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PA31.1-10 | Endocrine System — Graded Quiz
Graded
12 questions · Untimed · 2 attempts
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A 35-year-old woman from an iodine-sufficient region presents with a 4-year history of progressive weight gain, cold intolerance, constipation, and dry skin. TSH is 18 mIU/L (elevated); free T4 is 6 pmol/L (low). Anti-TPO antibodies are 1,840 IU/mL. Ultrasound shows a heterogeneous, hypoechoic gland with reduced volume. A thyroid biopsy is taken for academic purposes. Which histological finding BEST distinguishes this condition from de Quervain subacute thyroiditis at the microscopic level?
A
Neutrophilic infiltration within follicles — Hashimoto thyroiditis characteristically shows acute follicular rupture with neutrophils as the dominant infiltrate
B
Dense lymphocytic infiltrate with germinal centre formation, follicular atrophy, and Hürthle cell (oxyphilic) metaplasia of follicular epithelium — in contrast to de Quervain's, which shows granulomas with giant cells and absence of autoimmune lymphoid follicles
✓
C
Psammoma bodies within follicular colloid — pathognomonic of Hashimoto thyroiditis and distinguishing it from all other thyroid conditions
D
Massive follicular cyst formation with colloid distension (colloid goiter pattern) — the enlarged fluid-filled follicles distinguish Hashimoto from the granulomatous follicular rupture of de Quervain's
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A 27-year-old woman presents with 8 weeks of palpitations, tremor, heat intolerance, and weight loss of 6 kg. TSH is undetectable; free T4 is 42 pmol/L (markedly elevated). Radioactive iodine uptake (RAIU) is diffusely increased to 78% at 24 hours (normal <30%). She also has exophthalmos and bilateral pitting pretibial myxoedema. Which immunological mechanism DIRECTLY drives both the thyroid overactivity AND the ophthalmopathy in this condition?
A
Anti-TPO antibodies activate complement on thyroid follicular cells, causing direct cytotoxic destruction that releases pre-formed T3/T4 — the same antibody cross-reacts with orbital muscle calcium channels, causing muscle inflammation
B
IgG autoantibodies against the TSH receptor (TSI/TRAb) activate follicular cell adenylyl cyclase, mimicking TSH and driving unregulated T3/T4 synthesis; the same TSHR is expressed on orbital fibroblasts, where TSI binding causes fibroblast activation, GAG accumulation, and adipogenesis — explaining the ophthalmopathy independent of thyroid hormone levels
✓
C
CD8+ cytotoxic T cells attack both thyroid follicular cells and extraocular muscle fibres simultaneously in a classic organ-non-specific autoimmune pattern
D
Anti-Tg antibodies form immune complexes that deposit in the thyroid and the orbital apex, activating local complement and mast cells to produce both hyperthyroidism and proptosis through an Arthus-type reaction
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A 45-year-old man on long-term amiodarone therapy for recurrent atrial fibrillation is found on routine check to have TSH 0.05 mIU/L and free T4 78 pmol/L. He is euthyroid clinically. Thyroid ultrasound shows a normal-sized, hypervascular gland without nodules. RAIU is 8% (low). Anti-TPO and anti-Tg antibodies are negative. What is the MOST likely type of amiodarone-induced thyroid dysfunction and its primary pathophysiological mechanism?
A
Amiodarone-induced hypothyroidism (AIH) — the massive iodine load from amiodarone causes Wolff-Chaikoff block, preventing T4 synthesis; TSH should be elevated in hypothyroidism
B
Amiodarone-induced thyrotoxicosis Type 1 (AIT-1) — iodine excess from amiodarone provides substrate for autonomous thyroid tissue or triggering in a pre-existing abnormality; RAIU is low because the gland is saturated with iodine but still has residual tracer uptake reflecting active hormone synthesis
C
Amiodarone-induced thyrotoxicosis Type 2 (AIT-2) — a destructive thyroiditis caused by amiodarone's direct toxic effect on follicular cells, releasing pre-formed thyroid hormones; RAIU is near-zero because the gland is damaged and not actively trapping iodine; the gland is hypervascular on Doppler (in contrast to AIT-1 where vascularity increases)
✓
D
Thyrotoxicosis factitia — the patient is self-administering exogenous T4; amiodarone has no thyroid effect at therapeutic doses
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A 30-year-old woman undergoes fine-needle aspiration cytology (FNAC) of a 2.5 cm solitary thyroid nodule. The cytology report reads: 'Bethesda Category V (suspicious for malignancy) — nuclear features including ground-glass chromatin, nuclear grooves, pseudoinclusions, and microfollicular architecture are present; psammoma bodies identified.' Subsequent hemithyroidectomy histology shows follicular architecture only — no papillary fronds. At high power, the nuclei are pale, grooved, and have intranuclear pseudoinclusions. Capsule is intact. No vascular invasion. What is the CORRECT final histological diagnosis and why is architecture alone insufficient to classify this tumour?
A
Follicular carcinoma — follicular architecture + intact capsule is diagnostic; the nuclear features are irrelevant in a follicular-patterned tumour
B
Follicular adenoma — intact capsule with no invasion = benign regardless of nuclear features or psammoma bodies
C
Follicular variant of papillary thyroid carcinoma (FVPTC) — diagnosis of PTC depends on nuclear features (ground-glass chromatin, grooves, pseudoinclusions), NOT architectural pattern; follicular architecture with PTC nuclei = FVPTC, which behaves like PTC (lymph node spread, excellent prognosis) and should be managed as PTC
✓
D
Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) — the intact capsule and absence of invasion, combined with PTC-like nuclei, places this in the NIFTP category which is now classified as a borderline non-malignant lesion requiring lobectomy only
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A 55-year-old man is found to have a solitary 2.8 cm thyroid nodule on ultrasound done for neck pain. He is euthyroid. FNAC is performed: 'Bethesda Category IV (follicular neoplasm/suspicious for follicular neoplasm).' Molecular testing: BRAF wild-type, NRAS mutation detected. What is the CORRECT management and the pathological principle governing the inability to diagnose follicular carcinoma on cytology alone?
A
NRAS mutation confirms benign follicular adenoma — NRAS mutations are exclusively found in benign follicular adenomas and confirm non-malignant biology
B
Diagnostic hemithyroidectomy (lobectomy) is required — follicular carcinoma is diagnosed by demonstrating capsular invasion and/or vascular invasion on histological examination of the complete excised nodule; cytology cannot reveal these architectural features
✓
C
Total thyroidectomy is mandatory — NRAS mutation has 100% specificity for follicular carcinoma and mandates definitive surgical management before histology
D
Repeat FNAC in 6 months — NRAS mutation is a low-risk finding that allows deferring surgery; a Bethesda IV result with NRAS may resolve to a benign lesion on a second aspiration
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A 16-year-old girl with Type 1 diabetes mellitus is brought to the emergency department by her parents. She is drowsy, deeply breathing (Kussmaul respiration), and vomiting. Blood glucose is 32 mmol/L. Arterial blood gas: pH 7.12, PaCO2 18 mmHg, HCO3 7 mEq/L. Urine is strongly positive for ketones. Serum potassium is 5.6 mEq/L. She received insulin via her pump until 4 hours ago when the pump reservoir was found empty. What is the MOST immediately life-threatening electrolyte concern after insulin and fluid are started?
A
Hypernatraemia — the osmotic diuresis in DKA concentrates sodium; insulin drives sodium into cells, worsening hypernatraemia and causing cerebral oedema
B
Hypokalaemia — serum potassium of 5.6 mEq/L is falsely elevated by transcellular shift (acidosis drives K⁺ out of cells); insulin administration + fluid resuscitation + correction of acidosis will rapidly drive potassium INTO cells, potentially causing severe hypokalaemia and fatal cardiac arrhythmia
✓
C
Hyperphosphataemia — insulin reduces phosphate clearance; rising phosphate after insulin causes widespread calcification of cerebral vessels
D
Hypercalcaemia — DKA-associated bone resorption releases calcium; insulin drives calcium into cells, causing hypercalcaemia once baseline is restored
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A 58-year-old man with Type 2 diabetes mellitus of 18 years undergoes routine surveillance. His HbA1c is 9.2% (poorly controlled). Creatinine is 156 µmol/L (eGFR 42 mL/min/1.73m²). Urine protein:creatinine ratio is 680 mg/mmol (heavily proteinuric). Retinal examination shows new vessel formation (proliferative retinopathy). Biopsy of the kidney shows: diffuse mesangial matrix expansion, thickened glomerular basement membranes (GBM), and ovoid nodular deposits at the periphery of the glomerular tuft that stain strongly with PAS and are negative for Congo red. What is the SINGLE MOST IMPORTANT pathophysiological process linking ALL three target-organ complications in this patient?
A
Immune complex deposition in mesangium, GBM, and retinal capillaries from chronic hyperglycaemia-driven immune activation
B
Advanced glycation end-product (AGE) accumulation driving microvascular endothelial dysfunction and basement membrane thickening across all target organs, with mesangial nodule formation (Kimmelstiel-Wilson lesion) being the renal pathological expression of AGE-driven matrix expansion
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C
Mitochondrial reactive oxygen species (ROS) directly damage nuclear DNA in podocytes, retinal pericytes, and Schwann cells through a common mitochondrial pathway — the nodular deposits represent calcium oxalate from mitochondrial dysfunction
D
The HbA1c of 9.2% proves the kidney disease is drug-induced by metformin — metformin accumulates in the kidney at eGFR <45 and directly causes Kimmelstiel-Wilson deposits
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A 50-year-old man presents with fatigue, thirst, polyuria, abdominal pain, and nephrolithiasis (second episode in 2 years). Biochemistry: serum calcium 3.2 mmol/L (elevated), phosphate 0.6 mmol/L (low), intact PTH 310 pg/mL (markedly elevated, normal 10–65). Alkaline phosphatase is 420 IU/L. X-ray shows subperiosteal resorption of radial aspect of index finger and 'salt-and-pepper' skull. Imaging identifies a 1.8 cm parathyroid adenoma. What is the COMBINATION of biochemical and radiological findings that MOST specifically identifies the bone lesion of primary hyperparathyroidism and distinguishes it from myeloma?
A
Elevated ALP + hypercalcaemia — myeloma and hyperparathyroidism both cause hypercalcaemia but myeloma characteristically elevates ALP from extensive bone disease
B
Subperiosteal resorption at the radial aspect of the middle phalanges + PTH-mediated osteoclastic resorption pattern — myeloma causes lytic lesions (punched-out, with NO sclerotic rim) due to osteoclast activation from RANK-L/IL-6, but myeloma does NOT cause subperiosteal resorption or PTH elevation; the salt-and-pepper skull in HPT reflects PTH-mediated small lytic foci from osteoclastic tunnelling
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C
Hypercalcaemia with elevated PTH — myeloma does not cause PTH elevation and the combination of hypercalcaemia + elevated PTH exclusively identifies primary hyperparathyroidism, distinguishing it from all malignancy-related hypercalcaemia
D
Nephrolithiasis — only primary hyperparathyroidism causes nephrolithiasis; myeloma causes renal failure from cast nephropathy, not stones
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A 38-year-old woman presents with a 6-month history of progressive fatigue, weight loss of 9 kg, hyperpigmentation of the buccal mucosa and palmar creases, and postural hypotension. Serum cortisol at 8 AM is 62 nmol/L (severely low). ACTH stimulation test shows no cortisol rise. Plasma ACTH is 1,240 pg/mL (markedly elevated). Autoimmune screen: 21-hydroxylase antibodies positive. Abdominal CT shows small, atrophic adrenal glands bilaterally. What is the DIRECT molecular mechanism linking the 21-hydroxylase antibody to the adrenocortical insufficiency?
A
21-hydroxylase antibodies activate complement on adrenocortical cells, causing lysis of mineralocorticoid-producing cells in the zona glomerulosa specifically, while sparing glucocorticoid-producing cells — only mineralocorticoid deficiency results
B
Anti-21-hydroxylase IgG targets the enzyme 21-hydroxylase (CYP21A2), which catalyses the conversion of 17-hydroxyprogesterone to 11-deoxycortisol (cortisol precursor) and progesterone to 11-deoxycorticosterone (aldosterone precursor); antibody binding impairs enzyme function and, via T-cell-mediated destruction, causes progressive destruction of ALL three cortical zones — resulting in combined glucocorticoid + mineralocorticoid deficiency, which drives the ACTH elevation and hyperpigmentation via MSH cross-reactivity
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C
21-hydroxylase antibodies block ACTH receptors on adrenocortical cells, preventing cortisol stimulation — the high ACTH reflects compensatory pituitary upregulation to overcome the receptor block
D
21-hydroxylase antibody titres reflect chronic stress-induced cortisol depletion and are a consequence, not a cause, of adrenocortical insufficiency; they mark the autoimmune response to cortisol spillage from stressed, necrotic cells
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A 45-year-old woman presents with central obesity, moon face, purple striae, easy bruising, and proximal muscle weakness. Serum cortisol is elevated with loss of diurnal variation. Overnight 1 mg dexamethasone suppression test: cortisol 420 nmol/L (not suppressed). ACTH is elevated at 180 pg/mL. High-dose dexamethasone (8 mg overnight) suppresses cortisol by 65% (>50%). CRH stimulation test shows a robust ACTH and cortisol response. MRI pituitary shows a 4 mm hypointense lesion on dynamic contrast-enhanced imaging. What additional test is MOST important before surgical planning, and why?
A
PET scan — MRI-detected pituitary lesions must be confirmed metabolically before surgery as incidentalomas are common and FDG-PET can discriminate functional from non-functional adenomas
B
Inferior petrosal sinus sampling (IPSS) with CRH stimulation — required to confirm central (pituitary) ACTH source and lateralise the adenoma, because MRI detects only 60% of pituitary microadenomas and a positive IPSS central:peripheral ACTH ratio >2 (basal) or >3 (post-CRH) is required for biochemical confirmation before transsphenoidal surgery
✓
C
Whole-body CT for ectopic ACTH source — high-dose dexamethasone suppression of >50% and CRH response are not reliable distinguishing features; all ACTH-dependent Cushing syndrome requires CT to exclude a lung or mediastinal tumour
D
Adrenal vein sampling — required to determine which adrenal gland is producing excess cortisol in ACTH-dependent Cushing disease
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A 62-year-old woman presents with obstructive jaundice, painless progressive, and a 7 kg weight loss over 2 months. She reports a new onset of diabetes mellitus 5 months ago. On examination, a non-tender, palpable gallbladder is noted (Courvoisier sign). CT abdomen shows a 3.8 cm hypodense mass in the head of the pancreas, dilating both the common bile duct (double-duct sign) and main pancreatic duct. CA 19-9 is 840 U/mL. Which pathological feature of this tumour BEST explains the paradox of both a new-onset diabetes and obstructive jaundice occurring simultaneously?
A
The tumour replaces the islets of Langerhans causing autoimmune insulitis (Type 1 DM) while directly compressing the bile duct (obstructive jaundice)
B
Pancreatic ductal adenocarcinoma in the head of the pancreas directly obstructs the common bile duct (jaundice + Courvoisier sign) and simultaneously obstructs the main pancreatic duct, causing upstream destruction of exocrine and endocrine pancreas — islet loss and impaired beta-cell function produce new-onset diabetes, while the desmoplastic stroma promotes additional islet dysfunction through paracrine mechanisms
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C
The diabetes is a paraneoplastic endocrine syndrome caused by ACTH-like peptide secretion from a neuroendocrine component within the tumour; the jaundice is from hepatic metastases, not bile duct obstruction
D
The new-onset diabetes is caused by haematogenous liver metastases from the pancreatic cancer reducing hepatic insulin clearance, while the bile duct compression is from hepatic metastases, not a primary head mass
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A 5-year-old boy presents with an abdominal mass that is found to cross the midline on examination. He has periorbital bruising ('raccoon eyes') and bilateral proptosis. CT shows a right suprarenal calcified mass extending across the midline with liver metastases. Urine VMA and HVA are markedly elevated. Bone marrow biopsy shows clusters of small blue round cells forming rosette-like structures. N-MYC gene amplification is detected. Which statement about the MOLECULAR SIGNIFICANCE of N-MYC amplification in this condition is MOST accurate?
A
N-MYC amplification activates p53-mediated apoptosis, making this tumour exquisitely sensitive to standard platinum-based chemotherapy with >90% cure rate regardless of stage
B
N-MYC amplification is the single most important adverse prognostic marker in neuroblastoma — it drives rapid tumour proliferation, blocks neural differentiation, and is associated with Stage 4 disease, poor response to chemotherapy, and <30% 5-year survival in amplified vs ~90% in non-amplified localised disease
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C
N-MYC amplification causes paradoxical spontaneous regression — amplified tumours activate an intrinsic maturation programme converting neuroblast to ganglioneuroma, the same process that causes spontaneous regression in Stage 4S disease
D
N-MYC amplification is a favourable prognostic marker in children <18 months because the infantile immune system can neutralise amplified MYC protein through maternal antibody transfer
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