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Endocrinology

American Manual
of Examination
in Medicine
(2CK)

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Endocrinology American Manual of Examination in Medicine (2CK) Author Juan Simón Chacín .

...................................................................... 3 Syndrome of Inadequate Secretion of Vasopressin (SIADH) .....................1................... 12 Metabolic Syndrome...................3................ Paget’s Disease .......................... 1.............................. Adrenal Pathology ..................................1............................................................. 14 05...................2.......................................2..............................2..........................3.....................2. 3....................................................... 1 Acromegaly ............ Thyroid Pathology .............................................................. 10 Type 2 Diabetes Mellitus ...............4..........2...........................................1.............................................. Osteoporosis .............................. 1............. 7 03............................ 4............................................ Adrenal Failure ... 2 Hyperprolactinemia ...... 2.......................... Cushing’s Syndrome ............................................................ 2.................................4..... 3.A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK) Index 01.............................. 4........................................................................................ 15 06............ 8 Primary Hyperaldosteronism (PHA)......... 2................... 3............................. 5 Hypothyroidism ............. 15 5........................................3.... Hypothalamic-Pituitary Pathology ..... 1 1......................................................3......... 6 Thyroiditis........................... 4..... Thyroid Function Test.......1............................................................................................................................................................................................................................................................................... 14 5..........................3.. 1......................... 14 5.................. Type 1 Diabetes Mellitus ........................................................................... 6 Thyroid Nodule and Thyroid Cancer ..................................................... Multiple Endocrine Neoplasia (MEN) .......5..................................... 11 Treatment of Diabetes Mellitus ................4.............. 1..... 10 04.................................... Alteration in Hydrocarbonate Metabolism................... 8 Pheochromocytoma................................ Bone Pathology and Phosphocalcic Metabolism ................................................................................................. 5 2........... 8 3....................................................................................1................. Hyperparathyroidism ......................................4........................................................................................................................ 16 ...................... 4 02... 2........... 10 4.......................................5.............. 2 Diabetes Insipidus................... 9 Congenital Adrenal Hyperplasia (CAH) .......... 5 Hyperthyroidism ....................

hirsutism. • Patients present in half of the cases. • Intermediate results (from 5 to 20 pg/mL) will probably reveal an ACTH-dependent CS. adrenal hyperplasia and adrenal carcinoma) in about 15% to 20% and the ectopic CS as a result of paraneoplastic production of ACTH (bronchial carcinoma of small cells is the most frequent. autonomous production of cortisol as a result of adrenal pathology (adrenal CS because of adenomas. weight gain with growth rate delay. facial plethora. If > 20 pg/mL. after CRH administration. vinous red stretch marks. the most frequent endogenous cause is Cushing’s diseases (overproduction of ACTH due to a pituitary adenoma) in 65% to 70% of the cases. nephrolithiasis. it is ACTH-dependent and the next step is to perform a pituitary MRN. proximal myopathy and hyperpigmentation. • The 8 mg DXM Liddle’s test with a high dose (long high-dose dexamethasone suppression test) is a useful test to discrimi- 1 . Cushing’s Syndrome • • Cushing’s syndrome (CS) is a set of diverse symptoms. high blood pressure (HBP) and osteoporosis. due to an excess in cortisol production by the adrenal cortex (endogenous Cushing’s) or by sustained administration of glucocorticoids (exogenous and factitious Cushing’s). capillary fragility. symptoms and signs typical of CS may appear and cardinal manifestations consist of glucose intolerance. the first step will always be determining baseline ACTH to differentiate between ACTH-dependent CS (central or ectopic) and ACTH-independent CS (adrenal). so a CRH test will be taken (central CS keeps a hypothalamic pituitary-adrenal axis relatively intact). The most frequent cause is iatrogenic administration of steroids due to another reason. Signs: central obesity. high nocturnal salivary cortisol (measured between 11 p. alterations of carbohydrate metabolism (DM and carbohydrate intolerance). hematomas and capillary fragility. Diagnosis • Whatever the cause of excess cortisol production. there will always be an increased cortisol excretion. If ACTH is < 5 pg/mL (low or suppressed). proximal myopathy and cutaneous hyperpigmentation. edemas in lower extremities. abolition of its circadian rhythm and absence of cortisol secretion inhibition with a low dose of glucocorticoids. Therefore. moon facies.1. it is ACTH independent. carcinoid tumors.Endo c ri no l ogy HypothalamicChapter 01 Pituitary Pathology 1. and midnight) and combined suppression test with 2 mg of DXM + CRH stimulus: useful to differentiate people suffering from pseudo Cushing’s (it remains suppressed after CRH) from those with CS (they experience a high plasma concentration of cortisol and ACTH after CRH administration). The most specific are facial plethora. wine-red stretch marks and.m. • For etiologic diagnosis or diagnosis for localization. there is an increase in ACTH and cortisol at baseline in most patients with hypothalamic dysfunction or an ACTH-secreting pituitary tumor (macroadenoma and microadenoma). muscle weakness or proximal myopathy. • In ectopic CS cases. MRN). psychiatric alterations. Clinical presentation (Figure 1) Moon face Acne Capillary fragility Hirsutism Central obesity Wine-red stretch marks Muscle weakness Figure 1. CMT and pheochromocytoma) in 15%. muscle weakness. and midnight) and/or lack of suppression of basal plasma cortisol after administration of low doses of dexamethasone: nocturnal suppression with 1 mg of dexamethasone (Nugent test) and/or low-dose dexamethasone suppression test (classic test of 2 mg DXM or low-dose Liddle test). • There are “second-line tests” to be performed on patients who have had misleading results on a prior test and when there is a high clinical suspicion of Cushing’s syndrome: high late-night serum cortisol (measured between 11 p. hypopotassemic alkalosis. • Biochemical diagnosis of hypercortisolism requires two positive tests of the following (they are regarded as “first line test”): high cortisoluria 24 h. so the next step is to perform an adrenal imaging test (adrenal CT scan. and less frequently.m. menstrual cycle irregularity. Clinical presentation of Cushing’s syndrome • Characteristic features of Cushing’s Syndrome include (from the most frequent to the least) Symptoms: weight gain.

• Radiotherapy is utilized in diseased people who did not reach cure after surgery or when surgery is contraindicated or the patient rejects it. muscle weakness and arthralgia. Diagnosis • • • • • Random determinations of GH should not be used for the diagnosis of acromegaly. aminoglutethimide or metopirone). Treatment • Etiologic treatment of choice is surgery in adrenal pathology (adenomas and carcinoma) and in Cushing’s disease (via transsphenoidal approach). 1. carpal tunnel syndrome. the linear growth increases and results in gigantism. HBP. Hypothyroidism. Myocardiopathy (ventricular hypertrophy) and heart failure because of diastolic dysfunction. Hyperprolactinemia is present in a third of the cases. Three to ten times higher risk of having premalignant polyps and colon cancer. Acromegaly • Debilitating chronic disease because of an increased production of growth hormone (GH). headache. • When GH excess develops before epiphyseal plate closure in children. radiotherapy is a second or third choice treatment. A complete assessment of pituitary function is necessary to rule out the existence of panhypopituitarism. bilateral surgical adrenalectomy is needed when definitive treatments (surgery or radiotherapy) fail or side effects to drug treatment develop. Other tumors can cause hyperprolactinemia. while macroadenomas and most ectopic ACTH-secreting tumors do not do so.A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK) • nate patients with ACTH-secreting pituitary microadenoma. It is the second treatment of choice after somatostatin analogs. • When etiologic treatment is not possible or it did not turn out effective. Biochemical diagnosis is based on the presence of high IGF-I levels for age and sex along with a GH that is not suppressed after oral glucose overload (OGO). in the event curative criteria is not met or because of the appearance of severe side effects. At present. profuse sweating. These drugs can be used as a therapeutic first choice. • The medical treatment of choice in acromegaly is the somatostatin analogs (octreotide. Treatment • Transsphenoidal surgery is the choice in microadenomas and macroadenomas that are potentially resectable. exaggerated development of the tongue and coarsening facial features. like nonfunctioning adenomas and other selar masses.3..e. the tumor should be sought (thoracoabdominal CT scan. hypercalciuria and nephrolithiasis. diabetes mellitus among others). Hyperprolactinemia • Increase in prolactin levels. Also in ectopic tumors in which resection is possible. cal diabetes mellitus). • Occasionally.2. Sleep apnea. sleep apnea. it can improve response to medical treatment (“debulking”). A positive response occurs when cortisol in urine or plasma is reduced (> 90% of baseline) after DXM administration. chronic renal disease and hepatic cirrhosis are also causes of hyperprolactinemia (Table 1). deepening of skin crease. Every acromegaly sufferer must have a colonoscopy performed at the time of diagnosis and steps towards early detection of possible complications (i. Imaging studies (adrenal NMR) after hormonal diagnosis. a substitution treatment is required with glucocorticoids and mineral or corticoids. Then. • People suffering from this disorder may be insulin-resistant with abnormal hydrocarbon metabolism (glucose intolerance and clini- 2 1. In macroadenomas with wide extraselar extension although surgery is not curative. When a CS is ACTH-dependent and there is no clear tumoral image in the pituitary gland (≥ 6 mm) or there are hypopotassemia and/or metabolic alkalosis (more frequent in ectopic Cushing’s) a bilateral catheterization of inferior petrosal sinuses must be performed. because of compression of the pituitary stalk (and loss of dopamine inhibitory tone on lactotroph) cells. The demonstration after CRH stimulation of an ACTH peripheral gradient (higher level in petrosal sinus than in peripheral vein) enables locating the site of ACTH hypersecretion in the pituitary gland. Clinical presentation • Symptoms: progressive growth and enlargement of hands. octreoscan test or PET scan). which will reveal a selar lesion in most cases (macroadenoma is more frequent). the patients reject surgery or a macroadenoma is present with scarce possibilities of being completely resected with or without debulking. hepatomegaly and splenomegaly. • Pituitary radiotherapy is used in cases in which cure is not achieved after transsphenoidal surgery of Cushing’s disease. • The most common functioning pituitary tumor is prolactinoma. Bitemporal hemianopsia because of compression of the optical chiasm. The most frequent cause of hyperprolactinemia is pregnancy and the most frequent pathologic primary source is drugs intake. Pegvisomant. Weakness and tiredness. slow-release octreotide and lanreotide) which suppress GH secretion. goiter. a GH receptor antagonist is another alternative. habitually because of GH-secreting pituitary adenomas. when the surgical risk is unacceptable. feet and perimeter. Amenorrhea. hirsutism. • Signs: cavernous voice as a result of laryngeal hypertrophy. prognathism. If there is no gradient: there is an ectopic source producing ACTH. Increase in the frequency of nasal polyps and intracranial aneurysm. hence. it is necessary to resort to medical adrenalectomy (mitotane) or to inhibitors of cortisol synthesis (ketokonazole. wet and doughy hands. . A total of 75% of them are macroadenomas (greater than 1 cm). acanthosis nigricans and oily skin.

Also necrosis of vascular origin. In postmenopausal women compressive symptoms are also predominant. • In premenopausal women: galactorrhea. Nephrogenic ID: lack of ADH renal response. lithium administration. amphotericin B. • Inability to generate concentrated urine because of the absence of (partial or complete antidiuretic hormone secretion) or a defect in its action at renal level. decrease in libido . 3 . Prolactinomas (much in the same way as other pituitary adenomas) are classified into microadenomas (lesser than 1 cm) and macroadenomas (greater than 1 cm). Diabetes Insipidus Estrogens and anti-androgens Table 1. anomalies in the menstrual cycle. cranio-cephalic traumatisms. alcohol. In the following cases: . manifesting through sexual and reproductive function disorders. cidofovir. as well as the possible appearance of alterations in the visual field (by chiasmatic compression of a macroprolactinoma). brain or pituitary tumors. Indications for treatment of prolactinomas Amitriptyline Serotonin reuptake inhibitors Calcium antagonists · Macroprolactinomas. posterior to surgery or pituitary radiotherapy. Treatment • Treatment indications for prolactinomas are stated in Table 2. bothersome galactorrhea. severe hypogonadism with high risk of osteoporosis. • Diabetes insipidus is subdivided into: Central ID: the neurohypophysis is incapable of releasing ADH. as well as lesions in the stalk and in the hypothalamus. usually a macroadenoma. Prolactin levels > 250 μg/L are virtually diagnostic of a PRL-producing pituitary adenoma. chlorpromazine and phenytoin. didanosine. infections. Prolactin levels < 100 μg/L may be owing to microadenomas. PROLACTINOMAS: TREATMENT INDICATIONS · Microprolactinomas. hypopotassemia and tubulointerstitial nephropathy. with a decrease in LH and FSH (hypogonadotropic hypogonadism). bromocriptine). • Pharmacologic treatment is the treatment of choice: dopaminergic agonists (the most utilized are cabergoline. Prolactin levels > 100 μg/L in the absence of pregnancy are very likely to result from microprolactinoma. • In men: a decrease in libido.Endo c ri no l ogy · · PHYSIOLOGIC · HYPERSECRETION · · Tumors LESION OF THE HYPOTHALAMUS OR PITUITARY STALK · · · · · · Diagnosis Pregnancy Lactancy Stimulation of thorax wall Sleep Stress · · · · Craniopharyngioma Meningioma Dysgerminoma Metastasis Empty Turkish saddle Lymphocitary hypophysis Adenoma with stalk compression Granulomas Rathke’s cysts Radiation Traumatisms · Section of the pituitary stalk · Suprasellar surgery · Prolactinoma HYPOPHESEAL HYPERSECRETION · Acromegaly SYSTEMIC DISORDERS DRUGS · · · · Chronic renal failure Hypothyroidism Cirrhosis Comitial crisis Dopamine receptor antagonists · Phenothiazines: chlorpromazine · Butyrophenones: haloperidol · Thioxanthenes · Metoclopramide Dopamine synthesis inhibitors Methyldopa Cathecolamines depletion Reserpine • High prolactin baseline values. foscarnet. infertility because of anovulatory cycles or menorrhea. Decompressive surgery may also be necessary in tumors with a significant cystic or hemorrhagic component to relieve visual symptoms and headache. • Pituitary MRN to assess the existence of a lesion at that level. The most usual reasons are hypercalciuria. Causes comprise idiopathic causes. and to the remaining reasons for nonneoplastic hyperprolactinemia. They are always treated Verapamil 1.4. like oligomenorrhea. impotence and infertility. infiltrative illnesses.Women: desire for pregnancy.Men: decrease in libido or sexual potency. orlistat and V2 receptor antagonists (vaptans). ofloxacin. methoxyflurane. Etiology of hyperprolactinemia Clinical presentation • Hyperprolactemia generates inhibition of hypothalamic release of GnRH. sterility Opiates H2 antagonists Imipramines · Cimetidine · Ranitidine Table 2. • Surgical treatment is reserved for patients with persistent visual defects despite dopaminergic agonist treatment and for those patients who do not tolerate dopaminergic agonists. ifosfamide. Other related drugs are demeclocycline.

in general. neoplastic tissues or inflammatory tissues. of osmotic control. irritability. generally diminished osmolality < 300 mOsm/kg) and polydipsia continual thirst. dehydration signs. High AVP levels in plasma and urine All major criteria are needed for diagnosis. 4 Identify and correctly treat the triggering underlying cause whenever possible. the following symptoms become predominant: brain edema cerebral. psychosis.A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK) Clinical presentation • Symptoms: Persistent polyuria (> 3 L/day in adults. clofibrate. • When water access is not available (i. Hyponatremia 2. thyroid surgery · Drugs: chlorpropamide. acute respiratory failure.010. like agitation. neuroblastoma of olfactory nerve. oxytocin · Others: hypothyroidism. for example. The test involves comparing urine osmolarity after deprivation of water and the osmolarity obtained after DDAVP (ADH synthetic analog). • Normal function of the thirst center enables polydipsia to adjust to polyuria and avoid dehydration. • Other findings are detection of low levels of ureic nitrogen. at least partially. ictus. hereditary SIADH (constitutive activation of V2 receptor and mutations of hypothalamic osmoreceptors. Causes of inadequate secretion of AVP (SIADH) Clinical presentation • Clinical presentation depends. or thyroid or adrenal hypofunction (Table 4). adrenal failure. MAOI. together with unspecific changes in EEG. Syndrome of Inadequate Secretion of Vasopressin SIADH SIADH: ETIOLOGY · Neoplasias: lung microcytic. Diagnosis • Suspicion must be maintained on every patient with hyponatremia (< 135 mmol/L).. SIADH causes are listed in Table 3. • Brain MRN in central ID to rule out hypothalamic or pituitary lesions. cyclophosphamide. Minor criteria are optional Table 4. hypernatremia) the dehydration test is not necessary (it can even be dangerous). brain and neck tumors. HIV. > 2 L/day in children) of hypotonic urine (low density < 1. traumatisms. MAJOR MINOR 1. above all. Diagnosis • Dehydration test or thirst test (Miller test): simple and reliable form for the diagnosis of diabetes insipidus and distinguish ADH deficiency from other polyuric syndromes. Exclusion of hypothyroidism and adrenal failure 1. nausea and vomiting. • Sudden onset of symptoms.5. headache. ureic acid (< 4 mg/dL) and albumin in the presence of normal renal function and normal acid-base equilibrium and potassium. clofibrate and chlorpropamide. significant dehydration and hypernatremia. SSRI. then it is a nephrogenic ID. NSAIDs can be administered as coadjuvant (indomethacin). major surgery of thorax and abdomen. tricyclics. thymoma · Nonmalignant lung diseases: pneumonia. • The origin of this ADH can be the neurohypophysis. asthma. • If there is acute hyponatremia with CNS alteration. • If hyponatremia is mild (130-135 mEq/L) or of progressive development. with alteration of the level of consciousness. in central DI. symptoms are more unspecific. • Response to DDAVP administration: If the response implies urinary osmolarity doubles and diuresis decreases. it is a central ID. plasma hypoosmolality (< 275 mOsm/kg) and without maximum urine dilution (> 100 mOsm/kg). 1. vincristine. Lack of maximum urine dilution (urine osm > 100 mOsm/kg) 6. In ID (both central and nephrogenic) hypotonic polyuria persists after dehydration. If certain ADH reserve is conserved (partial CID) the response may involve carbamazepine. duodenum and pancreas neoplasias. Treatment • Central ID: hormonal substitution with DDAVP. • If hyponatremia is severe (< 125 mEq/L) or of an acute onset. orthostatic hypotension. in relation to plasma osmolarity and independent. mechanical ventilation · Alterations of CNS: infections. The next step will be direct administration of DDAVP. the institutionalized). neumothorax. but without edemas. coma and convulsions. vinblastine. No volume depletion (normal BP) 5. confusion. Diagnostic criteria for SIADH Treatment • Hyponatremia secondary to free water retention due to inappropriately high ADH secretion. If that is not the response. seniors. administration of diuretics that increase natriuresis. carbamazepine and derivatives. sensation of instability. while in primary polydipsia urine becomes concentrated. creatinine. on how fast plasma sodium levels go down. No edemas 4. Plasma hypo-osmolality 3. so most cases are normonatremic. (thiazides). atelectasis. temporal arteritis Table 3. • Nephrogenic ID: salt and water restriction. Pathologic hydric overload 2.e. • If the patient presents analytic alterations compatible with dehydration (elevated plasma osmolarity > 295 mOsm/L. anorexia. comitial crisis and even coma. subarachnoid hemorrhage or severe hyponatremia (< 125 mEq/L): . comitial crisis.

Salt contribution and low doses of furosemide. palpebral retraction. PRIMARY CENTRAL PRIMARY CENTRAL hypothyroidism hypothyroidism hyperthyroidism hyperthyroidism TSH  N or    T4L     Table 5. Interpretation of thyroid function test (N: normal) • Symptoms: plethoric aspect with nervousness. mental slowness. They can also be utilized in MTG. 5 .of antithyroid antibodies (including TSI) +/.1. with primary hyperthyroidism (with high T3 and T4). Indicated in case of SIADH of any etiology refractory to other therapies.2. Thyroidectomy can also be performed. muscular weakness. Thyroid Function Test • Determination of thyroid stimulating hormone (TSH): the best test for the screening of thyroid pathology and assessment of its function. • Symptomatic: propranolol for the control of adrenergic symptoms. Thyroid gammagraphy reveals a multinodular gland with several hyperfunctioning nodules that alternate with other normofunctioning or hypofunctioning nodules. atrial fibrillation). • Determination of total T4: it is not useful for the study of thyroid pathology. Vasopressin receptor antagonists (vaptans). proximal myopathy. excessive sweating and heat intolerance. • Antithyroid drugs (methimazole or propylthiouracil) in GD. increased appetite with paradoxic weight loss. TSH may be diminished or suppressed in primary hyperthyroidism. Exophthalmoses. • Toxic multinodular goiter (TMG) or hyperfunctioning is the most usual reason for hyperthyroidism in the elderly. There are also increased intestinal transit. It may be normal in subclinical hyperthyroidism (with low TSH). • For the etiologic diagnosis. In a gammagraphy.Endo c ri no l ogy Careful and progressive correction with hypertonic saline serum (correct Na+ 1-2 mEq/L/h in symptomatic patients 0. especially in the presence of large goiters. alopecia. depression. Clinical presentation Chapter 02 2. weakness. distal tremor. the patient is asymptomatic and sodium levels are over 125 mEq/L: Hydric restriction. myoclonias and hyperreflexia. Thyroid Pathology • Graves disease (GD) is the most common cause in middle-aged adults. Elevated values are usually related to primary hypothyroidism (with low T3 and T4) and low or suppressed values. acropachy. goiter that is diffuse and spongy in GD (it is irregular with a nodular surface in the SMB).3 mmol/L/h in asymptomatic sufferers with a maximum limit of 8 mEq/L/12 h. • Signs: wet skin. • If there is chronic hyponatremia. Treatment 2. • Thyroid gammagraphy: performed with iodine isotopes (I-131 and I-123) or with Tc-99 in the form of pertechnetate. elaborating a detailed clinical record and determining -according to clinical suspicion. it can manifest through weight loss. T4 values can be altered by this protein variation. • “Apathetic hyperthyroidism”: in advanced age. • Determination of free T4: of choice after TSH determination. for the screening of thyroid pathology. It has an autoimmune origin (presence of thyroid stimulating antibodies or TSI or TSH-R-Ab) that exists in association with: hyperthyroidism. • Determination of free T4: it is high in clinical hypothyroidism. See Table 5 for interpretation. Diagnosis • Determination of TSH: it is the most useful isolated initial determination for diagnosis. It is a useful test for the etiologic differential diagnosis of hyperthyroidism. emotional lability. • (Postpartum. subacute) thyroiditis may appear with an initial phase of hyperthyroidism as a result of inflammation and release of the preformed hormone. Hyperthyroidism • Hyperthyroidism is the clinical and analytic situation that results from the effect of excessive amounts of thyroid hormones circulating throughout body tissues and it is present with high values of T3 and T4. failure or intolerance to prior treatments. diffuse goiter and extrathyroidal signs (ophthalmic and derma signs). as T4 circulates in plasma and it is almost completely bound to its carrier protein (TBG). • Determination of free T3: it is indicated if TSH is low and T4 is normal. Lithium or demeclocycline. • The toxic adenoma is observed in the gammagraphy as a single nodule. Do not correct it faster to avoid central pontine myelinolysis (locked-in syndrome). Thyroid gammagraphy shows an abolished or “white” gland. decreases in performance. pruritus and alterations in the menstrual cycle (oligomenorrhea). apathy and arrhythmias or heart failure. • Definite treatment: radioactive iodine (I-131) is of choice in the USA for the treatment of GD. Graves disease reveals a generalized increased uptake.thyroid gammagraphy enables classification of most cases of hyperthyroidism. pretibial myxedema and thyroidal murmur can be appreciated in Graves disease. 12 mEq/L/24 h and 18 mEq/L in the first 48 hours). which intensely concentrates the radiotracer and with almost total suppression of the rest of the gland. arrhythmias (sinusoidal tachycardia. Not all characteristics are necessary for diagnosis.

infiltrative diseases. tachycardia. carpal tunnel syndrome and menstrual cycle disorders. and congenital alterations in thyroid hormone synthesis and thyroid agenesis.A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK) Complications Alopecia • Thyroid storm: emergency situation and of increased mortality (20% to 30%) characterized by irritability. Clinical Presentation (Figure 2) • Unspecific initial symptoms with progressive appearance: fatigue.v. • Other less frequent causes are external cervical irradiation. 2. It can also appear in a hypothyroid sufferer under treatment. • There is also another important factor: postablative hypothyroidism (radioiodine or surgery) or after administration of I-131 as a treatment for hyperthyroidism. spasticity Coarse. dementia and abnormal involuntary movements.4. Hypothyroidism • Situation that results from the lack of thyroid hormone effect on body tissues and presents with low levels of free T3 and T4. loss of appetite and weight gain. but less than 5% are of thyroid or hypothalamic origin. • Other types of thyroiditis -subacute and postpartum) usually appear with a hypothyroidism phase after an initial phase of hypothyroidism. lethargy. skin coldness. Adynamic ileum. who abruptly suspends medication. scarce body hair. Clinical presentation of hypothyroidism Complications • Myxedematous coma: severe complication of hypothyroidism with stupor and hypothermia. • Determining TSH: it is the most useful isolated initial determination for diagnosis. It may be normal in subclinical hypothyroidism with a high TSH). Amimia. postpartum thyroiditis postradiation and amiodarone-induced thyroiditis. likely to be mortal. for example. Primary thyroid causes constitute more than 95% of the cases. Hypothyroidism can be permanent. Mortality ranges from 30% to 60%.upper respiratory tract infection. • The remaining types of thyroiditis appear together with a painful goiter. 6 Constipation Carpal tunnel syndrome Weakness. • For the etiologic diagnosis. autoimmune or Hashimoto’s thyroiditis. Bradichardia and pericardial fluid accumulation (even obstruction of pericardial drainage). constipation. Macroglossia Intolerance to cold temperatures Bradypsychia Memory loss Palpebral edema Cardiomegaly Pericardial effusion Metrorrhagia 2. general discomfort and concomitant -or recent. . It requires immediate treatment with intravenous L-T4 together with hydrocortisone administration -so that an adrenal crisis will not be triggered. megacolon and intestinal obstruction. cold intolerance. propylthiouracil and corticoids. hypotension.until a normal pituitary-adrenal axis activity is achieved. dry and yellow skin Slowed Achilles reflex Weight gain Figure 2. Treatment • Hormonal replacement with levothyroxine (L-T4). • Signs: dry and coarse skin. It requires emergency treatment with i. Thyroiditis • A set of heterogeneous etiology processes and several clinical characteristics that appear with thyroid inflammation. Progressive deterioration of intellectual and motor activities. • Autoimmune etiology (Hashimoto’s thyroiditis) is the most common reason in developed countries. fever. delirium or coma. periorbitary edema and macroglossia. granulomatous or metastatic thyroiditis. drawing up a detailed clinical record and determining antithyroid antibodies enables classification of most cases of hypothyroidism. Prolonged relaxation phase of osteotendinous reflexes. The most common types of thyroiditis are (granulomatous subacute and viral thyroiditis or Quervain’s) thyroiditis. propranolol. amiodarone or tyrosine kinase inhibitors (that work as an oncologic treatment). vomiting and diarrhea. • Determination of free T4: it is low in clinical hypothyroidism. loss of body hair. Iodine or iodine contrasts can also be used. rigidity and muscle contracture. THS is increased in primary hypothyroidism and it is low or inappropriately normal in central hypothyroidism. Clinical presentation • Viral subacute (Quervain’s) thyroiditis presents with a painful goiter. paleness. a deep voice and sleep apnea may appear. Hashimoto’s thyroiditis presents with positive antithyroglobulin and antimycrosomal (antiTPO) which precipitate thyroid destruction. drugs like lithium.3. The most frequent cause of myxedematous coma is cold temperature exposure or performing surgery on a patient with untreated -or poorly treatedhypothyroidism. The most frequent cause of hypothyroidism world-wide is iodine deficiency.

Thyroid Nodule and Thyroid Cancer • The incidence of thyroid carcinoma in the population represents only a fraction of patients that have thyroid nodules. Diagnosis (Table 6) 2.e. Hyperfunctioning nodules are seldom malignant (< 1%). Treatment • Symptomatic: β-blockers in the hyperthyroidism phase. by inflammation during the hyperthyroidism phase.. vocal cords paralysis. hypoechogenicity. • They are usually asymptomatic at the time of diagnosis. and family record of medullary thyroid cancer (MTC). but early Calcified adenopathies hematic dissemination. In single nodules.nd and 3. all signs suggestive of malignancy). • Clinical findings that suggest malignancy are: rapid growth of the lesion. • Thyroid gammagraphy: presents with generalized hypocaptation of the gland. painless. • The use of antithyroid drugs is not indicated. More severe cases require corticosteroids. size > 4 cm.Endo c ri no l ogy Diagnosis Clinical presentation • Thyroiditis usually comprises two phases: 1) thyrotoxicosis followed by 2) hypothyroidism. as well as the presence of cervical anterior lymphoadenopathies. FOLLICULAR MEDULLARY ANAPLASTIC th th LYMPHOMA · Advanced age · 15% to 20% tumors of follicular epithelium Four ways: · Sporadic (80%) · MEN 2A · MEN 2B · Familial no MEN 6.5. 7. attached to superficial and/or deep planes. fixation to adjacent structures. They are incidentally found through imaging tests. . a CTA scan of the cervicalthoracic region. • Cervical examination will enable nodule localization and a description of the nodule’s characteristics: stony consistency. In milder cases of Quervain’s thyroiditis. Malignant tumors of the thyroid 7 . bone and and bone CNS metastasis Rapid growth with huge local invasion ulcerating skin - Marker Thyroglobulin Thyroglobulin Calcitonin/ACE - - I-131 Yes Yes No No No Prognosis The best Hürthle subtype: worse Bad clinical course The worst (months survival) Variable Table 6. those adjacent to the trachea/esophagus. dyspnea and cough). thyroid cancer incidence are also 5% per individual nodule. • If hypothyroidism: levothyroxine should be given. symptoms are usually controlled with ASA. multinodular goiters. and a history of radiation in childhood. • Thyroid ultrasound study: it makes it possible to assess the nodule features as well as the remainder of the gland and the presence or absence of pathologic cervical ganglia. although this phase may be temporary and not permanent. Horner’s syndrome. decades · 5% follicular epithelium tumors · Women 55-75 years of age · 5% of all thyroid tumors · Relation to Hashimoto’s thyroiditis and positive antiperoxidase antibodies Derived from Yes follicular epithelium Yes No Yes No Pathologic anatomy · Papillae with follicular elements and cells · “Sand-grain sized” calcifications or psammoma bodies (typical. and metastasis to CNS with lung. but rare) Capsular and/or capsule invasion is what differentiates it from benign follicular adenoma · Cell C accumulation with amyloid substance · Multicentric in familial forms · Gigantic and fusiform cells · Hard to differentiate from lymphomas or sarcomas Diffuse β lymphoma with large cells Growth. hence. The presence of microcalcifications.rd decade/ middle age · 70% follicular epithelium tumors · Relation to radiation in childhood • TSH determination: to rule out thyroid hyper or hypofunction. • Large nodules and. a carotid Doppler ultrasound test) or thyroid palpation. PAPILLARY Epidemiology · Bimodal distribution: 2. dissemination and metastasis Slow growth with neighboring structures invasion and lymphatic dissemination Slow growth. i. thyroid carcinoma incidence is approximately 5%. the thyroid function test varies according to the phase in which diagnosis is made. present adenopathies. especially. can produce compressive symptoms (dysphagia. and the presence of an irregular rim and an increased intranodal vascularization are all ultrasound signs of malignancy. • Hyperfunctioning nodules are present with signs and symptoms of hyperthyroidism.

Calcifications of joint cartilage and pinna sometimes occur. aggressive volume replenishment with physiologic saline solution and glucose to correct hypoglycemia. • Determining calcitonin: if MTC is suspected. Clinical presentation • Clinical manifestations are nonspecific and of insidious onset. descending pattern in alternate days). major surgery. • Central AI: only glucocorticoid replacement is needed. • Malignant cellularity: thyroidectomy. • “Common” symptoms of primary and secondary AI: asthenia and progressive weakness. • To prevent AI appearance in the case of chronic corticosteroid treatment. To differentiate malignant nodules from benign nodules.1.A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK) • Thyroid fine needle aspiration (FNA): test that offers the highest diagnostic yield. Treatment • Primary AI: hormone replacement with glucocorticoids and mineralocorticoids (hydrocortisone and fludrocortisone. The triggering cause must be researched and specifically addressed. which are preserved in secondary AI) can be observed. lymphocytosis and eosinophilia. • Tumors localized in the thoracoabdominal cavity. Adrenal Pathology Chapter 03 3. characterized by high fever. Treatment According to FNA results: • Benign cellularity: follow-up with palpation and ultrasound study to evaluate the nodule size or the appearance of malignancy suggestive signs. 3. AI diagnosis is confirmed when after 30 or 60 minutes of synthetic ACTH administration. nausea. Central AI secondary or tertiary: hypothalamic or pituitary illness that gives rise to ACTH or CRH deficiency (isolated or within hypopituitarism). • Baseline plasma ACTH: ACTH concentration rises in primary AI and it is reduced or inappropriately normal in secondary AI.. there is already mineralocorticoid activity and it is not necessary to administer fludrocortisone). an insulin hypoglycemia test must take place. nausea and vomiting). This test should be performed after four months of pituitary surgery or nine months of pituitary radiotherapy to assess possible central AI. even though according to etiology. Loss of 8 ancillary and pubic hair in women as adrenal androgen secretion decreases. the most frequent factor is autoimmune adrenalitis. there is also insufficient production of mineralocorticoids and adrenal androgens. Pheochromocytoma • Rare tumors that synthesize and release catecholamines. hyperpotassemia and metabolic acidosis (by mineralocorticoids deficiency. deep mycoses). except for lesions with abundant cellularity or follicular lesions. a slow scheduled tapering of steroid dose should be carried out (i. regular glucocorticoid dose should be doubled or tripled according to the severity of the situation. trauma or infection). . Prolonged suppression of hypothalamic-pituitary-adrenal axis activity because of exogenous steroid administration or endogenous steroid production. In primary AI. respectively).. • Adrenal insufficiency (AI) can be: Primary AI: a condition at adrenal level that destroys more than 90% of the cortex (Addison’s disease). • It is “10% tumor” because 10% are bilateral.v. dehydration. Values > 18 μg/dL rule AI out. 10% appear in children and 10% are malignant owing to the presence of metastasis at a distance.e. opportunist infections in AIDS patients. corticosteroids must be administered at stress doses (at these doses. weight loss and gastrointestinal discomfort (abdominal pain. normocytic anemia. Salt craving because of orthostatic hypotension. • Indeterminate cytology: repeat and assess FNA or perform hemithyroidectomy according to risk factors and clinical suspicion of malignancy. In the United States of America and the rest of the developed countries. hypoglycemia. • Exclusive symptoms of primary AI: mucocutaneous hyperpigmentation characteristic of compensatory increase in ACTH and its peptides. in which case. Ablation of remaining thyroid tissue with radioiodine in case of differentiated (papillary and follicular) thyroid carcinoma.2. outside the adrenal gland.e. • In case of stress (i. In this case. vomiting and hypotension that can evolve into a shock) i. vascular invasion needs to be proven. Adrenal Failure • Insufficient production of adrenal hormones. Between a 15% to 20% of patients present hypercalcemia of unclear origin. False negative results may be obtained because of absence of total atrophy of cranial nerves in the adrenal reticular fascicular region as a result of lack of endogenous ACTH. cortisol is unable to go over 18 μg/dL. Diagnosis • General analytics: hyponatremia hypoglycemia. which produce chromaffin cells of the sympathetic nervous system (adrenal medulla and sympathetic-parasympathetic ganglia). like CMV. Neisseria meningitidis. Intermediate values make a ACTH stimulation test mandatory. • In case of an adrenal crisis (acute form of AI. 10% are extra-adrenal. especially glucocorticoids. Also tuberculosis and other infections (N. • Baseline plasma cortisol at eight hours: values < 3 μg/dL are diagnostic of AI. • Stimulation test with 250 μg of ACTH: it is a reference test or gold standard in primary AI. are called extra-adrenal pheochromocytomas and tumors derived from cervical sympathetic-parasympathetic tissue are denominated paragangliomas.

profuse sweating. • Paroxysms or hypertensive crises are characterized by a significant increase in blood pressure accompanied by headache. Cytology of pheochromocytomas is contraindicated. It is usually kept in 60% of the cases. which if marked. is the most efficient method to detect extra-adrenal pheochromocytoma (either primary or metastatic). Clinical presentation • Hypertension is the most frequent manifestation. > 15 ng/dL) and aldosterone/activity quotient of plasma renin > 30. However. as an adenoma. which does not occur in primary hyperaldosteronism). the triggering factor cannot be identified on some occasions.receptor antagonist) or other potassium-sparing diuretics. • It is very important to be reminded that β-blockers are never to be administered until α blockade has been established. • PHA screening: determination of baseline aldosterone (it must be increased. medical treatment with α blockers is carried out. 9 . in repetitive doses. is present along with muscle weakness. phentolamine or nitroprussiate. anguish. fatigue. Primary Hyperaldosteronism PHA PHA occurs because of autonomous secretion of aldosterone through the glomerulus zone of the adrenal gland. muscle palsy.v. • Gammagraphy with MIBG (meta-iodobenzylguanidin). accompanied by nausea and vomiting. • Confirm biochemical diagnosis using the suppression test: saline physiologic serum infusion (the correct aldosterone suppression excludes diagnosis) or captopril test (ACE inhibition causes -in healthy people. A 60% originates in an aldosterone- • In unilateral pathology. palpitations. as well as electrocardiographic changes. Catheterism of adrenal veins is reserved (as it is invasive) for lesions < 1 cm (or with a negative CT) in individuals > 40 years of age. Preoperative volume load with salt. hypomagnesaemia. metabolic alkalosis. • In the event of a hypertensive crisis before the patient is fully established on an α blockade therapy. • PHA existence must be assessed in young patients who have their debut with HBP without risk factors or a family history (see Table 7 for screening indications for PHA). thoracic and abdominal pain. PHA: INDICATIONS FOR EARLY DETECTION · Moderate/severe HBP (SBP ≥ 160 and/or DBP ≥ 100 mmHg) · Hypertension resistant to pharmacologic treatment (SBP > 140 or DBP > 90 mmHg despite the use of three antihypertensive drugs · Patients with HBP and spontaneous or diuretic-induced hypopotassemia · HBP and adrenal incidentalomas · Patients with HBP and family history of HPB of early onset or cerebrovascular accidents in family members < 40 years of age · Hypertensive 1. β blockade if necessary with propranolol (to prevent tachycardias). unilateral adrenal hyperplasia or familial etiology. cramps and in severe cases. Treatment • The treatment of choice is laparoscopic pheochromocytoma resection. • Paroxysms are triggered by postural changes. hypopotassemia occurs. Clinical presentation • HBP is the predominant and universal finding. vincristine and dacarbazine.3. There is also chemotherapy administration with the use of cyclophosphamide. psychological stress. • PHA by bilateral hyperplasia is addressed with spironolactone (aldosterone. Hypertension is sometimes malignant and it is resistant to conventional treatment in almost every case. mild hypernatremia. anesthesia and surgery. • Because of increased renal excretion of potassium. Indications for early detection of primary hyperaldosteronism Diagnosis • General analytics: hypopotassemia. • PHA sensitive to glucocorticoids can be treated with small doses of corticosteroids or with potassium-sparing diuretics. Surgery should be conducted in a specialized center. paleness.st degree relatives of a patient diagnosed with PHA · HBP in children and young people (< 20 years of age) Table 7. as a hypertensive crisis would be triggered. the treatment of choice is laparoscopic extirpation. Valsalva’s maneuver.Endo c ri no l ogy • These tumors are commonly associated with multiple endocrine neoplasias (MEN) 2A and 2B. PHA can also result from adrenal bilateral micronodular or macronodular hyperplasia. Diagnosis • An increase in free catecholamines and/or metabolites (metanephrines) in 24-hour urine or plasma. There is greater prevalence of affectation of target organs (hypertensive retinopathy. once proper preoperative preparation has taken place. secreting adrenal adenoma (Conn’s syndrome). cardiopathy and nephropathy) in these kinds of patients. An aldosterone-secreting adrenal carcinoma is very rare. and imminent sensation of death. Polyuria and polydipsia because of nephrogenic ID. Treatment 3. Pre-op treatment consists of: α blockade with phenoxybenzamine at least 10-14 days before surgery. • When a pheochromocytoma is malignant and unresectable. i. • CT and abdominal MRl are the imaging techniques most commonly utilized to localize the tumor.a decrease in aldosterone. • Etiologic diagnostic takes place after biochemical diagnosis: abdominal CT. like glucocorticoid-remediable PHA. MIBG administration can be used if there is positive tumor uptake. like. triamterene or amiloride. physical exercises. some food and drugs. to prevent rebound hypotension in the immediate postoperative period. in which the prevalence of nonfunctioning adrenal adenomas is very high. with diastolic values over 110 mmHg.

• Result of the deficiency (usually absolute) in insulin secretion because of cell β cell destruction of the pancreas. anti-GAD (descarboxylase of glutamic acid) and anti-ZnT8 (zinc channel): The first three are more frequently positive in people with DM1. Congenital Adrenal Hyperplasia CAH • It consists of a group of adrenal steroidogenesis disorders stemming from a hereditary deficiency of one of the enzymes of steroid biosynthesis. • Nonclassic form: hyperandrogenism.4. Plasma glucose two hours after oral glucose overload (SOG) > 200 mg/dL. In 80% of the cases it is associated with a salt-wasting syndrome due to mineralocorticoids and cortisol. Differences between DM type 1 and 2 • Classic form: it presents with ambiguous genitalia in girls and precocious puberty in children. Treatment Diabetes mellitus (DM) is a set of heterogeneous syndromes of multifactorial etiopathogenesis. Chronic macrovascular and microvascular complications develop along the course of the disease. • These patients need insulin administration to prevent the appearance of ketoacidosis. . Alteration in Chapter 04 4. whose clinical presentation. anti-IA2 (associated protein with insulinoma 2). while partial defects are manifested after adolescence by hirsutism and virilization in women. • Congenital Adrenal Hyperplasia (CHA) is the most frequent adrenal disorder in childhood and it can be accompanied by severe deficiencies that endangers the life of a newborn. Plasma glycemia at random + compatible symptoms with DM > 200 mg/dL. Glycosylated hemoglobin (HbA1C) > 6. • Genetic predisposition associated with HLA-DR3 and DR-4. • Cardinal manifestations: polyuria. It is very similar to polycystic ovary syndrome. Clinical presentation • Diagnosis is confirmed by an increase in baseline 17-hydroxiprogesterone baseline and after ACTH stimulation. simulating physiologic secretion of the pancreas: baseline insulin and insulin before each meal (Figure 3).A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK) 3. Treatment • In the case of salt-wasting syndrome: reposition of salt and volume. If later. even asymptomatic finding Treatment Always insulin Diet. even with ketoacidosis Insidious.1. whose appearance is usually rapid and of short evolution. oligomenorrhea and subfertility in adolescents and grown women. whose common nexus is chronic hyperglycemia. Diagnosis • Diagnostic criteria for diabetes mellitus: Plasma glucose on an empty stomach > 126 mg/dL. • The treatment and management of CAH will be discussed further on in the Gynecology section. • Presence of antibodies pancreatic anti-islets. polyphagia and weight loss. oral antidiabetic drugs or insulin Tendency to ketosis Yes No Heritage Predisposition to HLA Concordance > 90% of identical twins Autoimmunity against β cell Yes No Insulin resistance No Yes Table 8. polydipsia. 10 • Insulin therapy in intensive pattern (subcutaneous. Type 1 Diabetes Mellitus Hydrocarbonate Metabolism (Table 8) • Type 1 DM typically affects children and adolescents with normal weight. 21-hidroxilase syndrome becomes severe. diagnosis and treatment will be discussed below: Clinical presentation DIABETES MELLITUS TYPE 1 DIABETES MELLITUS TYPE 2 Age < 40 years of age (typically children or adolescents) > 40 years of age Morphotype Normal or low weight Overweight or obesity Onset Abrupt. • Surgical correction of ambiguous genitalia in girls.5%. Type 1 DB is subdivided into 1A (positive autoimmunity) and 1B or idiopathic. bolus-baseline pattern or pump subcutaneous insulin infusion). Diagnosis • It constitutes 5% to 10% of the total cases of DM. • The most common form of CHA is 21-hydroxylase deficiency (autosomal recessive heritage in 95% of cases). with subsequent “accumulation” of cortisol precursors prior to enzyme deficiency. mineralocorticoid replacement must be administered. glucocorticoid administration.

at some point in their lives they could need it to control glycemia. • Diabetic type 2 patients do not require insulin administration to prevent ketosis appearance. However.Endo c ri no l ogy • Insulin characteristics are listed in Table 9. Guidelines for insulin treatment 4. etc). 2014) Insulinemia levels Table 9. known cardiovascular disease or advanced microvascular disease. renal function. Objectives of metabolic control (ADA. lipid profile and systematic early detection of comorbilities (microalbuminuria for diabetic nephropathy. despite achieving preprandial glycemia goals Blood pressure · < 140/80 mmHg (individualize) LDL Cholesterol · < 100 mg/dL · It is recommended < 70 mg/dL in patients with manifest cardiovascular disease HDL Cholesterol > 40 mg/dL in men and > 50 mg/dL in women Triglycerides < 150 mg/dL Suspension of smoking habit HOSPITALIZED PATIENT Critical patient < 180 mg/dL (range 140-180 mg/dL) Noncritical patient · Preprandial glycemia < 140 mg/dL · Any time blood glucose < 180 mg/dL · Unclear evidence to make a recommendation Table 10. Breakfast Rapid action insulins (control postprandial glycemia although regular or crystalline insulin can control preprandial glycemia of the following meal) Human recombinant insulin (rapid. At times. • It appear in subjects that present resistance to insulin and a relative (rather than absolute) insulin deficiency. • The control goal in most patients is an HbA1c < 7%. TYPE ONSET PEAK Br Lu Di Br Br Lu Di Br DURATION Prolonged or intermediate action insulins (control glycemia on an empty stomach and preprandial) Guidelines for intensified treatment Intermediate action NPH or NPL Guidelines for conventional treatment 2 hours 4-6 hours 12 hours Analogous of a prolonged action Glargine 2 hours It does not present 20-24 hours Detemir 2 hours It does not present 12-24 hours Br Lu Di Br Br Lu Di Br d. Postprandial glycemia could be a target if HbA1c is not controlled. polydipsia. • Cardinal manifestations: Polyuria. polyphagia and weight loss. regular or crystalline) 30 minutes 2-3 hours 6-8 hours Analogous with ultrarapid action Aspartic. comorbility. Type 2 Diabetes Mellitus • Type 2 DM makes up 80% to 90% of the total cases of DM. age/ life expectancy. of insidious. unnoticed hypoglycemias and individual aspects of the patient. See Table 10. progressive onset and of long duration in many cases. More or less tight glycemic objectives can be appropriate according to different patients. 11 . patients have their debut with chronic complications because of latent symptomatology. Clinical presentation • It is more frequent in adults and elderly people. lispro and glulisine 10 minutes 30-40 minutes 2-3 hours PARAMETER OBJECTIVE HbA1c < 7%* Preprandial Glycemia 70–130 mg/dL* Postprandial Glycemia < 180 mg/dL* * Goals should be individualized according to the duration of diabetes. especially in those with a central distribution or abdominal obesity. Types of insulin Lunch Lispro or aspartic or glulisine Lispro or aspartic or glulisine Dinner Lispro or aspartic or glulisine Glargine Detemir Detemir Figure 3. • The following manifestations must be monitored: blood pressure (objective: < 140/ < 80 mmHg).2. full neurologic examination. exploration of the patient’s retina through a fundoscopy or nonmydriatic retinography.

but not preventing hyperglycemia. Diagnosis • The same criteria as for diagnosis of DM1. gestation. If not treated precociously..7% · Personal history of gestational diabetes or macrosomic fetus · Arterial hypertension · An increase in triglycerides or a decrease in HDL · Women with polycystic ovary syndrome · Clinical conditions associated with insulin resistance (i. • Negative antibodies (although they are routinely requested). native Americans. • Exercise: Exercise of moderate intensity. but not exclusive of DM type 2. severe obesity or acanthosis nigricans) · Personal record of cardiovascular disease Table 11. Asian American and natives from the Pacific Islands) · People previously diagnosed with carbohydrate intolerance and altered glucose in fastening or HbA1c ≥ 5. dysplemia. unable to counteract the increase in contrarregulatory hormones caused by triggering stressing factors. given that the hypoglycemia risk factor is not high. together with diabetic cardinal symptomatology. In known diabetic patients. Prerenal and renal failure may occur because of dehydration. • Blood pressure should be controlled (objective: < 140/ < 80 mmHg). serum therapy. complete neurologic examination . lipid profile and early detection of comorbilities (microalbuminuria for diabetic nephropathy. Screening indications for diabetes mellitus in asymptomatic adult patients (ADA. • Blood pressure: Target 140/< 80 mmHg. moderate in carbohydrates (< 55%) and hypocaloric if there is overweight or obesity.st degree relatives with a record of diabetes · Ethnic group at high risk (Afro-Americans. infections (30% to 40% of the cases). although not exclusive of DM type 1. ACEIs are the treatment of choice. mainly glucagon. intravenous potassium administration. a history of DM in first degree relatives under 60 years of age). . presence of increased ketonic bodies in blood and urine. precipitating reasons are usually abandonment of insulin treatment. Clinical presentation: nausea. It occurs because of insulin deficiency and an increase in contrainsular hormones. HBP. by means of fundoscopy or nonmydriatic retinography. Regardless of age in individual with BMI ≥ 25 kg/m2 and some additional risk factor: · Sedentarism · 1. and endocrinopathies. asymptomatic people aged ≥ 45. Diagnosis: Hyperglycemia + metabolic acidosis with increased anion gap. vomiting and abdominal pain. Hispano-Americans. Acute Complications (Table 13) • Diabetic Ketoacidosis: Typical. 2010) Treatment • Monitoring goals are the same as for Type 1 DM patients (see Table 11). Some patients may have their debut with this disease. and regardless of age in case of patients with overweight or obesity (BMI ≥ 25 kg/m2) and some other risk factor for DM type 2 development (see Table 11). 4. Control of Comorbilities • Anti-aggregation: Primary prevention: men > 50 years of age or women > 10 years after menopause (in general > 60) with some major cardiovascular risk factor (family history of cardiovascular disease. bicarbonate (if pH < 7) and treatment of triggering cause. • DM2 screening in the general population: Every three years. examination of the patient’s retina. but ARA-2 if the former are not tolerated. renal function. During physical examination. outstanding manifestations are tachypnea. Insufficient response of insulin action because of insulin resistance. • Quit smoking habit. hypertension. • Metformin treatment may be commenced in a preventive manner in patients with prediabetes (glycemia on an empty stomach > 100 mg/dL. obnubilation and coma will develop. Residual insulin secretion is capable of minimizing or impedes ketosis. First manifestation of DM type 1 in 25% to 30% of cases. minimum 30 minutes a day. infections or severe intercurrent pathology. etc). smoking or albuminuria) or those patients at risk of having a cardiovascular event. in ten years is higher than 10%. hypertriglyceridemia. especially in elderly patients. 5 days a week. but < 126 mg/dL and/or after two hours of OGO > 140 and < 200 mg/dL) who are obese and who present another risk factor of diabetes (HbA1c > 6%. like Cushing’s syndrome or Graves-Basedow disease among others. dietary transgressions. Treatment with intravenous insulinotherapy. next page. surgery. Kussmaul respiration and dehydration signs. like dry mucosa. hypotension and a decrease in ocular globe pressure. • Hyperosmolar nonketotic hyperglycemia: Typical. Age ≥ 45 2. a decrease in HDL. Pharmacotherapy See Table 12. Treatment of Diabetes Mellitus Lifestyle • Diet: Low fat diet (< 30%).3. traumas. 12 • Weight loss: Goal: lose 5% to 10% of initial weight through diet and exercise.e.A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK) • Type 2 DM sufferers may develop hyperosmolar nonketotic hyperglycemia in cases of metabolic control. 1.

nd · Obesity therapeutic together with step in type metformin 2 DM · Its use also · Sitagliptin approved with approved in sulfonylureas monotherapy (increased risk and in of hypoglycemia combination and less weight with insulin loss) SULPHONYLUREAS MEGLITINIDES BIGUANIDES Active substance Mechanism of action Side effects · Glibenclamide · Glipizide · Gliclazide · Gliquidone · Glimepiride Insulin secretion stimulus in sustained way through bond to β cell receptor Severe and sustained hypoglycemia Contraindications · Pregnancy · Hepatopathy · RI Use · Repaglinide · Nateglinide Metformin Insulin secretion stimulus in acute way through bond to β cell receptor Liver resistance to insulin decreases GLUCOSIDASE INHIBITORS · Acarbose · Miglitol Transient inhibition of intestinal α-glucosidase · Scarcely Second · Postprandial First choice in type 2 DM effective therapeutic step glycemia · Control of in type 2 DM with control pospandrial pancreatic reserve · Elderly hyperglycemia people with some degree of decline in renal function TIAZOLIDINEDIONES · Pioglitazone · Rosiglitazone Hepatotoxicity Hydric retention Heart failure Osteoporosis in women Use not approved along with insulin Table 12. tricyclics. antibiotics and revascularization Arterial revascularization techniques Table 13. but rare) · · · · · Increase in · Nausea and vomiting transaminase (vildagliptin) (frequent) · Pancreatitis · Discrete increase in (very rare) respiratory · Deterioration of and urinary renal function tract infections · Pregnancy Situations Pregnant · Liver disease predisposing women and · Severe RI to lactic children acidosis · Hepatopathy · Heart failure · Rosiglitazone withdrawn in Europe due to an increase in coronary events Pregnant women and children Associated with metformin or in case of its contraindication mild-moderate RI · 2. slowing gastric emptying) resistant to DPP IV Hypoglycemia · GI GI discomfort (infrequent) discomfort (the most frequent) · Lactic acidosis (the most severe. rest. fludrocortisone · Diarrhea: loperamide · Gastroparesis: prokinetics and erythromycin ULCERS Debridement. Characteristics of oral antidiabetic drugs and noninsulin therapies in type 2 diabetes mellitus PREVENTION (early phases) Diabetic retinopathy Diabetic nephropathy Neuropathy and diabetic foot Macroangiopathy Strict glycemic control · Strict glycemic and HBC control · RAAS blockade (ACE inhibitors or ARBs) if microalbuminuria or macroalbuminuria or hypertension · Reduction of protein intake in chronic kidney disease · Strict glycemic control and foot care · Smoking cessation · · · · Strict HBC control Smoking cessation Antiplatelet therapy Lipid-lowering therapy SYMPTOMATIC TREATMENT (advanced phases) Photocoagulation Dialysis or kidney transplant NEUROPATHY · Pain: opiates. Prevention and treatment of chronic complications in DM 13 . duloxetine and capsaicin · Orthostatic hypotension: postural measures. anticonvulsants.Endo c ri no l ogy IV-DPP INHIBITORS · Sitagliptin · Vildagliptin · Saxagliptin ANALOGOUS OF GLP-1 · Exenatide · Liraglutide They decrease peripheral resistance (muscle and adipose tissue) to insulin by means of bond to PPAR-γ They increase endogenous GLP-1 half like dipeptidyl peptidase IV Similar effect to endogenous GLP-1 (increase in insulin secretion mediated through intake .

ketonic bodies can be traced in urine or serum. testosterone (men). Metabolic Syndrome • Association of several cardiovascular risk factors. Treatment involves reducing insulin dose to prevent nocturnal hypoglycemia. effective serum osmolality > 320 mOsm/kg and plasma bicarbonate (> 18 mEq/L). dyslipemia. • At least three out of five criteria are needed for MS diagnosis. Bone Pathology Chapter 05 and Phosphocalcic Metabolism 5. It usually occurs after sudden flexions. Diagnosis • Dual radiologic densitometry (DXA): loss of bone mass equal to or higher than 2. Distinction from Somogyi phenomenon is made by determining glycemia at 3 a. Other accompanying illnesses are also rheumatoid arthritis.4. as well as treatment of the triggering factor. TSH. Alteration of the level of consciousness. but sometimes there is a triggering factor. Complications of Insulin Treatment • Somogyi phenomena: an increase in fasting glycemia because of an increase in contrarregulatory cell in response to nocturnal hypoglycemia. from stupor up to coma (hyperosmolar coma). start with metformin can be assessed. • Calcium and vitamin D: this recommendation applies for all patients diagnosed with osteoporosis.1. 24-hour excreted calciuria. as well as specific treatment for the remaining in comorbilities (HBP and dyslipidemia). It happens more frequently in the middle and lower dorsal vertebrae and in lumbar spine. negative –or mildly positive. backbone fracture is the most common. given this clinical profile. 14 • For patients at high risk of developing DM type 2. in relation to GH nocturnal or circadian rhythm of cortisol. There are many definitions of the metabolic syndrome (MS). underlying infection process and general deterioration of the patient are also contributing factors. including abdominal obesity. systemic mastocytosis. Plasma glucose increase in the first hours in the morning. • Also called X syndrome. regardless they receive additional . serum proteinogram and screening of Cushing’s syndrome if clinical presentation is suggestive. Treatment: aggressive serum therapy. of acute onset with frequent irradiation toward the abdomen and backbone deformity. An increase in plasma glucose. 4. It is the more frequent metabolic bone disease. hypercortisolism and hypogonadism. Diagnosis Diagnosis criteria of ATP-III (2004) are as follow: • Abdominal circumference: > 102 cm (> 40 inches) in men and > 88 cm (> 35 inches) in women. Triggering factors: infection (in approximately 60% of the cases). • Vertebral bone fracture causes back pain. A 20% of the individuals suffering from Hyperosmolar hyperglycemic state (HHS) have not been previously diagnosed with DM. Osteoporosis • Loss of bone mass equal to or higher than 2. Clinical presentation • It is an asymptomatic disease until fracture appears. Glucose will be low if it is a Somogyi phenomenon and it will be normal if it is a dawn phenomenon. hypertension and glucose alteration. • Dawn phenomenon. Diagnosis: glycemia > 600 mg/dL. Abstinence of smoking habit. • HDL-cholesterol < 40 mg/dL in men and < 50 mg/dL in women. • Most of the cases belong to the primary osteoporosis or they are not associated to other diseases.5 SD (standard deviation) with respect to bone mass of young people of the same sex. PTH. • Conventional bone x-ray: it is little sensitive for osteopenia diagnosis. BP > 7. • Rule out secondary causes: full biochemical lab test that includes Ca. • Triglycerides > 150 mg/dL.30. electrolytic replacement and insulin therapy. Treatment • Change in life style: do exercise. ranges from 5% to 20% of cases. as a loss greater than 30% of bone mass is needed to be radiologically detected. Insulin should be increased if there is evidence of a dawn phenomenon so normoglycemia levels are maintained.m. P. • Blood pressure > 135/ > 85 mmHg or request antihypertensive medication. hyperthiroidism. as well as microthrombosis and disseminated vascular coagulation may occur. multiple myeloma and chronic treatment with corticoids among others. • Diseases present with secondary osteoporosis: hyperparathyroidism. Neurologic manifestations (as convulsions or transient hemiplegia). leaving therapy or inadequate treatment. • Fasting baseline insulin > 100 mg/dL. Treatment • Weight loss should be encouraged.A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK) Mortality. it has as a main pathophysiologic substrate insulin resistance. which can coexist in the same affected person. • Fractures in vertebral bodies and forearm distal radius (de Colles fracture) are frequent complication.5 SD with respect to bone mass of young people (3035 years of age) of the same sex. 25(OH) vitamin D. Clinical presentation: severe dehydration.

Both forms of the disease can appear in a sporadic way or as family disorders: MEN 1. Lab parameters (N: normal) We will mainly discuss primary hyperparathyroidism: Clinical presentation • Most cases diagnosed are asymptomatic and hypercalcemia is found by chance. • Tertiary hyperparathyroidism: the secondary increase in PTH over time in patients with chronic renal failure. • Sarcoma. Sarcoma is the most severe complication and is usually located in the femur. deoxypyridinoline and peptide). constipation. significantly reduce the risk for vertebral. MEN 2A. Calcium and vitamin D favor a reduction of fracture rates. familial hyperparathyroidism and jaw tumor syndromes. • The presence of viral inclusion bodies (paramixovirus) in osteoclasts enables supposing that a viral infection could be the origin of Paget’s disease in genetically predisposed individuals. • Characterized by an increase in bone resorption. • More frequent in men than in women and prevalence increases with age. pyridinoline. which can compress the medulla and can cause tetraplegia. Other parameters also help establish a diagnosis. hypercalcemia and hypercalciuria. procollagene) and bone resorption (hydroxyproline. which. 5. i. zoledronate. • Primary bone pain is the more habitual clinical manifestation. anemia. • Other manifestations are: headache. headache and facial pain. Biphosphonates is the treatment of choice. an increase in other parameters of bone formation (osteocalcin. acid phosphatase. fractures. hip fracture included. Tertiary hyperparathyroidism occurs when one gland -or more. with different effects on calcium and phosphorous depending on the specific cause. Hyperparathyroidism (Table 14) • Parathyroid glands produce parathyroid hormone (PTH). gout.3. ibandronate are all potent inhibitors of bone resorption. Treatment • Asymptomatic: they do not need treatment. • Symptomatic: (persistent pain. They reduce replacement and loss of bone mass. together with vitamin D and calcitonin. • Biphosphonates: alendronate. without having proven their effect on the prevention of femoral neck fractures. heart failure.. depression. primary hyperthyroidism is caused by autonomous secretion by a single or multiple parathyroid adenomas. 15 . problems with gait because of the difference in limb length. asthenia. Shown in 1% of the patients. with an increase in the venous return network in affected areas. coexistence of lytic and blastic areas. monoclonal antibody with a high affinity for RANKL. • Other manifestations are the gradual appearance of deformations or swelling in the limbs. PRIMARY Hyperparathyroidism SECONDARY Hyperparathyroidism TERTIARY Hyperparathyroidism PTHi    Calcemia  N or  N or    Phosphatemia  Table 14. They decrease vertebral fractures and femur neck fracture. depression and anxiety. 5. is responsible for calcium and phosphorous metabolism. Complications • Increase in cardiac output: an increased blood flow in bone. arthropathy because of proximity (the most frequent is the coxofemoral). bone deformity of rapid progression that results in gait difficulties. • Secondary hyperparathyroidism: a physiologic increase in PTH in renal failure or vitamin D deficiency is considered to prevent hypocalcemia. while hyperplasia is found in 15% of the cases and parathyroid carcinoma in < 1%. It rarely causes hypercalcemia. so the disease is usually present in the elderly. like an increase in bone size. • Nephrolithiasis because of hypercalciuria. acute pancreatitis and cholelitiasis are also present. backbone lower extremities pain. diminishing the incidence of vertebral fractures. • Bone gammagraphy: this enables checking the extent of the disease. bone fractures and reparation for orthopedic surgery).becomes autonomous (even remaining after renal transplantation). it can lead to hyperplasia of the parathyroid glands. Diagnosis • Biochemical: alkaline phosphatase is a good test choice for early detection and treatment response. chondrocalcinosis. which may give rise to heart failure in patients with prior cardiopathy. polyuria. followed by a compensatory increase in synthesis (bone replacement can be up to 20 times over normal values). • Pathologic fractures. • The most severe neurologic complications occur because of bone growth in the base of the cranium. proximal muscle weakness. the cranium. There is also a greater incidence of hyperuricemia and gout. • Denosumab. • Conventional bone x-ray: characteristic radiologic alterations.th cranial nerve in the internal auditory orifice.Endo c ri no l ogy pharmacological treatment or not. • Primary hyperparathyroidism: in 85% of cases. nonvertebral and hip fracture.2. the humerus. cortical thickening and alterations in the trabecular pattern. fatigue. band keratopathy. In postmenopausic women. Paget’s Disease The second most frequent osteopathy in developed countries. risedronate. • HBP is present in 50% to 70% of the patients. hearing loss owing to direct affectation of small internal bones in the inner ear or to compression of the 7. nerve compression. Hyperparathyroidism is defined as elevated values of PTH in plasma. • Selective estrogen response modifiers or SERMs -raloxifene and tamoxifen. osteoporosis and increased cardiovascular risk. compressive neurologic syndromes and bucco-dental disorders. “vertebras with rim-like appearance” and circumscribed osteoporosis. In theory. Peptic ulcer and gastritis. facial bones and pelvis. Differential diagnosis of hyperparathyroidism.e.

Associations in MEN 2 . a calcimimetic. pancreas and pituitary.. pheochromocytoma (bilaterality is more frequent than sporadic pheochromocytoma) and hyperparathyroidism (the most frequent form is hyperplasia as in MEN 1) (Table 17). it is indicated in secondary hyperparathyroidism in CRD and in primary hyperparathyroidism sufferers unsuitable for surgery because of accompanying comorbilities or in those affected by the disease who refuse surgery.e.A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK) • Bone disease.v.Serum calcium > 1 mg/dL over the upper limit of normality . hip and distal radius. but never low or suppressed. Nonfunctioning adrenal adenomas Table 16. Some patients show inappropriately normal values. Indications for surgery in asymptomatic primary hyperparathyroidism (Workshop. Renal ultrasound test.e. because of parathyroid hyperplasia). loop diuretics and i. Multiple Endocrine Chapter 06 • Neoplastic syndromes that affect multiple endocrine organs and that have hereditary etiology (autosomal dominant). Other changes are generalized or circumscribed osteopenia (salt and pepper skull) and subperiosteal resorption phenomena (radial zone of the middle phalanx of fingers) or generalized (clavicle). the combination of both techniques offer greater diagnostic yield and enables the performance of a minimally invasive surgery. • High values of intact PTH (PTHi) in relation to plasma calcemia. secure efficient hydration. Bone disease may be silent or cause local pain and even pathologic fractures. • Complications of diagnosis: bone densitometry (DEXA scan) to rule out osteopenia or osteoporosis. • Cinacalcet. symptomatic acute hypercalcemia. “The 3 Ps”: parathyroid. Pituitary tumors (40%): · Prolactin (20%) · Acromegaly (5%) · Combination of prolactin and GH (5%) · Nonsecretory (5%) · Others (TSH and so on) 4. pheochromocytoma should be surgically treated first. hypercalciuria and diminished phosphate tubular resorption. Parathyroid hyperplasia/adenoma (90%) 2. Lipomas (30%) 3. but not forced. Collagenomas (70%) 3. but the patient’s diet intake needs to be restricted.5 ED on T-score in backbone. • MEN 1 (Wermer’s syndrome) association of hyperparathyroidism (the most frequent manifestation. Nephrolithiasis and nephrocalcinosis. • When MTC and pheochromocytoma converge. Enteropancreatic tumor (70%): · Gastrinomas (40%) · Pancreatic polypeptide (20%) · Insulinoma (10%) · Other more rare (i. Treatment • Parathyroidectomy if the patient meets surgical criteria (Table 15). in lumbar spine. • Localization diagnosis: they should only be requested if surgical treatment is indicated. If there is a parathyroid adenoma. Biphosphonates. Appearance of bone cysts in long bones or “brown tumors” (accumulation of multinuclear giant osteoclasts). vipoma and glucagonoma) Any primary hyperparathyroidism that presents signs or symptoms related to hypercalcemia (i. 2008) 16 NONENDOCRINE MANIFESTATIONS 1. Facial angiofibromas (85%) 2. metabolic acidosis. total parathyroidectomy with implant in forearm muscles or sternocleidomastoid muscle or subtotal parathyroidectomy (leave a portion of the last gland). If any of the following occurs: parathyroid hyperplasia. hypophosphatemia. Therefore. • In asymptomatic patients. Multiple Endocrine Neoplasia (MEN) (Table 16). • To prevent secondary hyperparathyroidism development in CRD patients. • MEN type 2B consists of (aggressive) MTC with the presence of mucosa neuromas (tip of the tongue. one of the following criteria: . at least. nephrolithiasis) requires surgical indication right from the start Table 15. • In severe. Associations in MEN 1 SYNDROME MEN 2A · Under 50 years of age · Age ≥ 50 with. the most common manifestation). an adenomatous gland is removed. Diagnosis • General analytics: hypercalcemia. hip. increases circulating calcium affinity by its receptor resulting in a significant decrease in calcium and PTH levels.Mineral bone density under 2. oral phosphorus chelants must be administered.Decreased creatinine clearance (< 60 mL/min) . • MEN type 2A (Sipple’s syndrome) confluence of medullary thyroid cancer (or MTC. eyelids and digestive tract). femoral head or 1/3 distal of radius and/or any prior fracture because of fragility Neoplasia (MEN) CHARACTERISTICS · · · · · Medullary thyroid carcinoma Pheochromocytoma (50%) Hyperparathyroidism (10%) Lichenoid cutaneous amyloidosis Hirschprung’s disease Familial medullary · Medullary thyroid carcinoma thyroid carcinoma · It can be associated with Hirschprung’s disease MEN 2B · Medullary thyroid carcinoma (more precocious and aggressive than in MEN 2A) · Pheochromocytoma (40% to 50%) · Mucocutaneous ganglioneuromatosis (95%) · Marfanoid habitus (without ectopia lentis or aortic anomalies) Table 17. Cervical ultrasound and gammagraphy with Tc-sestamibi: currently. treatment involves abundant hydration.. ENDOCRINE MANIFESTATIONS 1. pituitary adenoma and cell tumors of pancreatic islets. • Renal affectation.