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