Primary Hyperaldosteronism (Conn Syndrome)

Risk factors

• Resistant hypertension (BP uncontrolled on 3+ antihypertensives including a diuretic)
• Hypertension with spontaneous or diuretic-induced hypokalemia
• Hypertension with adrenal incidentaloma
• Onset of hypertension at young age (<40)
• Family history of early stroke or aldosteronism
• Familial hyperaldosteronism types I-IV (rare; FH-I = glucocorticoid-remediable aldosteronism, CYP11B1/CYP11B2 chimeric gene)

Pathophysiology

Aldosterone activates mineralocorticoid receptors in distal nephron, increasing sodium reabsorption and potassium/hydrogen excretion. Volume expansion produces hypertension and feedback suppresses renin. Direct cardiovascular effects (independent of BP) drive vascular fibrosis, LVH, and increased stroke/MI risk compared to age- and BP-matched essential hypertension.

Clinical presentation

Differential diagnosis

• Essential hypertension — Normal aldosterone:renin ratio (ARR); no spontaneous hypokalemia
• Secondary hyperaldosteronism — High renin AND high aldosterone — renovascular disease, diuretic use, CHF, cirrhosis, renin-secreting tumor
• Cushing syndrome — Cortisol activates mineralocorticoid receptor (especially severe); 24-h UFC, dexamethasone suppression
• Apparent mineralocorticoid excess — Licorice ingestion or genetic 11β-HSD2 deficiency; cortisol acts as mineralocorticoid; low aldosterone AND low renin
• Liddle syndrome — AD gain-of-function ENaC mutation; HTN + hypokalemia with low aldosterone AND low renin; responds to amiloride, not spironolactone
• Pheochromocytoma — Paroxysmal HTN with catecholamine symptoms
• Renal artery stenosis — Bruit, asymmetric kidneys, high renin AND high aldosterone
• Diuretic-induced hypokalemia — Drug history; correct potassium and repeat ARR off thiazide if possible

Diagnostic workup

Diagnostic algorithm

flowchart TD
  A["Hypertension (ES 2025: screen all)<br/>especially resistant HTN, hypokalemia,<br/>OSA, adrenal incidentaloma"] --> B[Screen with ARR]
  B --> C{"Suppressed renin +<br/>aldo ≥10 ng/dL?"}
  C -->|No| D[Primary aldosteronism unlikely]
  C -->|Yes| E{Patient wants surgery?}
  E -->|No| K["MRA: spironolactone or eplerenone"]
  E -->|Yes| F{"Overt pattern?<br/>hypokalemia, renin undetectable,<br/>aldo >20 ng/dL"}
  F -->|Yes| G[Adrenal CT]
  F -->|No, intermediate| S["Suppression test:<br/>saline infusion / salt load"]
  S -->|Negative| D
  S -->|Positive| G
  G --> H["Adrenal venous sampling<br/>(unilateral vs bilateral)"]
  H --> I{Unilateral?}
  I -->|Yes| J[Laparoscopic adrenalectomy]
  I -->|No (bilateral)| K

Complications

• Stroke, MI, atrial fibrillation, heart failure — increased independent of BP
• Left ventricular hypertrophy, diastolic dysfunction
• Chronic kidney disease, proteinuria
• Severe hypokalemia → arrhythmia, rhabdomyolysis
• Post-adrenalectomy hyperkalemia (contralateral suppressed)

PANCE pearls

• Screen for primary aldosteronism: Endocrine Society 2025 suggests screening all adults with hypertension; AHA/ACC 2025 recommends it in resistant HTN (regardless of K), hypokalemia (spontaneous or diuretic-induced), OSA, adrenal incidentaloma, or family history of early-onset HTN or stroke before age 40, and says it may be considered in all stage 2 HTN. Most patients with PA have a normal potassium.
• ARR is the screening test — suppression testing (saline infusion, salt loading, etc.) is used when probability is intermediate, not in the overt pattern (spontaneous hypokalemia, undetectable renin, aldosterone >20 ng/dL). Imaging alone is NOT diagnostic.
• ADRENAL VENOUS SAMPLING is gold standard for localization before surgery — CT alone misclassifies many cases.
• Hold spironolactone for at least 4-6 weeks before ARR (false negatives).
• Aldosterone causes cardiovascular damage beyond what its BP elevation explains — treat aggressively even if BP is normalized by other agents.
• Liddle syndrome and apparent mineralocorticoid excess: HTN + hypokalemia with LOW aldosterone AND LOW renin — distinct entities; Liddle is treated with amiloride or triamterene (spironolactone ineffective), while AME responds to spironolactone/eplerenone or amiloride (stop licorice; dexamethasone for genetic AME).

References

• Endocrine Society 2025 — Primary Aldosteronism: An Endocrine Society Clinical Practice Guideline (Adler et al., J Clin Endocrinol Metab 2025;110:2453-2495)
• AHA/ACC 2025 — 2025 AHA/ACC/AANP/AAPA/ABC/ACCP/ACPM/AGS/AMA/ASPC/NMA/PCNA/SGIM Guideline for the Prevention, Detection, Evaluation and Management of High Blood Pressure in Adults (Jones et al., Hypertension 2025;82:e212-e316)
• AHA Resistant HTN 2018 — Resistant Hypertension: Detection, Evaluation, and Management (Carey et al., Hypertension 2018)