21-hydroxylase deficiency history and symptoms: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
No edit summary
 
(59 intermediate revisions by 6 users not shown)
Line 1: Line 1:
__NOTOC__
__NOTOC__
{{Congenital adrenal hyperplasia due to 21-hydroxylase deficiency}}
{{21-hydroxylase deficiency}}
{{CMG}}; '''Associate Editor-In-Chief:''' {{CZ}}
{{CMG}}; '''Associate Editor-In-Chief:''' {{MJ}}
==Overview==
==Overview==
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==
==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"
! rowspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" + |21-OH deficiency type
! colspan="3" align="center" style="background:#4479BA; color: #FFFFFF;" + |Common symptoms
! colspan="2" align="center" style="background:#4479BA; color: #FFFFFF;" + |Less common symptoms
|-
! 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]]


===Early-onset: Severe 21-hydroxylase deficient CAH===
* [[Clitoromegaly|Clitoral]] enlargement
The two most serious neonatal consequences of 21-hydroxylase deficiency occur when there is minimal measurable hydroxylase activity from prenatal life: severe virilization of female infants and life-threatening salt-wasting crises in the first month of life for XX and XY infants alike.
* [[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)


====Virilization of female infants====
* [[Hyperpigmentation]] of the [[scrotum]]
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.
* 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


Thus, depending on the severity of hyperandrogenism, a female infant can be mildly affected, obviously ambiguous, or so severely virilized as to appear to be a male. Andrea Prader devised the following Prader scale as a way of describing the degree of virilization.
* Male-typical cognitive pattern (better [[Performance status|performance]] on spatial tasks, worse performance on verbal tasks)
*An infant at stage 1 has a mildly large [[clitoris]] and slightly reduced vaginal opening size. This degree may go unnoticed or may be simply assumed to be within normal variation.
|
*Stages 2 and 3 represent progressively more severe degrees of virlization. The genitalia are obviously abnormal to the eye, with a phallus intermediate in size and a small vaginal opening.
* [[Testicular masses]] due to [[testicular]] [[Adrenal tumor|adrenal rest tumors]]
*Stage 4 looks more male than female, with an empty scrotum and a phallus the size of a normal penis, but not quite free enough of the perineum to be pulled onto the abdomen toward the umbilicus (i.e., what is termed a [[chordee]] in a male). The single small urethral/vaginal opening at the base or on the shaft of the phallus would be considered a [[hypospadias]] in a male. X-rays taken after dye injection into this opening reveal the internal connection with the upper vagina and uterus. This common opening can predispose to [[urinary obstruction]] and [[urinary tract infection|infection]].
* [[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]]
*Stage 5 denotes complete male virilization, with a normally formed penis with the urethral opening at or near the tip. The scrotum is normally formed but empty. The internal pelvic organs include normal ovaries and uterus, and the vagina connects internally with the urethra as in Stage 4. These infants are not visibly ambiguous are usually assumed to be ordinary boys with [[cryptorchidism|undescended testes]]. In most cases, the diagnosis of CAH is not suspected until signs of salt-wasting develop a week later.
|-
| 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


====Salt-wasting crises in infancy====
* Premature [[pubarche]]  
The excessive amounts of adrenal testosterone produce little effect on the genitalia of male infants with severe CAH. If a male infant with CAH is not detected by [[newborn screening]], he will appear healthy and normal and be quickly discharged home to his family.
* Advance [[bone age]]  
 
* Medication resistant [[cystic acne]]
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 CAH develop vomiting, severe dehydration, and circulatory collapse ([[Shock (medical)|shock]]) by the second or third week of life.
* Accelerated [[growth]] with tall stature as a child
 
|
===Childhood onset (simple virilizing) CAH===
* [[Clitoromegaly]]
Mutations that result in some residual 21-hydroxylase activity cause milder disease, traditionally termed '''simple virilizing CAH''' (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.
* [[Infertility]]  
 
* [[Alopecia]]
===Late onset (nonclassical) CAH===
* [[Primary amenorrhea]]  
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]]). Testosterone levels in these woman may be mildly elevated, or simply above average.
|
* [[Acne]]
* [[Infertility]]
|} 


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}
{{WH}}
{{WS}}
[[Category:Disease]]
[[Category:Disease]]
[[Category:Pediatrics]]
[[Category:Pediatrics]]
Line 35: Line 88:
[[Category:Genetic disorders]]
[[Category:Genetic disorders]]
[[Category:Intersexuality]]
[[Category:Intersexuality]]
 
[[Category:Medicine]]
{{WikiDoc Help Menu}}
[[Category: Up-To-Date]]​
{{WikiDoc Sources}}

Latest revision as of 15:36, 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 history and symptoms 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 history and symptoms

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 history and symptoms

CDC on 21-hydroxylase deficiency history and symptoms

21-hydroxylase deficiency history and symptoms in the news

Blogs on 21-hydroxylase deficiency history and symptoms

Directions to Hospitals Treating 21-Hydroxylase Deficiency

Risk calculators and risk factors for 21-hydroxylase deficiency history and symptoms

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.

Template:WH Template:WS​

Retrieved from "https://www.wikidoc.org/index.php?title=21-hydroxylase_deficiency_history_and_symptoms&oldid=1632237"