Management and Treatment of Primary Hyperaldosteronism

Diagnosis and Classification

The American College of Cardiology recommends screening for primary hyperaldosteronism in patients with resistant hypertension, hypokalemia, incidentally discovered adrenal mass, family history of early-onset hypertension, or stroke at a young age (<40 years) 1
The plasma aldosterone-to-renin ratio is the recommended screening test, according to the American College of Cardiology 1
Approximately 50% of primary aldosteronism cases are unilateral (usually aldosterone-producing adenoma) and 50% are bilateral (idiopathic hyperaldosteronism) 2, 3

The American College of Cardiology recommends laparoscopic unilateral adrenalectomy as the treatment of choice for unilateral disease 2, 3
Medical therapy with mineralocorticoid receptor antagonists (MRAs) is the cornerstone of treatment for bilateral disease, with spironolactone being the first-line treatment 2, 3
Low-dose dexamethasone treatment is recommended for familial hyperaldosteronism type 1 (glucocorticoid-remediable) 2

Hypokalemia is absent in the majority of primary aldosteronism cases and has low negative predictive value for diagnosis, according to the American College of Cardiology 1
Delayed diagnosis and treatment may lead to irreversible vascular remodeling, resulting in residual hypertension even after appropriate treatment 2
Adrenal vein sampling is crucial for accurate subtype determination but should be performed in specialized centers 2

Laparoscopic unilateral adrenalectomy is the treatment of choice for unilateral disease, which improves blood pressure in virtually 100% of patients and results in complete cure of hypertension in approximately 50% 4, 5
For patients who are not surgical candidates, medical therapy with MRAs is recommended 6

Eplerenone (50-100 mg daily in 1-2 doses) is an alternative MRA with fewer sexual side effects compared to spironolactone 7, 8

Avoid combining MRAs with other potassium-sparing medications or potassium supplements due to increased risk of hyperkalemia 7, 8
Use MRAs with caution in patients with significant renal dysfunction (eGFR <45 mL/min) 7, 8
Do not use MRAs in combination with ACE inhibitors or ARBs without careful monitoring due to increased risk of hyperkalemia 7, 8
Delayed diagnosis and treatment may lead to irreversible target organ damage, including cardiovascular and renal complications 4

The American College of Cardiology recommends eplerenone 50-100 mg daily for patients who develop gynecomastia, breast tenderness, or sexual dysfunction on spironolactone, with equal effectiveness to spironolactone for blood pressure control in bilateral idiopathic hyperaldosteronism 9, 10
The American Heart Association suggests verifying serum potassium ≤5.0 mEq/L and confirming serum creatinine <2.0-2.5 mg/dL or eGFR >30 mL/min before initiating any aldosterone antagonist, with discontinuation of potassium supplements 11, 12, 13

The American College of Cardiology advises against combining aldosterone antagonists with potassium supplements or potassium-sparing diuretics, ACE inhibitors or ARBs without close monitoring, and NSAIDs or COX-2 inhibitors due to increased risk of hyperkalemia and renal dysfunction 9, 11, 12, 13
The American Heart Association recommends checking potassium and creatinine at 3 days, 1 week, then monthly for the first 3 months, and subsequently monitoring every 3 months if stable 11, 12, 13

The American College of Cardiology guidelines identify spironolactone as the preferred agent for primary aldosteronism and resistant hypertension, with eplerenone listed as an alternative 9, 10

Screening threshold: An aldosterone‑to‑renin ratio (ARR) ≥ 30 combined with a plasma aldosterone concentration of ≥ 10–15 ng/dL identifies patients who should undergo confirmatory testing. 14
Confirmatory testing: Diagnosis is confirmed with either a saline infusion suppression test or an oral sodium‑loading protocol with 24‑hour urinary aldosterone measurement. 14
Prevalence of normokalemia: Approximately 50 % of individuals with primary aldosteronism do not exhibit hypokalemia, underscoring that low potassium should not be used as a screening criterion. 14

Surgical therapy: Laparoscopic unilateral adrenalectomy is the definitive treatment, producing blood‑pressure improvement in virtually all patients (≈ 100 %) and achieving complete hypertension cure in about half of them (≈ 50 %). 14

Medical therapy: Lifelong treatment with mineralocorticoid‑receptor antagonists (MRAs) is the cornerstone of management for bilateral adrenal hyperplasia. 14

Specialist referral: All patients with a confirmed diagnosis of primary aldosteronism should be referred to a hypertension specialist or endocrinologist for subtype determination and individualized treatment planning. 14