MCQ:

Question 1

A 65-year-old man with small-cell lung cancer develops hyponatraemia (Na⁺ 118 mmol/L), urine osmolality 520 mOsm/kg and euvolaemia. Which ectopic hormone production BEST explains this?

Accepted Answer

ADH → SIADH — SIADH from ectopic ADH secretion is the classic paraneoplastic syndrome of SCLC, giving euvolaemic hyponatraemia with high urine osmolality and low serum osmolality. PTHrP causes hypercalcaemia; ectopic ACTH causes Cushing's features.

Question 2

Which tumor marker combination MOST improves detection of early hepatocellular carcinoma (HCC)?

Accepted Answer

AFP + Des-γ-carboxyprothrombin (DCP/PIVKA-II) — DCP (PIVKA-II) combined with AFP significantly improves early HCC detection sensitivity. CEA and CA 19-9 are GI markers; CA 125/HE4 are ovarian markers.

Question 3

Hypercalcaemia in squamous-cell lung carcinoma WITHOUT bone metastases is caused by:

Accepted Answer

PTH-related peptide (PTHrP) — PTHrP mediates humoral hypercalcaemia of malignancy (HHM) by binding PTH receptors. True ectopic PTH is exceedingly rare. PTHrP suppresses endogenous PTH, distinguishing HHM from primary hyperparathyroidism.

Question 4

Anti-VGCC antibodies, proximal muscle weakness improving with repeated use, autonomic dysfunction in a SCLC patient. Diagnosis?

Accepted Answer

Lambert-Eaton Myasthenic Syndrome (LEMS) — LEMS: anti-voltage-gated calcium channel antibodies impair presynaptic ACh release. Associated with SCLC. Unlike MG, strength paradoxically improves with repeated stimulation (post-tetanic potentiation).

Question 5

Which tumor markers monitor treatment response in non-seminomatous testicular germ cell tumours?

Accepted Answer

AFP + β-hCG + LDH — AFP (yolk-sac elements), β-hCG (choriocarcinoma elements), and LDH are the key markers for NSGCT staging, prognosis and treatment monitoring. Pure seminomas rarely produce AFP.

Question 6

Ectopic ACTH syndrome from a lung tumour characteristically shows:

Accepted Answer

Very high cortisol + very high ACTH + hypokalaemic alkalosis, NOT suppressed by high-dose DST — Ectopic ACTH: very high ACTH → bilateral adrenal hyperplasia → very high cortisol, hypokalaemia (mineralocorticoid effect), metabolic alkalosis. Does NOT suppress with high-dose dexamethasone — distinguishing it from pituitary Cushing's disease.

Question 7

CA 125 is the primary serum marker for monitoring:

Accepted Answer

Epithelial ovarian cancer — CA 125 is used to monitor treatment response and detect relapse in epithelial ovarian cancer. HE4 combined with CA 125 (ROMA algorithm) improves preoperative malignancy risk stratification.

Question 8

Which marker is elevated in medullary thyroid carcinoma (MTC) and is used for post-operative surveillance?

Accepted Answer

Calcitonin + CEA — MTC arises from parafollicular C cells (which produce calcitonin). Calcitonin is the primary marker for diagnosis and surveillance; CEA is a secondary marker. Both rise with tumour recurrence.

Question 9

A 28-year-old woman has secondary amenorrhoea, galactorrhoea, prolactin 200 ng/mL, low FSH and LH. Most likely diagnosis?

Accepted Answer

Prolactinoma — Prolactin 200 ng/mL with galactorrhoea and suppressed gonadotropins strongly indicates a prolactinoma. Hyperprolactinaemia suppresses GnRH pulsatility → anovulation. POF has high FSH; PCOS has normal/high LH:FSH ratio; hypothalamic amenorrhoea has low normal prolactin.

Question 10

A 35-year-old man: infertility, gynaecomastia, small firm testes, 47,XXY karyotype, elevated FSH/LH, low testosterone. Diagnosis?

Accepted Answer

Klinefelter syndrome — Klinefelter (47,XXY): primary testicular failure → hypergonadotropic hypogonadism (high FSH/LH, low testosterone), small firm testes, azoospermia, gynaecomastia. Kallmann is hypogonadotropic with anosmia.

Question 11

A young man has anosmia, absent secondary sexual development, low LH/FSH/testosterone. MRI shows absent olfactory bulbs. Diagnosis?

Accepted Answer

Kallmann syndrome — Kallmann syndrome: defective GnRH neuron migration → hypogonadotropic hypogonadism + anosmia (absent olfactory bulbs on MRI). Treatment: pulsatile GnRH or gonadotropin replacement for fertility.

Question 12

Turner syndrome (45,X0) shows which hormonal pattern?

Accepted Answer

High FSH, high LH, low oestrogen — Turner syndrome: streak gonads → primary ovarian failure → very high FSH and LH (hypergonadotropic hypogonadism), low oestrogen, primary amenorrhoea. Short stature, webbed neck, bicuspid aortic valve, coarctation of aorta.

Question 13

21-hydroxylase deficiency, the MOST common cause of congenital adrenal hyperplasia, leads to:

Accepted Answer

Deficient cortisol and aldosterone, excess androgens — 21-hydroxylase deficiency blocks cortisol and aldosterone synthesis. The shunted pathway results in excess androgens, causing virilisation in females (ambiguous genitalia) and precocious puberty in males. Salt-wasting (aldosterone deficiency) is common.

Question 14

A premenopausal woman presents with hirsutism, acne, and irregular periods. Androgen levels are elevated, but LH/FSH ratio is normal. Ovarian ultrasound shows polycystic ovaries. Diagnosis?

Accepted Answer

Polycystic ovary syndrome (PCOS) — PCOS is diagnosed using the Rotterdam criteria (2 of 3): oligo/anovulation, polycystic ovaries on ultrasound, and clinical/biochemical hyperandrogenism. The normal LH/FSH ratio differentiates it from hypothalamic amenorrhoea. CAH and tumours are less common and usually have more severe hyperandrogenism.

Question 15

A patient with primary hypothyroidism will have:

Accepted Answer

High TSH, low Free T4 — Primary hypothyroidism is failure of the thyroid gland itself. The pituitary tries to compensate by increasing TSH production, leading to high TSH and low Free T4. Central hypothyroidism has low/normal TSH with low Free T4.

Question 16

Infertility in a male with a prolactinoma is due to:

Accepted Answer

Suppression of GnRH pulsatility by hyperprolactinaemia — Hyperprolactinaemia suppresses pulsatile GnRH release from the hypothalamus, leading to low LH and FSH (hypogonadotropic hypogonadism), and consequently low testosterone and impaired spermatogenesis. Testicular size is usually normal.

Question 17

A 70-year-old man with type 2 diabetes, hypertension, and recent weight gain develops Cushingoid features. Morning cortisol is 800 nmol/L (normal <500). ACTH is low. What is the MOST likely diagnosis?

Accepted Answer

Adrenal adenoma producing cortisol — Low ACTH with high cortisol indicates primary adrenal pathology. A unilateral adrenal adenoma or carcinoma secreting cortisol is the most likely cause of Cushing's syndrome in this scenario. Cushing's disease (pituitary) would have high ACTH.

Question 18

Secondary adrenal insufficiency is MOST accurately diagnosed using which test?

Accepted Answer

Short Synacthen test (SST) — The Short Synacthen Test (SST) assesses the adrenal glands' ability to respond to ACTH. A normal response is a cortisol level 500-550 nmol/L 30-60 minutes after Synacthen injection. ITT is the gold standard for assessing the entire HPA axis (including pituitary response) but is more complex and risky.

Question 19

Which of the following is NOT a typical feature of Graves' disease?

Accepted Answer

Toxic nodular goitre — Graves' disease is an autoimmune disorder causing diffuse toxic goitre and hyperthyroidism, typically mediated by TSH receptor antibodies (TRAb). Exophthalmos is a characteristic feature. Toxic nodular goitre (Plummer's disease) is a different cause of hyperthyroidism.

Question 20

A patient presents with fatigue, weight gain, constipation, and cold intolerance. Lab results show TSH 25 mIU/L (normal 0.4-4.0) and Free T4 8 pmol/L (normal 10-22). What is the most appropriate next step?

Accepted Answer

Start levothyroxine therapy immediately — The TSH is significantly elevated and Free T4 is low, confirming primary hypothyroidism. Levothyroxine therapy should be initiated promptly. TPO antibodies can confirm autoimmune aetiology but don't change initial management. TRH test is rarely used now. Repeating tests is unnecessary given the clear diagnosis.

Question 21

Diabetes insipidus (central) — which findings confirm it?

Accepted Answer

Low urine osmolality (<300 mOsm/kg) + high serum osmolality (>295 mOsm/kg) + significant thirst — Central DI: lack of ADH → inability to concentrate urine. Result: polyuria of dilute urine (low urine osmolality), leading to dehydration and hypernatraemia (high serum osmolality) if water intake is insufficient. Thirst is prominent. Water deprivation test is diagnostic.

Question 22

Secondary adrenal insufficiency is characterized by:

Accepted Answer

Low ACTH, low cortisol, low aldosterone — Secondary adrenal insufficiency is due to pituitary (ACTH) or hypothalamic (CRH) failure. This leads to low ACTH and consequently low cortisol production by the adrenal cortex. Aldosterone production is primarily controlled by the renin-angiotensin system and is usually preserved, though it can be affected if CRH deficiency is severe.

Question 23

A patient has high TSH and normal Free T4. This is MOST consistent with:

Accepted Answer

Subclinical hypothyroidism — Subclinical hypothyroidism is defined as a normal Free T4 level with an elevated TSH. It indicates early thyroid dysfunction. Primary hypothyroidism has low Free T4; central hypothyroidism has low/normal TSH with low Free T4.

Question 24

Which of the following hormone levels would be expected in a patient with Cushing's disease (pituitary adenoma)?

Accepted Answer

High ACTH, high cortisol — Cushing's disease is caused by a pituitary adenoma secreting excess ACTH. This excess ACTH stimulates the adrenal glands to produce excessive cortisol. Therefore, both ACTH and cortisol levels are high.

Question 25

Corrected calcium formula: albumin is 22 g/L, measured Ca²⁺ is 2.0 mmol/L. Corrected Ca²⁺ is approximately (add 0.02 per g/L below 40)?

Accepted Answer

2.36 mmol/L — Corrected Ca = Measured Ca + 0.02 × (40 − Measured Albumin). Corrected Ca = 2.0 + 0.02 × (40 − 22) = 2.0 + 0.02 × 18 = 2.0 + 0.36 = 2.36 mmol/L. Hypoalbuminaemia lowers total calcium but ionised (active) calcium may be normal. Always correct before interpreting calcium.

Question 26

Cardiac troponin (cTnI or cTnT) elevation is MOST specific for:

Accepted Answer

Myocardial necrosis (irreversible cardiomyocyte damage) — Cardiac troponins are released from irreversibly damaged cardiomyocytes and are the most sensitive/specific markers of MI. Rise 3–6 h post-infarct, peak 12–24 h, persist 7–14 days (cTnT). High-sensitivity troponin (hs-cTn) detects very small amounts and permits early rule-in/rule-out at 0/1–2 hours.

Question 27

Haemolytic jaundice is differentiated from hepatocellular jaundice by:

Accepted Answer

Elevated unconjugated bilirubin + high LDH + low haptoglobin + reticulocytosis — Haemolysis: unconjugated (indirect) hyperbilirubinaemia, elevated LDH (from RBC lysis), low haptoglobin (binds free Hb), reticulocytosis. Liver disease = mixed or conjugated hyperbilirubinaemia + high transaminases. Pre-hepatic (haemolytic) → dark urine (urobilinogen) but NO pale stools.

Question 28

Which is MORE sensitive AND specific for acute pancreatitis — amylase or lipase?

Accepted Answer

Lipase (more sensitive AND more specific; remains elevated longer than amylase) — Lipase: more sensitive (~95%) and more specific for acute pancreatitis than amylase. Lipase remains elevated 7–14 days vs amylase 3–5 days. Amylase is elevated in non-pancreatic conditions (salivary glands, perforated ulcer, renal failure). Lipase is preferred.

Question 29

Anaemia of CKD is characterised by:

Accepted Answer

Normochromic normocytic anaemia + EPO deficiency + high hepcidin → functional iron restriction (normal/high ferritin, low serum iron) — CKD anaemia: reduced EPO (failing kidneys), chronic inflammation → elevated hepcidin → ferroportin inhibition → iron trapped in stores → low serum iron but normal/high ferritin. Normochromic normocytic. Treatment: erythropoiesis-stimulating agents (ESA) + IV iron.

Question 30

In SIADH (syndrome of inappropriate ADH secretion), which pattern is expected?

Accepted Answer

Hyponatraemia, low plasma osmolality, concentrated urine (high urine osmolality and Na), euvolaemia — SIADH: excess ADH → water retention without Na retention → euvolaemic hyponatraemia, low plasma osmolality (<275), concentrated urine (osmolality 100 mOsm/kg, typically plasma osmolality), urine Na 20 mmol/L. Causes: SCLC, CNS disorders, drugs, pulmonary disease.

Question 31

Which lipoprotein is MOST atherogenic and is the primary LDL-lowering target?

Accepted Answer

LDL-cholesterol (and non-HDL-C) — LDL-cholesterol carries cholesterol to peripheral tissues and arterial walls → atherogenesis. LDL-C is the primary target for cardiovascular risk reduction (statins). Non-HDL-C (total − HDL) is an alternative target, capturing VLDL remnants and IDL as well.

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