Clinical Background
Congenital adrenal hyperplasia is an uncommon autosomal recessive genetic disorder that is caused by several distinct enzymatic defects, usually with subsequent virilization.
Epidemiology
- Incidence
- Most common adrenal disorder of infancy and childhood (1/3,000-5,000)
- More frequent in eastern European Jews (1/27 affected with nonclassical 21-hydroxylase deficiency)
- 21-hydroxylase deficiency is the most common defect (90%)
Risk Factors
- Genetic
- Enzymatic defects include:
- 21-hydroxylase (CYP21A2), 11-beta-hydroxylase (CYP11B1), 17-alpha-hydroxylase/17,20-lyase (CYP17), 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) and the very rare mitochondrial cholesterol side chain cleavage enzyme (P450scc)
- Mutations cause a block in adrenal glucocorticoid and mineralocorticoid synthesis
- Enzymatic defects include:
Pathophysiology
- 21-hydroxylase
- Blocked steroid synthesis causes adrenal insufficiency and compensatory elevation of ACTH
- ACTH elevation causes adrenal hyperplasia and additional precursor synthesis
- Precursor excess is shunted into the androgen synthesis pathway, causing virilization in females, premature sexual development in males and adrenal insufficiency
- 11-beta-hydroxylase - impaired conversion of 11-deoxycortisol to cortisol
- Accumulation of 11-deoxycorticosterone (a potent mineralocorticoid)
- Leads to mineralocorticoid excess with possible hypertension
- 17-alpha-hydroxylase/17, 20 lyase
- Rare disorder
- Decreased cortisol production and shunting of precursors into mineralocorticoid pathways
- Minimal testosterone or estrogen made
Clinical Presentation
- 21-hydroxylase
- Ambiguous genitalia (female), premature sexual development (male), salt wasting (hyperkalemia, hyponatremia, dehydration)
- 11-beta-hydroxylase
- Premature sexual development (male), hypertension and hypokalemia
- 17-alpha-hydroxylase
- Hypertension, hypokalemia, hypogonadism, lack of secondary sexual characteristics in females and males
- 3 beta-HSD2
- Feminized male, partial virilization of female
- Mitochondrial cholesterol side chain cleavage enzyme (P450scc)
- Very rare disorder
- Adult females present with milder forms of any of the diseases - classically present with hyperandrogenism at the time of puberty
Treatment
- Steroids to suppress pituitary ACTH secretion
See Also
