21-hydroxylase deficiency pathophysiology: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
 
(48 intermediate revisions by 7 users not shown)
Line 1: Line 1:
__NOTOC__
__NOTOC__
{{Congenital adrenal hyperplasia due to 21-hydroxylase deficiency}}
{{21-hydroxylase deficiency}}


{{CMG}} {{AE}} {{AAM}}
{{CMG}}; '''Associate Editor-In-Chief:''' {{MJ}}, {{AAM}}


==Overview==
==Overview==
Development of [[congenital adrenal hyperplasia]] due to 21-hydroxylase deficiency is the result of defective P450c21 enzyme.
The progression to 21-hydroxylase deficiency usually involves the defective conversion of [[17-hydroxyprogesterone]] to [[11-deoxycorticosterone|11-deoxycortisol]] which results in decreased [[cortisol]] synthesis and therefore increased [[corticotropin]] ([[ACTH|ACTH)]] secretion. The resulting [[adrenal]] stimulation leads to increased production of [[androgens]] due to shunting of the pathway to [[androgen]] synthesis. More than 95% of cases of [[congenital adrenal hyperplasia]] ([[Congenital adrenal hyperplasia|CAH]]) are caused by 21-hydroxylase deficiency. The clinical manifestations of [[congenital adrenal hyperplasia]] is closely related to the type and severity of disease. The severity of disease relates to the type of [[mutation]] which causes [[enzyme]] inactivity or hypo-activity. There is a lack of [[enzyme]] in classic form of 21-hydroxylase deficiency; while in the non-classic form, [[enzymatic]] activity is reduced but sufficient to maintain normal [[glucocorticoid]] and [[mineralocorticoid]] production. The [[gene]] responsible for 21-hydroxylase deficiency is [[CYP21A1|CYP21A]]. This [[gene]] is located within the [[Human leukocyte antigen|human leucocyte antigen]] class III region of [[chromosome 6]]. Meiotic [[recombination]] occurs in this genomic region as a result of the high degree of [[sequence homology]] between [[CYP21A2]] and its [[pseudogene]] [[CYP21A1]]. Approximately 70% of [[CYP21A2]] [[genetic mutation]] is due to [[gene conversion]] and [[Microdeletion|micro-deletions]] in [[CYP21A1]] [[gene]].


==Pathophysiology==
== Pathophysiology ==
The defective enzyme P450c21, commonly referred to as 21-hydroxylase (21-OH), is embedded in the smooth [[endoplasmic reticulum]] of the cells of the [[adrenal gland|adrenal cortex]]. It catalyzes [[hydroxylation]] of [[17-hydroxyprogesterone]] to 11-deoxycortisol in the [[glucocorticoid]] pathway from [[pregnenolone]] to [[cortisol]]. It also catalyzes hydroxylation of [[progesterone]] to 11-deoxycorticosterone (DOC) in the [[mineralocorticoid]] pathway from pregnenolone to [[aldosterone]].
===Pathogenesis===
Deficient activity of this enzyme reduces the efficiency of cortisol synthesis, with consequent elevation of [[adrenocorticotropic hormone]] ([[ACTH]]) levels and hyperplasia of the adrenal cortex. ACTH stimulates uptake of [[cholesterol]] and synthesis of pregnenolone. Steroid precursors up to and including progesterone, 17-hydroxypregnenolone, and especially 17-hydroxyprogesterone (17OHP) accumulate in the adrenal cortex and in circulating blood. Blood levels of 17OHP can reach 10-1000 times the normal concentration.
* [[21-hydroxylase]] enzyme is involved in the synthesis of [[aldosterone]] in [[zona glomerulosa]] and [[cortisol]] in [[zona fasciculata]]. Lack of 21-hydroxylase enzyme leads to decrease in [[cortisol]] and [[aldosterone]] levels and the rest of synthesis pathways produce extra [[androgens]] and lead to [[hirsutism]].
* More than 95% of all cases of [[congenital adrenal hyperplasia]] ([[CAH]]) are caused by 21-hydroxylase deficiency; the clinical manifestations of 21-hydroxylase deficiency is closely related to the type and severity of disease.
* The severity of disease relates to the type of [[mutation]], which causes [[enzyme]] inactivity or hypo activity.
* There is a lack of [[enzyme]] in classic type of [[21-hydroxylase]] deficiency; while in the non-classic form, enzymatic activity is reduced but sufficient to maintain normal [[glucocorticoid]] and [[mineralocorticoid]] production.
 
===Glucocorticoid pathway===
* In patients with 21-hydroxylase deficiency in [[zona fasciculata]], there is a defective conversion of [[17-hydroxyprogesterone]] to 11-[[deoxycortisol]] which results in decreased [[cortisol]] synthesis and therefore increased [[Corticotropin|corticotropin (ACTH)]] secretion.
===Mineralocorticoids pathway===
* In patients with 21-hydroxylase deficiency in [[zona glomerulosa]], there is a defective conversion of [[progesterone]] to 11-deoxycortisterone which results in decreased [[aldosterone]] synthesis.
* The lack of [[aldosterone]] causes large amounts of [[sodium]] loss in the [[urine]]. Urinary [[sodium]] concentrations are more than 50 mEq/L. As a result of high amount of [[sodium]] loss, [[blood volume]] and [[blood pressure]] can not be maintained in normal ranges.
* Due to [[mineralocorticoid]] deficiency, [[potassium]] and [[acid]] excretion are also impaired resulting in [[hyperkalemia]] and [[metabolic acidosis]].
* There is significant water loss and symptoms of [[dehydration]] due to salt wasting within the first two week of life. In severe form of [[CAH]], [[vomiting]], severe [[dehydration]], circulatory collapse and [[shock]]<nowiki/>develops in the second or third week of life.


Since 21-hydroxylase activity is not involved in synthesis of [[androgen]]s, a substantial fraction of the large amounts of 17-hydroxypregnenolone is diverted to synthesis of dehydroepiandrostenedione ([[DHEA]]), [[androstenedione]], and [[testosterone]] beginning in the third month of fetal life in both sexes.
===Androgen pathway===
* In the [[androgen]] synthesis pathway, 21-hydroxylase enzyme does not have a direct role; therefore with extra amount of other products from blocked [[cortisol]] and [[aldosterone]] synthesis, [[androgen]] pathway have extra [[Precursors|precursor]] [[metabolites]] resulting in [[androgen]] excess in the form of [[dehydroepiandrosterone]] and [[androstenedione]] accumulation.
* On the other hand, lack of [[cortisol]] removes the negative feedback on the [[pituitary gland]], resulting in an increase in [[ACTH]] level and consequently more increase in [[androgen]] synthesis pathway. High [[androgen]] level in [[21-hydroxylase]] deficient women during [[pregnancy]] causes [[ambiguous genitalia]] in female fetus; also in milder forms induces [[hirsutism]] and [[virilization]] in women. [[Adrenal]] [[androgens]] produce little effect on the [[genitalia]] of male [[infants]] with severe [[CAH]]. Excess [[androgen]] can cause [[precocious puberty]] in male child.


Synthesis of [[aldosterone]] is also dependent on 21-hydroxylase activity. Although fetal production is impaired, it causes no prenatal effects, as the [[placenta]]l connection allows maternal blood to "dialyze" the fetus and maintain both [[electrolyte]] balance and blood volume.<ref name="Wikipeadia">https://en.wikipedia.org/wiki/Congenital_adrenal_hyperplasia_due_to_21-hydroxylase_deficiency</ref>
Below is the [[hormonal]] pathway of [[adrenal]] [[steroids]] and related [[enzymes]], also the mechanism of 21 hydroxylase deficiency symptoms.<ref name="pmid10857554">{{cite journal |vauthors=White PC, Speiser PW |title=Congenital adrenal hyperplasia due to 21-hydroxylase deficiency |journal=Endocr. Rev. |volume=21 |issue=3 |pages=245–91 |year=2000 |pmid=10857554 |doi=10.1210/edrv.21.3.0398 |url=}}</ref><ref name="pmid20823466">{{cite journal |vauthors=Speiser PW, Azziz R, Baskin LS, Ghizzoni L, Hensle TW, Merke DP, Meyer-Bahlburg HF, Miller WL, Montori VM, Oberfield SE, Ritzen M, White PC |title=Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline |journal=J. Clin. Endocrinol. Metab. |volume=95 |issue=9 |pages=4133–60 |year=2010 |pmid=20823466 |pmc=2936060 |doi=10.1210/jc.2009-2631 |url=}}</ref>




===Genetics===
[[image:21 hydroxylase.gif|center|frame|800px|Adrenal steroid synthesis pathways in adrenal cortex and related enzymes <ref name="urlFile:Adrenal Steroids Pathways.svg - Wikimedia Commons">{{cite web |url=https://commons.wikimedia.org/wiki/File:Adrenal_Steroids_Pathways.svg|title=File:Adrenal Steroids Pathways.svg - Wikimedia Commons |format= |work= |accessdate=}}</ref>]]
[[Image:autorecessive.svg|thumb|300px|left|21-hydroxylase CAH is inherited in an [[autosomal recessive]] fashion]]
The ''CYP21'' gene for the P450c21 enzyme (also known as 21-hydroxylase) is at 6p21.3, amid genes ''HLA B'' and ''HLA DR'' coding for the major human histocompatibility loci ([[HLA]]). ''CYP21'' is paired with a nonfunctional [[pseudogene]] ''CYP21A''. Scores of abnormal [[allele]]s of CYP21 have been documented, most arising from [[recombination]]s of homologous regions of ''CYP21'' and ''CYP21A''. Differences in residual enzyme activity of the various alleles account for the various degrees of severity of the disease. Inheritance of all forms of 21-hydroxylase CAH is [[autosomal recessive]].


Persons affected by any forms of the disease have two abnormal alleles, and both parents are usually carriers ([[heterozygote]]s). When parents both carry an abnormal allele, each child has a 25% chance of having the disease, a 50% chance of being an [[asymptomatic carrier]] like parents, and a 25% chance of having two normal genes.  
== Genetics ==
* [[Congenital adrenal hyperplasia]] subtypes are all [[autosomal recessive]] and [[Monogenic disorder|monogenetic]]. The disease manifestation follows the [[allele]] that results in a more functional enzyme, and generally correlation between [[genotype]] and [[phenotype]] is good.<ref name="pmid20926536">{{cite journal |vauthors=Finkielstain GP, Chen W, Mehta SP, Fujimura FK, Hanna RM, Van Ryzin C, McDonnell NB, Merke DP |title=Comprehensive genetic analysis of 182 unrelated families with congenital adrenal hyperplasia due to 21-hydroxylase deficiency |journal=J. Clin. Endocrinol. Metab. |volume=96 |issue=1 |pages=E161–72 |year=2011 |pmid=20926536 |pmc=3038490 |doi=10.1210/jc.2010-0319 |url=}}</ref><ref name="pmid23359698">{{cite journal |vauthors=New MI, Abraham M, Gonzalez B, Dumic M, Razzaghy-Azar M, Chitayat D, Sun L, Zaidi M, Wilson RC, Yuen T |title=Genotype-phenotype correlation in 1,507 families with congenital adrenal hyperplasia owing to 21-hydroxylase deficiency |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=110 |issue=7 |pages=2611–6 |year=2013 |pmid=23359698 |pmc=3574953 |doi=10.1073/pnas.1300057110 |url=}}</ref>


It is now possible to test for [[heterozygote|heterozygosity]] by measuring 17-hydroxyprogesterone elevation after [[ACTH]] stimulation, or more recently by direct gene sequencing.<ref name="Wikipeadia">https://en.wikipedia.org/wiki/Congenital_adrenal_hyperplasia_due_to_21-hydroxylase_deficiency</ref><ref name="pmid19228439">{{cite journal| author=Trakakis E, Loghis C, Kassanos D| title=Congenital adrenal hyperplasia because of 21-hydroxylase deficiency. A genetic disorder of interest to obstetricians and gynecologists. | journal=Obstet Gynecol Surv | year= 2009 | volume= 64 | issue= 3 | pages= 177-89 | pmid=19228439 | doi=10.1097/OGX.0b013e318193301b | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19228439  }} </ref>
=== CYP21A gene ===
* The [[gene]] responsible for 21-hydroxylase deficiency is [[CYP21A1|CYP21A]]. This gene is located within the [[Human leukocyte antigen|human leucocyte antigen]] class III region of [[chromosome 6]].
[[CYP21A1|CYP21A]] gene has two types:


===Late onset (nonclassical) congenital adrenal hyperplasia===
===== CYP21A2 =====
Other alleles result in even milder degrees of hyperandrogenism that may not even cause problems in males and may not be recognized until adolescence or later in females. Mild androgen effects in young women may include [[hirsutism]], acne, or [[anovulation]] (which in turn can cause [[infertility]]).  
* An active [[gene]] called [[CYP21A2]], which encodes 21-hydroxylase, a [[cytochrome P450]] type II [[enzyme]] containing 495 [[amino acids]].


===== CYP21A1 =====
* This [[gene]] is a non-functional [[pseudogene]] named [[CYP21A1]] or CYP21P. This [[pseudogene]] produces an [[enzyme]] with no activity because it lacks eight bases from [[codons]] 110-112, which results in a [[stop codon]].<ref name="pmid3487786">{{cite journal |vauthors=White PC, New MI, Dupont B |title=Structure of human steroid 21-hydroxylase genes |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=83 |issue=14 |pages=5111–5 |year=1986 |pmid=3487786 |pmc=323900 |doi= |url=}}</ref>


====Virilization of female infants====
===== Mutation mechanisms: =====
Virilization of genetically female (XX) infants usually produces obvious [[ambiguous genitalia|genital ambiguity]]. Inside the pelvis, the [[ovary|ovaries]] are normal and since they have not been exposed to testicular [[antimullerian hormone]], the [[uterus]], [[fallopian tube]]s, upper vagina, and other mullerian structures are normally formed as well. However, the high levels of testosterone in the blood can enlarge the phallus, partially or completely close the vaginal opening, enclose the [[urethra]]l groove so that it opens at the base of the phallus, on the shaft or even at the tip like a boy. Testosterone can cause the [[labia]]l skin to become as thin and rugated as a [[scrotum]], but cannot produce palpable gonads (i.e., testes) in the folds.<ref name="Wikipeadia">https://en.wikipedia.org/wiki/Congenital_adrenal_hyperplasia_due_to_21-hydroxylase_deficiency</ref>
* Meiotic [[recombination]] events occurs in this [[genomic]] region as a result of the high degree of [[sequence homology]] between [[CYP21A2]] and its [[pseudogene]] [[CYP21A1]].  
** Approximately 70% of disease associated with [[CYP21A2]] is due to [[gene conversion]] and [[Microdeletion|microdeletions]] in [[CYP21A1]] [[gene]].
** Approximately 25% to 30% are [[Chimerism|chimeric]] [[genes]] due to large [[Deletion (genetics)|deletions]].
** Approximately 1% to 2% of cases are due to [[De novo mutation|de novo mutations]] because of high variability of the [[CYP21A2]] [[locus]].
** [[Chromosome 6]] [[uniparental disomy]] is rare cause of [[21-hydroxylase]] deficiency with an unknown [[prevalence]].  


===Childhood onset (simple virilizing) congenital adrenal hyperplasia===
* [[Gene]] [[mutations]] that completely inactivates [[CYP21A2]] [[gene]] will result in the classic type and salt-wasting subtype.  
Mutations that result in some residual 21-hydroxylase activity cause milder disease, traditionally termed '''simple virilizing congenital adrenal hyperplasia''' (SVCAH). In these children the [[mineralocorticoid]] deficiency is insignificant and salt-wasting does not occur. The [[androgen]] excess is mild enough that [[virilization]] is not apparent or goes unrecognized at birth and in early childhood. However, androgen levels are above normal and slowly rise during childhood, producing noticeable effects between 2 and 9 years of age.
* [[Gene]] [[mutations]] that maintain 1–2% of 21-hydroxylase activity will result in classic type and non-salt-wasting subtype. These patients have minimal [[aldosterone]] production that prevents a [[neonatal]] [[adrenal crisis]].<ref name="pmid2831244">{{cite journal |vauthors=Fiet J, Gueux B, Gourmelen M, Kuttenn F, Vexiau P, Couillin P, Pham-Huu-Trung MT, Villette JM, Raux-Demay MC, Galons H |title=Comparison of basal and adrenocorticotropin-stimulated plasma 21-deoxycortisol and 17-hydroxyprogesterone values as biological markers of late-onset adrenal hyperplasia |journal=J. Clin. Endocrinol. Metab. |volume=66 |issue=4 |pages=659–67 |year=1988 |pmid=2831244 |doi=10.1210/jcem-66-4-659 |url=}}</ref>
====Salt-wasting crises in infancy====
 
The excessive amounts of adrenal testosterone produce little effect on the genitalia of male infants with severe congenital adrenal hyperplasia. If a male infant with congenital adrenal hyperplasia is not detected by [[newborn screening]], he will appear healthy and normal and be quickly discharged home to his family. However, the lack of aldosterone results in a high rate of [[sodium]] loss in the urine. Urinary sodium concentrations may exceed 50 mEq/L. With this rate of salt loss, the infant cannot maintain blood volume, and [[hyponatremia|hyponatremic]] [[dehydration]] begins to develop by the end of the first week of life. [[Potassium]] and [[acid]] excretion are also impaired when [[mineralocorticoid]] activity is deficient, and [[hyperkalemia]] and [[metabolic acidosis]] gradually develop. Ability to maintain circulation is further limited by the effect of cortisol deficiency. The early symptoms are spitting and poor weight gain, but most infants with severe congenital adrenal hyperplasia develop vomiting, severe dehydration, and circulatory collapse ([[Shock (medical)|shock]]) by the second or third week of life.<ref name="Wikipeadia">https://en.wikipedia.org/wiki/Congenital_adrenal_hyperplasia_due_to_21-hydroxylase_deficiency</ref>
==Gross Pathology==
[[Gross]] [[pathology]] findings in patients with 21 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 of [[adrenal glands]]
*Cerebriform pattern in [[adrenal glands]] ([[pathognomonic]] sign)
*Normal [[ultrasound]] appearance
 
==Microscopic Pathology==
In [[21-hydroxylase]] deficiency [[microscopic]] findings may include:
* Diffuse [[Adrenal cortex|cortical]] [[hyperplasia]] with smaller [[Cell (biology)|cells]]  
* The [[Cell (biology)|cell]] [[cytoplasm]] can be [[Vacuolization|vacuolated]], and often more [[basophilic]].
* Rare [[mitotic]] figures may be present
* The [[hyperplastic]] [[Cell (biology)|cells]] typically lack features of [[atypia|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>
{|
|
[[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==
==References==
{{Reflist|2}}
{{Reflist|2}}
{{WH}}
{{WS}}
[[Category:Disease]]
[[Category:Disease]]
[[Category:Pediatrics]]
[[Category:Pediatrics]]
Line 43: Line 84:
[[Category:Genetic disorders]]
[[Category:Genetic disorders]]
[[Category:Intersexuality]]
[[Category:Intersexuality]]
{{WikiDoc Help Menu}}
[[Category:Medicine]]
{{WikiDoc Sources}}
[[Category: Up-To-Date]]
​

Latest revision as of 15:39, 24 July 2020

Congenital adrenal hyperplasia main page

21-hydroxylase deficiency Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating 21-Hydroxylase Deficiency from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

X Ray

CT

MRI

Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

21-hydroxylase deficiency pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of 21-hydroxylase deficiency pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on 21-hydroxylase deficiency pathophysiology

CDC on 21-hydroxylase deficiency pathophysiology

21-hydroxylase deficiency pathophysiology in the news

Blogs on 21-hydroxylase deficiency pathophysiology

Directions to Hospitals Treating 21-Hydroxylase Deficiency

Risk calculators and risk factors for 21-hydroxylase deficiency pathophysiology

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Mehrian Jafarizade, M.D [2], Ahmad Al Maradni, M.D. [3]

Overview

The progression to 21-hydroxylase deficiency usually involves the defective conversion of 17-hydroxyprogesterone to 11-deoxycortisol which results in decreased cortisol synthesis and therefore increased corticotropin (ACTH) secretion. The resulting adrenal stimulation leads to increased production of androgens due to shunting of the pathway to androgen synthesis. More than 95% of cases of congenital adrenal hyperplasia (CAH) are caused by 21-hydroxylase deficiency. The clinical manifestations of congenital adrenal hyperplasia is closely related to the type and severity of disease. The severity of disease relates to the type of mutation which causes enzyme inactivity or hypo-activity. There is a lack of enzyme in classic form of 21-hydroxylase deficiency; while in the non-classic form, enzymatic activity is reduced but sufficient to maintain normal glucocorticoid and mineralocorticoid production. The gene responsible for 21-hydroxylase deficiency is CYP21A. This gene is located within the human leucocyte antigen class III region of chromosome 6. Meiotic recombination occurs in this genomic region as a result of the high degree of sequence homology between CYP21A2 and its pseudogene CYP21A1. Approximately 70% of CYP21A2 genetic mutation is due to gene conversion and micro-deletions in CYP21A1 gene.

Pathophysiology

Pathogenesis

Glucocorticoid pathway

Mineralocorticoids pathway

Androgen pathway

Below is the hormonal pathway of adrenal steroids and related enzymes, also the mechanism of 21 hydroxylase deficiency symptoms.[1][2]


Adrenal steroid synthesis pathways in adrenal cortex and related enzymes [3]

Genetics

CYP21A gene

CYP21A gene has two types:

CYP21A2
CYP21A1
Mutation mechanisms:

Gross Pathology

Gross pathology findings in patients with 21 hydroxylase deficiency are:[8][9]

Microscopic Pathology

In 21-hydroxylase deficiency microscopic findings may include:

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)[10]
Adrenal gland, Cortex - Hyperplasia in a male rat from a chronic study. There are two adjacent foci of hyperplasia (H) in the zona fasciculata.[10]

References

  1. ↑ White PC, Speiser PW (2000). "Congenital adrenal hyperplasia due to 21-hydroxylase deficiency". Endocr. Rev. 21 (3): 245–91. doi:10.1210/edrv.21.3.0398. PMID 10857554.
  2. ↑ Speiser PW, Azziz R, Baskin LS, Ghizzoni L, Hensle TW, Merke DP, Meyer-Bahlburg HF, Miller WL, Montori VM, Oberfield SE, Ritzen M, White PC (2010). "Congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency: an Endocrine Society clinical practice guideline". J. Clin. Endocrinol. Metab. 95 (9): 4133–60. doi:10.1210/jc.2009-2631. PMC 2936060. PMID 20823466.
  3. ↑ "File:Adrenal Steroids Pathways.svg - Wikimedia Commons".
  4. ↑ Finkielstain GP, Chen W, Mehta SP, Fujimura FK, Hanna RM, Van Ryzin C, McDonnell NB, Merke DP (2011). "Comprehensive genetic analysis of 182 unrelated families with congenital adrenal hyperplasia due to 21-hydroxylase deficiency". J. Clin. Endocrinol. Metab. 96 (1): E161–72. doi:10.1210/jc.2010-0319. PMC 3038490. PMID 20926536.
  5. ↑ New MI, Abraham M, Gonzalez B, Dumic M, Razzaghy-Azar M, Chitayat D, Sun L, Zaidi M, Wilson RC, Yuen T (2013). "Genotype-phenotype correlation in 1,507 families with congenital adrenal hyperplasia owing to 21-hydroxylase deficiency". Proc. Natl. Acad. Sci. U.S.A. 110 (7): 2611–6. doi:10.1073/pnas.1300057110. PMC 3574953. PMID 23359698.
  6. ↑ White PC, New MI, Dupont B (1986). "Structure of human steroid 21-hydroxylase genes". Proc. Natl. Acad. Sci. U.S.A. 83 (14): 5111–5. PMC 323900. PMID 3487786.
  7. ↑ Fiet J, Gueux B, Gourmelen M, Kuttenn F, Vexiau P, Couillin P, Pham-Huu-Trung MT, Villette JM, Raux-Demay MC, Galons H (1988). "Comparison of basal and adrenocorticotropin-stimulated plasma 21-deoxycortisol and 17-hydroxyprogesterone values as biological markers of late-onset adrenal hyperplasia". J. Clin. Endocrinol. Metab. 66 (4): 659–67. doi:10.1210/jcem-66-4-659. PMID 2831244.
  8. ↑ Congenital adrenal hyperplasia. Dr Henry Knipe and Dr M Venkatesh . Radiopaedia.org 2015.http://radiopaedia.org/articles/congenital-adrenal-hyperplasia
  9. ↑ 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.
  10. ↑ 10.0 10.1 10.2 "Adrenal Gland - Hyperplasia - Nonneoplastic Lesion Atlas".

Template:WH Template:WS ​

Retrieved from "https://www.wikidoc.org/index.php?title=21-hydroxylase_deficiency_pathophysiology&oldid=1632247"