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Stem
A 50-year-old woman is referred to the hypertension clinic. Her blood pressure is 162/98 mmHg despite amlodipine 10 mg, lisinopril 20 mg and indapamide 2.5 mg daily. She complains of muscle cramps, fatigue and waking twice at night to pass urine. Bloods show potassium 2.9 mmol/L (on indapamide), sodium 142 mmol/L, creatinine 84 micromol/L and a venous bicarbonate of 32 mmol/L. An ECG shows prominent U waves. A serum aldosterone is 650 pmol/L (high) with a suppressed plasma renin, giving an aldosterone-to-renin ratio of 220 (reference under 30).
Questions
a) What is the most likely diagnosis, and which three features in the stem support it? (2 marks)
Model answer: Primary aldosteronism (Conn syndrome) (1 mark). Any three of: resistant hypertension (above target on three agents including a diuretic), hypokalaemia (spontaneous or diuretic-induced), metabolic alkalosis (raised bicarbonate), an elevated aldosterone-to-renin ratio with suppressed renin, or muscle weakness/cramps and nocturia from hypokalaemic nephrogenic diabetes insipidus (1 mark).
b) Outline the next two diagnostic steps after the screening test, naming the tests and their purpose. (3 marks)
Model answer: The ARR is the case-finding (screening) test and is already abnormal, so the next steps are: (1) CONFIRM autonomous aldosterone secretion with a suppression test — oral salt loading, saline infusion, fludrocortisone suppression, or a captopril challenge — in which aldosterone fails to suppress (stop the mineralocorticoid antagonist and correct interfering drugs first) (1.5 marks). (2) LOCALISE and subtype with CT of the adrenal glands for anatomy followed by adrenal venous sampling (AVS) to prove unilateral versus bilateral disease — AVS is the gold standard before surgery because CT cannot reliably distinguish a functioning adenoma from a non-functioning incidentaloma (1.5 marks).
c) Describe the treatment for (i) unilateral disease and (ii) bilateral disease. (3 marks)
Model answer: (i) Unilateral disease (adenoma or unilateral hyperplasia, proven by AVS): laparoscopic adrenalectomy — potentially curative; a mineralocorticoid receptor antagonist (spironolactone or eplerenone) is given beforehand to control blood pressure and correct potassium (1.5 marks). (ii) Bilateral adrenal hyperplasia (or a patient unfit/unwilling for surgery): medical therapy with a mineralocorticoid receptor antagonist — spironolactone first-line; switch to eplerenone if gynaecomastia, impotence or menstrual irregularity are intolerable; add other antihypertensives (ACEi/ARB, calcium-channel blocker) and sodium restriction (1.5 marks).
d) The patient asks whether a normal potassium would have excluded the diagnosis. Give two clinical settings in which you would screen regardless of the potassium, and name one condition that mimics primary aldosteronism but has a LOW aldosterone. (2 marks)
Model answer: A normal potassium does NOT exclude primary aldosteronism — most patients are normokalaemic. Screen regardless of potassium for any two of: resistant hypertension (above target on three agents including a diuretic), spontaneous or diuretic-induced hypokalaemia, an adrenal incidentaloma, or early-onset hypertension or stroke under 40 (or a family history) (1 mark). A mimic with LOW aldosterone (and low renin) is Liddle syndrome — an epithelial sodium channel (ENaC) gain-of-function pseudoaldosteronism, treated with amiloride (1 mark).