Endocrine Pathology

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Pituitary Gland Pathology Adenomas: Most common cause of hyperpituitarism. Classified by hormone produced. Prolactinomas: Most common pituitary adenoma. Symptoms: Galactorrhea, amenorrhea (females); decreased libido, erectile dysfunction (males). Treatment: Dopamine agonists (bromocriptine, cabergoline) or surgery. Growth Hormone (GH) Adenomas: Symptoms: Gigantism (children), Acromegaly (adults - coarse facial features, large hands/feet, joint pain, diabetes mellitus). Diagnosis: Elevated IGF-1, failure to suppress GH with oral glucose. Treatment: Surgery, somatostatin analogs (octreotide), GH receptor antagonists (pegvisomant). ACTH Adenomas (Corticotroph Adenomas): Causes Cushing's disease (excess ACTH $\to$ adrenal hyperplasia $\to$ excess cortisol). Symptoms: Central obesity, moon facies, buffalo hump, striae, hypertension, hyperglycemia. TSH Adenomas: Rare, causes hyperthyroidism. Non-functioning Adenomas: May cause mass effect symptoms (headache, bitemporal hemianopsia). Hypopituitarism: Deficiency of one or more pituitary hormones. Causes: Tumors (non-functioning adenomas), Sheehan syndrome (postpartum pituitary necrosis), empty sella syndrome, craniopharyngioma. Symptoms: Vary depending on hormones deficient (e.g., panhypopituitarism). Diabetes Insipidus (DI): Deficiency of ADH (central DI) or renal insensitivity to ADH (nephrogenic DI). Symptoms: Polyuria, polydipsia, hypernatremia. Diagnosis: Water deprivation test. Treatment: Desmopressin (central DI), HCTZ/amiloride (nephrogenic DI). Syndrome of Inappropriate ADH (SIADH): Excess ADH. Causes: Small cell lung carcinoma, CNS disorders, drugs. Symptoms: Hyponatremia, euvolemia. Treatment: Fluid restriction, demeclocycline. Thyroid Gland Pathology Hyperthyroidism (Thyrotoxicosis): Graves' Disease: Autoimmune, IgG antibodies stimulate TSH receptor. Symptoms: Goiter, exophthalmos, pretibial myxedema, heat intolerance, weight loss, tachycardia. Labs: $\downarrow$ TSH, $\uparrow$ T3/T4. Toxic Multinodular Goiter: Multiple hyperfunctioning nodules. Toxic Adenoma: Single hyperfunctioning nodule. Thyroiditis: Inflammation of thyroid. Subacute (de Quervain's): Painful, viral. Transient hyper $\to$ hypo $\to$ euthyroid. Silent (painless): Postpartum, transient hyper $\to$ hypo $\to$ euthyroid. Thyroid Storm: Acute, life-threatening exacerbation of hyperthyroidism. Hypothyroidism: Hashimoto's Thyroiditis: Autoimmune, most common cause in iodine-sufficient areas. Anti-TPO/anti-thyroglobulin antibodies. Symptoms: Goiter, cold intolerance, weight gain, fatigue, bradycardia, constipation. Labs: $\uparrow$ TSH, $\downarrow$ T3/T4. Iodine Deficiency: Most common cause worldwide. Congenital Hypothyroidism: Cretinism. Myxedema Coma: Severe, life-threatening hypothyroidism. Thyroid Neoplasms: Follicular Adenoma: Benign. No capsular or vascular invasion. Papillary Carcinoma: Most common (80%). Excellent prognosis. Orphan Annie eye nuclei, psammoma bodies. Spreads via lymphatics. Follicular Carcinoma: Second most common (15%). Good prognosis. Capsular and vascular invasion. Spreads hematogenously. Medullary Carcinoma: From parafollicular C cells. Produces calcitonin. Associated with MEN 2A/2B (RET oncogene). Anaplastic Carcinoma: Highly aggressive, poor prognosis. Older patients. Adrenal Gland Pathology Adrenal Cortex: Cushing's Syndrome: Excess cortisol. Causes: Exogenous glucocorticoids (most common), ACTH-producing pituitary adenoma (Cushing's disease), ectopic ACTH (small cell lung cancer), adrenal adenoma/carcinoma. Symptoms: Central obesity, moon facies, buffalo hump, striae, hypertension, hyperglycemia, muscle weakness. Diagnosis: 24-hr urinary free cortisol, midnight salivary cortisol, low-dose dexamethasone suppression test. Hyperaldosteronism: Primary (Conn's Syndrome): Adrenal adenoma or bilateral adrenal hyperplasia. $\uparrow$ aldosterone, $\downarrow$ renin. Secondary: Renal artery stenosis, CHF, cirrhosis. $\uparrow$ aldosterone, $\uparrow$ renin. Symptoms: Hypertension, hypokalemia, metabolic alkalosis. Adrenocortical Insufficiency (Addison's Disease): Primary chronic adrenal insufficiency. Causes: Autoimmune destruction (most common in developed countries), TB (worldwide), metastatic cancer. Symptoms: Fatigue, weakness, weight loss, hypotension, hyperpigmentation (due to $\uparrow$ ACTH), hyperkalemia, hyponatremia. Diagnosis: High ACTH, low cortisol, failure to respond to ACTH stimulation. Adrenal Crisis: Acute, severe adrenal insufficiency. Life-threatening. Congenital Adrenal Hyperplasia (CAH): Autosomal recessive enzyme deficiencies (e.g., 21-hydroxylase deficiency). Leads to impaired cortisol/aldosterone synthesis, excess androgens. Adrenal Medulla: Pheochromocytoma: Tumor of chromaffin cells, secretes catecholamines. Symptoms: Paroxysmal hypertension, palpitations, headache, sweating (PHEochromocytoma: Palpitations, Headache, Episodic sweating). Diagnosis: $\uparrow$ urinary metanephrines/VMA. Rule of 10s: 10% extra-adrenal, 10% bilateral, 10% malignant, 10% childhood, 10% familial. Treatment: Alpha blockers (phenoxybenzamine) then beta blockers, then surgery. Pancreatic Endocrine Pathology Diabetes Mellitus (DM): Type 1 DM: Autoimmune destruction of pancreatic $\beta$-cells. Absolute insulin deficiency. Onset: Childhood/adolescence. Symptoms: Polyuria, polydipsia, polyphagia, weight loss, DKA. Pathology: Insulitis, islet atrophy. Type 2 DM: Insulin resistance with relative insulin deficiency. Onset: Adulthood, associated with obesity. Pathology: Islet amyloid deposition. Complications: Microvascular (retinopathy, nephropathy, neuropathy), Macrovascular (atherosclerosis, MI, stroke, PVD). Pancreatic Endocrine Tumors: Insulinoma: Most common. Produces insulin $\to$ hypoglycemia. Whipple's triad (hypoglycemia symptoms, low blood glucose, relief with glucose). Gastrinoma (Zollinger-Ellison Syndrome): Produces gastrin $\to$ multiple peptic ulcers, diarrhea. Glucagonoma: Produces glucagon $\to$ hyperglycemia, necrolytic migratory erythema. Somatostatinoma: Produces somatostatin $\to$ diabetes, gallstones, steatorrhea. VIPoma (Verner-Morrison Syndrome): Produces vasoactive intestinal peptide (VIP) $\to$ watery diarrhea, hypokalemia, achlorhydria (WDHA syndrome). Parathyroid Gland Pathology Hyperparathyroidism: Primary: Parathyroid adenoma (most common), hyperplasia. $\uparrow$ PTH, $\uparrow$ Ca, $\downarrow$ PO4. Symptoms: "Stones, bones, groans, psychiatric overtones" (kidney stones, bone pain/fractures, abdominal pain, depression/fatigue). Secondary: Chronic renal failure (kidneys can't excrete PO4 $\to$ $\uparrow$ PO4 $\to$ $\downarrow$ Ca $\to$ compensatory $\uparrow$ PTH). $\uparrow$ PTH, $\downarrow$ Ca, $\uparrow$ PO4. Tertiary: Prolonged secondary hyperparathyroidism leads to autonomous PTH secretion. Hypoparathyroidism: Causes: Thyroid surgery (accidental removal), autoimmune. $\downarrow$ PTH, $\downarrow$ Ca, $\uparrow$ PO4. Symptoms: Tetany, muscle cramps, perioral numbness, Chvostek's sign (facial twitch with tap), Trousseau's sign (carpal spasm with BP cuff). Multiple Endocrine Neoplasia (MEN) Syndromes MEN 1 (Wermer Syndrome): Autosomal dominant, MEN1 gene mutation. "3 Ps": P ituitary adenomas P arathyroid hyperplasia (primary hyperparathyroidism) P ancreatic endocrine tumors (gastrinomas, insulinomas) MEN 2A (Sipple Syndrome): Autosomal dominant, RET proto-oncogene mutation. "2 Ps, 1 M": P heochromocytoma P arathyroid hyperplasia M edullary thyroid carcinoma MEN 2B: Autosomal dominant, RET proto-oncogene mutation. "1 P, 2 Ms": P heochromocytoma M edullary thyroid carcinoma M arfanoid habitus, mucosal neuromas