Primary Aldosteronism: Pathophysiology and Management

Pathophysiology

Primary aldosteronism is characterized by excessive and autonomous production of aldosterone by the adrenal glands, independent of the renin-angiotensin system, according to the American College of Cardiology and the American Heart Association 1, 2
Excessive aldosterone production induces hypertension, cardiovascular and renal damage, sodium retention, suppression of plasma renin activity, and increased potassium excretion, which can cause hypokalemia if prolonged and severe, as stated by the American College of Cardiology 2
Approximately 50% of patients with primary aldosteronism have unilateral increased aldosterone production, usually due to an aldosterone-producing adenoma or, rarely, unilateral adrenal hyperplasia, as reported by the American Heart Association 1, 2
The remaining 50% of patients have bilateral adrenal hyperplasia (idiopathic hyperaldosteronism), according to the American College of Cardiology and the American Heart Association 1, 2

The American College of Cardiology recommends screening for primary aldosteronism in adults with hypertension in the presence of certain concurrent conditions, including resistant hypertension, hypokalemia, incidentally discovered adrenal mass, family history of early-onset hypertension, and stroke at a young age (<40 years) 1, 2, 3
The aldosterone-to-renin ratio is recommended as a screening method, with a common cutoff value of 30 when plasma aldosterone concentration is reported in nanograms per deciliter (ng/dL) and plasma renin activity in nanograms per milliliter per hour (ng/mL/h), as stated by the American College of Cardiology 2
A plasma aldosterone concentration of at least 10 ng/dL is required to interpret the test as positive, according to the American College of Cardiology 2

The American College of Cardiology recommends unilateral laparoscopic adrenalectomy as the treatment of choice for unilateral primary aldosteronism, which improves blood pressure in nearly 100% of patients and achieves complete cure of hypertension in approximately 50% of cases, as reported by the Journal of the American College of Cardiology, but not from Praxis Medical Insights 4
Medical treatment with mineralocorticoid receptor antagonists (MRAs) is the basis of management for bilateral primary aldosteronism, with spironolactone as the first-line treatment, as recommended by the American College of Cardiology, but the specific details are from the Journal of the American College of Cardiology 2
The American Heart Association states that the effects of excessive aldosterone production are often reversible with unilateral laparoscopic adrenalectomy or treatment with MRAs, reducing adverse cardiovascular events associated with primary aldosteronism 2

Excess aldosterone exerts direct toxic effects on renal tubular cells through mechanisms independent of blood pressure elevation, leading to tubular injury, inflammation, and fibrosis that manifests as increased urinary markers of tubular damage, according to the American Heart Association 5
The toxic tissue effects of aldosterone produce widespread tissue fibrosis and increased kidney damage compared to patients with primary hypertension matched for blood pressure level, demonstrating that the damage occurs through mechanisms beyond hypertension alone, as reported by the American College of Cardiology 5
The deleterious effects of aldosterone overproduction are often reversible with unilateral laparoscopic adrenalectomy or treatment with mineralocorticoid receptor antagonists, which can improve cardiac and kidney function parameters, as stated by the American Heart Association 5
Patients with primary aldosteronism have a 12-fold increased risk of target organ damage including kidney injury compared to primary hypertension, emphasizing the importance of early diagnosis and treatment, according to the American College of Cardiology 5
Do not rely on the presence of hypokalemia to suspect renal damage, as it is absent in the majority of primary aldosteronism cases, yet tubular damage still occurs, as warned by the American Heart Association 5