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This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.
The Bottom Line
- Primary aldosteronism is a common secondary cause of resistant hypertension
- Classic clue: hypertension + hypokalemia + metabolic alkalosis, but potassium may be normal
- Screen with plasma aldosterone-renin ratio; aldosterone high and renin suppressed
- Unilateral aldosterone-producing adenoma: adrenalectomy; bilateral hyperplasia: mineralocorticoid receptor antagonist
- Spironolactone can cause gynecomastia; eplerenone is more selective
Overview
Primary hyperaldosteronism is autonomous aldosterone secretion independent of renin-angiotensin regulation. Aldosterone increases sodium retention, potassium and hydrogen ion excretion, and cardiovascular remodeling. It should be suspected in resistant hypertension, hypertension with spontaneous or diuretic-induced hypokalemia, adrenal incidentaloma with hypertension, early-onset hypertension, family history of early stroke, or hypertension with sleep apnea.
Epidemiology
Primary aldosteronism is more common than historically recognized and may account for a meaningful proportion of resistant hypertension. Major etiologies include unilateral aldosterone-producing adenoma and bilateral adrenal hyperplasia. Less common causes include unilateral adrenal hyperplasia, familial hyperaldosteronism, and adrenal carcinoma. Many patients are normokalemic, so absence of hypokalemia does not exclude the diagnosis.
Clinical Features
Symptoms
Often asymptomatic apart from hypertension
Muscle weakness, cramps, fatigue from hypokalemia
Polyuria or polydipsia from hypokalemia-induced nephrogenic diabetes insipidus
Headache or symptoms of severe hypertension
Palpitations or arrhythmia symptoms from hypokalemia
Signs
Sustained or resistant hypertension
Hypokalemia, sometimes precipitated by thiazide or loop diuretic
Metabolic alkalosis
No edema despite sodium retention because of aldosterone escape
Target organ damage disproportionate to apparent BP duration
Investigations
First-line
Plasma aldosterone-renin ratioScreening test: high aldosterone with suppressed renin. Correct hypokalemia before testing because low K+ can suppress aldosterone
BMPHypokalemia and metabolic alkalosis support diagnosis; potassium may be normal
Medication reviewMR antagonists, diuretics, ACEi/ARB, beta-blockers, and other antihypertensives can affect renin/aldosterone interpretation
Second-line
Confirmatory suppression testingSaline infusion, oral salt loading, fludrocortisone suppression, or captopril challenge depending on patient factors
Adrenal CTIdentify adrenal mass and exclude carcinoma after biochemical diagnosis
Urine potassiumConfirms renal potassium wasting when hypokalemia is present
Specialist
Adrenal venous samplingBest test to lateralize unilateral vs bilateral aldosterone secretion before surgery in most candidates
Genetic testingConsider familial hyperaldosteronism in young onset or strong family history
1
Who to screen
- Resistant hypertension; hypertension with hypokalemia; hypertension with adrenal incidentaloma
- Severe hypertension, early-onset hypertension, family history of early stroke, or hypertension with sleep apnea
2
Confirm diagnosis
- Screen with aldosterone-renin ratio under appropriate conditions
- Confirm autonomous aldosterone secretion unless classic severe phenotype makes confirmation unnecessary per specialist judgment
- Assess cardiovascular and renal risk because aldosterone excess causes damage beyond BP alone
3
Subtype and treat
- Unilateral disease: laparoscopic adrenalectomy if surgical candidate
- Bilateral adrenal hyperplasia or non-surgical candidate: spironolactone or eplerenone
- Correct hypokalemia and monitor renal function and potassium after treatment
4
Long-term care
- Monitor BP, potassium, creatinine, and renin response
- Continue cardiovascular risk reduction and adjust other antihypertensives as BP improves
Complications
- Cardiovascular disease: LVH, atrial fibrillation, stroke, MI, and heart failure risk exceed essential hypertension at similar BP
- Chronic kidney disease: Hyperfiltration may mask renal injury before treatment
- Arrhythmias: Hypokalemia increases ventricular arrhythmia risk
- Medication adverse effects: Spironolactone can cause gynecomastia, menstrual irregularity, and hyperkalemia
- Post-adrenalectomy hypoaldosteronism: Transient hyperkalemia can occur after unilateral adrenalectomy
USMLE Step 2 CK Exam Tips
- 1Most common endocrine cause of secondary hypertension tested: primary aldosteronism
- 2Hypertension + hypokalemia = aldosterone-renin ratio
- 3Renin is suppressed in primary hyperaldosteronism; both renin and aldosterone are high in secondary hyperaldosteronism
- 4No edema despite aldosterone excess because of aldosterone escape
- 5Adrenal CT does not prove lateralization; adrenal venous sampling is usually needed before surgery
- 6Unilateral adenoma = adrenalectomy; bilateral hyperplasia = spironolactone/eplerenone
- 7Hypokalemia can cause nephrogenic diabetes insipidus with polyuria
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