17 alpha-hydroxylase deficiency pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mehrian Jafarizade, M.D [2]
Overview
17α-hydroxylase deficiency is an uncommon form of congenital adrenal hyperplasia resulting from a defect in the gene CYP17A1, which encodes for the enzyme 17α-hydroxylase and 17,20-lyase. Congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency is transmitted in an autosomal recessive pattern. On gross pathology, thickening of the adrenal gland and cerebriform appearance are characteristic findings of congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency. On microscopic histopathological analysis, diffuse cortical hyperplasia and lipid-depleted cortical cells are characteristic findings of congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency.
Pathogenesis
- 17 alpha-hydroxylase deficiency is a form of congenital adrenal hyperplasia; that results from deficiency of the enzyme 17α-hydroxylase.
- Through the pathway of steroid biosynthesis, 17α-hydroxylase metabolizes pregnenolone, progesterone, 17-hydroxypregnenolone and 17-hydroxyprogesterone. In 17 alpha-hydroxylase deficiency steroid synthesis will be limited to progesterone, 11-deoxycorticosterone (DOC), and corticosterone.
- The most important features of 17 alpha-hydroxylase deficiency include hypertension, hypokalemia and sexual infantilism.
- Hypertension and hypokalemia result from accumulation of cortisol precursors, that they have mineralocorticoid characteristics.
- Sexual infantilism results from inability of adrenal cortex to synthesize androgens and estrogens.
- 17 hydroxylase enzyme functions as both a 17α-hydroxylase and a 17,20-lyase. The dual activities mediate three key transformations in cortisol and sex steroid synthesis:
- 17α-hydroxylase mediates the pathway: pregnenolone → 17-hydroxypregnenolone, also progesterone → 17-hydroxyprogesterone.
- 17,20-lyase mediates pathway 17-hydroxypregnenolone → Dehydroepiandrosterone, also 17-hydroxyprogesterone → androstenedione
These two enzyme deficiencies are different forms of defects of the same gene.
mineralocorticoid excess are the major clinical clue distinguishing the more complete 17α-hydroxylase deficiency from the 17,20-lyase deficiency, which only affects the sex steroids