Internal Medicine EOR: Endocrinology (Smarty PANCE)

What is acromegaly and its most common cause?

Excess GH after epiphyseal closure in adults; caused by pituitary adenoma (95% of cases)

What are the classic physical features of acromegaly? Use mnemonic GROWTH

Gap between teeth, Ring size increase, Oily skin/sweating, Widened nose/lips, Thick heel pad, Hands/feet enlargement

What is the screening test for acromegaly?

Insulin-like growth factor-1 (IGF-1) level - elevated and age-adjusted (best initial test)

What is the confirmatory test for acromegaly?

Oral glucose tolerance test (OGTT) with GH measurement - failure to suppress GH <1 ng/mL after glucose load confirms diagnosis

What is the first-line treatment for acromegaly?

Transsphenoidal pituitary adenoma resection - curative in 60-90% of microadenomas

What medications are used for acromegaly?

Somatostatin analogs (octreotide, lanreotide), dopamine agonists (cabergoline), GH receptor antagonist (pegvisomant)

What complications should be screened for in acromegaly?

Colonoscopy (increased colon cancer risk), echocardiogram (cardiomyopathy), sleep study (sleep apnea), glucose monitoring

What is Addison’s disease?

Primary adrenal insufficiency - destruction of adrenal cortex causing deficiency of cortisol, aldosterone, and androgens

What are the most common causes of Addison’s disease?

Autoimmune adrenalitis (80% in developed countries), tuberculosis (most common worldwide), adrenal hemorrhage, metastatic cancer

What are the classic symptoms of Addison’s disease? Use mnemonic ADDISON

Anorexia/weight loss, Darkening of skin, Dizziness/hypotension, Inability to handle stress, Salt craving, Orthostatic hypotension, Nausea/vomiting

What is the hallmark physical finding of Addison’s disease?

Hyperpigmentation of skin creases, buccal mucosa, nipples, old scars (due to elevated ACTH stimulating melanocytes)

What are the characteristic laboratory findings in Addison’s disease?

Hyponatremia, hyperkalemia, hypoglycemia, metabolic acidosis, elevated BUN/creatinine, eosinophilia

What is the diagnostic test for Addison’s disease?

ACTH stimulation test (cosyntropin test) - cortisol fails to rise >18-20 μg/dL after ACTH administration

What is the treatment for chronic Addison’s disease?

Hydrocortisone 15-25 mg daily (in divided doses) plus fludrocortisone 0.05-0.2 mg daily

What is adrenal crisis and its treatment?

Life-threatening acute adrenal insufficiency - treat with IV hydrocortisone 100mg bolus, then 50-100mg q6-8h, plus IV fluids

What is Cushing’s disease vs Cushing’s syndrome?

Cushing’s disease: excess cortisol due to pituitary ACTH-secreting adenoma; Cushing’s syndrome: excess cortisol from any cause

What are the classic physical features of Cushing’s syndrome? Use mnemonic CUSHINGS

Central obesity, Upper body fat pads, Striae (purple), Hirsutism, Infection susceptibility, Neuropsychiatric changes, Glucose intolerance, Skin thinning

What is the best screening test for Cushing’s syndrome?

24-hour urine free cortisol (UFC) or late-night salivary cortisol - both have high sensitivity

What is the dexamethasone suppression test?

Low-dose (1mg) overnight test - normal individuals suppress cortisol <1.8 μg/dL; Cushing’s patients fail to suppress

How is ACTH-dependent vs ACTH-independent Cushing’s differentiated?

Measure plasma ACTH: elevated (>20 pg/mL) = ACTH-dependent; suppressed (<10 pg/mL) = ACTH-independent

What is the high-dose dexamethasone suppression test used for?

Differentiates pituitary (suppresses >50%) from ectopic ACTH (fails to suppress) sources

What is the first-line treatment for Cushing’s disease?

Transsphenoidal pituitary adenoma resection - curative in 70-90% of microadenomas

What is diabetes insipidus?

Disorder characterized by polyuria (>3L/day) and polydipsia due to deficient ADH production (central) or action (nephrogenic)

What are the characteristic laboratory findings in diabetes insipidus?

Low urine osmolality (<300 mOsm/kg), high serum osmolality (>295 mOsm/kg), hypernatremia, low urine specific gravity (<1.005)

What is the water deprivation test used for?

Diagnostic test to differentiate central DI, nephrogenic DI, and primary polydipsia

What are the expected results of water deprivation test in central DI?

Urine osmolality remains low after dehydration but increases >50% after desmopressin administration

What are the expected results in nephrogenic DI?

Urine osmolality remains low after both dehydration AND desmopressin administration

What is the first-line treatment for central diabetes insipidus?

Desmopressin (DDAVP) - synthetic ADH analog given intranasally, orally, or subcutaneously

What is the treatment for nephrogenic diabetes insipidus?

Treat underlying cause, thiazide diuretics, amiloride, dietary sodium restriction, adequate fluid intake

What is the diagnostic criteria for diabetes mellitus?

Fasting glucose ≥126 mg/dL (on 2 occasions), HbA1c ≥6.5%, random glucose ≥200 mg/dL with symptoms, or 2-hour OGTT ≥200 mg/dL

What is the pathophysiology difference between Type 1 and Type 2 DM?

Type 1: autoimmune beta cell destruction, absolute insulin deficiency; Type 2: insulin resistance with relative insulin deficiency

What antibodies are associated with Type 1 diabetes?

Anti-GAD65, anti-insulin, anti-islet cell (ICA), anti-IA-2 antibodies - present in 85-90% at diagnosis

What is the HbA1c target for most non-pregnant adults with diabetes?

<7% for most adults; <6.5% for select patients; <8% for elderly or high hypoglycemia risk

What are the microvascular complications of diabetes? Use mnemonic REN

Retinopathy, nEuropathy (peripheral and autonomic), Nephropathy

What are the macrovascular complications of diabetes?

Coronary artery disease, cerebrovascular disease (stroke), peripheral arterial disease

What is the first-line medication for Type 2 diabetes?

Metformin 500-1000mg twice daily (unless contraindicated) - decreases hepatic glucose production

What are the contraindications to metformin?

eGFR <30 mL/min, acute kidney injury, severe liver disease, alcohol abuse, contrast dye (hold temporarily)

What are the SGLT2 inhibitors and their benefits?

Empagliflozin, canagliflozin, dapagliflozin - cardiovascular and renal benefits, promote weight loss

What is diabetic ketoacidosis (DKA)?

Life-threatening complication of Type 1 DM - hyperglycemia, ketosis, anion gap metabolic acidosis, dehydration

What are the diagnostic criteria for DKA?

Glucose >250 mg/dL, pH <7.3, bicarbonate <18 mEq/L, anion gap >10, ketonemia/ketonuria

What is the treatment for DKA?

IV fluids (NS), insulin infusion (0.1 units/kg/hr), potassium replacement, identify/treat precipitating cause

What is hyperosmolar hyperglycemic state (HHS)?

Life-threatening complication of Type 2 DM - severe hyperglycemia >600 mg/dL, hyperosmolality >320 mOsm/kg, NO ketoacidosis

What are the most common causes of hypercalcemia?

Primary hyperparathyroidism (outpatient), malignancy (inpatient) - account for 90% of cases

What are the classic symptoms of hypercalcemia? Use mnemonic STONES BONES GROANS MOANS

Stones (kidney), Bones (pain), Groans (GI - constipation, nausea), Psychiatric moans (confusion, depression)

What laboratory findings help differentiate causes of hypercalcemia?

Elevated PTH = primary hyperparathyroidism; Suppressed PTH = malignancy, vitamin D toxicity, granulomatous disease

What malignancies commonly cause hypercalcemia?

Lung cancer, breast cancer, multiple myeloma, lymphoma, renal cell carcinoma

What are the mechanisms of malignancy-related hypercalcemia?

PTHrP secretion (humoral hypercalcemia), osteolytic bone metastases, calcitriol production (lymphomas)

What is the treatment for mild hypercalcemia (Ca <12 mg/dL)?

Hydration, treat underlying cause, discontinue offending medications (thiazides, lithium, calcium, vitamin D)

What is the treatment for severe hypercalcemia (Ca >14 mg/dL)?

IV fluids (NS 200-300 mL/hr), calcitonin, bisphosphonates (zoledronic acid), treat underlying cause

What is the definition of hypernatremia?

Serum sodium >145 mEq/L - reflects water deficit relative to sodium (hyperosmolar state)

What are the three categories of hypernatremia by volume status?

Hypovolemic (water loss > sodium loss), Euvolemic (pure water loss), Hypervolemic (sodium gain > water gain)

What are the most common causes of hypovolemic hypernatremia?

Diarrhea, vomiting, diuretics, osmotic diuresis (hyperglycemia), excessive sweating

What are the causes of euvolemic hypernatremia?

Diabetes insipidus (central or nephrogenic), insensible losses (fever, tachypnea), inadequate water intake

What are the symptoms of hypernatremia?

Thirst, lethargy, confusion, seizures, coma; severe cases cause brain shrinkage and intracranial hemorrhage

What is the treatment approach for hypernatremia?

Replace free water deficit, correct slowly (0.5 mEq/L/hr, max 10-12 mEq/L/24hr) to avoid cerebral edema

How is free water deficit calculated?

Free water deficit = TBW × [(serum Na/140) - 1], where TBW = 0.6 × body weight (kg) in men, 0.5 in women

What is primary hyperparathyroidism?

Excess PTH secretion from parathyroid gland(s) causing hypercalcemia and hypophosphatemia

What is the most common cause of primary hyperparathyroidism?

Solitary parathyroid adenoma (80-85%), followed by parathyroid hyperplasia (15%), parathyroid carcinoma (<1%)

What are the classic laboratory findings in primary hyperparathyroidism?

Elevated or inappropriately normal PTH, hypercalcemia, hypophosphatemia, elevated 24-hour urine calcium

What are the complications of hyperparathyroidism? Use mnemonic STONES BONES GROANS MOANS

Kidney stones, Bone disease (osteoporosis, osteitis fibrosa cystica), GI symptoms, Psychiatric symptoms

What imaging is used to localize parathyroid adenomas?

Sestamibi scan (technetium-99m), neck ultrasound, 4D-CT scan (pre-operative localization)

What are the indications for parathyroidectomy in primary hyperparathyroidism?

Symptomatic disease, serum calcium >1 mg/dL above normal, age <50, osteoporosis, GFR <60, nephrolithiasis

What is the first-line treatment for primary hyperparathyroidism?

Parathyroidectomy - curative in >95% of cases with solitary adenoma

What is secondary hyperparathyroidism?

Elevated PTH in response to chronic hypocalcemia (usually from chronic kidney disease) - calcium typically low-normal

What is Graves’ disease?

Autoimmune hyperthyroidism caused by TSH receptor antibodies (TSI) - most common cause of hyperthyroidism

What are the classic symptoms of hyperthyroidism? Use mnemonic SWEATING

Sweating/heat intolerance, Weight loss, Emotional lability, Appetite increased, Tremor, Insomnia, Nervousness, Goiter/diarrhea

What physical findings are specific to Graves’ disease?

Diffuse goiter, ophthalmopathy (exophthalmos, lid lag), pretibial myxedema, thyroid bruit

What laboratory findings confirm hyperthyroidism?

Low/suppressed TSH, elevated free T4 and T3; TSI antibodies positive in Graves’ disease

What is the radioiodine uptake pattern in different causes of hyperthyroidism?

High uptake: Graves’, toxic adenoma, toxic multinodular goiter; Low uptake: thyroiditis, exogenous thyroid hormone

What are the treatment options for Graves’ disease?

Antithyroid drugs (methimazole, PTU), radioactive iodine ablation, thyroidectomy

What is thyroid storm?

Life-threatening thyrotoxicosis - fever >104°F, tachycardia, altered mental status, heart failure - medical emergency

How is thyroid storm treated?

PTU or methimazole, beta-blockers (propranolol), iodine solution, corticosteroids, supportive care, treat precipitating factors

What is subacute thyroiditis presentation?

Painful thyroid with fever following viral illness, elevated ESR, initial hyperthyroid phase followed by hypothyroid phase

What is postpartum thyroiditis?

Autoimmune thyroiditis within 12 months postpartum - painless hyperthyroid phase (1-4 months) followed by hypothyroid phase (4-8 months)

What is the definition of hypocalcemia?

Serum calcium <8.5 mg/dL (corrected for albumin); ionized calcium <4.6 mg/dL

What are the most common causes of hypocalcemia?

Hypoparathyroidism (post-surgical), vitamin D deficiency, chronic kidney disease, hypomagnesemia, acute pancreatitis

What are the neuromuscular symptoms of hypocalcemia? Use mnemonic CATS

Convulsions/seizures, Arrhythmias, Tetany/muscle spasms, Stridor/laryngospasm

What are the classic physical signs of hypocalcemia?

Chvostek’s sign (facial twitching with facial nerve tap), Trousseau’s sign (carpopedal spasm with BP cuff inflation)

What ECG changes are seen in hypocalcemia?

Prolonged QT interval (risk of torsades de pointes), T wave changes, heart block

What is the acute treatment for symptomatic hypocalcemia?

IV calcium gluconate 1-2g in 50-100mL D5W over 10-20 minutes, monitor cardiac rhythm

What is the chronic treatment for hypocalcemia?

Oral calcium supplementation (1-3g elemental calcium daily) plus vitamin D (calcitriol for hypoparathyroidism)

What is hypoparathyroidism?

Inadequate PTH production causing hypocalcemia and hyperphosphatemia

What is the most common cause of hypoparathyroidism?

Iatrogenic - post-thyroidectomy or parathyroidectomy (inadvertent removal or damage to parathyroid glands)

What are the laboratory findings in hypoparathyroidism?

Low or inappropriately normal PTH, hypocalcemia, hyperphosphatemia, low 25(OH) vitamin D

What is pseudohypoparathyroidism?

Genetic disorder with PTH resistance - elevated PTH but hypocalcemia (end-organ resistance to PTH)

What are the clinical features of pseudohypoparathyroidism?

Short stature, round face, short 4th/5th metacarpals, intellectual disability, subcutaneous ossifications (Albright hereditary osteodystrophy)

What is the chronic treatment for hypoparathyroidism?

Oral calcium (1-3g daily) plus calcitriol (0.25-2 mcg BID) - target low-normal calcium to avoid hypercalciuria

What is the definition of hyponatremia?

Serum sodium <135 mEq/L - most common electrolyte disorder in hospitalized patients

What are the three categories of hyponatremia by volume status?

Hypovolemic (sodium and water loss), Euvolemic (water excess), Hypervolemic (water > sodium retention)

What are the causes of euvolemic hyponatremia?

SIADH, hypothyroidism, adrenal insufficiency, primary polydipsia, beer potomania

What are the diagnostic criteria for SIADH?

Hyponatremia, low serum osmolality (<280), urine osmolality >100 mOsm/kg, urine sodium >20 mEq/L, euvolemic status

What are the symptoms of severe hyponatremia (<115 mEq/L)?

Seizures, coma, respiratory arrest, cerebral edema - neurologic emergency

What is the treatment for mild SIADH?

Fluid restriction (800-1000 mL/day), treat underlying cause, salt tablets

What is the treatment for severe symptomatic hyponatremia?

Hypertonic saline (3% NaCl) - correct no faster than 8-10 mEq/L per 24 hours to avoid osmotic demyelination syndrome

What is osmotic demyelination syndrome?

Devastating neurologic complication from too-rapid sodium correction - central pontine myelinolysis with permanent brain damage

What is hypothyroidism?

Inadequate thyroid hormone production resulting in decreased metabolic rate

What is the most common cause of hypothyroidism in iodine-sufficient areas?

Hashimoto’s thyroiditis (chronic autoimmune thyroiditis)

What are the classic symptoms of hypothyroidism? Use mnemonic TIRED

Tired/fatigue, Intolerance to cold, Rough/dry skin, Edema, Depression/memory problems

What laboratory findings confirm primary hypothyroidism?

Elevated TSH (>4.5 mIU/L) with low or low-normal free T4; TSH most sensitive screening test

What is subclinical hypothyroidism?

Elevated TSH (4.5-10 mIU/L) with normal free T4 - may progress to overt hypothyroidism