17 alpha-hydroxylase deficiency pathophysiology: Difference between revisions
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** [[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]]. | ||
==Genetics== | |||
* 17 alpha-hydroxylase deficiency is an [[inherited]] disease with an [[autosomal recessive]] pattern, which means both copies of the [[gene]] in each cell have [[gene]] [[mutations]]. | |||
* Commonly, the parents of an individual with an [[autosomal recessive]] condition each carry one copy of the mutated [[gene]], but they typically do not show signs and symptoms of the condition. | |||
<ref name="pmid28476231">{{cite journal |vauthors=Hannah-Shmouni F, Chen W, Merke DP |title=Genetics of Congenital Adrenal Hyperplasia |journal=Endocrinol. Metab. Clin. North Am. |volume=46 |issue=2 |pages=435–458 |year=2017 |pmid=28476231 |doi=10.1016/j.ecl.2017.01.008 |url=}}</ref> | |||
==Associated Conditions== | |||
* [[Ambiguous genitalia]] | |||
* [[Hypertension]] | |||
==Gross Pathology== | |||
[[Gross pathology]] findings in patients with 17 alpha-hydroxylase deficiency are:<ref name="radio">Congenital adrenal hyperplasia. Dr Henry Knipe and Dr M Venkatesh . Radiopaedia.org 2015.http://radiopaedia.org/articles/congenital-adrenal-hyperplasia</ref><ref name="pmid25372578">{{cite journal |vauthors=Teixeira SR, Elias PC, Andrade MT, Melo AF, Elias Junior J |title=The role of imaging in congenital adrenal hyperplasia |journal=Arq Bras Endocrinol Metabol |volume=58 |issue=7 |pages=701–8 |year=2014 |pmid=25372578 |doi= |url=}}</ref> | |||
*Enlarged [[adrenal glands]] | |||
*Wrinkled surface [[adrenal glands]] | |||
*Cerebriform pattern [[adrenal glands]] ([[pathognomonic]] sign) | |||
*Normal [[ultrasound]] appearances may also be seen | |||
*[[Testicular]] masses may be identified representing adrenal rest tissue | |||
==Microscopic Pathology== | |||
In 17 alpha-hydroxylase deficiency [[microscopic]] findings may include: | |||
* Diffuse cortical [[hyperplasia]] with smaller [[cells]] | |||
* The cell [[cytoplasm]] can be vacuolated, and often more [[basophilic]] | |||
* Rare [[mitotic]] figures may be present | |||
* The [[hyperplastic]] cells typically lack features of cellular [[atypia]].<ref name="urlAdrenal Gland - Hyperplasia - Nonneoplastic Lesion Atlas">{{cite web |url=https://ntp.niehs.nih.gov/nnl/endocrine/adrenal/hyperpl/index.htm |title=Adrenal Gland - Hyperplasia - Nonneoplastic Lesion Atlas |format= |work= |accessdate=}}</ref> | |||
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[[Image:Cah mic.jpg|thumb|200px|frame|Adrenal gland, Cortex - Hyperplasia in a female rat from a chronic study. There is a hyperplastic lesion (H) in which cortical cells are increased in number but are smaller in size than adjacent normal cortical cells (NC)<ref name="urlAdrenal Gland - Hyperplasia - Nonneoplastic Lesion Atlas">{{cite web |url=https://ntp.niehs.nih.gov/nnl/endocrine/adrenal/hyperpl/index.htm |title=Adrenal Gland - Hyperplasia - Nonneoplastic Lesion Atlas |format= |work= |accessdate=}}</ref>]] | |||
| | |||
[[Image:Cah.jpg|thumb|250px|frame|Adrenal gland, Cortex - Hyperplasia in a male rat from a chronic study. There are two adjacent foci of hyperplasia (H) in the zona fasciculata.<ref name="urlAdrenal Gland - Hyperplasia - Nonneoplastic Lesion Atlas">{{cite web |url=https://ntp.niehs.nih.gov/nnl/endocrine/adrenal/hyperpl/index.htm |title=Adrenal Gland - Hyperplasia - Nonneoplastic Lesion Atlas |format= |work= |accessdate=}}</ref>]] | |||
|} | |||
==References== | |||
{{Reflist|2}} | |||
Revision as of 21:07, 3 August 2017
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17 alpha-hydroxylase deficiency Microchapters |
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Differentiating 17 alpha-hydroxylase deficiency from other Diseases |
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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.
Genetics
- 17 alpha-hydroxylase deficiency is an inherited disease with an autosomal recessive pattern, which means both copies of the gene in each cell have gene mutations.
- Commonly, the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
Associated Conditions
Gross Pathology
Gross pathology findings in patients with 17 alpha-hydroxylase deficiency are:[2][3]
- Enlarged adrenal glands
- Wrinkled surface adrenal glands
- Cerebriform pattern adrenal glands (pathognomonic sign)
- Normal ultrasound appearances may also be seen
- Testicular masses may be identified representing adrenal rest tissue
Microscopic Pathology
In 17 alpha-hydroxylase deficiency microscopic findings may include:
- Diffuse cortical hyperplasia with smaller cells
- The cell cytoplasm can be vacuolated, and often more basophilic
- Rare mitotic figures may be present
- The hyperplastic cells typically lack features of cellular atypia.[4]
 |
 |
References
- ↑ Hannah-Shmouni F, Chen W, Merke DP (2017). "Genetics of Congenital Adrenal Hyperplasia". Endocrinol. Metab. Clin. North Am. 46 (2): 435–458. doi:10.1016/j.ecl.2017.01.008. PMID 28476231.
- ↑ Congenital adrenal hyperplasia. Dr Henry Knipe and Dr M Venkatesh . Radiopaedia.org 2015.http://radiopaedia.org/articles/congenital-adrenal-hyperplasia
- ↑ Teixeira SR, Elias PC, Andrade MT, Melo AF, Elias Junior J (2014). "The role of imaging in congenital adrenal hyperplasia". Arq Bras Endocrinol Metabol. 58 (7): 701–8. PMID 25372578.
- ↑ 4.0 4.1 4.2 "Adrenal Gland - Hyperplasia - Nonneoplastic Lesion Atlas".