Key Facts

Primary hyperaldosteronism is underdiagnosed. It should be screened for in all patients with resistant hypertension, hypokalaemia, or adrenal incidentaloma. The distinction between unilateral and bilateral disease is critical as it determines surgical vs medical management.

Epidemiology

~5-10% of hypertensive patients. Previously thought rare — now recognised as common due to improved screening. F:M 2:1 for adenoma.

Aetiology

Bilateral adrenal hyperplasia (~60%), aldosterone-producing adenoma (~35%), unilateral adrenal hyperplasia (~2%), adrenal carcinoma (<1%), familial hyperaldosteronism (type I — glucocorticoid-remediable).

Pathophysiology

Autonomous aldosterone secretion → ENaC activation in distal nephron → sodium retention (→ hypertension, volume expansion) and potassium/hydrogen ion excretion (→ hypokalaemia, metabolic alkalosis). Renin is suppressed by volume expansion (negative feedback). Aldosterone excess also directly damages cardiovascular system (fibrosis, inflammation) independent of BP.

Hypertension

• Often severe or resistant (uncontrolled on ≥3 drugs including a diuretic)
• Young onset hypertension (<40 years)

Hypokalaemia (Only ~30%)

• Muscle weakness, cramps
• Polyuria, polydipsia (nephrogenic DI from hypokalaemia)
• Cardiac arrhythmias (severe)

Metabolic

• Metabolic alkalosis
• Mild hypernatraemia

Other

• Fatigue
• Headache
• Glucose intolerance

Red Flags

• Severe hypokalaemia (<3.0 mmol/L) with hypertension → strong suspicion
• Resistant hypertension in young patient
• Adrenal incidentaloma + hypertension → always screen

Screening

• Aldosterone:Renin Ratio (ARR): raised aldosterone with suppressed renin
• Standardised conditions: morning sample, seated for 15 minutes; ideally stop interfering drugs (spironolactone ≥6 weeks, ACEi/ARB ≥2 weeks); use non-interfering antihypertensives (verapamil, doxazosin)
• Raised ARR in the context of hypokalaemia is very suggestive

Confirmatory

• Saline infusion test: IV 2L 0.9% NaCl over 4 hours; post-infusion aldosterone >240 pmol/L = failure to suppress = confirmed PA
• Alternative: oral sodium loading test, fludrocortisone suppression test

Subtype Differentiation

• CT adrenals: adenoma vs bilateral hyperplasia (NB: CT can be misleading — non-functioning adenomas are common)
• Adrenal venous sampling (AVS): gold standard for lateralisation; aldosterone lateralisation ratio >4:1 = unilateral disease

Other

• U&Es (K⁺), VBG (metabolic alkalosis)
• Genetic testing: if age <20 or family history (glucocorticoid-remediable aldosteronism)

Unilateral Disease (Adenoma/Unilateral Hyperplasia)

• Laparoscopic adrenalectomy: curative for BP in ~50%; cures hypokalaemia in >95%
• Pre-operative: correct hypokalaemia; spironolactone 4-6 weeks pre-op

Bilateral Disease (Bilateral Hyperplasia)

• Spironolactone 25-100 mg OD: first-line; MRA; reduces BP and corrects K⁺
• Side effects: gynaecomastia, breast tenderness, menstrual irregularity (anti-androgen effects)
• Eplerenone 50-100 mg BD: selective MRA; fewer anti-androgen side effects; alternative if spironolactone not tolerated
• Add other antihypertensives as needed (amiloride 10-20mg/day as alternative K⁺-sparing)

Monitoring

• BP, U&Es regularly
• Annual renal function, potassium

Referral Criteria

• Endocrinology: all confirmed/suspected PA
• Interventional radiology: AVS
• Endocrine surgery: unilateral disease

Unilateral adenoma: adrenalectomy cures hypokalaemia in >95% and hypertension in ~50% (remainder have improved BP control on fewer medications). Bilateral hyperplasia: good BP and K⁺ control with spironolactone; lifelong treatment needed. Primary hyperaldosteronism confers additional cardiovascular risk beyond that expected from BP alone (aldosterone-mediated cardiac/vascular fibrosis). Treatment reduces this excess risk.

Causes of Secondary Hypertension — Screening Indications for PA

Spironolactone vs Eplerenone