Hypertension and Secondary Hypertension — Advanced

Correct answer: Obtain ambulatory blood pressure monitoring (24-hour ABPM) and assess adherence. True resistant hypertension should be confirmed by demonstrating persistently elevated out-of-office blood pressure and ensuring adequate adherence and dosing. White-coat effect and non-adherence are common causes of apparent resistant hypertension. ABPM (or home BP monitoring) provides objective measurement outside the clinic; concurrently adherence should be optimised (pill counts, pharmacy records, direct questioning).

Why the others are less appropriate:
- Adding spironolactone (A) before confirming true resistance risks unnecessary drug exposure and side effects; spironolactone is often effective for true resistant hypertension but should be used after confirming resistance and evaluating secondary causes.
- Proceeding immediately to renin/aldosterone testing (B) or CT angiography (C) assumes a secondary cause without first confirming persistent out-of-office hypertension and adherence; this leads to unnecessary investigations and misinterpretation (medications can confound tests).
- Starting clonidine (E) is not appropriate to diagnose resistant hypertension and has adverse effects; it is not recommended as a next diagnostic or first-line intervention in this context.

In summary, before embarking on further investigations or adding fourth-line agents, confirm uncontrolled hypertension with ABPM and assess adherence.

Correct answer: Stop spironolactone for at least 4–6 weeks and switch to antihypertensives that have minimal effect on the ARR before testing. Mineralocorticoid receptor antagonists (spironolactone, eplerenone) markedly alter aldosterone and renin levels, rendering the ARR unreliable; they should be withdrawn for several weeks before ARR screening. If blood pressure needs treatment during washout, use agents that minimally affect ARR (e.g., verapamil, hydralazine, doxazosin, amlodipine), with close monitoring.

Why the others are less appropriate:
- Measuring ARR now (B) risks false-negative or false-positive results due to drug interference and is not reliable.
- Proceeding directly to CT (C) without biochemical confirmation is inappropriate because adrenal imaging alone cannot distinguish unilateral from bilateral disease and adenomas/incidentalomas are common; biochemical confirmation is required before imaging.
- Replacing spironolactone with high-dose amlodipine and measuring ARR the next day (D) is inadequate: the washout period for spironolactone is several weeks because of lasting effects on the aldosterone pathway.
- Adrenal vein sampling (E) is an invasive procedure used to lateralise disease after biochemical confirmation; it is not appropriate without prior reliable biochemical screening.

Thus the first step is cessation of interfering drugs with safe alternative antihypertensives and then ARR testing.

CT renal angiography is an appropriate non-invasive next test in a patient with a high pre-test probability of atherosclerotic renal-artery stenosis, reasonable kidney function, and difficulty tolerating MRI. Duplex ultrasound is a reasonable alternative where expertise is available. Invasive digital subtraction angiography is generally reserved for situations in which revascularisation is planned or non-invasive imaging is inconclusive, because it carries procedural and contrast risks.

Correct answer: Plasma-free metanephrines (or urinary fractionated metanephrines). Biochemical confirmation of pheochromocytoma is best achieved by measurement of plasma free metanephrines or 24-hour urinary fractionated metanephrines; these tests have high sensitivity. If results are equivocal, clonidine suppression or repeat testing may be used. Appropriate biochemical confirmation is required before any intervention.

Why the others are less appropriate:
- Plasma aldosterone and renin (A) assess mineralocorticoid excess, not catecholamine-secreting tumours.
- Serum cortisol at 0900 h (C) screens for Cushing's syndrome, not pheochromocytoma.
- Measuring plasma free normetanephrine only (D) is incomplete—both metanephrine and normetanephrine should be measured because tumours can produce one or both metabolites.
- Adrenal biopsy (E) is contraindicated prior to biochemical confirmation because biopsy can precipitate a hypertensive crisis and is not useful to diagnose functional adrenal tumours; biopsy of an adrenal mass is only considered in selected cases when metastasis is suspected and biochemical causes have been excluded.

After biochemical confirmation, localisation imaging and perioperative alpha- then beta-blockade are required for safe management.

Correct answer: Begin controlled intravenous BP reduction with a titratable agent (e.g., IV labetalol or nitroprusside). This presentation is consistent with malignant hypertensive emergency with microangiopathic haemolysis (hypertensive thrombotic microangiopathy). The priority is controlled reduction of mean arterial pressure using intravenous, titratable antihypertensives to limit further end-organ damage. Rapid but controlled lowering (not precipitous) is essential.

Why the others are less appropriate:
- Plasma exchange (A) is the treatment for TTP; although the lab picture can be similar, in hypertensive emergency the first step is BP control. TTP should be considered if features persist despite BP control or ADAMTS13 testing supports it.
- Rapid oral nifedipine (B) is not recommended—immediate large drops in BP with sublingual or rapid oral agents can cause ischaemia; IV titratable agents are preferred in hypertensive emergencies.
- High-dose corticosteroids and renal biopsy (D) are not initial steps and carry risk; biopsy is contraindicated acutely until BP is controlled and the diagnosis is clearer.
- Immediate haemodialysis (E) without addressing severe hypertension is inappropriate unless there is refractory uraemia or hyperkalaemia; BP control is the immediate priority.

After stabilisation, evaluate for secondary causes and manage complications; specialist input from nephrology and ophthalmology is required.

Correct answer: Stop the ACE inhibitor and arrange urgent renal imaging to assess for bilateral renal-artery stenosis. An acute rise in creatinine ≥30% after starting an ACE inhibitor suggests haemodynamically significant renal-artery stenosis (especially if bilateral or single functioning kidney) and ACEi should be stopped. Bilateral RAS can precipitate acute kidney injury due to dependence on angiotensin II–mediated efferent arteriolar constriction; cessation may permit recovery and further imaging/investigation is indicated.

Why the others are less appropriate:
- Continuing the ACE inhibitor (B) risks progression to severe AKI; the threshold for stopping is typically a creatinine rise >30% (some clinicians use >30–50%).
- Adding a loop diuretic (C) is unlikely to correct the cause and may worsen renal perfusion/hypovolaemia.
- Increasing ACE inhibitor dose (D) is contraindicated in the context of creatinine rise and oliguria.
- Arranging dialysis (E) may become necessary if uraemia, fluid overload or severe electrolyte disturbance occurs, but immediate management is to stop the offending agent and investigate reversible causes; dialysis is not the first reflex.

After stopping the ACE inhibitor, reassess renal function and consider imaging for RAS if creatinine remains abnormal or hypertension is resistant; multidisciplinary discussion is required for revascularisation decisions.

Correct answer: Aortic coarctation; perform CT aortography to define the anatomy for possible repair. The clinical triad of upper limb hypertension, brachial–femoral delay and differential blood pressures with weak femoral pulses is classical for coarctation of the aorta. In adults, CT aortography (or MR angiography if renal function permits) gives high-resolution anatomy to plan surgical or endovascular repair (stenting) and assess collateral circulation.

Why the others are less appropriate:
- Takayasu arteritis (A) can cause limb blood-pressure differences but typically affects young women and is an inflammatory large-vessel vasculitis; investigations may include imaging for vessel inflammation, but the described classical coarctation features (femoral delay) point to congenital coarctation.
- Subclavian steal (C) causes arm claudication and vertebrobasilar symptoms with reversal of vertebral flow, usually produces arm BP asymmetry but not the brachial–femoral delay or weak femoral pulses characteristic of coarctation.
- Horner's syndrome (D) causes ptosis, miosis and anhidrosis, unrelated to limb BP differences.
- Pulmonary hypertension (E) would not cause the peripheral findings described.

Appropriate referral to cardiothoracic/vascular services is required after imaging for definitive management.

Correct answer: 1 mg overnight dexamethasone suppression test (overnight DST) or late-night salivary cortisol. The recommended first-line screening tests for Cushing's syndrome are either late-night salivary cortisol (sensitive for loss of diurnal variation) or the 1 mg overnight dexamethasone suppression test; both are validated screening tools for endogenous hypercortisolism. Choice depends on clinical context and local availability.

Why the others are less appropriate:
- Random midday cortisol (A) is not reliable for screening because cortisol has diurnal variation.
- Plasma ACTH alone (B) is used after biochemical confirmation of hypercortisolism to distinguish ACTH-dependent from ACTH-independent causes; it is not a screening test.
- Serum aldosterone and renin (D) screen for primary aldosteronism, not Cushing's.
- Plasma free metanephrines (E) screen for pheochromocytoma, not cortisol excess.

Once hypercortisolism is biochemically confirmed, further testing (e.g., 24-hour urinary free cortisol, low-dose dexamethasone suppression, imaging, and ACTH measurement) is required to subtype and plan management.

Correct answer: Begin amiloride (an ENaC blocker). The clinical picture (early-onset hypertension, hypokalaemia, low renin and low aldosterone) strongly suggests Liddle's syndrome, an activating mutation of the epithelial sodium channel (ENaC). The appropriate specific therapy is an ENaC blocker such as amiloride (or triamterene). These agents directly inhibit the mutated channel and correct sodium retention and hypokalaemia.

Why the others are less appropriate:
- Spironolactone (A) acts at the mineralocorticoid receptor and is ineffective in Liddle's syndrome because aldosterone levels are low and the defect is downstream at the channel.
- ACE inhibitors (B) reduce angiotensin II and aldosterone but are inadequate as targeted therapy for genetic ENaC activation; they may reduce BP modestly but do not correct the channel defect.
- High-dose thiazide diuretics (D) may worsen hypokalaemia and are not specific treatment.
- Fludrocortisone (E) is a mineralocorticoid agonist and would worsen hypertension and hypokalaemia.

Genetic testing and family screening should be considered once clinical suspicion is high; ENaC blockade is the specific treatment.

Correct answer: Switch lisinopril to labetalol or nifedipine, as ACE inhibitors are contraindicated in pregnancy. ACE inhibitors (and ARBs) are teratogenic and associated with foetal renal dysplasia and oligohydramnios; they should be stopped preconception or as soon as pregnancy is recognised. First-line antihypertensives in pregnancy include labetalol, nifedipine (modified-release), and methyldopa depending on the clinical situation and local guidance.

Why the others are less appropriate:
- Continuing lisinopril (A) risks serious foetal adverse effects and is contraindicated.
- Replacing with an ARB (C) is also contraindicated—ARBs have similar teratogenic risks.
- Spironolactone (D) is generally avoided in pregnancy due to anti-androgenic effects and lack of safety data; it is not first-line for resistant hypertension in pregnancy.
- Atenolol (E) is associated with fetal growth restriction when used in pregnancy and is not the preferred agent; labetalol and nifedipine are preferred.

Management should involve obstetric and hypertension specialists, with drug changes ideally made before conception when possible.