What is Primary Aldosteronism?
Primary aldosteronism is a condition characterized by excessive and autonomous production of aldosterone by the adrenal glands that is independent of the renin-angiotensin system and cannot be suppressed with sodium loading, distinguishing it from normal physiologic aldosterone secretion. 1, 2
Pathophysiology
The hallmark of primary aldosteronism is aldosterone production that operates independently of renin and angiotensin II, meaning the adrenal glands produce excessive aldosterone regardless of the body's actual sodium status or blood pressure 1, 3
This autonomous aldosterone excess causes sodium retention, suppression of plasma renin activity, and increased potassium excretion in the distal renal tubule, which can lead to hypokalemia if prolonged and severe—though importantly, hypokalemia is absent in approximately 50% of cases 1, 2
The excessive aldosterone induces hypertension through volume expansion from sodium retention, but also causes direct toxic effects on cardiovascular and renal tissues that produce damage beyond what would be expected from elevated blood pressure alone 1, 3
Subtypes and Causes
Approximately 50% of patients have unilateral disease, most commonly an aldosterone-producing adenoma (a solitary benign tumor that autonomously secretes aldosterone), or rarely unilateral adrenal hyperplasia 1, 2
The remaining 50% have bilateral adrenal hyperplasia (also called idiopathic hyperaldosteronism), where both adrenal glands produce excess aldosterone 1
Recent genetic discoveries show that somatic mutations drive autonomous aldosterone production in most adenomas, and rare germline mutations cause familial forms (familial hyperaldosteronism types 1-4) 4, 3
Clinical Significance and Prevalence
Primary aldosteronism is the most common endocrine cause of hypertension, affecting 5-10% of all hypertensive patients and up to 20% of those with resistant hypertension 2, 5
Despite being common, it remains markedly underdiagnosed—only about 2% of eligible patients are actually tested and diagnosed 6, 5
Patients with primary aldosteronism have dramatically worse cardiovascular outcomes than those with primary hypertension at equivalent blood pressure levels, including 3.7-fold increased heart failure, 4.2-fold increased stroke, 6.5-fold increased myocardial infarction, and 12.1-fold increased atrial fibrillation 2
Target Organ Damage
The toxic tissue effects of aldosterone produce widespread fibrosis and increased cardiovascular and kidney damage through mechanisms independent of blood pressure elevation 1, 3
Excess aldosterone exerts direct toxic effects on renal tubular cells, leading to tubular injury, inflammation, and fibrosis with increased urinary markers of tubular damage 1
Importantly, these deleterious effects are often reversible with appropriate treatment—either surgical removal of a unilateral adenoma or medical therapy with mineralocorticoid receptor antagonists 1
Key Clinical Features
Hypertension is the primary manifestation, often resistant to standard antihypertensive therapy (blood pressure not controlled on 3 medications including a diuretic) 6
Hypokalemia should NOT be relied upon as a screening marker—it is absent in the majority of cases 6, 2
The condition can present across a wide spectrum of severity, from mild to overt forms, all of which correlate with increased cardiovascular risk 3