Glucocorticoid Regimens in the Treatment of Congenital Adrenal Hyperplasia: A Systematic Review and Meta-Analysis

Abstract

Management of congenital adrenal hyperplasia (CAH) requires both glucocorticoid replacement and suppression of adrenal androgen synthesis. It is recommended that children with CAH be treated with hydrocortisone, but the appropriate glucocorticoid regimen in adults is uncertain. In order to review the outcomes of different glucocorticoid regimens in the management of CAH, a systematic search of PubMed/MEDLINE and Web of Science was conducted, including reports published up to 25 February 2019. Studies that compared at least two types of glucocorticoid preparation were included. The following information was extracted from each study: first author, year of publication, number and characteristics of patients and control subjects, types and doses of glucocorticoid regimen used, study design and outcomes [ e.g., biochemical tests, weight, height, body mass index (BMI), bone mineral density (BMD)]. A total of 23 studies were included in the qualitative synthesis, with 19 included in the quantitative synthesis. Dexamethasone was associated with the greatest degree of adrenal suppression; there was no significant difference in 17-hydroxyprogesterone (17OHP) and androstenedione levels between patients treated with hydrocortisone or prednisolone. Patients treated with dexamethasone had the lowest BMD and the highest BMI. Although dexamethasone therapy is associated with significantly lower 17OHP and androstenedione levels, it is also associated with more adverse effects. There do not appear to be significant differences between hydrocortisone and prednisolone therapy, and the choice of agent should be based on individual patient factors.

Bone mineral density and fractures in congenital adrenal hyperplasia: Findings from the dsd‐LIFE study

“…These findings are in accordance with Jääskeleinen et al reporting that adult CAH patients receiving hydrocortisone had better BMD than those on prednisone, prednisolone or dexamethasone . A recent meta‐analysis showed similar findings . The results of the current study showing that prednisolone vs. hydrocortisone‐caused worse trochanter Z‐scores are in accordance with these previous studies.…”

“…14 A recent meta-analysis showed similar findings. 35 The results of the current study showing that prednisolone vs. hydrocortisone-caused worse trochanter Z-scores are in accordance with these previous studies.…”

Therapy options for adrenal insufficiency and recommendations for the management of adrenal crisis

“…Chronic cortisol replacement with long-acting synthetic glucocorticoids is less desirable as it exerts unfavorable night time glucocorticoid activity as a consequence of the longer biological half-lives and has limited options for dose titration. Longer-acting GC replacement regimen have shown to be associated with more adverse effects [ 13 , 15 – 18 ].…”

Clinical outcomes and characteristics of P30L mutations in congenital adrenal hyperplasia due to 21-hydroxylase deficiency

“…Hydrocortisone is the drug of choice in newborn and children with confirmed SV form [ 103 ]. However, appropriate glucocorticoid regimen (hydrocortisone, prednisolone, dexamethasone, or combinations) with or without mineralocorticoid therapy in adults is still uncertain [ 104 – 106 ]. Some SV patients may benefit from adding mineralocorticoids based on the studies showing higher plasma renin activity in SV patients including patients carrying P30L mutation.…”