Congenital adrenal hyperplasia overview

Congenital adrenal hyperplasia main page
Overview
Classification 21-hydroxylase deficiency
11β-hydroxylase deficiency
17 alpha-hydroxylase deficiency
3 beta-hydroxysteroid dehydrogenase deficiency
Cytochrome P450-oxidoreductase (POR) deficiency (ORD)
Lipoid congenital adrenal hyperplasia
Differential Diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mehrian Jafarizade, M.D [2]

Overview

Congenital adrenal hyperplasia (CAH) refers to any of several autosomal recessive conditions resulting from biochemical paths of the steroidogenesis of cortisol from cholesterol by the adrenal glands. Most of these conditions involve greater or lesser production of sex steroids and can alter development of primary or secondary sex characteristics in affected infants, children, and adults. Only a small minority of people with CAH can be said to have an intersex condition, but this attracted American public attention in the late 1990s and many accounts of varying accuracy have appeared in the popular media. Approximately 95% of cases of CAH are due to 21-hydroxylase deficiency. Prenatal diagnosis can be made in both of these disorders by chorionic villous sampling, but this can only be done at 8-10 weeks. In order to prevent the deleterious effect of excess androgens on genital (and brain!) development, therapy must be started earlier. This is most often considered if there is an affected sibling. Treatment is dexamethasone, which is not degraded by the placenta, but is associated with significant maternal weight gain, hypertension, and edema.

Pathophisiology

Classification

Congenital adrenal hyperplasia is classified into seven types based on the genetic causes that lead to hyperplasia and hormonal imbalance.

Disease		History and symptoms		Laboratory findings		Defective gene
		Blood pressure	Genitalia		K levels
21-hydroxylase deficiency	Classic type	Low in salt-wasting Normal in non-salt-wasting	Female: ambiguous Male: normal or scrotal pigmentation and large phallus	Increased: 17-OHP Progesterone Androstenedione DHEA Decreased: Aldosterone Corticosterone (salt-wasting) Cortisol (simple virilizing)	High in salt wasting type Normal in non salt wasting	CYP21A1 and CYP21A2 gene
	Non-classic type	Normal	Female: virilization after puberty Male: normal appearance	Increased: 17-OHP Exaggerated androstene-dione, DHEA, and 17-OHP response to ACTH	Normal	CYP21A1 and CYP21A2 gene
17a-Hydroxylase deficiency		Hypertension	Female: normal Male: ambiguous	Increased DOC, corticosterone Decreased 17OH-steroids, cortisol, aldosterone, androgens and estrogens	Low	CYP17A1
11β-hydroxylase deficiency		Hypertension	Female: ambiguous Male: normal or scrotal pigmentation and large phallus	Indreased DOC, 11-deoxycortisol Decreased corticosterone, cortisol, aldosterone, androgens	Low	CYP11B1
3-beta-hydroxysteroid dehydrogenase				Increased: DHEA 17-OH pregneno-lone Pregnenolone Decreased: Cortisol Aldosterone	High
Cytochrome P450-oxidoreductase (POR) deficiency (ORD)
Congenital lipoid adrenal hyperplasia
Cholesterol side-chain cleavage enzyme deficiency