Year 3: Endocrine and Metabolic Pathology — Part 2

Question 1

Riedel's thyroiditis is characterized by

Accepted Answer

Rock-hard thyroid due to replacement by dense fibrous tissue extending beyond the capsule — Riedel's = fibroinflammatory condition replacing thyroid with keloid-like fibrosis extending into surrounding structures. Presents as a rock-hard fixed neck mass mimicking malignancy. Associated with other fibrosclerosing conditions (retroperitoneal fibrosis, sclerosing cholangitis). IgG4-related disease.

Question 2

Thyroid storm is a life-threatening complication of hyperthyroidism precipitated by

Accepted Answer

Stress, surgery, infection, or radioiodine in uncontrolled hyperthyroidism — Thyroid storm: hyperpyrexia, tachycardia/arrhythmias, agitation, vomiting, high-output cardiac failure. Mortality ~20–30%. Treatment: propylthiouracil (blocks synthesis AND T4→T3 conversion) + Lugol's iodine + propranolol + steroids + supportive care.

Question 3

Myxedema coma is the most severe form of hypothyroidism. It presents with

Accepted Answer

Hypothermia, bradycardia, hypoventilation, and altered consciousness — Myxedema coma = decompensated severe hypothyroidism. Precipitated by cold, infection, or sedatives in elderly. Features: hypothermia, bradycardia, hypoventilation, hyponatremia, hypoglycemia, altered consciousness. Treatment: IV T3/T4 + hydrocortisone + supportive care.

Question 4

Sick euthyroid syndrome (non-thyroidal illness syndrome) is characterized by

Accepted Answer

Low T3, low/normal T4, and low/normal TSH in a severely ill patient — Seen in critical illness, starvation, major surgery. Reduced peripheral conversion of T4 to T3 (more rT3 produced instead). TSH is usually low/normal. NOT true hypothyroidism — thyroid replacement generally not indicated and may be harmful.

Question 5

Toxic multinodular goiter (Plummer's disease) differs from Graves' disease in that

Accepted Answer

It occurs in older patients with long-standing goiter and lacks TSI antibodies and eye signs — Toxic MNG = autonomous function of multiple nodules in a pre-existing goiter. Occurs in iodine-deficient areas in older patients. No TSI, no ophthalmopathy. Treated with radioiodine or surgery. Hot nodules on Tc-99m scan.

Question 6

DiGeorge syndrome (22q11.2 deletion) causes hypoparathyroidism because of

Accepted Answer

Failure of development of 3rd and 4th pharyngeal pouches leading to absent parathyroids and thymus — 22q11 deletion → absent/hypoplastic parathyroids (hypocalcemia/tetany) + absent thymus (T-cell deficiency) + conotruncal cardiac defects. Remember: CATCH-22 — Cardiac defects, Abnormal facies, Thymic hypoplasia, Cleft palate, Hypocalcemia, 22q11.

Question 7

Pseudohypoparathyroidism is characterized by

Accepted Answer

End-organ resistance to PTH causing hypocalcemia despite elevated PTH — Pseudohypoparathyroidism (PHP): PTH is elevated but kidneys/bones fail to respond. Type 1a (Albright hereditary osteodystrophy): short stature, round face, short 4th metacarpal, obesity, mental retardation + hormone resistance. Caused by GNAS mutations.

Question 8

Tertiary hyperparathyroidism differs from secondary in that

Accepted Answer

It develops when chronically hyperplastic parathyroids develop autonomous function, causing hypercalcemia — Tertiary HPT: prolonged secondary HPT → one or more glands develop autonomous PTH secretion → hypercalcemia even after correction of the original cause (e.g., post-renal transplant). PTH elevated + calcium now HIGH. May require parathyroidectomy.

Question 9

Adrenocortical carcinoma is characterized by

Accepted Answer

Large tumor (often >6cm), poor prognosis, may secrete multiple hormones — ACC is rare but aggressive. Typically large at presentation. May hypersecrete cortisol, androgens, aldosterone, or estrogen causing mixed endocrine syndromes. Associated with Li-Fraumeni syndrome (TP53 mutations) and Beckwith-Wiedemann syndrome. 5-year survival ~35%.

Question 10

Nelson's syndrome occurs after bilateral adrenalectomy for Cushing's disease because

Accepted Answer

Removal of cortisol feedback allows the pre-existing pituitary corticotroph adenoma to grow rapidly, causing hyperpigmentation and mass effects — After bilateral adrenalectomy, loss of cortisol negative feedback → rapid growth of ACTH-secreting pituitary adenoma → very high ACTH (hyperpigmentation) + local mass effects (headache, visual field defects). Prevented by pituitary irradiation before adrenalectomy.

Question 11

Empty sella syndrome occurs when

Accepted Answer

CSF herniates through an incompetent diaphragma sellae compressing and flattening the pituitary — Primary empty sella: CSF herniation through defective diaphragma sellae compresses pituitary against sella floor. Usually incidental finding on MRI. Pituitary function typically normal. Secondary: follows surgery, radiation, or infarction (Sheehan's).

Question 12

Hyperprolactinemia can be caused by all of the following EXCEPT

Accepted Answer

Dopamine agonist drugs (bromocriptine) — Dopamine AGONISTS (bromocriptine, cabergoline) TREAT hyperprolactinemia — they mimic dopamine which normally inhibits prolactin release. Causes of hyperprolactinemia: prolactinoma, stalk compression, dopamine antagonists (antipsychotics, metoclopramide, domperidone), hypothyroidism, pregnancy, renal failure.

Question 13

MODY (Maturity Onset Diabetes of the Young) differs from Type 1 and Type 2 DM in that

Accepted Answer

It is caused by single gene mutations affecting beta cell function, inherited in autosomal dominant pattern — MODY = monogenic diabetes. Multiple subtypes (MODY1-6). Most common: MODY2 (glucokinase mutation — mild, stable hyperglycemia) and MODY3 (HNF-1α mutation — progressive, responds to sulfonylureas). Onset <25 years, non-obese, family history in 3 generations. No autoantibodies.

Question 14

Gestational diabetes mellitus (GDM) is best described as

Accepted Answer

Any degree of glucose intolerance first recognized during pregnancy — GDM: placental hormones (HPL, progesterone, cortisol) cause insulin resistance. Risk factors: obesity, family history, previous macrosomic baby, PCOS. Complications: macrosomia, shoulder dystocia, neonatal hypoglycemia, polyhydramnios. ~50% develop T2DM later in life. Screened with OGTT at 24–28 weeks.

Question 15

Diabetic retinopathy — which feature distinguishes PROLIFERATIVE from non-proliferative (background) retinopathy?

Accepted Answer

New vessel formation (neovascularization) on the retina or disc — Non-proliferative (background): microaneurysms (earliest), dot/blot hemorrhages, hard exudates, cotton wool spots (nerve fiber layer infarcts). Proliferative: neovascularization → vitreous hemorrhage, tractional retinal detachment, rubeosis iridis → blindness. Treatment: laser photocoagulation + anti-VEGF (bevacizumab).

Question 16

Hyperosmolar hyperglycemic state (HHS) differs from DKA in that

Accepted Answer

It occurs in Type 2 DM with profound hyperglycemia, hyperosmolarity, but minimal/no ketosis — HHS: glucose often 33 mmol/L, osmolality 320 mOsm/kg, NO significant ketosis (residual insulin prevents lipolysis). Higher mortality than DKA (~15% vs 1–5%). Precipitated by infection, dehydration, diuretics in elderly T2DM patients. Treatment: slow rehydration + insulin.

Question 17

Gaucher's disease, the most common lysosomal storage disease, is caused by deficiency of

Accepted Answer

Glucocerebrosidase → glucocerebroside accumulation in macrophages — Autosomal recessive. Gaucher cells = lipid-laden macrophages with "crumpled tissue paper" cytoplasm. Affects liver, spleen (massive), bone marrow. Type 1 (non-neuronopathic) = most common, no CNS involvement. Treatment: enzyme replacement therapy (imiglucerase).

Question 18

Niemann-Pick disease Type A is caused by deficiency of

Accepted Answer

Sphingomyelinase → sphingomyelin accumulation in neurons and macrophages — Niemann-Pick Type A: severe sphingomyelinase deficiency → sphingomyelin in neurons (neurodegeneration) + macrophages (hepatosplenomegaly). Cherry-red spot on macula. Death by age 3. Type B: partial deficiency, no CNS involvement. Foam cells (lipid-laden macrophages) in bone marrow.

Question 19

Tay-Sachs disease is caused by deficiency of hexosaminidase A leading to accumulation of

Accepted Answer

GM2 ganglioside in neurons causing progressive neurodegeneration — Autosomal recessive, Ashkenazi Jewish population. GM2 ganglioside accumulates in neurons → progressive neurodegeneration, cherry-red macula spot, exaggerated startle response, hypotonia → death by age 5. Unlike Niemann-Pick, NO hepatosplenomegaly. No treatment — prenatal diagnosis essential.

Question 20

Von Gierke's disease (Type 1 glycogen storage disease) is caused by

Accepted Answer

Glucose-6-phosphatase deficiency → glycogen and fat accumulation in liver and kidneys — Von Gierke (GSD Type 1): G6Pase deficiency → glucose cannot be released from liver → severe fasting hypoglycemia + massive hepatomegaly + renomegaly + hyperlipidemia + hyperuricemia (gout). Lactic acidosis. Treatment: continuous glucose/cornstarch feeds.

Question 21

Pompe's disease (GSD Type 2) is caused by acid maltase deficiency and is unique among glycogen storage diseases because

Accepted Answer

Glycogen accumulates in lysosomes (a lysosomal storage disease) — Pompe = only GSD that is also a lysosomal storage disease. Glycogen accumulates in lysosomes of heart, skeletal muscle, liver. Infantile form: cardiomegaly, hypotonia, respiratory failure → death by age 2. Treatment: enzyme replacement (alglucosidase alfa). Remember: "Pompe trashes the pump" (heart).

Question 22

McArdle's disease (GSD Type 5) classically presents with

Accepted Answer

Muscle cramps, myoglobinuria after exercise, and failure of venous lactate to rise with forearm exercise — McArdle = myophosphorylase deficiency → muscle cannot break down glycogen → exercise intolerance, painful cramps, myoglobinuria (risk of renal failure). Ischemic forearm exercise test: no rise in lactate (but ammonia rises normally). Second wind phenomenon (switch to fatty acid oxidation after initial cramps).

Question 23

Phenylketonuria (PKU) is caused by deficiency of phenylalanine hydroxylase. Untreated it causes

Accepted Answer

Severe intellectual disability, seizures, musty odor, fair skin and hair, eczema — Phenylalanine accumulates → phenylketones in urine (musty/mousy odor). Blocks tyrosine synthesis → decreased melanin (fair skin/hair/eyes). Autosomal recessive. Diagnosed on newborn screening (Guthrie test/tandem mass spectrometry). Treatment: phenylalanine-restricted diet + sapropterin in BH4-responsive cases. Start treatment immediately to prevent intellectual disability.

Question 24

Familial hypercholesterolemia (FH) is most commonly caused by

Accepted Answer

Defective LDL receptor leading to markedly elevated LDL cholesterol — FH: autosomal dominant LDL receptor mutations. Heterozygous FH (~1:250): LDL 2–3× normal, premature atherosclerosis, tendon xanthomas, corneal arcus. Homozygous FH: LDL 6–8× normal, MI in childhood. Treatment: high-intensity statins + ezetimibe + PCSK9 inhibitors (evolocumab/alirocumab).

Question 25

Acute intermittent porphyria (AIP) is caused by deficiency of porphobilinogen deaminase. The classic triad is

Accepted Answer

Abdominal pain, neuropsychiatric symptoms, and dark urine (no skin rash) — AIP: autosomal dominant, porphyrin precursors (ALA, PBG) accumulate in urine. Classic triad: severe colicky abdominal pain + neuropsychiatric features (psychosis, neuropathy) + dark/port-wine urine. NO photosensitivity (unlike porphyria cutanea tarda). Precipitated by: alcohol, drugs (OCP, barbiturates, sulfonamides), fasting, infection. Treatment: IV hemin + glucose loading + avoid triggers.

Question 26

Porphyria cutanea tarda (PCT) differs from AIP in that

Accepted Answer

It presents with blistering photosensitive skin lesions on sun-exposed areas with NO neurologic features — PCT: uroporphyrinogen decarboxylase deficiency → uroporphyrin accumulation → photosensitive blistering, skin fragility, hypertrichosis. Associated with alcohol, hepatitis C, hemochromatosis, estrogens. Urine fluoresces pink under Wood's lamp. Treatment: phlebotomy + chloroquine.

Question 27

A TSH-secreting pituitary adenoma (thyrotropinoma) causes

Accepted Answer

Hyperthyroidism with elevated TSH (inappropriately normal/high for the T4 level) — TSH-oma = rare (<1% of pituitary adenomas). Autonomous TSH secretion → hyperthyroidism (high T3/T4) but TSH is NOT suppressed (inappropriately normal or elevated). Key distinguishing point from Graves'/toxic nodule where TSH is suppressed. Treat with somatostatin analogues (octreotide) + surgery.

Question 28

An adrenal incidentaloma is an adrenal mass 1cm found incidentally. The first step in workup is

Accepted Answer

Biochemical evaluation to exclude functional tumor (pheo, Cushing's, Conn's) before any intervention — All incidentalomas require: 24hr urine metanephrines (exclude pheo — MUST do before any procedure), 1mg overnight dexamethasone suppression test (exclude subclinical Cushing's), plasma aldosterone:renin ratio if hypertensive (exclude Conn's). CT features suggesting malignancy: 4cm, irregular borders, heterogeneous, HU 10 (lipid-poor).

Question 29

Diabetic Charcot joint (neuropathic arthropathy) results from

Accepted Answer

Loss of protective pain sensation leading to repeated unrecognized trauma and joint destruction — Peripheral neuropathy → loss of pain sensation → repeated micro/macro trauma without protective reflexes → progressive joint destruction, deformity, instability. Most commonly affects foot/ankle. X-ray: 5 Ds — Distension, Density increase, Debris, Dislocation, Destruction. Rocker bottom foot deformity. Treatment: offloading, total contact casting.

Question 30

Diabetic proliferative retinopathy develops because of

Accepted Answer

Chronic retinal ischemia triggering VEGF release which drives pathologic neovascularization — Capillary non-perfusion + chronic ischemia → VEGF (vascular endothelial growth factor) upregulation → neovascularization on retinal surface and disc (NVD/NVE). New vessels are fragile → vitreous hemorrhage → tractional retinal detachment → blindness. Treatment: panretinal laser photocoagulation + intravitreal anti-VEGF (bevacizumab/ranibizumab).

Year 3: Endocrine and Metabolic Pathology — Part 2

Questions, Answers & Explanations