Clinical outcomes in 21-hydroxylase deficiency

Abstract

Purpose of review The introduction of synthetic glucocorticoids 70 years ago made survival possible in classic 21-hydroxylase deficiency (21OHD). The currently used glucocorticoid therapy may lead to unphysiological dosing with negative consequencies on health in addition to the problems that may arise due to androgen over-exposure. Recent findings Fertility in females with 21OHD seemed to be impaired, especially in the salt-wasting (SW) phenotype but when pregnancies did occur there was a higher risk for gestational diabetes and cesearean section. Increased fat mass, body mass index, insulin resistance and frequency of autoimmune disorders as well as impaired echocardiographic parameters and lower bone mineral density were found in 21OHD compared to controls. Negative effects on cognitive functions have been identified. Adrenal tumors, especially myelolipomas, were prevalent. Increased knowledge on steroid metabolism in 21OHD and urine steroid profiling may improve assessment of treatment efficacy. Nevanimibe, abiraterone acetate and anastrozole may have a place in the future management of 21OHD. Long-acting glucocorticoids may be a less favorable, especially dexamethasone. Summary The various clinical outcomes need regular monitoring. Negative consequencies are to large extent the result of the unphysiological glucocorticoid replacement. Modern management with improved follow-up and future addition of new drugs may improve outcomes.

Epidemiology and diagnostic trends of congenital adrenal hyperplasia in Denmark: a retrospective, population-based study

“…Deficiency of 21-hydroxylase (21-OHD) due to biallelic pathogenic variants in CYP21A2 is the most frequent form, accounting for up to 99% of all CAH cases. 1 , 2 21-OHD is characterized by impaired cortisol and aldosterone synthesis and concomitant accumulation of precursors shifted towards the non-affected androgen steroidogenic pathway resulting in increased androgen synthesis. The clinical presentation is closely related to the severity of enzymatic deficiency resulting in a continuum of phenotypes (salt-wasting (SW), simple-virilizing (SV) and non-classic (NC) CAH).…”

Increased Prevalence of Fractures in Congenital Adrenal Hyperplasia: A Swedish Population-based National Cohort Study

“…However, balancing the treatment to avoid hyperandrogenism as well as hypercortisolism is challenging both for clinicians and patients. The glucocorticoid doses needed for adequate hypothalamic-pituitary-adrenal axis suppression are mostly supraphysiological, causing negative clinical outcomes ( 6 ).…”

Genotype-phenotype correlation in patients with 21-hydroxylase deficiency

“…CAH is an autosomal recessive disease caused by deficient enzymes including 21OH, 11β-hydroxylase, 17α-hydroxylase, 3β-hydroxysteroid dehydrogenase type 2, steroidogenic acute regulatory protein, and P450 oxidoreductase ( 12 ). 21OHD-caused CAH is found 1 in every 10 000 to 20 000 new born ( 13 ) with diverse phenotype. Complete inactive CYP21A2 results in deficiencies of both glucocorticoid and mineralocorticoid, and severe adrenal-derived androgen excess.…”