
examinations and testing should be done monthly for 6 months. If a physical
cause exists, it will almost always be found within this time
 If an organic cause is present, this simple approach will find it more than
75% of the time
 If an organic cause is not identified in 6 months, one is unlikely to be found
These undifferentiated patients, however, do well and have an excellent
prognosis, assuming they do not have continued and progressive weight loss
 Differential Diagnosis (1)
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 Ankylosing spondylitis  Medications

 Bilateral lesions of the lateral Angiotensin-converting enzyme
hypothalamus (hypothalamic anorexia) inhibitors (distortion of taste)
 Decreased food intake/malnutrition Antidepressants
Abdominal angina Clonidine
Anorexia of aging Digoxin
Chronic/recurrent nausea/vomiting Nonsteroidal antiinflammatory
Dementia/Alzheimer's disease agents
Esophageal disease/dysphagia Sedatives
Esophagitis Theophylline
Neoplasm  Obstructive gastrointestinal disease
Neuromuscular dysfunction (including pyloric obstruction due to
Reflux chronic peptic ulcer disease)
Scleroderma  Oral disease
Stricture Loose dentures
Poor or absent teeth
Other oral diseases
 Differential Diagnosis (2)
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 Pain  Extensive exercise

 Poor social situation
 Postantrectomy (especially Billroth
II) or gastrectomy
 Poverty
 Unpalatable diets
 Endocrine disorders
Adrenal insufficiency
Diabetes mellitus
Diabetic neuropathic cachexia
Hypercalcemia
Panhypopituitarism
Pheochromocytoma
Thyrotoxicosis
 Infection, especially
Amebic abscess
Bacterial endocarditis
Chronic suppurative
pleuropulmonary disease (e.g.,
emphysema)
Cryptosporidiosis
Fungal diseases
Giardiasis
Human immunodeficiency virus
(HIV)
Mycobacterium avium pulmonary
infections
Parasitic infestations
Paraspinal/epidural abscess
Tuberculosis
Visceral leishmaniasis
 Differential Diagnosis (3)
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 Maldigestion/malabsorption  Myelofibrosis
Inflammatory bowel disease  Myotonic dystrophy
Pernicious anemia  Parkinson's disease
 Malignancy, especially  Pink disease (mercury poisoning in
Biliary children)
Breast  Psychiatric disease
Gastrointestinal Anorexia nervosa
Glucagonoma Anxiety disorders
Hepatic Bulimia
Leukemia Conversion disorders
Lymphoma Depression
Myeloma Manipulative behaviors
Pancreatic Psychosis/paranoia
Pulmonary Schizophrenia
Somatostatinoma Substance abuse
 Differential Diagnosis (4)
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 Severe chronic organ failure

Heart failure (cardiac cachexia)
Hepatic disease
Pulmonary disease
Renal failure
 Systemic lupus erythematosus
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 Differential Overview
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❑ Diabetes ❑ Low cardiac output

❑ Depression ❑ Anorexia nervosa
❑ Inadequate intake ❑ Malabsorption
❑ Drugs ❑ Chronic infection
❑ Hyperthyroidism ❑ Adrenal insufficiency
❑ Occult cancer ❑ Emphysema
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 Major causes of weight loss
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 Impact of Involuntary Weight Loss
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Patient's risk of morbidity and mortality increases.

The clinician may first notice that the patient is listless,

apathetic, or weak, which may be associated with anemia

The functioning of the diaphragm and thoracic muscles may be

diminished, which may cause respiratory compromise

With depletion of subcutaneous fat, the patient's skin turgor may be

impaired, especially in the extremities. Muscle wasting may occur,
first in the quadriceps (the gravity/balance muscles, which may
contribute to leaning or falls)
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 Impact of Involuntary Weight Loss
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 Peripheral edema may occur, independent of heart failure or

any other cardiovascular disease due to decreased oncotic
pressure and increased extracellular fluid.
 Patient may experience glossitis, or cracking at the edges of
the mouth, and he or she may lose hair or the luster of the hair
may change.
 Increased risk for infection-particularly pneumonia-due to
compromised cell-mediated immunity.
 Protein in the diaphragm and intercostal muscles has been
depleted, impairing the patient's ability to deep breathe,
expectorate, and clear microbes from the lungs.
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 Clinical finding(1)
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 Diabetes :
 At the onset, weight loss is primarily caused by osmotic diuresis with
polyuria/nocturia.
 Later glycosuria produces caloric loss, combined with the increased catabolic state of
insulin deficiency and glucagon excess.
 In a patient with new diabetes and prominent weight loss, consider underlying
pancreatic cancer.
 Depression
 It is recognized by sadness, anhedonia, anorexia, and sleep disturbance.
 Inadequate intake
 Common causes include painful oral lesions (phenytoin gum hypertrophy, vitamin
deficiency glossitis, heavy metal intoxication, candidiasis, poor dentition)
 Solitary living in the elderly, early dementia, food fads, abnormal taste (hepatitis,
zinc deficiency, drugs)
 Abdominal pain associated with eating (intestinal ischemia).
 Protein-calorie malnutrition, the skin is dry and baggy. There is weakness, tremor,
polyuria, edema, and ascites.
 Clinical finding(2)
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 Drugs
 Weight loss is associated with cholestyramine, digoxin, diuretics, oral
hypoglycemics, cytotoxics, amphetamines, and sibutramine.
 Hyperthyroidism
 Despite an increased appetite, weight loss occurs. Tachycardia, fine tremor,
silky skin, and eye signs (exophthalmos or lid lag)
 Apathetic hyperthyroidism can occur in elderly patients producing
listlessness and tachycardia or atrial fibrillation.
 Occult cancer
 Pancreatic cancer is the prototype, with aversion to food, and weight loss
(20 to 40 lbs.) that precedes visceral pain or jaundice, and is not
proportional to size of the tumor.
 Gastric and pancreatic cancer, moderate in prostate, colon, and lung
cancer, and mild in breast cancer.
 Pathophysiology
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 Clinical finding(3)
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Low cardiac output

• Easy fatigability, dyspnea on exertion, bibasilar rales, peripheral edema,
third and/or fourth heart sounds, and jugular venous distension are found.
Anorexia nervosa
• The patient is preoccupied with body weight, yet is unconcerned about being
obviously very thin.
• Overactivity, often the form of vigorous exercise, despite cachexia.
Malabsorption
• Fat malabsorption produces sticky and greasy stools, borborygmi,
abdominal distension, and vague abdominal pain
• Associated with loss of lipid-soluble vitamins, which sometimes produces
peripheral neuropathy, anemia, dermatitis, or bleeding.
• Sprue causes a malabsorption syndrome, bone pain with compression
deformities, and anxiety/depression.
 Clinical finding(4)
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Chronic infection
• Fever is the key sign. Common occult causes include bacterial
endocarditis, osteomyelitis, tuberculosis, and HIV.
Adrenal insufficiency
• Fatigue, hypotension, and hyperpigmentation—especially when
seen in the palmar creases or buccal mucosa—are important
findings.
Emphysemia
• Cachexia occurs in “pink puffers.” The patient will have a smoking
history, a barrel chest with reduced breath sounds, and will be
dyspneic on exertion
 Management
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 Identify and address the underlying cause

 Appetite disturbance of depression may be reversed by
antidepressant medications
 Pancreatic enzymes for pancreatic malabsorption
 Referral to nutritionist if necessary
 Referral to social services if necessary
 Anorexia of malignancy and AIDS can be treated with
megestrol acetate or dronabinol
 Aggressive treatment of anorexia nervosa, including
evaluation for electrolyte and cardiac disorders and
consultation with psychiatrist or psychologist
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