21-hydroxylase deficiency history and symptoms: Difference between revisions

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__NOTOC__
__NOTOC__
{{Congenital adrenal hyperplasia due to 21-hydroxylase deficiency}}
{{21-hydroxylase deficiency}}
{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}} {{AAM}}
{{CMG}}; '''Associate Editor-In-Chief:''' {{MJ}}
==Overview==
==Overview==
Symptoms of 21-hydroxylase deficient congenital adrenal hyperplasia include [[dehydration]], [[vomiting]], and [[weight loss]]. Late symptoms include [[virilization]] and [[infertility]].
Symptoms of 21-hydroxylase deficiency range from severe to mild or asymptomatic forms, depending on the degree of [[21-Hydroxylase|21-hydroxylase]] enzyme deficiency. There are three main clinical phenotypes: classic salt-wasting, classic non-salt-wasting (simple [[virilizing]]), and non-classic (late-onset). In classical type, main symptoms can be severe [[hypotension]] due to [[adrenal crisis]], [[ambiguous genitalia]] in females, and no symptoms or larger [[Phallus (genus)|phallus]] in males. In non-classic types, infants and male patients may have no symptoms and females may show [[virilization]] symptoms after [[puberty]].
 
==History and Symptoms==
__NOTOC__
{{Congenital adrenal hyperplasia}}
 
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{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}}
 
==Overview==
Classic CAH  salt-wasting CAH Baby girls with ambiguous genitalia with life-threatening cases of vomiting, weight loss and dehydration in a baby’s first few weeks of life or simple virilizing CAH but girls will have ambiguous genitalia. baby boys may have enlarged penises. nonclassic or late onset CAH Patients don't show any signs in early life but show  premature pubarche, acne, hirsutism.


==History and Symptoms==
==History and Symptoms==
Symptoms of 21-hydroxylase deficiency range from mild to severe. Some asymptomatic forms have also been identified. Variability of symptoms depends upon the degree of 21-hydroxylase enzyme deficiency. There are three main clinical phenotypes: classic salt-wasting, classic non-salt-wasting (virilization), and non-classic (late-onset):<ref name="pmid11148508">{{cite journal| author=Eugster EA, Dimeglio LA, Wright JC, Freidenberg GR, Seshadri R, Pescovitz OH| title=Height outcome in congenital adrenal hyperplasia caused by 21-hydroxylase deficiency: a meta-analysis. | journal=J Pediatr | year= 2001 | volume= 138 | issue= 1 | pages= 26-32 | pmid=11148508 | doi=10.1067/mpd.2001.110527 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11148508  }}</ref><ref name="pmid19100266">{{cite journal| author=Mathews GA, Fane BA, Conway GS, Brook CG, Hines M| title=Personality and congenital adrenal hyperplasia: possible effects of prenatal androgen exposure. | journal=Horm Behav | year= 2009 | volume= 55 | issue= 2 | pages= 285-91 | pmid=19100266 | doi=10.1016/j.yhbeh.2008.11.007 | pmc=3296092 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19100266  }}</ref><ref name="pmid3491959">{{cite journal| author=Mulaikal RM, Migeon CJ, Rock JA| title=Fertility rates in female patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. | journal=N Engl J Med | year= 1987 | volume= 316 | issue= 4 | pages= 178-82 | pmid=3491959 | doi=10.1056/NEJM198701223160402 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3491959  }}</ref><ref name="pmid12665708">{{cite journal| author=Stikkelbroeck NM, Hermus AR, Braat DD, Otten BJ| title=Fertility in women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. | journal=Obstet Gynecol Surv | year= 2003 | volume= 58 | issue= 4 | pages= 275-84 | pmid=12665708 | doi=10.1097/01.OGX.0000062966.93819.5B | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12665708  }}</ref><ref name="pmid18420648">{{cite journal| author=Hagenfeldt K, Janson PO, Holmdahl G, Falhammar H, Filipsson H, Frisén L et al.| title=Fertility and pregnancy outcome in women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. | journal=Hum Reprod | year= 2008 | volume= 23 | issue= 7 | pages= 1607-13 | pmid=18420648 | doi=10.1093/humrep/den118 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18420648  }}</ref><ref name="pmid15554889">{{cite journal |vauthors=van der Kamp HJ, Wit JM |title=Neonatal screening for congenital adrenal hyperplasia |journal=Eur. J. Endocrinol. |volume=151 Suppl 3 |issue= |pages=U71–5 |year=2004 |pmid=15554889 |doi= |url=}}</ref><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="pmid9047259">{{cite journal |vauthors=Zucker KJ, Bradley SJ, Oliver G, Blake J, Fleming S, Hood J |title=Psychosexual development of women with congenital adrenal hyperplasia |journal=Horm Behav |volume=30 |issue=4 |pages=300–18 |year=1996 |pmid=9047259 |doi=10.1006/hbeh.1996.0038 |url=}}</ref>
{| class="wikitable"
{| class="wikitable"
!21-OH deficiency type
! rowspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" + |21-OH deficiency type
!Common symptoms
! colspan="3" align="center" style="background:#4479BA; color: #FFFFFF;" + |Common symptoms
!Less common symptoms
! colspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" + |Less common symptoms
|-
|-
|Classical salt wasting
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Infancy
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Female
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Male
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Female
! align="center" style="background:#4479BA; color: #FFFFFF;" + |Male
|-
| align="center" style="background:#DCDCDC;" + |Classic type
|
|
In salt wasting type
* [[Vomiting]]
* [[Weight loss]]
* [[Dehydration]] in a baby’s first few weeks of life
|
|
* [[Ambiguous genitalia]]
* [[Clitoromegaly|Clitoral]] enlargement
* [[Labial fusion]]
* Deep voice
* More aggressive tendencies than unaffected healthy women
* Early [[puberty]]
* Adult [[short stature]]
* Male-typical [[sexual behavior]] in girls and [[cross-gender]] role behavior
* Decreased [[fertility]] due to [[Hyperandrogenism|hyperandrogenemia]] and [[Anovulatory cycle|anovulatory cycles]] ([[fertility]] rate depends the enzyme amount)
|
|
|-
* Normal appearing at birth  (mostly)
|Classical non-salt wasting
 
|
* [[Hyperpigmentation]] of the [[scrotum]]
* Enlarged [[Phallus (genus)|phallus]]
* Deep voice
* [[Muscle]] growth
* Early [[virilization]] at two to four years of age with ([[pubic hair]], [[Growth spurts|growth spurt]], adult [[body odor]])
|
|
* [[Cognitive function]] disturbance such as IQ impairment
* Male-typical cognitive pattern (better [[Performance status|performance]] on spatial tasks, worse performance on verbal tasks)
|
|
* [[Testicular masses]] due to [[testicular]] [[Adrenal tumor|adrenal rest tumors]]
* [[Infertility]] due to [[seminiferous tubule]] obstruction, [[gonadal]] dysfunction as a result of testicular [[Adrenal tumor|adrenal rest tumors]], these [[tumors]] caused by high level of [[ACTH]]
|-
|-
|Late onset disease
| align="center" style="background:#DCDCDC;" + |Non-classic type
|
|
* No symptoms
|
|
* [[Hirsutism]], [[acne]] and [[Menstrual irregularities|menstrual irregularity]] in young women
* Premature [[pubarche]]
* Advance [[bone age]]
* Medication resistant [[cystic acne]]
* Accelerated growth with tall stature as a child in pre-[[pubertal]] period
* Early [[pubarche]] or [[sexual]] precocity in school age children
* Mild [[subfertility]] due to [[Hyperandrogenism|hyperandrogenemia]] and [[Anovulatory cycle|anovulatory cycles]] ([[fertility]] rate depends the [[enzyme]] amount)
|
|
|}
* No symptoms


=== '''Congenital adrenal hyperplasia symotpms differ according to type of disease and gender of patient:''' ===
* Premature [[pubarche]]  
 
* Advance [[bone age]]  
==== '''Classic CAH or early onset:''' ====
* Medication resistant [[cystic acne]]
Classic cases of congenital adrenal hyperplasia come in two forms:
* Accelerated [[growth]] with tall stature as a child
 
|
'''Salt-wasting CAH'''
* [[Clitoromegaly]]
* Baby girls with ambiguous genitalia.
* [[Infertility]]  
* Baby boys may have enlarged penises and develop masculine features before puberty.
* [[Alopecia]]
* Salt-wasting CAH can lead to life-threatening cases of vomiting, weight loss and dehydration in a baby’s first few weeks of life.
* [[Primary amenorrhea]]  
'''simple virilizing CAH'''
|
* Patients don't show hypotension, hyperkalemia and acidosis crisis but:
* [[Acne]]
* Girls will have ambiguous genitalia.
* [[Infertility]]
* Baby boys may have enlarged penises.
|} 
 
==== '''Nonclassic or late onset CAH''' ====
Patients don't show any signs in early life but show premature puberty, acne, hirsutism, and menstrual irregularity.
* Children with CAH are at risk for adult short stature due to high levels of sex hormones causing premature epiphyseal closure.<ref name="pmid11148508">{{cite journal| author=Eugster EA, Dimeglio LA, Wright JC, Freidenberg GR, Seshadri R, Pescovitz OH| title=Height outcome in congenital adrenal hyperplasia caused by 21-hydroxylase deficiency: a meta-analysis. | journal=J Pediatr | year= 2001 | volume= 138 | issue= 1 | pages= 26-32 | pmid=11148508 | doi=10.1067/mpd.2001.110527 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11148508  }}</ref>
* Female patients with classic CAH have more male-typical palying<ref name="pmid19100266">{{cite journal| author=Mathews GA, Fane BA, Conway GS, Brook CG, Hines M| title=Personality and congenital adrenal hyperplasia: possible effects of prenatal androgen exposure. | journal=Horm Behav | year= 2009 | volume= 55 | issue= 2 | pages= 285-91 | pmid=19100266 | doi=10.1016/j.yhbeh.2008.11.007 | pmc=3296092 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19100266  }}</ref>and greater aggressive tendencies.
* Fertility rates in women are low.<ref name="pmid3491959">{{cite journal| author=Mulaikal RM, Migeon CJ, Rock JA| title=Fertility rates in female patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. | journal=N Engl J Med | year= 1987 | volume= 316 | issue= 4 | pages= 178-82 | pmid=3491959 | doi=10.1056/NEJM198701223160402 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3491959  }}</ref>Hyperandrogenism results in anovulatory cycles.<ref name="pmid12665708">{{cite journal| author=Stikkelbroeck NM, Hermus AR, Braat DD, Otten BJ| title=Fertility in women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. | journal=Obstet Gynecol Surv | year= 2003 | volume= 58 | issue= 4 | pages= 275-84 | pmid=12665708 | doi=10.1097/01.OGX.0000062966.93819.5B | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12665708  }}</ref>Genital malformations from congenital ambiguous genitals may contribute to low fertility.<ref name="pmid18420648">{{cite journal| author=Hagenfeldt K, Janson PO, Holmdahl G, Falhammar H, Filipsson H, Frisén L et al.| title=Fertility and pregnancy outcome in women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency. | journal=Hum Reprod | year= 2008 | volume= 23 | issue= 7 | pages= 1607-13 | pmid=18420648 | doi=10.1093/humrep/den118 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18420648  }}</ref>Careful management with monitoring of androgen levels during gestation is indicated.<ref name="pmid10084573">{{cite journal| author=Lo JC, Schwitzgebel VM, Tyrrell JB, Fitzgerald PA, Kaplan SL, Conte FA et al.| title=Normal female infants born of mothers with classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency. | journal=J Clin Endocrinol Metab | year= 1999 | volume= 84 | issue= 3 | pages= 930-6 | pmid=10084573 | doi=10.1210/jcem.84.3.5565 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=10084573  }}</ref>
* Males show testicular adrenal tumors which are testicular masses of adrenal-like tissue.<ref name="pmid12835972">{{cite journal| author=Stikkelbroeck NM, Suliman HM, Otten BJ, Hermus AR, Blickman JG, Jager GJ| title=Testicular adrenal rest tumours in postpubertal males with congenital adrenal hyperplasia: sonographic and MR features. | journal=Eur Radiol | year= 2003 | volume= 13 | issue= 7 | pages= 1597-603 | pmid=12835972 | doi=10.1007/s00330-002-1786-3 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12835972  }}</ref>They are more common in patients with the salt-losing form than the simple virilizing form.<ref name="pmid15198296">{{cite journal| author=Stikkelbroeck NM, Hermus AR, Suliman HM, Jager GJ, Otten BJ| title=Asymptomatic testicular adrenal rest tumours in adolescent and adult males with congenital adrenal hyperplasia: basal and follow-up investigation after 2.6 years. | journal=J Pediatr Endocrinol Metab | year= 2004 | volume= 17 | issue= 4 | pages= 645-53 | pmid=15198296 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15198296  }}</ref>They may lead to obstruction of seminiferous tubules and infertility. Other causes of low fertility is impaired spermatogenesis.<ref name="pmid128359722">{{cite journal| author=Stikkelbroeck NM, Suliman HM, Otten BJ, Hermus AR, Blickman JG, Jager GJ| title=Testicular adrenal rest tumours in postpubertal males with congenital adrenal hyperplasia: sonographic and MR features. | journal=Eur Radiol | year= 2003 | volume= 13 | issue= 7 | pages= 1597-603 | pmid=12835972 | doi=10.1007/s00330-002-1786-3 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12835972  }}</ref>
* Fertility rates are related to the severity of the mutation.<ref name="pmid18029470">{{cite journal| author=Nordenskjöld A, Holmdahl G, Frisén L, Falhammar H, Filipsson H, Thorén M et al.| title=Type of mutation and surgical procedure affect long-term quality of life for women with congenital adrenal hyperplasia. | journal=J Clin Endocrinol Metab | year= 2008 | volume= 93 | issue= 2 | pages= 380-6 | pmid=18029470 | doi=10.1210/jc.2007-0556 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18029470  }}</ref>
 
==References==
{{Reflist|2}}
 
Symptoms of 21-hydroxylase deficient congenital adrenal hyperplasia include:
===Symptoms of adrenal hyperplasia in infants===
In this form of congenital adrenal hyperplasia, newborns develop severe symptoms shortly after birth due to loss of salt, which include:
*[[Dehydration]]
*[[Weight loss]]
*[[Vomiting]]
===Symptoms of adrenal hyperplasia in children===
*[[Ambiguous genitalia]] or [[virilizing]] genitalia in girls (often appearing more male than female: deep voice, early appearance of pubic and armpit hair, and excessive hair growth and facial hair)
*Early appearance of [[masculinization]] characteristics in boys (deep voice, early appearance of pubic and armpit hair, enlarged [[penis]], small [[testes]], and well-developed muscles)
===Symptoms of adrenal hyperplasia in adults===
Symptoms of adrenal hyperplasia in children and adults may include:
*[[Metrorrhagia]] and [[amenorrhea]] in girls
*[[Infertility]]


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor-In-Chief: Mehrian Jafarizade, M.D [2]

Overview

Symptoms of 21-hydroxylase deficiency range from severe to mild or asymptomatic forms, depending on the degree of 21-hydroxylase enzyme deficiency. There are three main clinical phenotypes: classic salt-wasting, classic non-salt-wasting (simple virilizing), and non-classic (late-onset). In classical type, main symptoms can be severe hypotension due to adrenal crisis, ambiguous genitalia in females, and no symptoms or larger phallus in males. In non-classic types, infants and male patients may have no symptoms and females may show virilization symptoms after puberty.

History and Symptoms

Symptoms of 21-hydroxylase deficiency range from mild to severe. Some asymptomatic forms have also been identified. Variability of symptoms depends upon the degree of 21-hydroxylase enzyme deficiency. There are three main clinical phenotypes: classic salt-wasting, classic non-salt-wasting (virilization), and non-classic (late-onset):[1][2][3][4][5][6][7][8]

21-OH deficiency type Common symptoms Less common symptoms
Infancy Female Male Female Male
Classic type

In salt wasting type

  • Normal appearing at birth (mostly)
  • Male-typical cognitive pattern (better performance on spatial tasks, worse performance on verbal tasks)
Non-classic type
  • No symptoms
  • No symptoms

 

References

  1. ↑ Eugster EA, Dimeglio LA, Wright JC, Freidenberg GR, Seshadri R, Pescovitz OH (2001). "Height outcome in congenital adrenal hyperplasia caused by 21-hydroxylase deficiency: a meta-analysis". J Pediatr. 138 (1): 26–32. doi:10.1067/mpd.2001.110527. PMID 11148508.
  2. ↑ Mathews GA, Fane BA, Conway GS, Brook CG, Hines M (2009). "Personality and congenital adrenal hyperplasia: possible effects of prenatal androgen exposure". Horm Behav. 55 (2): 285–91. doi:10.1016/j.yhbeh.2008.11.007. PMC 3296092. PMID 19100266.
  3. ↑ Mulaikal RM, Migeon CJ, Rock JA (1987). "Fertility rates in female patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency". N Engl J Med. 316 (4): 178–82. doi:10.1056/NEJM198701223160402. PMID 3491959.
  4. ↑ Stikkelbroeck NM, Hermus AR, Braat DD, Otten BJ (2003). "Fertility in women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency". Obstet Gynecol Surv. 58 (4): 275–84. doi:10.1097/01.OGX.0000062966.93819.5B. PMID 12665708.
  5. ↑ Hagenfeldt K, Janson PO, Holmdahl G, Falhammar H, Filipsson H, Frisén L; et al. (2008). "Fertility and pregnancy outcome in women with congenital adrenal hyperplasia due to 21-hydroxylase deficiency". Hum Reprod. 23 (7): 1607–13. doi:10.1093/humrep/den118. PMID 18420648.
  6. ↑ van der Kamp HJ, Wit JM (2004). "Neonatal screening for congenital adrenal hyperplasia". Eur. J. Endocrinol. 151 Suppl 3: U71–5. PMID 15554889.
  7. ↑ 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.
  8. ↑ Zucker KJ, Bradley SJ, Oliver G, Blake J, Fleming S, Hood J (1996). "Psychosexual development of women with congenital adrenal hyperplasia". Horm Behav. 30 (4): 300–18. doi:10.1006/hbeh.1996.0038. PMID 9047259.

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