Primary aldosteronism

What changes during this transition

Primary aldosteronism is the single most important 'hypertension you should not be calling essential hypertension' diagnosis in adult medicine — and the diagnostic miss rate is the editorial point. PA accounts for 5-10% of all hypertension and roughly 20% of resistant hypertension, yet the screening rate in eligible patients is in the low single digits across most health systems. People accumulate years of antihypertensives, atrial fibrillation, strokes, and chronic kidney disease that were structurally preventable with an Aldosterone-to-Renin Ratio (ARR) drawn at the front of the workup. The pathophysiology is autonomous: aldosterone-producing tissue (a unilateral adenoma — Conn syndrome — or bilateral adrenal hyperplasia) secretes mineralocorticoid independent of the renin-angiotensin loop. The downstream cascade is sodium retention, potassium wasting (though normokalemic PA is now recognized as the majority phenotype — the 'you need hypokalemia to screen' teaching is wrong and has done diagnostic damage for decades), volume expansion, and direct mineralocorticoid receptor activity on heart, vessel, and kidney that drives atrial fibrillation at roughly 3x the rate of essential hypertension at matched blood pressure, stroke at roughly 2x, and myocardial infarction at roughly 2x. The workup has a fixed shape. Screening is the ARR, drawn off interfering medications where possible — mineralocorticoid receptor antagonists, beta blockers, and ACE inhibitors/ARBs all distort the result. A positive ARR (typically >20-30 with aldosterone >15 ng/dL, though cutoffs vary by lab) triggers a confirmatory test: saline suppression, oral salt loading with 24-hour urine aldosterone, captopril challenge, or fludrocortisone suppression. Adrenal CT comes next — but CT misses small APAs and over-calls non-functioning adrenal incidentalomas, which is exactly why adrenal vein sampling (AVS) is the gold standard for lateralization in patients over 35 who are surgical candidates. AVS is technically difficult, performed at experienced centers, and is the single step that distinguishes unilateral disease (surgically curable) from bilateral disease (lifelong medical management). Treatment forks at lateralization. Unilateral APA — Conn syndrome — gets laparoscopic adrenalectomy, with clinical or biochemical cure in roughly 50% and meaningful improvement in most of the remainder. Bilateral adrenal hyperplasia gets mineralocorticoid receptor antagonism: spironolactone first-line (effective but anti-androgenic at clinical doses — gynecomastia, breast tenderness, menstrual irregularity, erectile dysfunction); eplerenone for selectivity in patients who can't tolerate spironolactone (cleaner side effect profile but less potent); finerenone (Kerendia) as the non-steroidal MRA approved 2021 for diabetic CKD with emerging PA application via FIDELIO-DKD and FIGARO-DKD; esaxerenone as the non-steroidal MRA approved in Japan 2019. Potassium and magnesium repletion run alongside; dietary sodium restriction matters but the response curve is more complex than in essential hypertension. The paradigm-shift drug class is aldosterone synthase inhibition. Baxdrostat (CIN-107) hits aldosterone synthesis at the CYP11B2 enzyme, with the BrigHTN Phase 2 trial reading out positive in 2022 for treatment-resistant hypertension and Phase 3 programs ongoing. Lorundrostat (MLS-101) is the parallel program — Target-HTN Phase 2 positive 2024, Phase 3 ongoing. If these readouts hold, aldosterone synthesis blockade becomes a meaningfully different intervention than receptor antagonism: blocking the hormone at source rather than blocking its action at receptor. Peptides do not occupy a therapeutic seat at this table. The peptides users will see promoted in adrenal or hypertension framings — BPC-157 with 'adrenal healing' claims, NMN with general blood-pressure narratives, Thymosin alpha-1 with adrenal-autoimmune misframing — are not interventions for autonomous aldosterone secretion driven by clonal adenoma or bilateral hyperplasia. Substrate exists here so /ask can give honest answers when users ask. The story is: get screened, get diagnosed correctly, get treated by an endocrinologist with the right algorithm.