Randomised controlled trial of growth effect of hydrocortisone in congenital adrenal hyperplasia

• Published in: Archives of disease in childhood Vol. 77; no. 3; pp. 214 - 218
• Main Authors: Silva, Ivani Novato, Kater, Claudio Elias, Cunha, Cristiane de Freitas, Viana, Marcos Borato
• Format: Journal Article
• Language: English
• Published: London BMJ Publishing Group Ltd and Royal College of Paediatrics and Child Health 01.09.1997; BMJ; BMJ Publishing Group LTD; BMJ Group
• Subjects: 17-alpha-Hydroxyprogesterone - blood; Adolescent; Adrenal Hyperplasia, Congenital - drug therapy; Adrenals. Adrenal axis. Renin-angiotensin system (diseases); Androgens; Androstenedione - blood; Biological and medical sciences; Body Composition; Body Height - drug effects; Bones, joints and connective tissue. Antiinflammatory agents; Child; Child, Preschool; Children & youth; congenital adrenal hyperplasia; Cross-Over Studies; Dose-Response Relationship, Drug; Endocrinopathies; Female; Females; growth; Growth Disorders - blood; Growth Disorders - chemically induced; Humans; hydrocortisone; Hydrocortisone - adverse effects; Hydrocortisone - therapeutic use; Individual Differences; Infant; Insulin-like growth factors; Laboratories; Male; Malignant tumors; Measurement Techniques; Medical Evaluation; Medical sciences; Mixed Function Oxygenases - deficiency; Original; Patients; Pharmacology. Drug treatments; Physical Examinations; Physical growth; Prospective Studies; Puberty; Scientific Concepts; Testosterone; Testosterone - blood; Velocity; Endocrinopathy; Human; Short term; Corticosteroid; Adrenal cortex diseases; Enzyme; Growth; Toxicity; Deficiency; Hyperadrenocorticism; Hydrocortisone; Enzymopathy; Congenital adrenal hyperplasia syndrome; Chemotherapy; Treatment; Surveillance; Adrenal gland diseases; Oxidoreductases; Hormonal investigation; Sex steroid hormone; Child; Steroid 21-monooxygenase
• ISSN: 0003-9888; 1468-2044
• DOI: 10.1136/adc.77.3.214

The influence of 15 or 25 mg/m2 of daily oral hydrocortisone with fludrocortisone 0.1 mg/day on growth and laboratory findings was evaluated in a prospective randomised crossover trial over 12 months in 26 children with 21-hydroxylase deficiency. Nine non-salt losers had fludrocortisone stopped for a further six month period. Height velocity was significantly decreased during treatment with 25 mg/m2 as compared with 15 mg/m2. This was the most sensitive indicator of corticosteroid treatment excess. A dose dependent effect upon plasma concentrations of 17-hydroxyprogesterone, testosterone, and androstenedione was found but increased values were still detected in more than half of the determinations made during the 25 mg/m2 period. Height velocity and 17-hydroxyprogesterone concentrations were positively correlated. Growth hormone response to clonidine stimulation and insulin-like growth factor-1 concentrations were both within reference values and there was no difference between treatment periods. Withdrawal of fludrocortisone did not result in any difference for the non-salt losers. It was concluded that 25 mg/m2 of hydrocortisone depressed growth in children with congenital adrenal hyperplasia, and that full suppression, or even normalisation, of plasma concentrations of 17-hydroxyprogesterone and androgens should not be considered a treatment goal, but instead an indication of corticosteroid treatment excess.