Recent advances in diagnosis, treatment, and outcome of congenital adrenal hyperplasia due to 21-hydroxylase deficiency

Abstract

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21-OHD) is an autosomal-recessive disease causing cortisol deficiency, aldosterone deficiency and hyperandrogenism. Diagnosis of 21-OHD is confirmed by steroid analysis in newborn screening or later on. Standard medical treatment consists of oral glucocorticoid and mineralocorticoid administration in order to suppress adrenal androgens and to compensate for adrenal steroid deficiencies. However, available treatment is far from ideal, and not much is known about the long-term outcome in CAH as trials in patients in adulthood or old age are rare. Here we briefly describe the pathophysiology, clinical picture, genetics and epidemiology of 21-OHD. This is followed by a comprehensive review of the recent advances in diagnosis, treatment and outcome. Novel insights have been gained in the fields of newborn screening, specific steroid measurement utilizing mass spectrometry, genetics, glucocorticoid stress dosing, additive medical therapy, prenatal treatment, side-effects of medical treatment, adrenomedullary involvement, metabolic morbidity, fertility and gender identity. However, many issues are still unresolved, and novel questions, which will have to be answered in the future, arise with every new finding.

Children with classic congenital adrenal hyperplasia experience salt loss and hypoglycemia: evaluation of adrenal crises during the first 6 years of life

“…Early detection of CAH by neonatal screening has been widely acknowledged to prevent morbidity and mortality from severe adrenal crises before diagnosis (6,11). However, thus far, little has been published about the success of crisis prevention in the years after detection by screening.…”

Diagnostic Evaluation of Enzyme Activity Related to Steroid Metabolism by Mass Spectrometry-Based Steroid Profiling

“…1,19,20 However, timeconsuming sample preparation steps, including chemical derivatization, prevent its use as a routine screening assay; therefore, LC-MS methods have been established for the detection of plasma 17-OHP. 21 In recent, an LC-MS method using a dried blood spot (DBS) was developed for use in newborn screening.…”

Mineralocorticoid Deficiency and Treatment in Congenital Adrenal Hyperplasia

“…The I172N CYP21 mutation is mainly associated with simple virilizing CAH but can also cause salt wasting CAH [8]. A significant difference exists between the degree of genotype-phenotype correlation demonstrated in relation to the concentration of aldosterone and that of genital phenotype [9]. The relationship with degree of virilization with genotype and aldosterone concentration is less predictable as various genetic factors regulate androgen biosynthesis and sensitivity or the ability to retain sodium through extra-adrenal mechanisms [9, 10].…”