Congenital Adrenal Hyperplasia (CAH) Clinical Trial
Official title:
Salt Wasting, Hydro-sodium Balance and Fludrocortisone Requirement in Congenital Adrenal Hyperplasia
Congenital adrenal hyperplasia (CAH) in its classic neonatal form with severe salt-wasting represents a challenge for pediatric endocrinologists in order to maintain sodium balance, especially as the physiopathology and optimal therapeutic management of this urinary salt loss remain poorly studied, particularly during the neonatal period. The human kidney presents the characteristic of being immature at birth with a functional tubulopathy associating sodium wasting and difficulty to concentrate urine, in connection with a transient renal resistance to aldosterone action, which is exacerbated in case of CAH by insufficiency of aldosterone production. The objective of project is therefore to study the secretion profiles of plasma and urinary steroids in neonates with classical salt-wasting form of CAH before treatment and under treatment with Fludrocortisone and Hydrocortisone during the first months of life, using an advanced technology: LC-MSMS (Liquid chromatography coupled with tandem mass spectrometry). The study of the existence of a correlation between plasma and urinary steroid profiles will also make it possible to subsequently consider simplified medical follow-up for these patients. This project will lead to a better understanding of sodium handling and steroid secretion and excretion profiles in CAH neonates, in order to improve the therapeutic management of mineralocorticoid replacement in these patients.
Congenital adrenal hyperplasia in its severe salt-wasting form is a challenge in order to maintain sodium balance. The pathophysiology of this impaired sodium balance is still poorly investigated as well as its therapeutic management, notably in the neonatal period. Consensus practice guidelines have been established for hydrocortisone replacement therapy, in order to maintain negative feedback on the pituitary-adrenal axis to prevent from virilization and excessive growth velocity. However, mineralocorticoid substitution and sodium supplementation is currently empirically adapted based on weight gain and renin levels. There is significant need for improvement of this essential part of CAH treatment. Particularly, CAH patients have higher risk of adverse cardio-vascular outcomes, which could relate to an excessive glucocorticoid and/or mineralocorticoid exposure in early infancy rather than to the genotype of the patient. A clinical human study in classical CAH neonates, using Liquid Chromatography coupled to tandem Mass Spectrometry LC-MS/MS technology will assess prospectively plasma and urinary steroid profiling (precursors and substitute hormones, notably Fludrocortisone dosages) during the first six months of life, before and under treatment; and in correlation with genotype. Thirty neonates (boys and girls) diagnosed with a severe form of CAH and followed in one of the 5 following French reference tertiary centers: Robert Debré Hospital, Paris; Necker Hospital, Paris; Bicetre Hospital, Le Kremlin-Bicetre; Trousseau Hospital, Paris; Lyon Hospital, , will be included in the study and will be followed for a period of six months. The duration of inclusion will be 24 months. Genotyping will be processed for all children in Lyon.This project will lead to a better understanding of sodium handling and steroid secretion and excretion profiles in CAH neonates, in order to improve management of mineralocorticoid replacement. ;
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