Congenital Adrenal Hyperplasia

Abstract

The congenital adrenal hyperplasias comprise a family of autosomal recessive disorders that disrupt adrenal steroidogenesis. The most common form is due to 21-hydroxylase deficiency associated with mutations in the 21-hydroxylase gene, which is located at chromosome 6p21. The clinical features associated with each disorder of adrenal steroidogenesis represent a clinical spectrum that reflect the consequences of the specific mutations. Treatment goals include normal linear growth velocity and "on-time" puberty in affected children. For adolescent and adult women, treatment goals include regularization of menses, prevention of progression of hirsutism, and preservation of fertility. For adolescent and adult men, prevention and early treatment of testicular adrenal rest tumors is beneficial. In this article key aspects regarding pathophysiology, diagnosis, and treatment of congenital adrenal hyperplasia are reviewed.

Keywords: Ambiguous genitalia; CYP21A2; Congenital adrenal hyperplasia; Hyperandrogenism; Premature adrenarche; Premature pubarche.

Figure 1

Cartoon of RCCX unit gene. Flanking genes, CYP21A2, and CYP21A1P are located in the class III region of the MHC on chromosome 6p21.3. RP1 encodes a nuclear threonine/serine protein kinase. C4A (Rodgers blood group) and C4B (Chido blood group) encode functional complement 4. TNXB encodes tenascin, an extracellular protein. TNXA is the deleted form of TNXB and encodes a pseudogene. RP2 is the truncated form of RP1.

Figure 2

Pathways of steroid hormone synthesis. Key: StAR, steroidogeneic acute regulatory protein; CYP11A1, cholesterol desmolase; CYP21A2, 21-hydroxylase; HSD3B2, 3β-hydroxysteroid dehydrogenase; CYP11B1, 11β-hydroxylase; CYP11B2, aldosterone synthase; CYP17A1, 17α-hydroxyase/17,20-lyase; P450, P450 oxidoreductase; AKR1C3, 17β-hydroxysteroid dehydrogenase type 5; SULT2A1, steroid sulfotransferase 2A1; DOC, 11-deoxycorticosterone; 11OHAD, 11-hydroxyandrostenedione; Adiol, 5-androstendiol; 11KAD, 11-ketoandrostenedione; 11OHT, 11-hydroxytestosterone; 11KT, 11-ketotestosterone.

Figure 3

Modified Ferriman-Gallwey Scoring System. This semi-objective scoring system is based on observation of nine body areas including upper lip, chin, chest, arm, upper abdomen, lower abdomen, upper back, lower back, and thighs. The areas are scored from 1 (minimal terminal hairs present) to 4 (equivalent to a hairy man). If no terminal hairs are noted in the specific body area being examined the score is zero. Clinically terminal hair hairs can be distinguished from vellus hairs primarily by their length (i.e. greater than 0.5 cm) and the fact that they are usually pigmented (reprinted with kind permission of Ricardo Azziz, copyright 1997)