Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is an autosomal recessive disease in which adrenal synthesis of glucocorticoids and mineralocorticoids is impaired and steroid biosynthesis is directed toward the formation of excessive androgens. Persistently high androgens will accelerate bone maturation and reduce final adult height.
Objectives: To assess the efficacy of androgen antagonist Flutamide and aromatase inhibitor Tastolactone when added to the standard treatment of CAH (Hydrocortisone and fludrocortisone) in normalizing growth rate and rate of bone maturation and to test the effect in lowering cortisol clearance that intended lower daily Hydrocortisone doses and further improving the final height.
Methods: In April 2016 we searched the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE/PubMed, Embase, and CINAHL, in each search we considered searching for original review, references and the update. We also explored other internet sources and we hand searched abstracts from the meetings and conferences (updated search on October 2017).
Types of outcome measures: Primary outcomes: rate of bone maturation, rate of growth velocity and cortisol level (blood and urine). Secondary outcomes: adrenal androgen levels and ACTH level.
Main result: We included six studies involving 102 participants of children with classical congenital adrenal hyperplasia. Four RCTs and two cohort studies compared adding Flutamide and Tastolactone or letrozole to hydrocortisone and fludrocortisone in comparison to the standard treatment, studies are pooled with subgroup analysis. Growth rate and bone rate of maturation were significantly decreased in the experimental group with 95% CI: (−2.39, 0.49) for the growth rate and significantly lower 95% CI: (−1.38, −0.29) for the bone rate of maturation. Two studies were testing the direct effect of this regimen on decreasing cortisol clearance. Total body cortisol excretion was significantly low when patients received the four-drugs (P≤0.001) and (P<0.01) , 95% CI: (−28.14, 2.31) than patients who were on the standard treatment. Final analysis indicated favorable results and high precision supporting this new treatment combination.
Conclusion: Although the result of this review and analysis was in favor of the efficacy of this potentially new treatment in normalizing growth rate and rate of bone maturation to improve final height in children with classical CAH, the safety of androgen antagonist in different dosage regimens also need to be investigated with more trials. A large scale RCTs is recommended.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology