Primary Aldosteronism

Primary aldosteronism (PA) is autonomous aldosterone production independent of the renin-angiotensin system. It is the most common cause of secondary hypertension, affecting 5-13% of all hypertensive patients and up to 20% of resistant HTN. Two main subtypes: bilateral adrenal hyperplasia (BAH, ~60%) and aldosterone-producing adenoma (APA / Conn's syndrome, ~35%). The distinction matters because APA is surgically curable while BAH is treated medically. Classic lab triad: hypertension + hypokalemia + metabolic alkalosis, but most patients are normokalemic (hypokalemia is present in only 30-50%). PA causes cardiovascular damage disproportionate to BP -higher rates of stroke, MI, AF, and HF than essential HTN at the same BP level. PASO, 2017

• Step 1 -Screening (ARR): Plasma aldosterone concentration (PAC) / plasma renin activity (PRA) = aldosterone-to-renin ratio. ARR > 30 with PAC ≥ 10-15 ng/dL = positive screen. Draw morning, seated, K⁺-repleted. Hold interfering medications: spironolactone × 6 weeks, eplerenone × 6 weeks, ACEi/ARB acceptable (may cause false negatives). Endocrine Society, 2016
• Who to screen: Resistant HTN (≥ 3 drugs), HTN + hypokalemia, HTN + adrenal incidentaloma, HTN onset < 40, severe HTN (≥ 160/100), HTN + family history of early stroke or PA
• Step 2 -Confirmatory test (suppress aldosterone):
  • IV saline infusion test: 2L NS over 4h → measure PAC. If PAC > 10 ng/dL post-infusion = confirmed (aldosterone should suppress but doesn't).
  • Oral salt loading: High-sodium diet × 3 days → 24h urine aldosterone. > 12 mcg/24h = confirmed.
  • Fludrocortisone suppression test: Fludrocortisone 0.1 mg q6h × 4 days → PAC remains > 6. Most specific but rarely used (cumbersome, risk of hypokalemia).
• Step 3 -Subtype differentiation + localization:
  • CT adrenals -look for unilateral adenoma (> 1 cm). BUT: CT is wrong 38% of the time (nonfunctioning incidentaloma mimics APA, or microadenoma is missed).
  • Adrenal vein sampling (AVS) -gold standard to lateralize aldosterone production. Lateralization ratio ≥ 4:1 = unilateral source → surgery. Essential for ALL surgical candidates unless: age < 35 with clear > 1 cm unilateral adenoma + normal contralateral.

• Unilateral APA (Conn's): Laparoscopic adrenalectomy -cures hypokalemia in nearly all, cures or improves HTN in 50-80%. Pre-op: control BP and K⁺ with MRA (spironolactone or eplerenone). Post-op: monitor K⁺ (contralateral zona glomerulosa may be suppressed → transient hypoaldosteronism).
• Bilateral adrenal hyperplasia: Medical therapy with mineralocorticoid receptor antagonists (MRA):
  • Spironolactone 25-100 mg daily -most effective MRA. Anti-androgenic side effects: gynecomastia (up to 50% in men), menstrual irregularity, decreased libido. PATHWAY-2, 2015
  • Adjunct: Sodium restriction (< 2g/day), additional antihypertensives as needed (CCB, thiazide)
  • Monitoring K⁺ on MRA: Hyperkalemia risk, especially with CKD or ACEi/ARB combo. Check K⁺ + Cr at 1 week, 4 weeks, then q3-6 months.
  Monitoring

• K⁺ + Cr at 1 week, 4 weeks, then q3-6 months on MRA -hyperkalemia risk (especially with CKD, ACEi/ARB)
• BP -target < 130/80. Most patients need additional antihypertensives besides MRA.
• ARR is NOT useful for monitoring -it's only a screening test. Follow clinical endpoints (BP, K⁺).
• Post-adrenalectomy: Check K⁺ and aldosterone at 1 month. Expect transient hyperkalemia (suppressed contralateral adrenal). Hold MRA. Resume antihypertensives only if BP remains elevated.
• Annual cardiovascular risk assessment -PA causes disproportionate end-organ damage. Screen for AF, LVH (echo), proteinuria.