Pseudoaldosteronism (Liddle's Syndrome): Evidence for Increased Cell Membrane Permeability to Na+

Abstract

A 10-month boy was found to have pseudoaldosteronism (Ps. Ald.) characterized by hypertension (178/116), alkalosis (HCO3–35 mEq/1, pH-7.50), hypokalemia (3.0 mEq/1) and very low aldosterone secretion rates (ARS) (0.9–5.8 μg/d). The hypertension and hypokalemic alkalosis were worsened by salt-loading and unchanged by treatment with spironolactone and dexamethasone. Treatment with triamterene, plus severe Na+ restriction (<2 mEq/d) for 12 days, led to normal b.p., and serum electrolytes, and an elevation of the ASR (60 μg/d). Long-term therapy has been successful with triamterene, hydrochlorthiazide and moderate salt restriction. Because triamterene is a specific therapy for Ps. A.d. and because it reduces epithelial surface Na+ permeability of isolated frog skin, an increased permeability to Na+ of the luminal membrane of distal renal tubular cells is postulated in Ps. Ald. On no therapy, the patient's RBC Na+ uptake was increased (2.6 μEq/c.c. cellls/h) compared to controls (1.9 μEq/c.c. cells/h, p <0.01), and RBC [Na+] was 15.7 mEq/1 (controls – 10.1 ±1 mEq/I, p <0.01) After 2 weeks of severe Na+ restriction and triameterene therapy, RBC Na+ uptake was 2.35 μEq/c.c. cells/h (significant decrease, p <0.01) and RBC [Na+] was 11.9 mEq/1. Thus, RBC's show the increased Na+ permeability and increased [Na+] postulated for the distal tubular cells, in which the increased [Na+] would stimulate the Na+-K+ exchange pump leading to Na+ retention and K+ excretion.