Makindo Medical Notes

🧬 Liddle's syndrome is a rare inherited cause of secondary hypertension. It presents with hypokalaemic hypertension, metabolic alkalosis, and suppressed renin + aldosterone levels — hence termed “pseudo-hyperaldosteronism”.

About 🔎

• Liddle's syndrome: Autosomal dominant genetic disorder.
• Mutation in the ENaC (Epithelial Sodium Channel) of the renal collecting ducts ➝ excessive sodium reabsorption ➝ hypertension.
• Potassium wasting causes hypokalaemia, weakness, and arrhythmia risk.
• Very rare but important to recognise in young patients with resistant hypertension.

Clinical Features 🧑‍⚕️

• 📈 Hypertension: Early onset, often severe.
• 💤 Weakness & Fatigue: From hypokalaemia.
• ⚡ Muscle cramps: Due to low potassium and metabolic alkalosis.
• 🌙 Nocturia & Polyuria: From impaired renal concentrating ability.
• 🫀 Arrhythmias: Severe hypokalaemia may trigger dangerous cardiac rhythms.

Investigations 🧪

• 🟢 Serum Potassium: Low (hypokalaemia).
• 🟢 ABG: Metabolic alkalosis.
• 🔻 Plasma Renin Activity: Suppressed.
• 🔻 Aldosterone: Suppressed (distinguishes from Conn’s syndrome).
• 🧬 Genetic Testing: Can confirm ENaC mutation.

Differential Diagnosis 🔍

• Conn’s Syndrome (Primary Hyperaldosteronism): Both present with hypertension + hypokalaemia, but Conn’s has high aldosterone levels, while Liddle’s has low aldosterone.
• Apparent Mineralocorticoid Excess (AME): Enzyme defect (11β-HSD2) or liquorice ingestion; also causes pseudo-hyperaldosteronism but via cortisol effect on mineralocorticoid receptors.

Management 💊

• 🥗 Low Sodium Diet: First-line to reduce hypertension.
• 💊 Amiloride or Triamterene: Block ENaC directly ➝ correct hypertension and hypokalaemia.
• ❌ Spironolactone ineffective: Because aldosterone is already low; mechanism is sodium channel mutation, not aldosterone excess.
• 👀 Lifelong treatment is usually required, with good prognosis if controlled.

Exam Clinical Pearl ✨

If you see a young patient with hypertension, hypokalaemia, metabolic alkalosis and low renin & aldosterone ➝ think **Liddle’s syndrome**. Treatment is with amiloride, not spironolactone.