PLAB 1 (UKMLA AKT) endocrinology & metabolism questions

In an asymptomatic patient, diabetes mellitus cannot be diagnosed on a single abnormal glucose value; it requires two abnormal results (fasting plasma glucose ≥7.0 mmol/L, random plasma glucose ≥11.1 mmol/L, or HbA1c ≥48 mmol/mol) on separate occasions. This patient has two fasting readings above the 7.0 mmol/L threshold, which is diagnostic. In symptomatic patients, a single abnormal result is sufficient. HbA1c of 40 mmol/mol is in the normal range and does not support a diagnosis.

• B. A single random glucose is insufficient in an asymptomatic patient and this value alone is not diagnostic without a second confirmatory test.
• C. A single abnormal random glucose with symptoms is diagnostic, but this scenario describes an asymptomatic patient, so this option does not apply here.
• D. An HbA1c of 40 mmol/mol (6.1%) is within the normal range (below 42 mmol/mol) and does not indicate diabetes.
• E. A fasting glucose of 6.2 mmol/L is below the diagnostic threshold of 7.0 mmol/L, placing it in the impaired fasting glucose range.

NICE defines gestational diabetes using a 75 g OGTT with thresholds of fasting plasma glucose ≥5.6 mmol/L or 2-hour plasma glucose ≥7.8 mmol/L; only one abnormal value is required for diagnosis. Here the fasting value is normal (5.2 mmol/L) but the 2-hour value of 8.2 mmol/L exceeds the 7.8 mmol/L threshold, confirming gestational diabetes. Management should begin with dietary and lifestyle advice, with metformin or insulin added if glucose targets are not met. This is distinct from pre-existing type 2 diabetes, which is not newly diagnosed in pregnancy based on this single test alone.

• B. The fasting value of 5.2 mmol/L is below the 5.6 mmol/L threshold and is therefore normal.
• C. The 2-hour value exceeds the diagnostic threshold of 7.8 mmol/L, so the test is abnormal.
• D. This presentation reflects gestational diabetes, not an overt new diagnosis of type 2 diabetes, and insulin is not the automatic first-line treatment.
• E. There is no separate 'impaired glucose tolerance' category in pregnancy; this result meets the NICE diagnostic threshold for gestational diabetes.

Type 1 diabetes should be suspected in younger, lean patients presenting with an acute onset of osmotic symptoms, weight loss and significant ketonuria, even in adulthood. The combination of a normal BMI, rapid symptom onset and marked ketosis points towards absolute insulin deficiency rather than insulin resistance. Type 2 diabetes typically presents in overweight individuals with a more insidious course and is less commonly associated with significant ketosis. Urgent referral for insulin initiation is required rather than oral hypoglycaemic therapy.

• A. There is no history of steroid use or other precipitant to suggest a drug-induced cause.
• C. Latent autoimmune diabetes of adults typically has a slower, more insidious onset without significant ketosis at presentation.
• D. Maturity-onset diabetes of the young usually has a strong family history and a milder, non-ketotic presentation.
• E. Type 2 diabetes is more common in overweight patients with a gradual onset and is not typically associated with significant ketonuria.

HbA1c reflects the average glucose exposure over the lifespan of red blood cells, typically around 120 days. In conditions with increased red cell turnover or haemolysis, such as sickle cell disease, red cells survive for a shorter time, giving glucose less time to glycate haemoglobin, which falsely lowers the HbA1c relative to true glycaemic control. In this situation, NICE guidance recommends using fructosamine or average home capillary glucose monitoring instead of HbA1c to assess control. This discrepancy explains why the reported HbA1c of 38 mmol/mol underestimates the patient's true level of hyperglycaemia.

• A. HbA1c is directly dependent on red cell lifespan, and altered turnover is a recognised limitation of its use in such patients.
• B. Increased red cell lifespan would falsely raise HbA1c, but sickle cell disease shortens red cell lifespan, so this is the opposite effect.
• C. There is no information suggesting glucometer error, and this does not explain the physiological basis of the discrepancy.
• E. The glucose readings are consistent and more reliable here; the HbA1c is the test affected by the underlying haemoglobinopathy.

NICE recommends that patients with type 2 diabetes who have established cardiovascular disease, such as prior myocardial infarction, should have an SGLT2 inhibitor added to metformin due to proven cardiovascular benefit demonstrated in large outcome trials. Dapagliflozin reduces the risk of major cardiovascular events and heart failure hospitalisation in this population, and the patient's renal function is adequate for its use. Sulfonylureas, DPP-4 inhibitors and alpha-glucosidase inhibitors do not have the same evidence base for cardiovascular risk reduction in this context.

• A. Gliclazide is an acceptable second-line agent but lacks evidence for cardiovascular benefit and carries a hypoglycaemia risk.
• B. Sitagliptin has a neutral cardiovascular effect and does not provide the cardiovascular risk reduction seen with SGLT2 inhibitors in this population.
• D. Acarbose is rarely used due to poor tolerability and has no cardiovascular outcome benefit.
• E. Pioglitazone is contraindicated in patients with heart failure risk and is not the preferred choice in established cardiovascular disease.

Metformin should have its dose reviewed and reduced when eGFR falls below 45 mL/min/1.73m², with increased monitoring of renal function, due to the increased risk of lactic acidosis as renal clearance of the drug declines. Metformin is generally stopped only when eGFR falls below 30 mL/min/1.73m². At an eGFR of 42 mL/min/1.73m², continuing at full dose is inappropriate, but outright cessation or switching to insulin is premature. Dose reduction with closer monitoring, for example every 3 to 6 months, is the recommended approach according to BNF guidance.

• A. Continuing the full dose without adjustment increases the risk of lactic acidosis as renal clearance declines.
• C. Increasing the dose would raise the risk of toxicity in the context of declining renal function.
• D. Switching to pioglitazone is not indicated when metformin can be safely continued at a reduced dose.
• E. Metformin is not stopped until eGFR falls below 30 mL/min/1.73m², so this is premature at this level of renal function.

Sick day rules for type 1 diabetes advise that insulin should never be stopped during intercurrent illness, even if oral intake is reduced, because insulin requirements often increase due to the stress response, raising the risk of diabetic ketoacidosis. Patients should continue their usual insulin doses, increase the frequency of blood glucose and ketone monitoring, maintain hydration, and may need corrective doses of rapid-acting insulin if ketones are rising. This patient's ketone level of 0.8 mmol/L is mildly elevated but does not yet indicate ketoacidosis, so hospital attendance is not required at this stage provided she can manage fluids and monitor closely with safety-net advice given.

• A. Stopping insulin during illness is dangerous and increases the risk of diabetic ketoacidosis, as insulin requirements often rise rather than fall.
• B. Reducing basal insulin and omitting bolus doses would worsen hyperglycaemia and risk ketoacidosis during illness.
• C. Basal insulin should never be omitted during illness, as it is required to prevent ketosis even when not eating.
• D. Her ketone level and clinical state do not yet meet criteria for emergency department attendance, and insulin should not be stopped.

All patients with diabetes mellitus aged 12 years and over should be referred for digital retinal photography screening at the time of diagnosis, as retinopathy can be asymptomatic in its early stages and is a leading cause of preventable blindness in working-age adults. The NHS Diabetic Eye Screening Programme then repeats screening annually, or every two years if two consecutive screens show no retinopathy. Waiting for symptoms risks missing sight-threatening retinopathy that is treatable with early laser or anti-VEGF therapy. Screening is not linked to insulin status or an arbitrary duration since diagnosis.

• A. Screening should begin at diagnosis, not be deferred for years.
• C. A 10-year delay would miss early, treatable retinopathy.
• D. Screening is based on diagnosis of diabetes, not on insulin requirement.
• E. Retinopathy is often asymptomatic until advanced, so waiting for symptoms delays treatment.

The diagnostic criteria for DKA are capillary blood glucose above 11 mmol/L (or known diabetes), blood ketones above 3 mmol/L (or significant ketonuria), and venous pH below 7.3 or bicarbonate below 15 mmol/L. This patient meets all three criteria, confirming DKA, and the tachypnoea reflects compensatory Kussmaul breathing. Hyperosmolar hyperglycaemic state typically occurs in type 2 diabetes with much higher glucose, minimal ketosis and near-normal pH. Alcoholic and starvation ketosis do not typically cause glucose this high, and lactic acidosis would show an elevated lactate rather than significant ketosis as the primary driver.

• A. Lactic acidosis is driven by elevated lactate, not ketones, as the primary metabolic abnormality.
• B. Alcoholic ketoacidosis occurs with alcohol excess and does not typically cause glucose this elevated.
• D. Starvation ketosis causes mild ketosis without significant acidosis or marked hyperglycaemia.
• E. HHS features much higher glucose and osmolality with minimal acidosis or ketosis, unlike this picture.

Current UK guidance (Joint British Diabetes Societies) recommends starting a fixed-rate intravenous insulin infusion at 0.1 units/kg/hour alongside continued intravenous fluid resuscitation, without waiting for ketones to normalise. This suppresses ketogenesis and lipolysis while glucose-containing fluids are added once capillary glucose falls below 14 mmol/L. Sodium bicarbonate is not recommended in DKA as it can worsen intracellular acidosis and hypokalaemia. A variable-rate sliding scale is not the recommended initial regimen for DKA, and glucagon is irrelevant since this is hyperglycaemic ketoacidosis, not hypoglycaemia.

• A. Glucagon raises glucose and is used for hypoglycaemia, which is the opposite problem here.
• B. Insulin should be started promptly alongside fluids, not delayed until ketones normalise.
• C. Bicarbonate is not recommended in DKA as it can paradoxically worsen acidosis and cause hypokalaemia.
• D. A variable-rate sliding scale is not the first-line regimen for DKA; fixed-rate insulin is recommended.

Insulin drives potassium into cells, so serum potassium commonly falls during DKA treatment even when the starting level is normal or high. Potassium should be added to replacement fluids once levels fall below 5.5 mmol/L, with close monitoring, and here the level has dropped to 3.1 mmol/L, requiring correction to prevent dangerous hypokalaemia and arrhythmia. Insulin should not be stopped, as it is essential to resolve ketosis; instead, potassium is replaced alongside it. Calcium gluconate is used for hyperkalaemia with ECG changes, which is not the situation here, and potassium must be rechecked far sooner than 12 hours, typically hourly initially.

• A. Insulin must be continued to resolve ketoacidosis; potassium is corrected alongside it, not by stopping insulin.
• B. Potassium needs to be rechecked much more frequently than every 12 hours during DKA treatment, typically hourly.
• C. Subcutaneous insulin is not appropriate during acute DKA management; intravenous fixed-rate insulin should continue.
• D. Calcium gluconate is used to treat hyperkalaemia with ECG changes, not hypokalaemia.

This child shows classic signs of cerebral oedema complicating DKA treatment: headache, reduced consciousness, bradycardia and hypertension (Cushing's triad). Cerebral oedema is a medical emergency, particularly in children, and treatment with hypertonic (2.7% or 3%) saline or mannitol should be given immediately without waiting for imaging, as delay risks death or permanent neurological damage. Fluid rates should be reviewed and reduced, not increased, as excessive fluid administration is a recognised risk factor. Imaging may follow once the patient is stabilised but must not delay emergency treatment.

• A. Glucose bolus is not indicated; the problem is cerebral oedema, not hypoglycaemia.
• B. Treatment must not be delayed for imaging; mannitol or hypertonic saline should be given immediately on clinical suspicion.
• D. Increasing insulin does not address cerebral oedema and is not the emergency intervention needed.
• E. Increasing fluid rate would worsen cerebral oedema; fluids should be reduced and osmotic therapy given.

This presentation, marked hyperglycaemia, minimal ketosis, near-normal pH and significantly raised osmolality, is characteristic of hyperosmolar hyperglycaemic state (HHS) rather than DKA. Management of HHS prioritises slow, careful fluid resuscitation with 0.9% sodium chloride, since these often elderly patients are at high risk of rapid osmotic shifts causing cerebral oedema or central pontine myelinolysis if corrected too quickly. Insulin is often not required initially, as fluids alone can lower glucose substantially, and is only added later at a low fixed rate if glucose stops falling with fluids. Bicarbonate is not indicated as there is no significant acidosis, and dextrose would worsen hyperglycaemia.

• A. Dextrose would worsen the hyperglycaemia and is not appropriate as the primary resuscitation fluid.
• B. There is no significant acidosis here, so bicarbonate is not indicated.
• D. Subcutaneous insulin and oral fluids are inadequate for this severely hyperosmolar, dehydrated patient.
• E. Insulin is not first-line in HHS; rapid insulin administration risks precipitous osmotic shifts before adequate fluid replacement.

In a conscious patient with hypoglycaemia who is able to swallow safely, the first-line treatment is oral fast-acting carbohydrate, such as glucose tablets, a sugary drink or glucose gel, repeated if blood glucose remains low after the first dose. Since he remains hypoglycaemic after one attempt, a further dose of fast-acting carbohydrate should be given before considering escalation. Intramuscular glucagon and intravenous glucose are reserved for patients who are unconscious, unable to swallow safely, or have failed repeated oral treatment. Ambulance transfer is not yet necessary for a conscious, cooperative patient who can be managed at home.

• A. Intravenous glucose is reserved for patients who cannot take oral treatment or who are unconscious.
• B. Intravenous 20% glucose is excessive and unnecessary when oral treatment can still be tried in a conscious, cooperative patient.
• C. Glucagon is used when oral treatment fails or the patient cannot swallow safely, not as the next step after one unsuccessful oral dose.
• E. Hospital admission is not yet required; repeated oral carbohydrate should be tried first in a conscious patient at home.

Sulfonylureas such as gliclazide have a long half-life and stimulate prolonged endogenous insulin release, so hypoglycaemia frequently recurs after initial correction. Patients with sulfonylurea-induced hypoglycaemia should be admitted for a period of glucose monitoring, often with a continuous intravenous glucose infusion, because a single bolus of glucose only provides transient correction. Discharge after one successful correction risks a dangerous recurrence once the glucose bolus wears off while the sulfonylurea is still active. Monitoring typically continues for at least 24-48 hours depending on the agent and renal function.

• A. A single bolus is inadequate because sulfonylurea effect persists for many hours, risking recurrent hypoglycaemia after discharge
• B. Oral glucose and brief observation is insufficient given the recurrence already demonstrated and long sulfonylurea half-life
• C. Glucagon depletes glycogen stores and is less effective in repeated dosing; discharge is unsafe given the ongoing sulfonylurea effect
• E. Dose adjustment is appropriate later but does not address the immediate risk of recurrent severe hypoglycaemia needing monitoring now

NICE recommends annual screening for diabetic nephropathy using a urine albumin:creatinine ratio (ACR) on an early morning urine sample, as this is sensitive enough to detect microalbuminuria before overt proteinuria develops. Standard urine dipstick only detects higher levels of protein and misses microalbuminuria, the earliest marker of diabetic kidney disease. A 24-hour collection is more cumbersome and not required for routine screening. Serum creatinine and eGFR should be checked alongside ACR but do not detect early glomerular damage as sensitively.

• A. Ultrasound assesses structural abnormalities, not the functional marker of early nephropathy
• B. eGFR alone can remain normal despite early microalbuminuria, so it is not sufficient as the sole screening test
• C. A 24-hour collection is accurate but impractical for routine annual screening compared with a spot ACR
• D. Dipstick protein detects only macroalbuminuria and misses the microalbuminuria stage that ACR identifies

ACE inhibitors such as ramipril reduce intraglomerular pressure by dilating the efferent arteriole more than the afferent arteriole, lowering intraglomerular filtration pressure and reducing proteinuria independent of their systemic blood pressure effect. This renoprotective action slows progression of diabetic nephropathy and is recommended once microalbuminuria is confirmed, even if blood pressure is only mildly elevated. Potassium and renal function should be monitored after starting treatment. Calcium channel blockers and thiazides lower blood pressure but lack this specific antiproteinuric mechanism.

• A. Calcium channel blockers do not reduce intraglomerular pressure in the same renoprotective way and are not first-line for microalbuminuria
• C. Thiazide diuretics lower blood pressure but do not have the specific antiproteinuric, efferent arteriolar dilating effect of ACE inhibitors
• D. Loop diuretics are used for fluid overload, not for renoprotection in early diabetic nephropathy
• E. Alpha-blockers treat hypertension but have no specific role in reducing diabetic proteinuria

NICE guidance on neuropathic pain recommends amitriptyline, duloxetine, gabapentin or pregabalin as first-line options for painful diabetic peripheral neuropathy. Amitriptyline works by inhibiting reuptake of noradrenaline and serotonin, modulating descending pain pathways rather than treating nociceptive pain. Simple analgesics such as paracetamol and NSAIDs are not effective for neuropathic pain because the mechanism is not inflammatory or nociceptive. Opioids are not recommended as first-line therapy for chronic neuropathic pain due to limited efficacy and dependence risk.

• A. Paracetamol targets nociceptive pain pathways and has little efficacy in neuropathic pain
• B. Opioids are not first-line for chronic neuropathic pain due to limited long-term efficacy and risk of dependence
• D. NSAIDs act on inflammatory pain pathways and are not effective for neuropathic pain
• E. Benzodiazepines have no established role in the management of diabetic peripheral neuropathy

Diabetic gastroparesis results from autonomic neuropathy affecting the vagus nerve, leading to delayed gastric emptying. Typical features include early satiety, bloating, nausea and vomiting of food eaten hours earlier, often with erratic glycaemic control because food absorption becomes unpredictable. A normal endoscopy excludes mechanical causes such as ulceration or malignancy, supporting a functional motility disorder. Diagnosis is usually confirmed with a gastric emptying study, and management includes dietary modification and prokinetic agents such as metoclopramide or domperidone.

• A. Coeliac disease causes malabsorption and diarrhoea rather than delayed gastric emptying with vomiting of old food
• B. Peptic ulcer disease would typically show mucosal abnormality on endoscopy, which was normal here
• D. Chronic pancreatitis typically causes epigastric pain and steatorrhoea rather than this pattern of delayed gastric emptying
• E. A normal endoscopy makes a structural obstructing malignancy unlikely

A raised TSH with a low free T4 confirms primary hypothyroidism, as the pituitary increases TSH output in response to insufficient thyroid hormone production. In healthy adults without cardiac disease, the BNF recommends starting levothyroxine at 50-100 micrograms once daily, with dose titration based on repeat TSH after 6-8 weeks. Lower starting doses such as 25 micrograms are reserved for elderly patients or those with ischaemic heart disease, to avoid precipitating angina or arrhythmia. The confirmed primary hypothyroidism pattern here, in a patient without cardiac risk, justifies the standard starting dose.

• B. This dose is far higher than any recommended starting regimen and would cause iatrogenic thyrotoxicosis
• C. This dose is subtherapeutic even as a cautious starting dose for most adults
• D. This dose is excessive as a starting dose and risks precipitating thyrotoxic symptoms or arrhythmia
• E. This lower dose is used cautiously in elderly patients or those with cardiac disease, not in this fit younger patient

After starting or changing the dose of levothyroxine, TSH takes approximately 4-6 weeks to equilibrate to the new steady state because of the long half-life of thyroid hormone and the time needed for pituitary feedback to adjust. Testing too early, as proposed at only four weeks, risks a result that does not yet reflect the true effect of the current dose, potentially leading to inappropriate dose changes. The standard approach is to wait a further 4-6 weeks from the last dose change before rechecking TSH and titrating the dose accordingly. Once a stable, euthyroid dose is established, monitoring can move to annual testing.

• A. Stopping treatment is inappropriate as the patient has confirmed hypothyroidism requiring ongoing replacement
• B. Changing the dose without allowing adequate equilibration time risks over- or under-treatment
• C. Testing immediately at this point does not allow adequate time for TSH to reach a new steady state after the dose was started
• E. Annual testing is appropriate once a stable dose is established, not immediately after initiation

The combination of hyperthyroidism, lid retraction (eye signs) and pretibial myxoedema (non-pitting shin thickening) strongly suggests Graves' disease. TSH receptor antibodies (TRAb), which stimulate the thyroid and are also implicated in the orbitopathy and dermopathy, are positive in over 95% of cases and are the most specific confirmatory test. Anti-TPO antibodies are less specific, being positive in Graves' disease but also commonly in Hashimoto's thyroiditis. A diffuse, symmetrical goitre with systemic features of autoimmunity points away from a toxic nodule.

• B. Thyroglobulin is a marker used in differentiated thyroid cancer follow-up, not for diagnosing Graves' disease.
• C. Anti-TPO antibodies are less specific and are also raised in Hashimoto's thyroiditis.
• D. Calcitonin is a tumour marker for medullary thyroid carcinoma, unrelated to this presentation.
• E. A single hot nodule would suggest a toxic adenoma, not the diffuse autoimmune picture described here.

Carbimazole is the first-line antithyroid drug for most patients with Graves' disease, either as a titration regimen for 12-18 months or as part of a block-and-replace strategy, and response is typically reviewed after 4-6 weeks. Radioiodine is contraindicated if pregnancy is planned within the next 6 months due to radiation risk to a future fetus, making it unsuitable here given her wish to conceive soon. Propylthiouracil is reserved for the first trimester of pregnancy or thyroid storm because of a higher risk of hepatotoxicity compared with carbimazole.

• A. Radioiodine now would still require a 6-month contraception period and is not first-line when carbimazole has not yet been trialled.
• B. Radioiodine should not be used as a bridge to pregnancy; it requires a delay of at least 6 months before conception and is not the standard first-line approach.
• C. Propylthiouracil carries a higher hepatotoxicity risk and is reserved for the first trimester of pregnancy or thyroid storm, not routine first-line use.
• D. Surgery is reserved for specific indications such as large goitre with compressive symptoms, suspected malignancy or patient preference after medical therapy, not as first-line treatment.

Carbimazole can rarely cause agranulocytosis, which typically presents with sore throat, fever, mouth ulcers or other signs of infection, usually within the first few months of treatment. Patients must be counselled to stop the drug immediately and seek urgent medical review with a full blood count if these symptoms occur, as agranulocytosis can be life-threatening if treatment continues. This is a specific BNF warning for carbimazole and is tested because missing it can lead to severe, potentially fatal sepsis.

• A. Switching drugs without checking the blood count first delays identification of a potentially life-threatening complication.
• B. Continuing carbimazole at any dose while agranulocytosis is unexcluded is unsafe; the drug should be stopped immediately.
• C. Routine, delayed blood tests are inappropriate; an urgent full blood count is needed given the risk of agranulocytosis.
• D. Sore throat and fever in a patient on carbimazole must never be dismissed as minor; agranulocytosis must be excluded urgently.

This presentation, with fever, tachyarrhythmia, altered mental status and a precipitating infection in a patient with known Graves' disease, is consistent with thyroid storm, a medical emergency with significant mortality. Management includes a beta-blocker (intravenous propranolol) to control adrenergic symptoms, hydrocortisone to reduce peripheral T4 to T3 conversion and cover for relative adrenal insufficiency, and a high-dose antithyroid drug (propylthiouracil or carbimazole) to block hormone synthesis, alongside supportive care and treatment of any precipitant such as infection. Oral therapy alone is inadequate in this critically unwell patient who needs rapid, multi-pronged treatment.

• A. Diuretics and fluid restriction do not address the underlying thyrotoxic crisis and are not standard thyroid storm therapy.
• B. Radioiodine is not used acutely in thyroid storm and is not given intravenously.
• D. Surgery is not performed in the acute unstable phase of thyroid storm; it may be considered later once the patient is stabilised.
• E. Oral carbimazole alone is insufficient; thyroid storm requires a combination of beta-blockade, steroids and antithyroid drugs with close monitoring, not ward-level observation.

Myxoedema coma is a life-threatening decompensation of severe, longstanding untreated hypothyroidism, classically presenting with hypothermia, bradycardia, hypotension, hypoglycaemia and depressed consciousness, often precipitated by stopping thyroid replacement or an intercurrent illness in an elderly patient. The history of untreated hypothyroidism combined with this constellation of findings is the key clue. Management requires intravenous levothyroxine (or liothyronine), intravenous hydrocortisone to cover possible coexisting adrenal insufficiency, and supportive care including slow rewarming, in a critical care setting.

• A. Addisonian crisis can cause hypotension and hypoglycaemia but does not typically cause the profound hypothermia and bradycardia seen here, and there is a clear history pointing to hypothyroidism.
• C. Hepatic encephalopathy does not explain the hypothermia, bradycardia and hypoglycaemia in this context.
• D. Diabetic ketoacidosis presents with hyperglycaemia and acidosis, not hypoglycaemia and bradycardia.
• E. Sepsis usually causes fever and tachycardia rather than hypothermia with bradycardia, though it can be a precipitant of myxoedema coma.

Subacute (de Quervain's) thyroiditis typically follows a viral upper respiratory tract infection and presents with a painful, tender goitre, raised inflammatory markers and negative thyroid autoantibodies. It classically causes a transient hyperthyroid phase, due to the release of preformed hormone from damaged follicular cells, followed weeks later by a hypothyroid phase before eventual recovery. The pain radiating to the jaw and the markedly raised ESR help distinguish it from the painless goitre of Graves' disease.

• B. Toxic multinodular goitre causes hyperthyroidism but does not typically cause a painful, tender gland or a preceding viral illness.
• C. Acute suppurative thyroiditis is a bacterial infection presenting with marked systemic sepsis and often an abscess, not this subacute post-viral course.
• D. Hashimoto's thyroiditis is usually painless and associated with positive anti-TPO antibodies, and typically presents with hypothyroidism rather than an acute hyperthyroid phase.
• E. Graves' disease typically causes a painless, diffuse goitre and would usually be associated with positive TSH receptor antibodies, not a tender gland with a very high ESR.

The short Synacthen (ACTH stimulation) test is the gold-standard confirmatory investigation for adrenal insufficiency. Synthetic ACTH is given and cortisol measured at baseline, 30 and 60 minutes; failure of cortisol to rise above approximately 420-500 nmol/L (assay-dependent) confirms adrenal insufficiency, as the adrenal glands cannot respond to stimulation. A low random cortisol with hyponatraemia and hyperkalaemia is suggestive but not diagnostic, since cortisol levels vary throughout the day. Plasma ACTH helps distinguish primary from secondary causes once adrenal insufficiency is confirmed, but it does not itself establish the diagnosis.

• A. 24-hour urinary free cortisol is used to screen for cortisol excess (Cushing's syndrome), not deficiency.
• B. ACTH level helps determine whether insufficiency is primary or secondary but does not confirm the diagnosis itself.
• C. The insulin tolerance test assesses growth hormone and ACTH reserve in suspected hypopituitarism and carries risks of severe hypoglycaemia; it is not first-line for suspected primary adrenal insufficiency.
• E. Overnight dexamethasone suppression testing is used to screen for Cushing's syndrome, the opposite clinical problem.

This presentation, hypotension, tachycardia, confusion and hypoglycaemia in a patient with known adrenal insufficiency who cannot tolerate oral intake, is an Addisonian crisis, a medical emergency. Management requires an immediate intravenous bolus of hydrocortisone 100 mg, followed by 100 mg every 6 hours (or a continuous infusion), combined with aggressive intravenous fluid resuscitation using 0.9% sodium chloride to correct hypovolaemia and hyponatraemia. Oral medication is inappropriate because vomiting prevents absorption and the patient needs rapid, reliable correction of both cortisol deficiency and circulatory collapse. Glucose should also be corrected if hypoglycaemic, but fluid and steroid replacement are the priority actions that address the underlying crisis.

• A. Intramuscular fludrocortisone is not used in acute crisis management; intravenous hydrocortisone and fluids are required.
• B. Dexamethasone is not first-line in an acute crisis; hydrocortisone is preferred, and dextrose alone will not correct the hypovolaemic shock.
• D. Fluid resuscitation must not be withheld; hypotensive shock requires immediate intravenous fluids alongside steroid replacement.
• E. Oral treatment is inappropriate in a vomiting, shocked patient who cannot absorb oral medication reliably.

Resistant hypertension with unprovoked hypokalaemia and a suppressed renin with elevated aldosterone (high aldosterone:renin ratio) points to autonomous aldosterone secretion, most commonly from an adrenal adenoma or bilateral adrenal hyperplasia. This combination of findings is the classic screening pattern recommended by NICE and endocrine guidelines for suspected primary hyperaldosteronism. Confirmatory testing (saline suppression test) and adrenal CT or adrenal vein sampling follow a positive screen.

• A. Cushing's syndrome can cause hypertension and hypokalaemia but renin and aldosterone are typically normal, and other cushingoid features would be expected.
• B. Renal artery stenosis causes hypertension through activation of the renin-angiotensin system, so renin would be high, not low.
• C. Liddle syndrome causes hypokalaemic hypertension but through a renal sodium channel mutation with low aldosterone and low renin, not elevated aldosterone.
• D. Phaeochromocytoma causes episodic hypertension with palpitations, sweating and headache, not a low-renin hypokalaemic picture.

Episodic headache, palpitations, sweating and hypertension are classic for catecholamine-secreting phaeochromocytoma. Plasma free metanephrines (or 24-hour urinary fractionated metanephrines) have the highest sensitivity for this condition because metanephrines are produced continuously by tumour metabolism, unlike catecholamines themselves which fluctuate episodically. A positive biochemical result is followed by CT or MRI of the adrenals to localise the tumour.

• B. Abdominal ultrasound is insufficiently sensitive for adrenal lesions and is not the recommended first-line test; biochemical confirmation precedes imaging.
• C. Thyroid-stimulating hormone would be checked if thyrotoxicosis were suspected, but the episodic, self-limiting nature of symptoms is more typical of catecholamine excess.
• D. Dexamethasone suppression testing is used to diagnose Cushing's syndrome, not phaeochromocytoma.
• E. 24-hour urinary cortisol screens for Cushing's syndrome, which does not explain discrete episodic attacks with complete resolution.

Cabergoline, a dopamine agonist, is the first-line treatment for prolactinoma regardless of tumour size, because dopamine normally inhibits prolactin secretion and dopamine agonists both lower prolactin levels and shrink the tumour in most patients. It is preferred over bromocriptine due to better tolerability and once- or twice-weekly dosing. Surgery is reserved for patients who do not respond to or cannot tolerate dopamine agonists, or who have visual compromise despite medical therapy.

• A. Radiotherapy is used as a later option for residual or recurrent tumours, not first-line treatment.
• B. Hydrocortisone is used for cortisol deficiency, which is not present here.
• C. Surgery is reserved for cases resistant to dopamine agonists or with significant mass effect unresponsive to medical treatment, not as first-line therapy.
• E. Octreotide is a somatostatin analogue used for acromegaly or other growth hormone or TSH-secreting tumours, not prolactinomas.

Clinical features of acral and facial overgrowth with excessive sweating strongly suggest acromegaly from a growth-hormone-secreting pituitary tumour. Serum IGF-1 is the recommended initial screening test because it reflects integrated growth hormone secretion over time and is not subject to the pulsatile, episodic fluctuations of growth hormone itself. If IGF-1 is elevated, the diagnosis is confirmed with an oral glucose tolerance test, in which failure of growth hormone to suppress below 1 microgram/L supports acromegaly.

• B. The water deprivation test is used to diagnose diabetes insipidus, not acromegaly.
• C. Thyroid-stimulating hormone would be relevant if hypothyroidism were suspected, which does not fit this clinical picture.
• D. The short Synacthen test assesses adrenal cortisol reserve and is used to investigate adrenal insufficiency, not acromegaly.
• E. A single random growth hormone level is unreliable because secretion is pulsatile and can be normal or low at any given moment despite underlying acromegaly.

Bitemporal hemianopia results from compression of the crossing nasal retinal fibres at the optic chiasm, most commonly by an expanding pituitary macroadenoma growing upward from the sella turcica. The nasal fibres carry information from the temporal visual fields, so their compression causes loss of the outer (temporal) fields bilaterally while central vision is preserved until late disease. MRI of the pituitary fossa is the investigation of choice, alongside formal visual field testing and pituitary hormone profile.

• B. Glaucoma causes gradual peripheral field loss but typically produces arcuate scotomas and optic disc cupping, not a bitemporal pattern.
• C. Central retinal vein occlusion causes sudden unilateral visual loss with retinal haemorrhages on fundoscopy, not a bilateral field defect.
• D. Optic neuritis typically causes unilateral loss of visual acuity and colour vision with pain on eye movement, not a bitemporal field defect.
• E. Occipital lobe infarction causes a homonymous hemianopia affecting the same side of the visual field in both eyes, not a bitemporal pattern.

Sudden headache, visual disturbance, ophthalmoplegia and haemodynamic instability in a patient with a known pituitary tumour suggest pituitary apoplexy, caused by haemorrhage or infarction of the gland. This is an endocrine emergency because acute secondary adrenal insufficiency can cause life-threatening hypotension, so intravenous hydrocortisone must be given immediately, even before imaging confirmation, alongside fluid resuscitation. Urgent MRI confirms the diagnosis and neurosurgical review is needed to assess the need for decompression.

• A. Cabergoline treats prolactin-secreting tumours but has no role in the acute management of apoplexy with haemodynamic instability.
• B. Lumbar puncture risks herniation in the context of a sellar mass with raised intracranial pressure and is not indicated.
• C. Levothyroxine is given once pituitary thyroid axis failure is confirmed, but hydrocortisone replacement takes priority to prevent cardiovascular collapse.
• D. Mannitol is used to reduce raised intracranial pressure from cerebral oedema, not the priority here, where cortisol replacement is immediately life-saving.

Failure to concentrate urine despite fluid restriction, with a subsequent substantial rise in urine osmolality after desmopressin administration, indicates that the renal tubules can respond normally to antidiuretic hormone once it is supplied exogenously. This pattern confirms a deficiency of endogenous antidiuretic hormone secretion from the posterior pituitary, that is, cranial diabetes insipidus. In nephrogenic diabetes insipidus, the kidneys are unresponsive to antidiuretic hormone, so urine osmolality would remain low even after desmopressin.

• A. SIADH causes water retention and hyponatraemia with concentrated urine, the opposite picture of dilute polyuria with high serum sodium.
• B. Primary polydipsia results from excessive water intake suppressing antidiuretic hormone; urine osmolality typically rises substantially with fluid restriction alone before desmopressin is given.
• C. Diabetes mellitus causes osmotic polyuria from glycosuria, but normal plasma glucose excludes this and it does not explain the desmopressin response pattern.
• D. In nephrogenic diabetes insipidus the renal tubules are resistant to antidiuretic hormone, so urine osmolality would fail to rise significantly even after desmopressin is given.

This patient has hypotonic hyponatraemia with urine osmolality inappropriately higher than plasma osmolality, and a raised urine sodium, in a euvolaemic patient with normal thyroid and adrenal function. This pattern defines SIADH, where excess ADH causes water retention and dilutional hyponatraemia despite low plasma osmolality. Small cell lung cancer is a classic ectopic source of ADH secretion. Other causes to exclude include SSRIs, CNS pathology, and pneumonia.

• A. CKD would be expected to show a raised urea and other markers of renal impairment, not seen here.
• C. Primary polydipsia causes hyponatraemia with appropriately dilute (low osmolality) urine.
• D. Addison's disease would typically cause hyperkalaemia and hypotension, and adrenal function is stated as normal.
• E. Diabetes insipidus causes hypernatraemia with dilute urine, the opposite picture.

In chronic, mild-to-moderate, asymptomatic or mildly symptomatic SIADH, first-line management is fluid restriction, typically to around 1-1.5 litres per day, alongside addressing the underlying cause such as stopping the offending SSRI. Hypertonic saline is reserved for severe or symptomatic hyponatraemia with confusion, seizures, or reduced consciousness. Vasopressin receptor antagonists or demeclocycline are considered second-line if fluid restriction fails.

• A. Hypertonic saline is reserved for severe symptomatic hyponatraemia with neurological features, not seen here.
• B. Demeclocycline is a second-line option used only if fluid restriction fails.
• D. Isotonic saline is ineffective in SIADH because the sodium is excreted while water is retained, often worsening hyponatraemia.
• E. Furosemide is not first-line therapy for SIADH and risks further electrolyte disturbance.

Osmotic demyelination syndrome (central pontine myelinolysis) occurs when chronic hyponatraemia is corrected too rapidly, with sodium rising more than 8-10 mmol/L in 24 hours or more than 18 mmol/L in 48 hours. The rapid osmotic shift causes demyelination of pontine and extrapontine neurons, producing a delayed onset of dysarthria, dysphagia, quadriparesis, and altered consciousness, typically 2-6 days after correction. Sodium correction should be gradual, with close monitoring to avoid overcorrection.

• A. Ischaemic stroke typically produces a sudden focal deficit, not a delayed symmetrical presentation after sodium correction.
• B. Wernicke's encephalopathy presents with ophthalmoplegia, ataxia, and confusion, related to thiamine deficiency, not sodium correction.
• D. Cerebral oedema from hyponatraemia would present acutely with worsening of the original symptoms, not several days after correction.
• E. Hypertensive encephalopathy requires markedly elevated blood pressure, which is not described here.

Raised corrected calcium with a raised (or inappropriately normal) PTH and low phosphate is the classic biochemical pattern of primary hyperparathyroidism. A single parathyroid adenoma accounts for roughly 80-85% of cases, far more common than hyperplasia or carcinoma. Symptoms such as constipation, low mood, and bone pain reflect the effects of hypercalcaemia. Parathyroid carcinoma is rare and usually associated with markedly higher calcium and a palpable neck mass.

• A. Multiple myeloma causes hypercalcaemia with a suppressed PTH, not a raised one.
• B. Parathyroid carcinoma is a rare cause, typically presenting with very high calcium and a palpable neck mass.
• C. Familial hypocalciuric hypercalcaemia is rare and associated with low urinary calcium excretion, usually identified incidentally.
• D. Vitamin D deficiency causes secondary hyperparathyroidism with low or low-normal calcium, not hypercalcaemia.

Parathyroidectomy is the definitive treatment for symptomatic primary hyperparathyroidism, curing the disease by removing the source of excess PTH. Indications for surgery include symptomatic disease (renal stones, osteoporosis, fractures) or asymptomatic disease meeting specific criteria such as marked hypercalcaemia, significant renal impairment, or reduced bone density. Bisphosphonates and cinacalcet may be used to manage hypercalcaemia medically in patients unfit for or declining surgery, but they do not address the underlying cause.

• A. Supplementation does not treat the cause and would risk worsening hypercalcaemia.
• B. Zoledronic acid is used for acute hypercalcaemia management, not as definitive treatment of primary hyperparathyroidism.
• D. Cinacalcet lowers PTH secretion and is used in patients unsuitable for surgery, not as first-line definitive treatment.
• E. Alendronic acid can reduce bone turnover but does not treat the underlying parathyroid pathology.

Hypercalcaemia of malignancy, here likely due to PTH-related peptide from a squamous cell carcinoma, presents with a suppressed PTH distinguishing it from primary hyperparathyroidism. Initial management is rehydration with intravenous 0.9% sodium chloride to correct volume depletion and promote renal calcium excretion, followed by an intravenous bisphosphonate such as zoledronic acid to inhibit osteoclastic bone resorption. Bisphosphonates take 2-4 days to take full effect, so fluids are started immediately while awaiting this response.

• A. Cinacalcet is used for hyperparathyroidism, not first-line for hypercalcaemia of malignancy.
• B. Dialysis is reserved for severe hypercalcaemia with renal failure unresponsive to standard measures.
• D. Calcitonin alone has a rapid but short-lived effect and is not standard first-line monotherapy.
• E. Furosemide is not recommended first-line and can worsen dehydration if given before adequate rehydration.

Inadvertent removal or devascularisation of the parathyroid glands during thyroidectomy can cause acute hypoparathyroidism and hypocalcaemia. Perioral and peripheral paraesthesia are early symptoms. A positive Chvostek's sign (facial twitching on tapping the facial nerve) and Trousseau's sign (carpal spasm on cuff inflation) both reflect neuromuscular irritability from hypocalcaemia. Diagnosis is confirmed with a low corrected calcium and low or undetectable PTH, and treatment is with calcium and vitamin D replacement.

• B. A wound haematoma would present with neck swelling and respiratory distress, not these neurological signs.
• C. Recurrent laryngeal nerve injury causes hoarseness or voice change, not tetany or paraesthesia.
• D. Thyroid storm presents with fever, tachycardia, and agitation, not tetany signs.
• E. Hypomagnesaemia can cause similar signs but is far less common than hypoparathyroidism after thyroidectomy and is not the primary diagnosis here.

Osteomalacia results from vitamin D deficiency causing defective mineralisation of bone. The biochemical pattern is low or low-normal calcium, low phosphate, raised alkaline phosphatase from increased osteoblastic activity, and a compensatory secondary rise in PTH. Risk factors include reduced sunlight exposure, as in housebound elderly patients. Clinically it presents with diffuse bone pain, tenderness, and a proximal myopathy causing a waddling gait, distinguishing it from osteoporosis, which has normal biochemistry.

• A. CKD-mineral bone disorder is associated with renal impairment, which is not described here.
• C. Osteoporosis has normal calcium, phosphate, and alkaline phosphatase, with the diagnosis based on bone density rather than biochemistry.
• D. Paget's disease typically shows an isolated raised alkaline phosphatase with normal calcium, phosphate and PTH.
• E. Primary hyperparathyroidism causes raised calcium and low phosphate, not low calcium.

When the initial FRAX score without BMD falls in an intermediate range, NICE/NOGG guidance recommends arranging a DEXA scan and recalculating the FRAX score with the BMD value before deciding on treatment. This avoids starting bisphosphonates unnecessarily and avoids missing someone who truly needs treatment. Only after recalculation is the fracture risk compared against the intervention threshold to decide on drug treatment.

• A. A spinal X-ray is not part of the standard fracture risk assessment pathway.
• B. Supplementation alone does not address the need for formal risk recalculation with BMD.
• C. An intermediate FRAX result requires further assessment with DEXA, not simple reassurance.
• E. Starting treatment before a DEXA scan is premature when the initial risk is intermediate.

Oral bisphosphonates such as alendronic acid are poorly absorbed and highly irritant to the oesophageal mucosa, so they must be swallowed whole with plenty of water on an empty stomach, followed by remaining upright and avoiding food, drink or other medicines for at least 30 minutes. This reduces the risk of oesophagitis and oesophageal ulceration. Patients should also be counselled on good dental hygiene and to report jaw pain, as bisphosphonates carry a small risk of osteonecrosis of the jaw, particularly with dental extractions.

• A. Dissolving in milk reduces absorption and is not the recommended administration method.
• C. Food, including large meals, significantly reduces absorption of oral bisphosphonates.
• D. Fruit juice, like other drinks besides plain water, reduces absorption and should be avoided.
• E. Lying flat after taking the tablet increases the risk of oesophageal reflux and ulceration.

Paget's disease of bone typically presents with bone pain and deformity (such as bowing of a long bone) with an isolated markedly raised alkaline phosphatase but normal calcium, phosphate and PTH, reflecting localised increased bone turnover without a generalised metabolic bone disturbance. This biochemical pattern distinguishes it from other causes of bone pain and raised ALP. Plain X-ray typically shows characteristic lytic and sclerotic changes, and bisphosphonates are first-line treatment for symptomatic disease.

• A. Osteomalacia causes low calcium and phosphate with raised ALP, not normal calcium and phosphate.
• B. Bone metastases usually cause raised calcium and are unlikely to present with isolated bowing and normal calcium/phosphate.
• C. Myeloma typically causes raised calcium, renal impairment and normal (not markedly raised) ALP.
• D. Primary hyperparathyroidism causes raised calcium with low phosphate, not a normal calcium-phosphate profile.

A creatine kinase level more than 5 times the upper limit of normal with significant myalgia indicates clinically important statin-induced myopathy, so the statin should be stopped and other causes of muscle symptoms and raised CK (such as hypothyroidism or excessive exercise) investigated. Liver transaminases up to 3 times the upper limit of normal are usually acceptable to continue, but the combination here with marked CK rise and myalgia warrants stopping. Rechallenge with a lower dose or different statin can be considered once symptoms resolve and CK normalises.

• A. Continuing with symptomatic myopathy and markedly raised CK risks progression to rhabdomyolysis.
• C. Reducing the dose while continuing does not adequately address significant symptomatic myopathy with high CK.
• D. Adding another lipid-lowering drug does not address the need to stop the statin causing myopathy.
• E. Switching to another statin while symptomatic and CK is markedly raised is inappropriate before stopping and reassessing.

This patient meets the Simon Broome criteria for familial hypercholesterolaemia: an LDL cholesterol above 4.9 mmol/L (or total cholesterol above 7.5 mmol/L) in an adult, together with tendon xanthomata and a first-degree relative with premature myocardial infarction (before age 50 for men). Familial hypercholesterolaemia is an autosomal dominant condition, most commonly due to LDL receptor mutations, causing markedly elevated LDL from birth and early cardiovascular disease. Diagnosis prompts cascade testing of first-degree relatives and high-intensity statin therapy.

• A. Metabolic syndrome involves a cluster of findings including obesity, hypertension and dyslipidaemia, not isolated very high LDL with tendon xanthomata.
• B. Hypothyroidism can raise cholesterol but does not explain tendon xanthomata or the strong family history of premature MI; thyroid function would need to be checked but is not the primary diagnosis here.
• D. Polygenic hypercholesterolaemia causes milder elevations in cholesterol and does not typically cause tendon xanthomata.
• E. Lipoprotein lipase deficiency causes severe hypertriglyceridaemia with eruptive xanthomata, not isolated high LDL with tendon xanthomata.

This patient's combination of parathyroid, pituitary and pancreatic tumours is characteristic of MEN type 1, caused by mutations in the MEN1 gene encoding menin. Relatives of patients with MEN1 should be screened for the classic triad of parathyroid adenomas, pituitary tumours and pancreatic neuroendocrine tumours (including gastrinomas and insulinomas), as these are the most common associated tumours. Medullary thyroid carcinoma and phaeochromocytoma are features of MEN type 2, not MEN type 1.

• A. Medullary thyroid carcinoma is associated with MEN type 2, not MEN type 1.
• B. Phaeochromocytoma is a feature of MEN type 2, not the type 1 pattern seen here.
• D. Mucosal neuromas are a feature of MEN type 2B, not MEN type 1.
• E. C-cell hyperplasia is a precursor to medullary thyroid carcinoma, part of MEN type 2.