Congenital adrenal hyperplasia due to 3β-hydroxysteroid dehydrogenase deficiency | |
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Cortisol | |
Classification and external resources | |
Specialty | endocrinology |
ICD-10 | E25.0 |
ICD-9-CM | 255.2 |
OMIM | 201810 |
DiseasesDB | 4 |
eMedicine | ped/1051 |
MeSH | D000312 |
3β-Hydroxysteroid dehydrogenase II deficient congenital adrenal hyperplasia (3β-HSD CAH) is an uncommon form of congenital adrenal hyperplasia (CAH) resulting from a mutation in the gene for one of the key enzymes in cortisol synthesis by the adrenal gland, 3β-hydroxysteroid dehydrogenase (3β-HSD) type II (HSD3B2). As a result, higher levels of 17OH-pregnenolone appear in the blood with adrenocorticotropic hormone (ACTH) challenge, which stimulates adrenal corticosteroid synthesis.
There is a wide spectrum of clinical presentations of 3β-HSD CAH, from mild to severe forms. The uncommon severe form results from a complete loss of enzymatic activity and manifests itself in infancy as salt wasting due to the loss of mineralocorticoids. Milder forms resulting from incomplete loss of 3β-HSD type II function do not present with adrenal crisis, but can still produce virilization of genetically female infants and undervirilization of genetically male infants. As a result, this form of primary hypoadrenalism is the only form of CAH that can cause ambiguous genitalia in both genetic sexes.
3β-HSD II mediates three parallel dehydrogenase/isomerase reactions in the adrenals that convert Δ4 to Δ5 steroids: pregnenolone to progesterone, 17α-hydroxypregnenolone to 17α-hydroxyprogesterone, and DHEA to androstenedione. 3β-HSD II also mediates an alternate route of testosterone synthesis from androstenediol in the testes. 3β-HSD deficiency results in large elevations of pregnenolone, 17α-hydroxypregnenolone, and DHEA.