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[Resistant HTN or HTN + hypokalemia<br/>or adrenal incidentaloma] --> B[Screen with ARR]
  B --> C{ARR elevated<br/>+ aldo >15 ng/dL?}
  C -->|No| D[Primary aldosteronism unlikely]
  C -->|Yes| E[Confirmatory test:<br/>saline infusion / salt load]
  E --> F{Confirmatory positive?}
  F -->|No| D
  F -->|Yes| G[Adrenal CT]
  G --> H[Adrenal venous sampling<br/>(unilateral vs bilateral)]
  H --> I{Unilateral?}
  I -->|Yes| J[Laparoscopic adrenalectomy]
  I -->|No (bilateral)| K[MRA: spironolactone or eplerenone]

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

• Test for primary aldosteronism in: resistant HTN, HTN + spontaneous hypokalemia, HTN + adrenal incidentaloma, family history, or onset before age 40.
• ARR is the screening test — confirmatory testing required (saline infusion, salt loading, etc.). 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, treated with amiloride.

References

• Endocrine Society 2016 — The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment (Funder et al., J Clin Endocrinol Metab 2016)
• AHA/ACC 2017 — Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults (Whelton et al., Hypertension 2018)
• AHA Resistant HTN 2018 — Resistant Hypertension: Detection, Evaluation, and Management (Carey et al., Hypertension 2018)