Growth hormone activates renin-aldosterone system in children with idiopathic short stature and in a pseudohypoaldosteronism patient with a mutation in epithelial sodium channel alpha subunit

Growth hormone (GH) treatment causes salt and water retention, and this eff ect has been suggested to be mediated by activation of epithelial sodium ch annel (ENaC). Multi-system pseudohypoaldosteronism (PHA) is a salt wasting disease resulting from mutations in ENaC subunit genes. We examined effects of GH therapy for 12-21 months on the renin-angiotensin-aldosterone system (RAAS) in 12 children with idiopathic short stature (ISS) and a PHA patien t with defective ENaC function and concomitant GH deficiency. On GH therapy (0.7 U/kg/week), plasma renin activity (PRA), serum aldosterone and insuli n-like growth factor-I (IGF-I) levels were periodically determined every 1- 3 months in all children. The PHA patient was studied for 6 yr during which time serum, urine, and sweat electrolytes and secretion rate were also exa mined before, on and off GH therapy. In the PHA patient, mean plasma aldost erone concentration, 7.7 nmol/l (278 ng/dl) before therapy (n = 9) rose to 73 nmol/l (2650 ng/dl) 10 months after GH. PRA and IGF-I increased similarl y, reaching a plateau between 8 and 13 months. Off GH, there was a decrease to pretreatment levels in 30 months. Aldosterone and PRA strongly correlat ed with IGF-I (r = 0.66 and 0.67). GH therapy also improved the growth rate , and increased both sweat secretion rate and Na+/K+ ratio. In children wit h ISS, aldosterone and IGF-I peaked 6-12 months after GH. Off GH their leve ls normalized in 3 months. These findings indicate that long-term GH activa tes the RAAS in both children with ISS and a PHA patient, and that this eff ect does not depend on a fully functional ENaC. (C) 2001 Elsevier Science L td. All rights reserved.