AMC MCQ (CAT) endocrinology questions

Gestational diabetes is diagnosed at 24-28 weeks using a 75 g OGTT if any one of the following is met: fasting glucose ≥5.1 mmol/L, 1-hour glucose ≥10.0 mmol/L, or 2-hour glucose ≥8.5 mmol/L. Only one abnormal value is required for diagnosis, unlike the two-value requirement for non-pregnant diabetes diagnosis. In this case, the 1-hour value of 10.8 mmol/L exceeds the 10.0 mmol/L threshold, which is diagnostic regardless of the fasting and 2-hour results. This reflects the ADIPS (Australasian Diabetes in Pregnancy Society) criteria adopted in Australian antenatal guidelines.

• A. Only one abnormal value among the three is required for diagnosis; the fasting value being normal does not exclude gestational diabetes.
• B. The 1-hour value of 10.8 mmol/L meets the diagnostic threshold for gestational diabetes.
• D. There is no intermediate category of impaired glucose tolerance in pregnancy; the OGTT result is diagnostic as given.
• E. No confirmatory testing on a separate day is required in pregnancy; a single qualifying OGTT value is diagnostic.

Aboriginal and Torres Strait Islander adults have a substantially higher prevalence and earlier onset of type 2 diabetes compared with the general Australian population. The RACGP Red Book recommends that screening for type 2 diabetes in this population should begin from age 18 years (compared with age 40 in the general population), using fasting glucose or HbA1c, and be repeated every 3 years, or annually if risk factors are present. This reflects the need for earlier and more frequent case-finding to reduce the burden of undiagnosed diabetes and its complications in this population. An OGTT is not mandated as the first-line test; fasting glucose or HbA1c remain appropriate initial options.

• B. Age 40 is the general population threshold; Aboriginal and Torres Strait Islander people require earlier screening from age 18.
• C. Screening should be proactive and risk-based rather than waiting for symptoms to develop.
• D. Fasting glucose or HbA1c are appropriate first-line tests; an OGTT is not mandatory for initial screening.
• E. Screening should begin now at age 33, not be deferred further, given the recommended starting age of 18.

This patient has severe diabetic ketoacidosis, with pH <7.1, marked hyperglycaemia, significant ketonaemia and clinical evidence of hypovolaemia (tachycardia, hypotension, drowsiness). The first priority in DKA management is restoring circulating volume with intravenous isotonic sodium chloride, as the patient is significantly dehydrated and fluid resuscitation improves tissue perfusion and begins to lower glucose even before insulin is started. Insulin infusion should be commenced after initial fluid resuscitation has begun, typically within the first hour, to avoid precipitating cardiovascular collapse or a rapid osmotic shift. Bicarbonate is not routinely used in DKA, as it can worsen intracellular acidosis and paradoxical CNS acidosis, and is reserved for extreme, life-threatening acidosis with specialist involvement.

• B. Insulin infusion is commenced after initial fluid resuscitation is underway, not as the very first step.
• C. Dextrose is not given initially; isotonic sodium chloride is used first to restore volume and is withheld until glucose falls to a target range.
• D. Bicarbonate is not routinely recommended in DKA and may worsen outcomes; it is not the first step.
• E. Subcutaneous insulin is not used in DKA because absorption is unreliable in a dehydrated, acidotic patient.

SGLT2 inhibitors such as empagliflozin promote glycosuria and can precipitate ketoacidosis with only mildly elevated or even near-normal glucose levels, a phenomenon termed euglycaemic DKA. This occurs because the drug lowers the renal glucose threshold, masking the degree of hyperglycaemia while ongoing lipolysis and ketogenesis continue, often triggered by reduced carbohydrate intake, illness, or dehydration as in this patient's recent gastroenteritis. The combination of significant metabolic acidosis (pH 7.21, bicarbonate 14 mmol/L) and elevated ketones (4.1 mmol/L) despite a glucose of only 10.2 mmol/L is the hallmark of this presentation, and SGLT2 inhibitors should be withheld immediately with standard DKA management otherwise initiated. Clinicians must maintain a high index of suspicion for this diagnosis in SGLT2 inhibitor users with unexplained acidosis, even when glucose is unremarkable.

• A. Starvation ketosis does not usually cause this degree of acidosis (pH 7.21, bicarbonate 14 mmol/L).
• C. Metformin-associated lactic acidosis does not typically cause this degree of ketonaemia and usually occurs with renal impairment or hypoperfusion.
• D. There is no information given suggesting significant renal impairment as the primary cause of this acidosis.
• E. There is no history of alcohol use provided to support alcoholic ketoacidosis.

This presentation, marked hyperglycaemia, minimal ketosis, near-normal pH, elevated serum osmolality and significant dehydration in an elderly patient, is consistent with hyperosmolar hyperglycaemic state (HHS) rather than DKA. The immediate priority in HHS is fluid resuscitation with intravenous isotonic sodium chloride to correct the profound volume deficit and hyperosmolality, as these patients are typically more dehydrated than those with DKA and rapid glucose-lowering with insulin before adequate fluid replacement can cause dangerous shifts in osmolality and cardiovascular collapse. Insulin is generally withheld or given at a lower rate until fluid resuscitation has commenced and glucose is falling, since fluids alone often reduce glucose substantially. Hypotonic fluids are avoided initially because they can cause a rapid fall in osmolality, raising the risk of cerebral oedema.

• A. Insulin is not the immediate priority in HHS; it is commenced after or alongside fluid resuscitation, usually at a lower rate than in DKA.
• B. Subcutaneous insulin bolus is inappropriate and rapid glucose correction risks dangerous osmotic shifts.
• C. Hypotonic fluid is not first-line; isotonic sodium chloride is preferred initially to avoid a too-rapid fall in serum osmolality.
• D. Bicarbonate is not indicated as the pH is near normal and HHS is not primarily an acidotic state.

Sick day management for type 1 diabetes requires continuing basal insulin even when oral intake is reduced, because stopping basal insulin risks rapid progression to diabetic ketoacidosis. Rapid-acting insulin should be continued and supplemented with correction doses based on frequent blood glucose and ketone monitoring, typically every 2-4 hours. Fluid and carbohydrate intake should be maintained with easily tolerated options such as sugary drinks or icy poles if solid food is not tolerated. Insulin should never be omitted during intercurrent illness in type 1 diabetes, as this is a major precipitant of DKA.

• A. Reducing basal insulin during illness increases the risk of hyperglycaemia and ketosis, which typically rise despite reduced food intake.
• B. Omitting basal insulin is dangerous even if bolus doses are adjusted for reduced intake.
• C. Stopping all insulin removes basal cover and risks rapid onset of ketosis and DKA.
• E. Sulfonylureas are not used in type 1 diabetes, which is characterised by absolute insulin deficiency.

In an unconscious patient with severe hypoglycaemia where intravenous access cannot be promptly obtained, intramuscular glucagon 1 mg is the appropriate emergency treatment according to Therapeutic Guidelines. Glucagon stimulates hepatic glycogenolysis and gluconeogenesis, raising blood glucose within 10-15 minutes, and does not require IV access. Oral glucose is contraindicated in an unconscious patient due to aspiration risk. Intravenous dextrose is preferred when access is readily available, but treatment should not be delayed while repeated IV attempts are made.

• A. Naloxone treats opioid toxicity, not hypoglycaemia, and is not indicated here.
• B. Withholding treatment is dangerous; severe hypoglycaemia requires immediate correction regardless of insulin dosing.
• C. Delaying treatment until IV access is secured is inappropriate when IM glucagon can be given immediately.
• D. Oral administration risks aspiration in an unconscious patient and should never be used.

SGLT2 inhibitors such as dapagliflozin are the preferred second-line agent in patients with type 2 diabetes and coexisting heart failure, as large trials have demonstrated reductions in heart failure hospitalisation and cardiovascular death independent of glycaemic effect. They act by inhibiting glucose reabsorption in the proximal renal tubule, producing glycosuria, natriuresis and modest weight loss. Current eTG and cardiology guidelines recommend SGLT2 inhibitors in this setting regardless of baseline HbA1c, given their proven cardiorenal benefit. This patient's eGFR of 62 mL/min/1.73m² is adequate for initiation.

• B. Pioglitazone causes fluid retention and is contraindicated in heart failure as it can precipitate decompensation.
• C. Sitagliptin is weight-neutral but lacks proven cardiovascular or heart failure benefit compared with SGLT2 inhibitors.
• D. Gliclazide offers no cardiovascular benefit and carries a hypoglycaemia risk without addressing heart failure.
• E. Acarbose has a weak glucose-lowering effect and no evidence for benefit in heart failure.

GLP-1 receptor agonists such as semaglutide are associated with a small but recognised increased risk of acute pancreatitis, and patients should be counselled to seek urgent review if they develop severe, persistent abdominal pain, particularly radiating to the back. The mechanism is not fully established but may relate to effects on exocrine pancreatic secretion and ductal cell proliferation. Alongside this risk, GLP-1 agonists provide significant benefits including weight loss, improved glycaemic control and cardiovascular risk reduction. Patients with a history of pancreatitis should generally avoid this drug class.

• A. Peripheral oedema is not a characteristic adverse effect of GLP-1 agonists; it is more associated with agents such as thiazolidinediones.
• B. Hepatotoxicity is not a characteristic concern with GLP-1 receptor agonists.
• C. Bradycardia is not a recognised major adverse effect of this drug class.
• D. GLP-1 agonists are not primarily associated with progressive renal impairment; they are generally considered renally favourable.

Sulfonylureas such as gliclazide are renally excreted and carry a significant risk of hypoglycaemia in older patients, particularly when renal function declines, as reduced clearance prolongs drug action. This patient's symptoms of afternoon confusion and sweating are consistent with hypoglycaemic episodes, and her HbA1c of 6.4% indicates she is already over-treated relative to a reasonable target in this frail population. Guidelines recommend reducing or ceasing sulfonylureas when eGFR falls, especially in elderly patients at higher falls risk from hypoglycaemia. Ongoing use at this dose places her at risk of further falls and serious harm.

• A. Continuing unchanged therapy ignores clear evidence of symptomatic hypoglycaemia and declining renal clearance.
• B. A higher-dose formulation would further increase hypoglycaemia risk rather than reduce it.
• D. Increasing the dose would worsen her hypoglycaemia risk and is inappropriate given her symptoms and HbA1c.
• E. Adding metformin does not address the immediate hypoglycaemia risk from gliclazide and metformin has its own renal dose limits.

Consistently elevated pre-breakfast glucose with normal overnight readings (7-8 mmol/L at 3 am) and acceptable pre-lunch and pre-dinner values suggests inadequate basal insulin coverage in the early morning hours rather than a dawn phenomenon from overcorrection or waning insulin action overnight. Since the overnight 3 am readings are not low, this is not the Somogyi phenomenon (rebound hyperglycaemia after nocturnal hypoglycaemia), which would otherwise be a key differential. The appropriate adjustment is to increase the evening glargine dose to improve basal coverage through to the morning, rather than adjusting a mealtime bolus which would not address the fasting pattern.

• B. The previous evening's dinner aspart has resolved well before the following morning and does not explain a sustained fasting pattern.
• C. Decreasing glargine would worsen the elevated fasting glucose seen each morning.
• D. Decreasing breakfast aspart would not affect pre-breakfast readings and would worsen post-breakfast control.
• E. Breakfast aspart affects post-breakfast glucose, not the pre-breakfast fasting reading.

The RACGP Red Book recommends annual screening for diabetic complications in all patients with type 2 diabetes, comprising dilated fundus examination (or retinal photography) for retinopathy, urine albumin:creatinine ratio for nephropathy, foot examination (including monofilament and pulses) for neuropathy and peripheral vascular disease, and a lipid profile for cardiovascular risk. This comprehensive annual review allows early detection and intervention before symptoms develop, as diabetic complications are frequently asymptomatic in early stages. HbA1c monitoring is done more frequently (every 3-6 months) and is separate from this annual complication screen.

• A. Nerve conduction studies are not part of routine annual screening; monofilament testing is the standard screening tool.
• C. An oral glucose tolerance test is used for diagnosis, not for monitoring an already diagnosed diabetic or screening for complications.
• D. Screening only the eyes misses asymptomatic renal, foot and cardiovascular risk that require annual assessment.
• E. Albumin:creatinine ratio alone omits retinal, foot and lipid screening required annually.

A persistently elevated ACR (microalbuminuria) on two of three samples over 3-6 months, in the absence of a confounding cause such as infection, confirms diabetic nephropathy. Therapeutic Guidelines recommend initiating an ACE inhibitor (or angiotensin receptor blocker if ACE inhibitor intolerant) regardless of blood pressure, as these agents reduce intraglomerular pressure and slow progression of albuminuria and renal decline. SGLT2 inhibitors provide additional renoprotection but are used as an adjunct to, not a substitute for, renin-angiotensin system blockade. Renal biopsy is reserved for atypical presentations, not typical diabetic nephropathy.

• A. Severe protein restriction is not recommended and may contribute to malnutrition without proven renal benefit at this stage.
• B. SGLT2 inhibitors are added to, not substituted for, ACE inhibitor therapy in diabetic nephropathy.
• D. Biopsy is unnecessary in a typical presentation of diabetic nephropathy with a clear clinical picture.
• E. Delaying treatment risks progression; confirmed microalbuminuria warrants immediate pharmacological intervention.

Reduced monofilament sensation indicates loss of protective sensation and places the patient at high risk of unnoticed trauma leading to foot ulceration. Management focuses on prevention: referral to a podiatrist for ongoing foot care, patient education on daily self-inspection, appropriate well-fitting footwear, and avoiding walking barefoot. Pedal pulses being intact confirms adequate arterial supply but does not exclude neuropathic risk, as neuropathy and vascular disease are assessed separately. Pharmacological treatment for painful neuropathy is not indicated here as the patient has sensory loss rather than painful symptoms.

• A. Palpable pulses assess vascular status only; they do not negate the risk from sensory neuropathy.
• B. Doppler studies are not indicated as pulses are palpable and there are no ischaemic symptoms or signs.
• C. Pregabalin treats painful neuropathy symptoms, not asymptomatic sensory loss, and does not address ulcer prevention.
• E. Annual review alone without intervention is inadequate once loss of protective sensation is identified.

The clinical picture of diffuse goitre with bruit, ophthalmopathy, tachycardia and biochemical hyperthyroidism is classic for Graves' disease, an autoimmune condition caused by stimulating TSH receptor antibodies. These antibodies activate the TSH receptor, causing diffuse glandular hyperplasia and increased hormone synthesis, which is reflected as diffusely increased uptake on a technetium or iodine uptake scan. Thyroid bruit and ophthalmopathy are features specific to Graves' disease and not seen in toxic nodular goitre or thyroiditis. A focal area of increased uptake would suggest a toxic adenoma rather than Graves' disease.

• A. Diffusely reduced uptake with negative antibodies suggests thyroiditis (e.g. subacute or postpartum), not Graves' disease.
• B. Elevated calcitonin with a cold nodule suggests medullary thyroid carcinoma, unrelated to this presentation.
• C. Thyroglobulin antibodies and patchy reduced uptake suggest Hashimoto's thyroiditis, not Graves' disease.
• E. A focal uptake pattern with negative antibodies is typical of a toxic adenoma, not Graves' disease.

Carbimazole can cause agranulocytosis, a rare but potentially life-threatening idiosyncratic adverse effect that typically presents with fever, sore throat, mouth ulcers or other signs of infection, usually within the first 3 months of treatment. Patients must be advised to stop the drug immediately and seek urgent medical assessment with a full blood count if these symptoms occur, rather than waiting for a scheduled routine blood test, as agranulocytosis can develop rapidly between tests. Routine blood count monitoring is not sensitive enough to reliably detect this complication before symptoms occur, making patient education on symptom recognition the most critical safety measure.

• A. Photosensitivity is not a recognised major adverse effect of carbimazole.
• B. Agranulocytosis is not prevented by taking carbimazole with food; this relates to minimising gastrointestinal upset only.
• C. Mild nausea is a common, minor side effect and does not require cessation of therapy.
• D. Routine 6-monthly blood counts do not reliably detect agranulocytosis, which can occur suddenly between tests.

This presentation, with fever, tachyarrhythmia, altered mental state and gastrointestinal symptoms in a patient with underlying Graves' disease precipitated by the stress of surgery, is consistent with thyroid storm, a life-threatening endocrine emergency. Initial management should not await biochemical confirmation and includes a beta-blocker (propranolol) to control adrenergic symptoms, a thionamide (propylthiouracil is preferred acutely as it also blocks peripheral T4 to T3 conversion) to reduce hormone synthesis, and corticosteroids (hydrocortisone) to block peripheral conversion and cover possible relative adrenal insufficiency. Supportive care with fluids and cooling is also required, but definitive thyroid-specific therapy must be started promptly alongside this.

• B. Thyroidectomy is not performed in the acute unstable setting of thyroid storm and carries excessive risk.
• C. Radioactive iodine is contraindicated in thyroid storm and is not an emergency intravenous therapy.
• D. Treatment must not be delayed pending biochemistry in a clinically evident life-threatening presentation.
• E. Oral carbimazole alone without beta-blockade and steroids is insufficient for this emergency and delays necessary multi-agent therapy.

Subacute (de Quervain) thyroiditis is a self-limiting condition, often following a viral upper respiratory illness, characterised by a painful, tender, firm goitre, markedly elevated ESR and CRP, and a transient hyperthyroid phase caused by release of preformed hormone from damaged follicular cells. TSH receptor antibodies are typically negative, distinguishing it from Graves' disease, and thyroid pain and systemic inflammatory markers are the key differentiating clinical features. The hyperthyroid phase is usually followed by a transient hypothyroid phase before recovery, and management is supportive with analgesia, with corticosteroids reserved for severe cases.

• A. Toxic multinodular goitre typically occurs in older patients with a non-tender nodular gland and does not cause marked ESR elevation.
• B. Acute suppurative thyroiditis presents with marked local erythema, fluctuance and systemic sepsis, usually in immunocompromised patients, and is rare.
• D. Hashimoto's thyroiditis usually presents with a non-tender goitre and hypothyroidism or euthyroidism, not an acutely painful gland with transient hyperthyroidism.
• E. Graves' disease typically presents with a non-tender goitre and positive TSH receptor antibodies, not a painful gland with negative antibodies.

Propylthiouracil is preferred over carbimazole (and its active metabolite methimazole) during the first trimester of pregnancy because carbimazole is associated with a small increased risk of congenital malformations, including aplasia cutis and choanal or oesophageal atresia, when exposure occurs during early organogenesis. Propylthiouracil carries a risk of hepatotoxicity, so therapy is typically switched to carbimazole after the first trimester once organogenesis is complete. Radioactive iodine is absolutely contraindicated in pregnancy due to fetal thyroid ablation, and levothyroxine would worsen rather than treat hyperthyroidism.

• A. Methimazole is the active metabolite of carbimazole and carries the same first-trimester teratogenic risk.
• B. Radioactive iodine is contraindicated throughout pregnancy as it crosses the placenta and ablates the fetal thyroid.
• C. Carbimazole is avoided in the first trimester due to the risk of teratogenicity including aplasia cutis and choanal atresia.
• E. Levothyroxine treats hypothyroidism and would exacerbate the biochemical hyperthyroidism present in this patient.

A low morning cortisol with an elevated ACTH strongly suggests primary adrenal insufficiency, but the diagnosis should be confirmed with a short synacthen test, which measures serum cortisol before and 30-60 minutes after synthetic ACTH administration. A failure of cortisol to rise appropriately confirms adrenal failure. This test is safe, quick and is the standard confirmatory investigation per Therapeutic Guidelines. The insulin tolerance test is used for assessing the hypothalamic-pituitary-adrenal axis in suspected secondary insufficiency but carries risk and is rarely used in general practice.

• B. Used to assess growth hormone or ACTH reserve in suspected pituitary disease, not first-line for confirming primary adrenal insufficiency, and carries hypoglycaemia risk.
• C. Used to investigate diabetes insipidus, not adrenal insufficiency.
• D. Not validated as a confirmatory test for adrenal insufficiency; salivary cortisol is used mainly in Cushing's screening.
• E. Used to diagnose Cushing's syndrome, the opposite clinical problem.

This patient is in adrenal crisis, precipitated by an intercurrent illness and inability to take oral steroids, presenting with hypotension, tachycardia and hypoglycaemia. Immediate treatment is intravenous hydrocortisone 100 mg as a bolus, followed by aggressive intravenous fluid resuscitation with normal saline and correction of hypoglycaemia, with further hydrocortisone 50-100 mg every 6 hours or by infusion. Oral therapy is inappropriate because vomiting and shock prevent reliable absorption. Fludrocortisone is not used acutely because high-dose hydrocortisone already provides sufficient mineralocorticoid activity.

• B. Fludrocortisone is not used in acute crisis; high-dose hydrocortisone provides adequate mineralocorticoid effect.
• C. Dexamethasone lacks mineralocorticoid activity and is not the preferred agent in adrenal crisis.
• D. Adrenaline is not indicated here; this is not anaphylaxis, and the hypotension is due to glucocorticoid deficiency.
• E. Oral administration is unreliable in a vomiting, shocked patient and the dose is inadequate for crisis management.

Patients on long-term corticosteroid therapy have a suppressed hypothalamic-pituitary-adrenal axis and cannot mount an adequate endogenous cortisol response to the physiological stress of major surgery, risking an adrenal crisis. Therapeutic Guidelines recommend supplemental intravenous hydrocortisone, typically 50-100 mg at induction for major surgery, with continued stress dosing and tapering back to the patient's maintenance dose over one to two days as recovery progresses. Simply continuing the usual oral dose is inadequate because it does not cover the markedly increased cortisol demand of surgical stress. Abruptly stopping corticosteroids before surgery risks precipitating acute adrenal insufficiency.

• A. Inhaled corticosteroids do not provide systemic cortisol cover and are inappropriate substitution for perioperative stress dosing.
• B. Abrupt cessation risks acute adrenal crisis due to HPA axis suppression from chronic steroid use.
• C. Her usual maintenance dose does not provide the extra cortisol required to meet surgical stress demand.
• D. Chronic oral dose doubling for a week is unnecessary and not the standard perioperative approach; stress dosing is given at the time of surgery.

The overnight 1 mg dexamethasone suppression test is a convenient, widely used first-line outpatient screening test for Cushing's syndrome, along with 24-hour urinary free cortisol and late-night salivary cortisol. Failure of serum cortisol to suppress below 50 nmol/L the following morning suggests autonomous cortisol production and warrants further work-up. High-dose dexamethasone suppression and CRH stimulation testing are used later to determine the cause of confirmed Cushing's syndrome, not to screen for it. Plasma ACTH is useful in differentiating ACTH-dependent from independent causes once the diagnosis is biochemically confirmed, not for initial screening.

• A. An invasive localisation procedure used to confirm a pituitary source in equivocal ACTH-dependent cases, not a screening test.
• B. Useful for determining ACTH-dependence once Cushing's syndrome is confirmed, not as an initial screening test.
• D. A specialised test used in localisation work-up, not first-line screening.
• E. Used to distinguish pituitary (Cushing's disease) from ectopic causes after the diagnosis is confirmed, not for initial screening.

Resistant hypertension with unprovoked or diuretic-associated hypokalaemia is a classic presentation of primary hyperaldosteronism, and the plasma aldosterone-to-renin ratio is the recommended first-line screening test. An elevated ratio with suppressed renin suggests autonomous aldosterone secretion and warrants confirmatory testing, such as a saline suppression test, followed by adrenal imaging to localise the source. Medications such as ACE inhibitors, ARBs and diuretics can affect the ratio and ideally should be ceased or accounted for, though irbesartan here does not preclude initial screening. Renal artery imaging is appropriate for suspected renovascular hypertension, which typically does not cause hypokalaemia.

• A. Used for suspected renovascular hypertension, which classically does not cause hypokalaemia.
• C. Used to screen for Cushing's syndrome, not primary hyperaldosteronism.
• D. Used to screen for Cushing's syndrome, which does not typically present with this degree of isolated hypokalaemia and resistant hypertension pattern.
• E. Used to screen for phaeochromocytoma, which usually presents with episodic symptoms such as palpitations, headache and diaphoresis.

Dopamine agonists such as cabergoline are first-line treatment for prolactinomas of any size, as they act on D2 receptors on lactotroph cells to suppress prolactin secretion and typically shrink tumour volume, restoring menstrual function and fertility. Cabergoline is preferred over bromocriptine due to greater efficacy, tolerability and more convenient twice-weekly dosing. Surgery is reserved for patients who are intolerant of or resistant to dopamine agonist therapy, or those with acute visual compromise requiring urgent decompression. Radiotherapy is a later option for persistent or recurrent disease after failed medical and surgical therapy.

• A. A somatostatin analogue used for acromegaly, not prolactinomas.
• B. Surgery is reserved for dopamine agonist resistance or intolerance, or acute visual threat, not as first-line therapy for a prolactinoma without mass effect compromising vision.
• C. Reserved for cases of persistent disease refractory to medical and surgical therapy.
• D. Does not treat the underlying tumour or normalise prolactin; it may mask symptoms of oestrogen deficiency without reducing prolactin secretion or tumour size.

Growth hormone secretion is pulsatile, so a random GH level is unreliable for diagnosis. The confirmatory test for acromegaly is an oral glucose tolerance test with GH measured at baseline and intervals afterward; failure of GH to suppress below 0.4 microgram/L confirms autonomous GH secretion. This is done after an elevated IGF-1 has raised clinical suspicion. Pituitary imaging is performed after biochemical confirmation to localise the adenoma, not to diagnose the disease itself.

• A. MRI is used for localisation after biochemical confirmation, not as the confirmatory test.
• C. Prolactin may be mildly elevated in some somatotroph adenomas but does not confirm acromegaly.
• D. Urinary free cortisol is used to assess for Cushing syndrome, not acromegaly.
• E. Random GH is unreliable due to pulsatile secretion and cannot confirm or exclude acromegaly.

This presentation of sudden headache, ophthalmoplegia, visual field defect and hypotension in a patient with a known pituitary adenoma is classic for pituitary apoplexy, caused by haemorrhage or infarction of the gland. Non-contrast CT brain is the most appropriate immediate investigation as it is rapidly available and can detect haemorrhage within the sella, while also screening for other causes of acute severe headache such as subarachnoid haemorrhage. MRI with pituitary protocol is more sensitive and should follow once the patient is stable, but CT should not be delayed in the acute setting. Urgent corticosteroid replacement should also be considered given the risk of acute adrenal insufficiency.

• A. Lumbar puncture is not indicated as the first investigation and risks herniation if there is a mass effect; CT should precede it if considered at all.
• B. Visual evoked potentials are not used in the acute assessment of suspected apoplexy.
• C. EEG has no role in the diagnosis of pituitary apoplexy.
• E. Prolactin may be mildly elevated from stalk compression but does not guide the acute diagnosis.

Failure to concentrate urine despite water deprivation, followed by a marked rise in urine osmolality after desmopressin (greater than 50% increase), indicates a deficiency of endogenous antidiuretic hormone that responds to exogenous replacement. This pattern confirms central diabetes insipidus, typically due to impaired hypothalamic-pituitary ADH production. In nephrogenic diabetes insipidus, the kidneys are unresponsive to ADH, so urine osmolality would fail to rise significantly after desmopressin. Further evaluation should include pituitary MRI to look for a structural cause.

• A. Chronic kidney disease would show impaired urine concentration but a blunted, not robust, response to desmopressin, and would be accompanied by reduced renal function markers.
• B. Primary polydipsia typically shows low plasma osmolality and the urine would concentrate adequately during water deprivation alone.
• C. Normal plasma glucose excludes osmotic diuresis from diabetes mellitus.
• E. Nephrogenic DI would show minimal response to desmopressin because the renal tubules are unresponsive to ADH.

SIADH is characterised by hyponatraemia with low serum osmolality, inappropriately concentrated urine (urine osmolality greater than 100 mOsm/kg), urine sodium above 30 mmol/L, and clinical euvolaemia, in the absence of diuretics, adrenal insufficiency or hypothyroidism. Small cell lung cancer is a well-recognised cause through ectopic ADH secretion. Adrenal insufficiency and hypothyroidism must be excluded biochemically, as both have been done here with normal results. Management involves fluid restriction and treating the underlying malignancy.

• A. The patient is not on diuretics, so this is not the cause.
• B. Hypothyroidism is excluded by normal thyroid function tests.
• C. Adrenal insufficiency is excluded by the normal morning cortisol.
• D. Primary polydipsia would show dilute urine (low urine osmolality), not the concentrated urine seen here.

Primary hyperparathyroidism is diagnosed when serum calcium is elevated with a PTH level that is frankly raised or inappropriately within the normal range, given that high calcium should normally suppress PTH secretion. The accompanying low serum phosphate reflects the phosphaturic effect of PTH on the renal tubule. Secondary hyperparathyroidism produces a raised PTH but with low or normal calcium due to an underlying stimulus such as renal failure or vitamin D deficiency, neither of which fits here. Malignancy-associated hypercalcaemia, through PTH-related peptide, characteristically suppresses PTH rather than raising it.

• A. Vitamin D toxicity causes hypercalcaemia with suppressed PTH and typically elevated vitamin D levels, which are normal here.
• B. Familial hypocalciuric hypercalcaemia typically shows mildly elevated calcium with low urinary calcium excretion and usually a normal or only mildly elevated PTH; it is distinguished by a calcium-to-creatinine clearance ratio below 0.01, not assessed here, and is far less common than primary hyperparathyroidism.
• C. Malignancy-related hypercalcaemia via PTH-related peptide suppresses endogenous PTH, which would be low, not elevated.
• E. Secondary hyperparathyroidism occurs with low or normal calcium and a stimulus such as renal impairment or vitamin D deficiency, both excluded here.

Surgical referral for parathyroidectomy is indicated in asymptomatic primary hyperparathyroidism when any of the following criteria are met: serum calcium more than 0.25 mmol/L above the upper limit of normal, reduced eGFR below 60 mL/min/1.73m², 24-hour urinary calcium above 10 mmol/day with increased stone risk, or a T-score of -2.5 or lower at any site (lumbar spine, hip, or distal radius). This patient meets the bone density criterion with a T-score of -2.7 at the distal radius, a site characteristically affected by cortical bone loss in primary hyperparathyroidism. Parathyroidectomy is curative and is preferred over medical therapy when surgical criteria are met in a fit candidate.

• B. Observation without intervention is inappropriate once a surgical criterion, here the T-score threshold, is met.
• C. Thiazides worsen hypercalcaemia by increasing renal calcium reabsorption and are contraindicated in primary hyperparathyroidism.
• D. Bisphosphonates may be used if surgery is declined or contraindicated, but definitive treatment is indicated here given she meets surgical criteria.
• E. Cinacalcet is reserved for patients unsuitable for surgery to control calcium levels, not first-line when surgical criteria are met.

Hypercalcaemia of malignancy is most commonly mediated by tumour secretion of PTH-related peptide (PTHrP), which mimics PTH action on bone and kidney, causing suppressed endogenous PTH, as seen here. Initial management requires rehydration with intravenous isotonic saline to correct volume depletion and improve renal calcium clearance, followed by an intravenous bisphosphonate such as zoledronic acid to inhibit osteoclast-mediated bone resorption, which takes effect over 2-4 days. Loop diuretics should not be used until the patient is adequately rehydrated, as they can worsen volume depletion and are not first-line therapy. Calcitonin may provide a rapid but short-lived reduction in calcium and can be used as a bridging measure while awaiting bisphosphonate effect, but is not sole therapy.

• A. Furosemide is not used first-line and risks worsening dehydration and hypercalcaemia if given before volume repletion.
• B. Calcitriol increases calcium absorption and would worsen hypercalcaemia; it is used for hypocalcaemic states, not hypercalcaemia.
• C. Calcitonin alone has a rapid but short-lived and modest effect and is not definitive sole therapy.
• D. Glucocorticoids are first-line only for hypercalcaemia due to granulomatous disease, lymphoma or vitamin D toxicity, not typical solid organ malignancy-associated PTHrP-mediated hypercalcaemia.

Aboriginal and Torres Strait Islander people, particularly those with darker skin, who are veiled, or who spend limited time outdoors, are at higher risk of vitamin D deficiency, and this risk is compounded in pregnancy because of fetal and neonatal consequences including neonatal hypocalcaemia and rickets. RACGP and eTG guidance recommends sensible sun exposure of skin (face, arms, hands) for short periods outside peak UV times as the first-line preventive measure, with testing and supplementation when levels are low or exposure is inadequate. Darker skin pigmentation reduces cutaneous vitamin D synthesis efficiency, so sun exposure needs are higher, not negated. Dietary sources alone are insufficient to meet requirements in Australia. Antenatal vitamin D status should be assessed and managed during pregnancy, not deferred.

• A. Vitamin D status should be addressed during pregnancy given risks to fetal bone health and neonatal hypocalcaemia.
• B. High-dose infrequent dosing without baseline testing is not recommended practice and carries a toxicity risk.
• C. Melanin reduces, not eliminates the need for sun exposure; darker skin requires more UV exposure to generate equivalent vitamin D.
• D. Dietary sources alone provide insufficient vitamin D to correct or prevent deficiency in at-risk groups.

Postoperative hypoparathyroidism from inadvertent parathyroid gland damage or devascularisation during thyroidectomy causes acute hypocalcaemia, presenting with perioral and peripheral paraesthesiae, a positive Chvostek sign, and a prolonged QTc that can progress to tetany, seizures or arrhythmia. Symptomatic hypocalcaemia with a corrected calcium below approximately 1.9 mmol/L and ECG changes warrants intravenous calcium gluconate given slowly with cardiac monitoring, as per eTG guidance for acute symptomatic hypocalcaemia. Oral calcium and vitamin D analogues such as calcitriol are used for maintenance once the patient is stabilised, not as sole initial therapy in symptomatic acute hypocalcaemia with ECG changes. Magnesium should be checked and corrected if low, but it does not replace calcium replacement when hypocalcaemia is symptomatic.

• A. Oral therapy alone is inadequate for symptomatic hypocalcaemia with ECG changes and risks progression to tetany or arrhythmia.
• C. This degree of hypocalcaemia with tetany signs and QTc prolongation is a medical emergency requiring treatment, not observation.
• D. Calcitriol speeds intestinal calcium absorption but acts too slowly for acute symptomatic hypocalcaemia and omits immediate calcium replacement.
• E. Magnesium correction supports calcium homeostasis but does not substitute for direct calcium replacement in symptomatic hypocalcaemia.

The Dutch Lipid Clinic Network Criteria score points across family history, clinical history, physical examination findings such as tendon xanthomas, and LDL-cholesterol level, with a score above 8 indicating definite familial hypercholesterolaemia. Tendon xanthomas score highly, as does a markedly elevated LDL-cholesterol such as this patient's 7.6 mmol/L, and a family history of premature coronary disease adds further points, together supporting a definite clinical diagnosis. Isolated arcus without other features is nonspecific and carries little diagnostic weight. Elevated triglycerides with normal LDL-cholesterol suggests a different lipid disorder, not familial hypercholesterolaemia. Cascade testing of first-degree relatives is recommended once an index case is identified, to detect further affected family members.

• B. This lipid pattern is more consistent with another dyslipidaemia than familial hypercholesterolaemia.
• C. A mildly elevated LDL alone without xanthomas or family history scores low and does not support a definite diagnosis.
• D. Hypertension without dyslipidaemia in a relative does not contribute to the Dutch Lipid Clinic score.
• E. Corneal arcus alone, especially without other criteria, contributes minimal diagnostic weight.

Statin-associated muscle symptoms are a recognised adverse effect, and eTG guidance recommends measuring creatine kinase and liver function tests when new myalgia develops on statin therapy, to assess for myopathy and hepatotoxicity before deciding on further management. If creatine kinase is significantly elevated or symptoms are severe, the statin should be withheld; if mildly elevated or normal, options include continuing with monitoring, switching to a different statin, or reducing the dose. Stopping permanently without assessment denies the patient future cardiovascular risk reduction unnecessarily, since many patients tolerate an alternative statin or lower dose. Reassurance without investigation risks missing significant myopathy. Adding a fibrate or increasing the statin dose without assessing the cause of symptoms increases the risk of rhabdomyolysis.

• B. Muscle symptoms should be investigated rather than dismissed, as untreated myopathy can progress.
• C. Permanent avoidance without investigation is premature; many patients can tolerate an alternative statin or adjusted dose.
• D. Increasing the dose while symptomatic risks worsening myopathy before the cause is assessed.
• E. Combining a fibrate with a statin without assessment increases myopathy and rhabdomyolysis risk.

Australian absolute cardiovascular disease risk calculators stratify five-year risk as low (under 10%), intermediate (10-15%), or high (over 15%), or automatically high if certain conditions such as diabetes with microalbuminuria or significant chronic kidney disease are present. At 8% five-year risk with no risk-qualifying comorbidities, this patient falls into the low-risk category, where guidelines recommend lifestyle modification as the primary intervention and risk reassessment every two years, reserving pharmacotherapy for intermediate or high risk or when individual risk factors are the primary driver. Starting a statin or antihypertensive immediately is not indicated at low absolute risk without another strong individual indication. Total cholesterol alone does not determine treatment decisions, since absolute risk incorporates multiple factors including age, blood pressure, and HDL-cholesterol. Fibrates are not first-line primary prevention therapy.

• A. Her risk is low, not high, and antihypertensive therapy is not indicated given her normal blood pressure.
• B. Fibrates are not recommended as first-line primary prevention lipid-lowering therapy.
• C. Immediate high-intensity statin therapy is not indicated at low calculated absolute risk without another compelling individual indication.
• D. Total cholesterol alone does not reflect overall absolute cardiovascular risk, which combines multiple factors.

The Rotterdam criteria diagnose polycystic ovary syndrome when at least two of three features are present: oligo- or anovulation, clinical or biochemical hyperandrogenism, and polycystic ovarian morphology on ultrasound, after exclusion of other causes. This patient has irregular cycles, clinical hyperandrogenism with hirsutism and mildly elevated testosterone, and polycystic ovarian morphology, meeting all three criteria. A normal 17-hydroxyprogesterone excludes congenital adrenal hyperplasia, and normal prolactin and TSH exclude hyperprolactinaemia and thyroid dysfunction as the cause of her irregular cycles. An androgen-secreting tumour typically causes rapidly progressive virilisation with markedly elevated testosterone, which is not seen here.

• A. A normal 17-hydroxyprogesterone level excludes this diagnosis.
• B. Androgen-secreting tumours cause markedly elevated testosterone and rapid virilisation, not mild elevation with a chronic course.
• C. Normal TSH excludes thyroid dysfunction as the cause of her symptoms.
• E. Normal prolactin excludes this as the cause of her menstrual irregularity.

This man has low testosterone with elevated LH and FSH, the biochemical pattern of primary (hypergonadotropic) hypogonadism, indicating testicular failure with loss of negative feedback on the hypothalamic-pituitary axis. Small, firm testes are consistent with a testicular cause such as Klinefelter syndrome, prior orchitis or chemotherapy-induced damage, warranting karyotype testing if not previously diagnosed. Pituitary macroadenoma, haemochromatosis and opioid use typically cause secondary (hypogonadotropic) hypogonadism, where LH and FSH are low or inappropriately normal rather than elevated. Normal prolactin and ferritin further argue against a pituitary or iron-overload cause.

• A. Haemochromatosis causes secondary hypogonadism via pituitary iron deposition; ferritin here is normal and LH/FSH would be low.
• C. Opioids suppress the hypothalamic-pituitary axis causing secondary hypogonadism with low LH/FSH, not the elevated levels seen here.
• D. Prolactin is normal, excluding this as the cause.
• E. A pituitary macroadenoma causes secondary hypogonadism with low or inappropriately normal LH/FSH, not elevated levels.

Known or suspected prostate cancer is an absolute contraindication to testosterone therapy because exogenous testosterone can stimulate growth of androgen-sensitive prostate malignancy. Before starting therapy, PSA and digital rectal examination should be assessed, and ongoing monitoring is required because of the theoretical risk of promoting subclinical disease. Severe untreated sleep apnoea and significant erythrocytosis (haematocrit above 0.54) are relative contraindications or require correction first, but a haematocrit of 0.52 is borderline and not an absolute contraindication on its own. Obesity and a family history of prostate cancer at an older age are risk factors warranting caution and closer monitoring, not absolute contraindications.

• A. Obesity is a risk factor for low testosterone and a reason for caution, not an absolute contraindication.
• B. A paternal history of prostate cancer at age 75 warrants closer monitoring but is not an absolute contraindication.
• C. Haematocrit above 0.54 is the threshold of concern for erythrocytosis; 0.52 does not meet this and is not absolute.
• E. Severe untreated OSA is a relative contraindication that should be treated before or alongside testosterone therapy, not an absolute one.

This woman has the classic triad of multiple endocrine neoplasia type 1 (MEN1): primary hyperparathyroidism (hypercalcaemia with elevated PTH), a pancreatic neuroendocrine tumour (gastrinoma causing Zollinger-Ellison syndrome with refractory ulcers and diarrhoea), and a pituitary adenoma, together with a family history of a parathyroid tumour suggesting autosomal dominant inheritance. MEN1 is caused by mutations in the MEN1 tumour suppressor gene encoding menin. MEN2A features medullary thyroid carcinoma, phaeochromocytoma and primary hyperparathyroidism but not pituitary or pancreatic tumours. Von Hippel-Lindau syndrome involves haemangioblastomas, renal cell carcinoma and phaeochromocytoma, not this combination. The combination of three separate endocrine tumours with a strong family history excludes sporadic or incidental diagnoses.

• A. The combination of three separate tumours plus family history indicates a genetic syndrome, not coincidental findings.
• B. MEN2A involves medullary thyroid carcinoma and phaeochromocytoma, not pituitary adenomas or gastrinomas.
• D. A sporadic gastrinoma would not explain the concurrent hyperparathyroidism, pituitary adenoma and family history.
• E. Von Hippel-Lindau syndrome causes haemangioblastomas and renal/adrenal tumours, not this endocrine triad.

Autoimmune Addison disease commonly occurs as part of autoimmune polyglandular syndrome, most frequently type 2, which clusters autoimmune adrenal insufficiency with autoimmune thyroid disease (Hashimoto thyroiditis or Graves disease) and type 1 diabetes mellitus. This clustering occurs because of shared genetic susceptibility (HLA associations) and a common underlying predisposition to organ-specific autoimmunity, with loss of self-tolerance affecting multiple endocrine glands. Patients with autoimmune Addison disease should therefore have thyroid function and thyroid autoantibodies checked, along with screening for diabetes and coeliac disease. Acromegaly, Cushing syndrome, primary hyperaldosteronism and phaeochromocytoma are not part of the autoimmune polyglandular syndrome cluster and have different, non-autoimmune pathophysiology.

• B. Cushing syndrome results from cortisol excess, the opposite process to Addison disease, and is not an autoimmune cluster condition.
• C. Phaeochromocytoma arises from adrenal medullary chromaffin cells and is not an autoimmune condition linked to this syndrome.
• D. Primary hyperaldosteronism is usually due to adrenal adenoma or hyperplasia, not autoimmune disease.
• E. Acromegaly results from a growth hormone-secreting pituitary adenoma, not autoimmune disease, and is not part of this cluster.

This presentation, with markedly elevated free T4 and free T3, absent goitre and reduced vascularity on Doppler ultrasound, is characteristic of amiodarone-induced thyrotoxicosis type 2, caused by a direct destructive (cytotoxic) effect of amiodarone or its metabolites on thyroid follicular cells, releasing preformed thyroid hormone without increased synthesis. This is distinct from type 1, which occurs in patients with underlying nodular goitre or latent Graves disease, where the iodine load from amiodarone drives excess synthesis in autonomously functioning tissue and is typically associated with increased vascularity on Doppler. Management of type 2 favours corticosteroids, whereas type 1 is managed with thionamides. Amiodarone does not directly suppress pituitary TSH secretion as the primary mechanism of thyrotoxicosis, and the clinical and ultrasound findings here do not support an autoimmune or granulomatous process.

• A. Amiodarone can transiently affect TSH early in therapy but this is not the mechanism of the destructive thyrotoxicosis seen here.
• B. There is no history or antibody evidence suggesting Hashimoto disease, and this pattern is thyrotoxic, not primarily hypothyroid.
• C. Type 1 occurs on a background of nodular or autonomous thyroid tissue and shows increased, not reduced, vascularity on Doppler.
• D. Subacute granulomatous thyroiditis is a distinct viral-associated condition with a painful, tender goitre, which is absent here.

The biochemical picture of elevated TSH with low free T4 confirms primary (thyroidal) hypothyroidism, and in iodine-replete countries like Australia the most common cause is Hashimoto's (autoimmune) thyroiditis. It results from lymphocytic infiltration of the thyroid and circulating anti-thyroid peroxidase antibodies, often with a firm, non-tender, diffusely enlarged gland. Subacute thyroiditis typically causes a painful gland and a transient thyrotoxic phase before hypothyroidism. Riedel's thyroiditis is rare and causes a hard, fibrotic, fixed gland. A pituitary cause would present with low or inappropriately normal TSH, not elevated.

• A. Iodine-induced hypothyroidism is uncommon in Australia given iodine fortification of bread and is not the most common cause.
• B. Subacute thyroiditis classically presents with a painful, tender thyroid and an initial hyperthyroid phase.
• C. Riedel's thyroiditis is rare and causes a hard, woody, fixed thyroid, not the picture described.
• D. A pituitary adenoma causing secondary hypothyroidism would present with low or low-normal TSH, not markedly elevated TSH.

Levothyroxine has a long half-life of approximately 7 days, so steady-state serum levels and the resulting change in TSH take several weeks to stabilise. Therapeutic Guidelines recommend rechecking TSH approximately 6 weeks after starting or changing the dose, allowing adequate time for the pituitary-thyroid axis to re-equilibrate before further dose adjustment. Testing earlier risks a misleading result that does not reflect the new steady state. Waiting 12 months or relying on symptoms alone delays necessary dose correction and risks prolonged under- or over-treatment.

• A. Timing relative to the daily dose does not reflect the weeks-long equilibration of TSH and is not the recommended approach.
• B. Symptom improvement is subjective and unreliable; biochemical monitoring is required to guide dose titration.
• C. Twelve months is far too long an interval for initial dose titration and risks prolonged under- or over-treatment.
• D. One week is too soon; TSH has not yet re-equilibrated to the new dose.

Subclinical hypothyroidism is defined as an elevated TSH with a normal free T4. In an asymptomatic patient with TSH persistently below 10 mU/L and negative thyroid antibodies, current guidelines favour observation with annual monitoring of thyroid function rather than immediate treatment, as progression to overt hypothyroidism is not certain and treatment has not shown clear benefit in this group. Treatment is more strongly considered when TSH exceeds 10 mU/L, when the patient is symptomatic, pregnant or planning pregnancy, or when thyroid peroxidase antibodies are positive indicating higher risk of progression. Antithyroid drugs and radioiodine are treatments for hyperthyroidism, not relevant here.

• A. Carbimazole is an antithyroid drug used for hyperthyroidism, not for hypothyroidism.
• B. Starting levothyroxine is not routinely recommended in asymptomatic patients with TSH under 10 mU/L and negative antibodies.
• C. Radioactive iodine ablation treats hyperthyroidism, not hypothyroidism, and is inappropriate here.
• E. This dose is even less justified than the lower dose option given the same reasoning against treatment.

Myxoedema coma is a life-threatening decompensation of severe, longstanding untreated hypothyroidism, classically precipitated by cold exposure, infection or medication non-adherence in elderly patients. The combination of hypothermia, bradycardia, hypotension, hypoventilation and altered consciousness in a patient with a thyroidectomy scar and features suggesting undertreated hypothyroidism (dry skin, periorbital puffiness, missed medication) is highly suggestive. It requires urgent intravenous thyroid hormone replacement and corticosteroids, along with supportive care and treatment of any precipitating illness. Hypoglycaemia and sepsis can cause altered consciousness but do not explain the dry skin, puffiness and goitre scar together.

• A. Septic shock usually presents with warm skin, tachycardia and fever rather than hypothermia and bradycardia.
• B. Addisonian crisis typically causes tachycardia and hyperpigmentation, not the specific combination seen here with a thyroidectomy scar.
• D. A cerebrovascular accident would not explain the hypothermia, bradycardia and skin findings as a unifying diagnosis.
• E. Hypoglycaemia typically causes tachycardia and sweating rather than bradycardia and the described skin and neck findings.

In the assessment of a thyroid nodule, the first step is to measure serum TSH to determine thyroid functional status, as this guides the subsequent pathway. If TSH is suppressed, a radionuclide scan is used to identify a hyperfunctioning (autonomous) nodule, which carries a low risk of malignancy and does not require fine-needle aspiration. If TSH is normal or elevated, the nodule is assessed with ultrasound to characterise its features and determine whether fine-needle aspiration is warranted based on size and sonographic risk features. Measuring calcitonin routinely for every nodule is not recommended in current guidelines without specific clinical suspicion of medullary carcinoma.

• A. Routine calcitonin testing for all thyroid nodules is not recommended without specific clinical suspicion of medullary carcinoma.
• C. Fine-needle aspiration should follow TSH and ultrasound assessment, not precede them.
• D. Ultrasound is important but is performed after TSH to guide whether and how fine-needle aspiration should proceed.
• E. A radionuclide scan is only indicated if TSH is found to be suppressed, so it is not the first test.

Papillary thyroid carcinoma is the most common thyroid cancer subtype, accounting for the majority of thyroid malignancies, and has characteristic cytological features including papillary architecture, nuclear grooves, intranuclear cytoplasmic inclusions ('pseudo-inclusions') and the classic 'ground-glass' or 'Orphan Annie eye' nuclei. It typically occurs in younger patients, often spreads via lymphatics to cervical lymph nodes, and generally carries an excellent prognosis with appropriate surgical management and risk-stratified follow-up. Medullary carcinoma arises from calcitonin-secreting C cells and has a different cytological appearance. Anaplastic carcinoma is aggressive and typically occurs in older patients with rapidly enlarging masses.

• A. Multinodular goitre is a benign condition and would not show the malignant nuclear features described on cytology.
• B. Follicular carcinoma is diagnosed on evidence of capsular or vascular invasion on histology, not by the nuclear features described on cytology.
• D. Medullary thyroid carcinoma arises from C cells and shows amyloid stroma on histology, not the papillary nuclear features described.
• E. Anaplastic carcinoma typically presents in older patients with a rapidly growing, invasive mass and shows highly pleomorphic, undifferentiated cells.

Medullary thyroid carcinoma arises from calcitonin-secreting parafollicular C cells and is associated with multiple endocrine neoplasia type 2 (MEN2) syndromes in a significant proportion of cases, caused by germline mutations in the RET proto-oncogene. The family history of early sudden death and phaeochromocytoma in a sibling strongly raises suspicion of an underlying MEN2 syndrome, warranting genetic counselling and RET mutation testing in the patient and screening of at-risk relatives. Identifying a RET mutation has implications for screening for phaeochromocytoma and primary hyperparathyroidism, and for prophylactic thyroidectomy in mutation-positive relatives. Thyroglobulin and radioactive iodine are relevant to follicular-cell-derived cancers, not medullary carcinoma, which is not iodine-avid and does not produce thyroglobulin.

• A. Given the family history suggesting MEN2, genetic evaluation takes priority over routine ultrasound surveillance alone.
• B. Thyroglobulin is a marker for follicular-cell-derived thyroid cancers; medullary carcinoma is monitored with calcitonin and CEA, not thyroglobulin.
• C. Medullary thyroid carcinoma cells are not derived from follicular cells and do not take up radioactive iodine.
• E. Thyroid hormone suppression therapy is used in differentiated (follicular-cell) thyroid cancers, not medullary carcinoma, which is not TSH-dependent.