Nonclassic Congenital Adrenal Hyperplasia: What Do Endocrinologists Need to Know?

Abstract

Congenital adrenal hyperplasia encompasses a group of autosomal recessive defects in cortisol biosynthesis, and 21-hydroxylase deficiency accounts for 95% of such cases. Non-classic 21-hydroxylase deficiency is due to partial enzymatic defects, which present with normal cortisol synthesis, but excessive production of adrenal androgens, including 11-oxygenated androgens. Non-classic 21-hydroxylase deficiency is relatively common, and its phenotype resembles closely that of polycystic ovary syndrome. This review focuses primarily on non-classic 21-hydroxylase deficiency, its clinical features, diagnosis, and management.

Keywords: 21-Hydroxylase deficiency; Adrenal; Adrenal cortex; Androgens; Congenital adrenal hyperplasia.

Figure 1 :. Steroidogenic pathway

Genetic defects in 21-hydroxylase result in accumulation of 17α-hydroxyprogesterone, which is diverted towards androgens, including: androstenedione, testosterone, and 11-oxygenated androgens (11OHA4 and 11OHT); the latter two are oxidized to 11KA4 and 11KT, respectively, in the kidneys and other tissues. Abbreviations: StAR: steroidogenic acute regulatory protein; CYP11A1, cholesterol side-chain cleavage; HSD3β2, 3β-hydroxysteroid dehydrogenase type 2; CYP17A1, 17α-hydroxylase/17,20-lyase; CYB5A, cytochrome b5 type A; CYP11B1, 11β-hydroxylase; AKR1C3, 17β-hydroxysteroid dehydrogenase type 5; HSD11B2, 11β-hydroxysteroid dehydrogenase, type 2; SULT2A1, sulfotransferase 2A1; SRD5A2, steroid 5α-reductase type 2; DHEA: dehydroepiandrosterone; DHEAS: dehydroepiandrosterone sulfate; 11OHA4: 11β-hydroxyandrostenedione; 11OHT: 11β-hydroxytestosterone; 11KA4: 11-ketoandrostenedione; 11KT: 11-ketotestosterone;.