21-hydroxylase deficiency pathophysiology: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
No edit summary
No edit summary
Line 5: Line 5:


==Overview==
==Overview==
The progression to 21-hydroxylase deficiency usually involves the a 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 [[mutation]] type which is 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]].
The progression to 21-hydroxylase deficiency usually involves the a 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 [[mutation]] type which is 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 ==
Line 13: Line 13:
* The severity of disease relates to the [[mutation]] type, which casues [[enzyme]] inactivity or hypo activity.  
* The severity of disease relates to the [[mutation]] type, which casues [[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.
* 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.
* Below is the hormonal pathway of [[adrenal]] [[steroids]] and related enzymes.<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>
* Below is the [[hormonal]] pathway of [[adrenal]] [[steroids]] and related [[enzymes]].<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>




Line 21: Line 21:
* [[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><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>
* [[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><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>


* Responsible gene 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:
=== CYP21A gene ===
*# An active [[gene]] called [[CYP21A2]], which encodes 21-hydroxylase, a [[cytochrome P450]] type II enzyme of 495 [[amino acids]].
* 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]].
*# The other 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>
* [[CYP21A1|CYP21A]] gene has two types:
'''(a) Functional variant:'''
* An active [[gene]] called [[CYP21A2]], which encodes 21-hydroxylase, a [[cytochrome P450]] type II [[enzyme]] of 495 [[amino acids]].
'''(b) Non-funtional variant'''
* The other [[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>


* Meiotic [[recombination]] events occurs in this genomic region as a result of the high degree of [[sequence homology]] between [[CYP21A2]] and its [[pseudogene]] [[CYP21A1]].  
* 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 [[CYP21A2]] disease is due to [[gene conversion]] and [[Microdeletion|microdeletions]] in [[CYP21A1]] gene.  
** Approximately 70% of [[CYP21A2]] disease is due to [[gene conversion]] and [[Microdeletion|microdeletions]] in [[CYP21A1]] [[gene]].  
** Approximately 25% to 30% are chimeric [[genes]] due to large [[Deletion (genetics)|deletions]].  
** 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]].   
** 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]].  
** [[Chromosome 6]] [[uniparental disomy]] is rare cause of 21-hydroxylase deficiency with an unknown [[prevalence]].  


* [[Gene]] [[mutations]] that completely inactivate [[CYP21A2]] gene will result in the classic type and salt-wasting subtype.  
* [[Gene]] [[mutations]] that completely inactivate [[CYP21A2]] [[gene]] will result in the classic type and salt-wasting subtype.  
* [[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>
* [[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>


Line 37: Line 41:
[[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>
[[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]]
*Enlarged [[adrenal glands]]
*Wrinkled surface [[adrenal glands]]
*Wrinkled surface of [[adrenal glands]]
*Cerebriform pattern [[adrenal glands]] ([[pathognomonic]] sign)
*Cerebriform pattern in [[adrenal glands]] ([[pathognomonic]] sign)
*Normal [[ultrasound]] appearances may also be seen
*Normal [[ultrasound]] appearance
*[[Testicular masses]] may be identified representing [[adrenal]] rest tissue
*[[Testicular masses]] may be identified representing [[adrenal]] rest tissue


==Microscopic Pathology==
==Microscopic Pathology==
In 21 hydroxylase deficiency [[microscopic]] findings may include:
In 21 hydroxylase deficiency [[microscopic]] findings may include:
* Diffuse cortical [[hyperplasia]] with smaller cells  
* Diffuse [[Adrenal cortex|cortical]] [[hyperplasia]] with smaller [[Cell (biology)|cells]]
* The cell [[cytoplasm]] can be vacuolated, and often more [[basophilic]].
* The [[Cell (biology)|cell]] [[cytoplasm]] can be [[Vacuolization|vacuolated]], and often more [[basophilic]].
* Rare [[mitotic]] figures may be present
* 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>
* 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>
{|
{|
|
|

Revision as of 18:10, 24 August 2017

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]

Overview

The progression to 21-hydroxylase deficiency usually involves the a 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 mutation type which is 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

  • In patients with 21-hydroxylase deficiency, there is a 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.
  • 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 mutation type, which casues 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.
  • Below is the hormonal pathway of adrenal steroids and related enzymes.[1][2]


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

Genetics

CYP21A gene

(a) Functional variant:

(b) Non-funtional variant

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. ↑ 4.0 4.1 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".
Retrieved from "https://www.wikidoc.org/index.php?title=21-hydroxylase_deficiency_pathophysiology&oldid=1346141"