Year 3: Endocrine and Metabolic Pathology

Question 1

Which antibody directly causes hyperthyroidism in Graves' disease?

Accepted Answer

TSH receptor-stimulating immunoglobulin (TSI) — TSI binds and continuously activates TSH receptors causing unregulated thyroid hormone production. Unique features: exophthalmos and pretibial myxedema. ---

Question 2

Hashimoto's thyroiditis histologic hallmark is

Accepted Answer

Dense lymphocytic infiltration with germinal centers and Hürthle cell change — Lymphoplasmacytic infiltration + Hürthle cell metaplasia. Anti-TPO antibodies elevated. Most common cause of hypothyroidism in iodine-sufficient regions. ---

Question 3

A painful thyroid following flu-like illness with transient hyperthyroidism and granulomatous histology is

Accepted Answer

De Quervain's (subacute granulomatous) thyroiditis — De Quervain's follows viral infection. Course: hyperthyroidism → hypothyroidism → recovery. ESR markedly elevated. ---

Question 4

The most common thyroid cancer with Orphan Annie eye nuclei, nuclear grooves, and psammoma bodies is

Accepted Answer

Papillary carcinoma — ~80% of thyroid cancers. Spreads via lymphatics. Associated with RET/PTC rearrangements and prior radiation exposure. ---

Question 5

Medullary thyroid carcinoma arises from parafollicular C cells and characteristically shows

Accepted Answer

Amyloid deposits in stroma derived from procalcitonin — C cells produce calcitonin. Associated with MEN2A and MEN2B via RET mutations. Calcitonin = tumor marker. ---

Question 6

Follicular carcinoma of the thyroid is distinguished from follicular adenoma by

Accepted Answer

Capsular and vascular invasion on histology — FNA cannot distinguish the two. Only capsular penetration or vascular invasion on excised specimen confirms carcinoma. Spreads hematogenously to bone and lung. ---

Question 7

Anaplastic thyroid carcinoma is best described as

Accepted Answer

One of the most lethal human cancers with median survival of months — Undifferentiated, typically in elderly. Rapid local invasion. Does not take up radioiodine. Near 100% mortality. ---

Question 8

A midline neck swelling that moves with BOTH swallowing and tongue protrusion is

Accepted Answer

Thyroglossal duct cyst — Connected to base of tongue via fibrous tract through hyoid bone. Most common congenital neck mass. ---

Question 9

The most common cause of primary hyperparathyroidism is

Accepted Answer

Solitary parathyroid adenoma — ~85% of cases. Classic: Bones, Stones, Groans, Psychic moans. PTH elevated + hypercalcemia + hypophosphatemia. ---

Question 10

Secondary hyperparathyroidism most commonly results from

Accepted Answer

Chronic renal failure causing hypocalcemia — CRF → decreased vitamin D activation + hyperphosphatemia → hypocalcemia → compensatory four-gland hyperplasia. Calcium is low/normal, not elevated. ---

Question 11

Brown tumors of bone are caused by

Accepted Answer

Prolonged severe hyperparathyroidism — Collections of osteoclasts, macrophages, and hemosiderin replacing bone. X-ray: "salt and pepper" skull + subperiosteal resorption of radial aspect of middle phalanges. ---

Question 12

Trousseau's sign for hypocalcemia involves

Accepted Answer

Carpopedal spasm on inflating BP cuff above systolic for 3 minutes — More sensitive and specific than Chvostek's. Carpal spasm (main d'accoucheur). Most common cause of hypoparathyroidism = inadvertent surgical removal. ---

Question 13

The most common OVERALL cause of Cushing's syndrome is

Accepted Answer

Exogenous corticosteroid administration — Iatrogenic = most common overall. Among endogenous causes, Cushing's disease (pituitary adenoma) = ~70%. Features: central obesity, moon face, buffalo hump, purple striae. ---

Question 14

In Cushing's disease (pituitary adenoma), cortisol on dexamethasone suppression testing is

Accepted Answer

Not suppressed by low dose but IS suppressed by high dose — Pituitary adenoma retains partial feedback sensitivity. Ectopic ACTH and adrenal tumors = unsuppressed by either dose. Key distinguishing test. ---

Question 15

Conn's syndrome (primary hyperaldosteronism) presents with hypertension, hypokalemia, and

Accepted Answer

Low plasma renin (suppressed) — Autonomous aldosterone → Na retention + K wasting + volume expansion → suppresses renin. Low renin distinguishes primary from secondary hyperaldosteronism. ---

Question 16

The most common cause of Addison's disease in developed countries is

Accepted Answer

Autoimmune adrenalitis — Autoimmune = most common in developed world. TB = most common worldwide. 90% of cortex must be destroyed before symptoms appear. Features: hyperpigmentation, hyponatremia, hyperkalemia, hypotension. ---

Question 17

Waterhouse-Friderichsen syndrome is bilateral adrenal hemorrhage typically caused by

Accepted Answer

Neisseria meningitidis septicemia — Meningococcal septicemia → DIC → bilateral adrenal hemorrhage → acute adrenal crisis + purpuric rash + shock. Fulminant, often fatal. ---

Question 18

Pheochromocytoma rule of 10s: 10% bilateral, 10% malignant, 10% extra-adrenal. Which else is correct?

Accepted Answer

10% occur in children and 10% are familial — Catecholamine-secreting tumor causing paroxysmal hypertension, headache, palpitations, sweating. Associated with MEN2A/2B, VHL, NF1. Diagnose with 24hr urine metanephrines. ---

Question 19

The most common cause of congenital adrenal hyperplasia (CAH) is

Accepted Answer

21-hydroxylase deficiency — ~95% of CAH. Blocks cortisol and aldosterone synthesis → precursors shunted to androgens. Elevated 17-hydroxyprogesterone is the diagnostic marker. ---

Question 20

Neuroblastoma, the most common extracranial solid tumor of childhood, arises from

Accepted Answer

Adrenal medulla / sympathetic ganglia — Neural crest-derived. Secretes catecholamines → elevated urinary VMA and HVA. N-myc amplification = poor prognosis. ---

Question 21

Excess growth hormone after epiphyseal fusion causes acromegaly. Before fusion it causes

Accepted Answer

Gigantism — Pre-fusion GH excess = gigantism. Post-fusion = acromegaly: enlarged hands/feet, prognathism, coarse features, organomegaly. IGF-1 is the best screening test. ---

Question 22

Sheehan's syndrome is postpartum pituitary necrosis. Its first clinical sign is

Accepted Answer

Failure of lactation followed by panhypopituitarism — Massive postpartum hemorrhage → ischemic necrosis of enlarged pituitary. First sign: failure to lactate (prolactin deficiency). Later: loss of all anterior pituitary hormones. ---

Question 23

Craniopharyngioma arises from Rathke's pouch remnants. Its characteristic imaging finding is

Accepted Answer

Calcification on CT — Calcification almost pathognomonic on CT. Most common suprasellar tumor in children. Causes bitemporal hemianopia, hypopituitarism, diabetes insipidus. Benign but locally destructive. ---

Question 24

The most common functional pituitary adenoma is

Accepted Answer

Prolactinoma — Women: galactorrhea, amenorrhea, infertility. Men: hypogonadism, erectile dysfunction. First-line treatment: dopamine agonists (bromocriptine, cabergoline) — NOT surgery. ---

Question 25

Central diabetes insipidus is distinguished from nephrogenic DI by

Accepted Answer

Response to desmopressin (ADH analogue) — Water deprivation then desmopressin: central DI responds (urine concentrates). Nephrogenic DI = no response (renal resistance to ADH). ---

Question 26

Type 1 DM is caused by autoimmune beta cell destruction. HLA associations include

Accepted Answer

HLA-DR3 and DR4 — Anti-islet cell, anti-insulin, and anti-GAD antibodies present. Absolute insulin deficiency → prone to DKA. Islets show insulitis (lymphocytic infiltration). ---

Question 27

The pathologic hallmark of Type 2 DM in the pancreas is

Accepted Answer

Islet amyloid (amylin/IAPP) deposition — IAPP/amylin co-secreted with insulin deposits as amyloid replacing beta cells. Pathogenesis: insulin resistance + relative insulin deficiency. Associated with obesity. ---

Question 28

Kimmelstiel-Wilson nodular glomerulosclerosis is pathognomonic of

Accepted Answer

Diabetic nephropathy — Early: GBM thickening + mesangial expansion. Advanced: diffuse + nodular (Kimmelstiel-Wilson) glomerulosclerosis. Leading cause of ESRD worldwide. ---

Question 29

DKA occurs in Type 1 DM due to absolute insulin deficiency causing

Accepted Answer

Uncontrolled lipolysis, ketogenesis, and high anion gap metabolic acidosis — Insulin deficiency → unrestrained glucagon → massive lipolysis → hepatic ketogenesis. Results in HAGMA + dehydration + Kussmaul breathing + fruity breath. ---

Question 30

HbA1c reflects average blood glucose over

Accepted Answer

2–3 months (lifespan of RBC) — HbA1c ≥6.5% = diagnostic of DM. Target in treatment <7%. Falsely low in haemolytic anaemia. Gold standard for monitoring glycaemic control. ---

Question 31

The 'glove and stocking' sensory neuropathy of diabetes is primarily caused by

Accepted Answer

Non-enzymatic glycation + polyol pathway causing osmotic nerve damage — Sorbitol accumulates via aldose reductase → osmotic damage to Schwann cells. Most common diabetic complication. Risk of painless foot ulcers and Charcot joint. ---

Question 32

Monosodium urate crystals in gout appear under polarized light as

Accepted Answer

Needle-shaped and negatively birefringent — MSU = needle-shaped, negatively birefringent (yellow when parallel to slow axis). First MTP joint (podagra) is classic. Causes: overproduction or underexcretion of uric acid. ---

Question 33

Pseudogout (CPPD) crystals are

Accepted Answer

Rhomboid-shaped and weakly positively birefringent — CPPD = rhomboid, weakly positively birefringent (blue when parallel to slow axis). Chondrocalcinosis on X-ray. Commonly affects knee in elderly. Associated with hyperparathyroidism, hemochromatosis. ---

Question 34

Wilson's disease is caused by ATP7B mutations leading to

Accepted Answer

Defective copper transport and copper accumulation in liver, brain, and eyes — Autosomal recessive. Copper accumulates in liver (cirrhosis), basal ganglia, eyes (Kayser-Fleischer rings), kidneys. Serum ceruloplasmin LOW. Treatment: D-penicillamine or trientine. ---

Question 35

Kayser-Fleischer rings in Wilson's disease represent

Accepted Answer

Copper deposition in Descemet's membrane of the cornea — Golden-brown rings at corneal periphery. Best seen on slit-lamp. Pathognomonic of Wilson's with neurologic involvement. Present in 95% with neurologic disease. ---

Question 36

Primary (AL) amyloidosis is associated with

Accepted Answer

Plasma cell dyscrasias (multiple myeloma) — AL = immunoglobulin light chains from clonal plasma cells. Affects heart (restrictive cardiomyopathy), kidneys (nephrotic syndrome), liver, tongue (macroglossia). ---

Question 37

Secondary (AA) amyloidosis complicates

Accepted Answer

Chronic inflammatory diseases (TB, RA, osteomyelitis) — AA = serum amyloid A protein elevated in chronic inflammation. Kidneys and liver primarily affected. Also complicates familial Mediterranean fever. ---

Question 38

Metabolic syndrome diagnosis requires at least 3 of 5 criteria. These are

Accepted Answer

Central obesity, hypertension, elevated triglycerides, low HDL, elevated fasting glucose — Greatly increases CV risk and T2DM risk. Associated with NAFLD, PCOS, sleep apnoea. ---

Question 39

MEN1 (Wermer syndrome) classically involves the '3 Ps'

Accepted Answer

Pituitary, parathyroid, and pancreas — MEN1 gene (menin) mutation. Parathyroid hyperplasia (~95%), Pancreatic NETs (gastrinoma most common), Pituitary adenoma (prolactinoma most common). ---

Question 40

MEN2A (Sipple syndrome) includes

Accepted Answer

Medullary thyroid Ca + pheochromocytoma + parathyroid hyperplasia — RET mutations. MTC (~100%) + pheo (~50%) + parathyroid (~20%). MEN2B = same minus parathyroid PLUS mucosal neuromas + marfanoid habitus. ---

Question 41

Zollinger-Ellison syndrome is caused by a gastrinoma presenting with

Accepted Answer

Multiple recurrent peptic ulcers in unusual locations due to hypergastrinemia — Pancreatic/duodenal gastrinoma → massive acid hypersecretion → ulcers including 4th duodenum and jejunum. ~25% associated with MEN1. ---

Question 42

Whipple's triad for insulinoma consists of

Accepted Answer

Symptoms of hypoglycaemia + documented low blood glucose + relief with glucose — Most common pancreatic NET, 90% benign. Suppressed C-peptide during hypoglycaemia if exogenous insulin; elevated C-peptide in insulinoma. ---

Question 43

Carcinoid syndrome (flushing, diarrhea, right heart disease) occurs when carcinoid tumors

Accepted Answer

Metastasize to the liver, bypassing hepatic inactivation of serotonin — Hepatic portal blood inactivates serotonin — symptoms only occur with liver metastases (or primary lung carcinoids). Diagnosis: 24hr urine 5-HIAA. ---

Question 44

Primary hemochromatosis is caused by mutations in

Accepted Answer

HFE gene causing excessive iron absorption — C282Y most common mutation. Iron deposits in liver (cirrhosis), pancreas (diabetes), heart (cardiomyopathy), skin (bronze pigmentation). Treatment: phlebotomy. ---

Question 45

'Bronze diabetes' is the classic triad of hemochromatosis consisting of

Accepted Answer

Skin bronzing + diabetes mellitus + cirrhosis — Iron deposition in skin (bronze pigmentation) + pancreatic beta cells (DM) + liver (cirrhosis). Increased risk of hepatocellular carcinoma. Also: arthropathy, hypogonadism, cardiomyopathy. ---

Question 46

Amyloid shows apple-green birefringence on Congo red staining due to its

Accepted Answer

Cross-beta pleated sheet fibril arrangement — All amyloids share cross-beta pleated sheet configuration regardless of precursor protein. EM shows non-branching 7–10nm fibrils. Amyloid P component (SAP) present in all types. ---

Question 47

The adrenal cortex zones GFR produce respectively (outer to inner)

Accepted Answer

Aldosterone, cortisol, androgens — "GFR = Salt, Sugar, Sex." Glomerulosa = Aldosterone, Fasciculata = Cortisol, Reticularis = Androgens. Medulla = Catecholamines. ---

Question 48

Iodine deficiency goiter causes thyroid enlargement because

Accepted Answer

Low T3/T4 → elevated TSH → drives follicular cell hyperplasia and hypertrophy — Most common cause of goiter worldwide = iodine deficiency. Treatment: iodine supplementation. Endemic goiter = affects 10% of a population. ---

Question 49

The early morning hyperglycaemia of the 'dawn phenomenon' is caused by

Accepted Answer

Overnight surges in counter-regulatory hormones (GH and cortisol) — GH and cortisol increase hepatic glucose production overnight → pre-breakfast hyperglycaemia. Distinguish from Somogyi effect (nocturnal hypoglycaemia → rebound) — different mechanism and management. ---

Question 50

SIADH causes

Accepted Answer

Hyponatraemia with low serum osmolality and inappropriately concentrated urine — Excess ADH → water retention → dilutional hyponatraemia + concentrated urine (osmolality 100 mOsm/kg). Most common ectopic cause: small cell lung cancer. Treatment: fluid restriction ± tolvaptan.

Year 3: Endocrine and Metabolic Pathology

Questions, Answers & Explanations