17 alpha-hydroxylase deficiency pathophysiology: Difference between revisions
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{{17 alpha-hydroxylase deficiency}} | {{17 alpha-hydroxylase deficiency}} | ||
{{CMG}}; {{AE}} {{MJ}} | {{CMG}}; {{AE}} {{MJ}} | ||
==Overview== | ==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. | 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== | ==Pathogenesis== | ||
* | * [[CYP17A1]] gene defects can cause two type of enzyme deficiencies. 17α-hydroxylase enzyme deficiency and 17,20-lyase deficiency. The dual activities mediate 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]] → [[DHEA|Dehydroepiandrosterone]], also [[17-hydroxyprogesterone]] → [[androstenedione]] | |||
* [[Mineralocorticoid excess]] are the major clinical clue distinguishing the 17α-hydroxylase deficiency from the 17,20-lyase deficiency, which only affects the sex steroids. | |||
* In 17 alpha-hydroxylase deficiency [[steroid biosynthesis]] will be limited to [[progesterone]], [[11-deoxycorticosterone]] ([[Deoxycorticosterone|DOC]]), and [[corticosterone]]. | |||
* [[11-deoxycorticosterone]] ([[Deoxycorticosterone|DOC)]] binds to the mineralocorticoid receptor and its excess amounts in 17 alpha-hydroxylase deficiency causes [[aldosterone]] effects such as volume expansion, [[hypertension]], and [[hypokalemia]]. Also, [[11-deoxycorticosterone]] ([[Deoxycorticosterone|DOC)]] effects will suppress [[renin]] and [[aldosterone]] production. | |||
* The most important features of 17 alpha-hydroxylase deficiency include [[hypertension]], [[hypokalemia]] and [[sexual infantilism]]. | * 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. | ** [[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]]. | ** [[Sexual infantilism]] results from inability of [[adrenal cortex]] to synthesize [[androgens]] and [[estrogens]]. | ||
Revision as of 21:04, 3 August 2017
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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
- CYP17A1 gene defects can cause two type of enzyme deficiencies. 17α-hydroxylase enzyme deficiency and 17,20-lyase deficiency. The dual activities mediate 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
- Mineralocorticoid excess are the major clinical clue distinguishing the 17α-hydroxylase deficiency from the 17,20-lyase deficiency, which only affects the sex steroids.
- In 17 alpha-hydroxylase deficiency steroid biosynthesis will be limited to progesterone, 11-deoxycorticosterone (DOC), and corticosterone.
- 11-deoxycorticosterone (DOC) binds to the mineralocorticoid receptor and its excess amounts in 17 alpha-hydroxylase deficiency causes aldosterone effects such as volume expansion, hypertension, and hypokalemia. Also, 11-deoxycorticosterone (DOC) effects will suppress renin and aldosterone production.
- 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.