A 48-year-old woman presents to her physician for follow up due to persistently elevated blood pressure despite treatment with multiple medications. She reports taking her medications consistently and follows a low-sodium diet. She has occasional muscle weakness and cramping but denies episodic headaches, diaphoresis, palpitations, weight gain, easy bruising, or use of licorice-containing products. Her medical history includes hypertension diagnosed at age 36 and obstructive sleep apnea treated with continuous positive airway pressure (CPAP). Medications include amlodipine, lisinopril, hydrochlorothiazide, and doxazosin. Temperature is 36.8°C (98.2°F), blood pressure is 168/96 mm Hg in both arms, pulse is 72/min, and respiratory rate is 14/min. BMI is 29 kg/m². Cardiopulmonary examination is normal. There are no abdominal bruits, cushingoid features, or peripheral edema.
Laboratory studies show:
Sodium: 145 mEq/L
Potassium: 3.0 mEq/L
Bicarbonate: 31 mEq/L
Creatinine: 0.9 mg/dL
Hydrochlorothiazide and lisinopril are discontinued, potassium is corrected, and interfering medications are adjusted before hormonal testing. Repeat studies demonstrate a suppressed plasma renin activity and an elevated plasma aldosterone concentration, with an increased aldosterone-to-renin ratio.
Which of the following is the most appropriate next step in management?
The correct answer is:
B) Confirmatory aldosterone-suppression testing
This patient has resistant hypertension, spontaneous hypokalemia, metabolic alkalosis, suppressed renin activity, and an elevated aldosterone-to-renin ratio, all of which strongly suggest primary hyperaldosteronism. However, the aldosterone-to-renin ratio is a screening test rather than a definitive diagnostic test. The next step is generally confirmatory testing to demonstrate autonomous aldosterone production that cannot be appropriately suppressed.
Confirmatory options include saline infusion testing, oral sodium loading, fludrocortisone suppression testing, and the captopril challenge test. In a patient without severe uncontrolled hypertension, advanced kidney disease, or decompensated heart failure, saline infusion testing is commonly used. Failure of aldosterone to suppress after sodium loading supports the diagnosis of primary hyperaldosteronism.
Excess aldosterone increases sodium reabsorption in principal cells of the collecting duct while promoting renal potassium and hydrogen ion secretion. This produces hypertension, hypokalemia, and metabolic alkalosis. Sodium retention also expands intravascular volume, which suppresses renin release. Significant peripheral edema is uncommon because escape mechanisms, including increased natriuretic peptide secretion and pressure natriuresis, limit progressive volume expansion.
After biochemical confirmation, adrenal imaging is obtained to evaluate for an adrenal adenoma or bilateral adrenal hyperplasia. However, imaging alone cannot reliably establish whether an adrenal lesion is producing excess aldosterone. Most patients who are surgical candidates subsequently undergo adrenal vein sampling to distinguish unilateral from bilateral secretion before adrenalectomy.
Answer choice A: Adrenal vein sampling, is incorrect.
Adrenal vein sampling is used for subtype classification after primary hyperaldosteronism has been biochemically confirmed. It determines whether aldosterone secretion is unilateral, which may be treated with adrenalectomy, or bilateral, which is treated medically with a mineralocorticoid receptor antagonist. Performing this invasive procedure before confirming autonomous aldosterone secretion would be premature.
Answer choice C: CT angiography of the renal arteries, is incorrect.
Renovascular hypertension can cause resistant hypertension and is associated with abdominal bruits, asymmetric kidney size, recurrent flash pulmonary edema, or an acute rise in creatinine after initiation of an ACE inhibitor. Renal artery stenosis activates the renin-angiotensin-aldosterone system and therefore usually causes elevated renin activity. This patient’s suppressed renin level favors primary aldosterone excess rather than renovascular disease.
Answer choice D: Dexamethasone suppression testing, is incorrect.
Dexamethasone suppression testing is used to evaluate suspected endogenous hypercortisolism. Cushing syndrome can cause hypertension and hypokalemia when cortisol levels are sufficiently high to activate mineralocorticoid receptors, but patients often have central weight gain, proximal muscle weakness, easy bruising, purple striae, or glucose intolerance. The elevated aldosterone level with suppressed renin is more consistent with primary hyperaldosteronism.
Answer choice E: Plasma free metanephrine measurement, is incorrect.
Plasma free or urinary fractionated metanephrines are used to evaluate pheochromocytoma. Pheochromocytoma typically causes episodic or sustained hypertension accompanied by headaches, palpitations, diaphoresis, tremor, or panic-like symptoms. It does not characteristically cause suppressed renin with elevated aldosterone, hypokalemia, and metabolic alkalosis.
Key Learning Point
An elevated aldosterone-to-renin ratio is the preferred screening test for primary hyperaldosteronism. In most patients, autonomous aldosterone secretion should then be confirmed with suppression testing before adrenal imaging and adrenal vein sampling are used to determine the disease subtype.
