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==Pathogenesis==
__NOTOC__
*
 
===Mineralocorticoid Effects===
{{CMG}}; {{AE}} {{MJ}}
* The adrenal cortex is hyperplastic and overstimulated, with no impairment of the mineralocorticoid pathway. Consequently, levels of deoxycorticosterone, [[corticosterone]], and 18-deoxycorticosterone are elevated. Although these precursors of [[aldosterone]] are weaker mineralocorticoids, the extreme elevations usually provide enough volume expansion, blood pressure elevation, and potassium depletion to suppress [[renin]] and aldosterone production. Some persons with 17α-hydroxylase deficiency develop [[hypertension]] in infancy, and nearly 90% do so by late childhood. The low-renin [[hypertension]] is often accompanied by [[hypokalemia]] due to urinary potassium wasting and [[metabolic alkalosis]]. '''These features of mineralocorticoid excess are the major clinical clue distinguishing the more complete 17α-hydroxylase deficiency from the 17,20-lyase deficiency, which only affects the sex steroids.''' Treatment with glucocorticoid suppresses ACTH, returns mineralocorticoid production toward normal, and lowers blood pressure.
 
===Glucocorticoid Effects===
{{SI}}
* Although production of cortisol is inefficient enough to normalize ACTH, the 50-100-fold elevations of [[corticosterone]] have enough weak [[glucocorticoid]] activity to prevent glucocorticoid deficiency and adrenal crisis.
 
===Sex Steroid Effects===
==Overview==
* Genetic XX females affected by 17α-hydroxylase deficiency are born with normal female internal and external anatomy. At the expected time of [[puberty]], neither the adrenals nor the ovaries can produce sex steroids, so neither breast development nor pubic hair appears. Investigation of delayed puberty yields elevated [[gonadotropin]]s and normal karyotype while imaging confirms the presence of ovaries and an infantile uterus. Discovery of hypertension and hypokalemic [[alkalosis]] usually suggests the presence of one of the proximal forms of congenital adrenal hyperplasia, and the characteristic mineralocorticoid elevations confirm the specific diagnosis.
 
* A few milder forms of this deficiency in genetic females have allowed relatively normal breast development and irregular menstruation. Evidence suggests that only 5% of normal enzyme activity may be enough to allow at least the physical changes of female puberty, if not [[ovulation]] and fertility. In these girls, the elevated blood pressure was the primary clinical problem.
==Historical Perspective==
* 17α-Hydroxylase deficiency in genetic males (XY) results in moderate to severe reduction of fetal [[testosterone]] production by both adrenals and testes. [[virilization|Undervirilization]] is variable and sometimes complete. The appearance of the external [[genitalia]] ranges from normal female to ambiguous to mildly underdeveloped male. The most commonly described phenotype is a small [[phallus]], [[perineum|perineal]] [[hypospadias]], small blind pseudovaginal pouch, and intra-abdominal or [[inguinal canal|inguinal]] testes. [[Wolffian duct]] derivatives are hypoplastic or normal, depending on the degree of testosterone deficiency. Some of those with partial virilization develop [[gynecomastia]] at puberty even though masculinization is reduced. The presence of hypertension in the majority distinguishes them from other forms of partial androgen deficiency or [[androgen insensitivity syndrome|insensitivity]]. Fertility is impaired in those with more than minimal testosterone deficiency.
3 beta-hydroxysteroid dehydrogenase deficiency first time described in 1962, a patient with ambiguous genitalia and salt wasting.<ref name="pmid13968789">{{cite journal |vauthors=BONGIOVANNI AM |title=The adrenogenital syndrome with deficiency of 3 beta-hydroxysteroid dehydrogenase |journal=J. Clin. Invest. |volume=41 |issue= |pages=2086–92 |year=1962 |pmid=13968789 |pmc=291138 |doi=10.1172/JCI104666 |url=}}</ref>
<references />
 
==Classification==
There are three types of 3 beta-hydroxysteroid dehydrogenase deficiency: the salt-wasting, non-salt-wasting, and non-classic types.
==Pathophysiology==
*The pathogenesis of 3 beta-hydroxysteroid dehydrogenase deficiency is characterized by impaired pathway biosynthesis of progestins, mineralocorticoids, glucocorticoids, and androgens (therefore estrogen. As a result of [[cortisol]] absence, [[corticotropin]] ([[ACTH]]) secretion increases leads to produce 3-hydroxy-delta-5-steroids pregnenolone, 17-hydroxypregnenolone, and dehydroepiandrosterone (DHEA), also their sulfates.<ref name="pmid13968789">{{cite journal |vauthors=BONGIOVANNI AM |title=The adrenogenital syndrome with deficiency of 3 beta-hydroxysteroid dehydrogenase |journal=J. Clin. Invest. |volume=41 |issue= |pages=2086–92 |year=1962 |pmid=13968789 |pmc=291138 |doi=10.1172/JCI104666 |url=}}</ref>
==Causes==
* 3 beta-hydroxysteroid dehydrogenase deficiency is caused by a mutation in the HSD3B2 gene.
==Differentiating [disease name] from other Diseases==
* 3 beta-hydroxysteroid dehydrogenase deficiency must be differentiated from other diseases that cause ambiguous genitalia such as:
* [[21-hydroxylase deficiency]]
* [[11-β hydroxylase deficiency]]
* [[17-α hydroxylase deficiency]]
* Gestational [[hyperandrogenism]]
* [[P450-oxidoreductase deficiency]]
==Epidemiology and Demographics==
* The prevalence of 3 beta-hydroxysteroid dehydrogenase deficiency is unknown. At least 60 affected individuals have been reported.<ref name="url3-beta-hydroxysteroid dehydrogenase deficiency - Genetics Home Reference">{{cite web |url=https://ghr.nlm.nih.gov/condition/3-beta-hydroxysteroid-dehydrogenase-deficiency#statistics |title=3-beta-hydroxysteroid dehydrogenase deficiency - Genetics Home Reference |format= |work= |accessdate=}}</ref>
==Risk Factors==
*Common risk factors in the development of 3 beta-hydroxysteroid dehydrogenase deficiency is family history of this disease.  
 
== Diagnosis ==
=== Symptoms ===
* Symptoms of 3 beta-hydroxysteroid dehydrogenase deficiency may include the following:<ref name="pmid7626445">{{cite journal |vauthors=Simard J, Rheaume E, Mebarki F, Sanchez R, New MI, Morel Y, Labrie F |title=Molecular basis of human 3 beta-hydroxysteroid dehydrogenase deficiency |journal=J. Steroid Biochem. Mol. Biol. |volume=53 |issue=1-6 |pages=127–38 |year=1995 |pmid=7626445 |doi= |url=}}</ref>
Symptoms of both cortisol and aldosterone deficiency:
:* Feeding difficulties
:* [[Vomiting]]
:* [[Volume depletion]]
:* [[Muscle weakness]]
 
* Undervirilization in newborn males.
* Mild virilization and clitoromegaly in newborn female because of peripheral conversion of DHEA sulfate (DHEAS) to testosterone.
=== Physical Examination ===
*Physical examination may be remarkable for:
Undervirilization in newborn males and mild virilization and clitoromegaly in newborn female.  
 
=== Laboratory Findings ===
Hormonal criteria described for 3 beta-hydroxysteroid dehydrogenase deficiency based on delta-5-17-hydroxypregnenolone levels as following:<ref name="pmid12050224">{{cite journal |vauthors=Lutfallah C, Wang W, Mason JI, Chang YT, Haider A, Rich B, Castro-Magana M, Copeland KC, David R, Pang S |title=Newly proposed hormonal criteria via genotypic proof for type II 3beta-hydroxysteroid dehydrogenase deficiency |journal=J. Clin. Endocrinol. Metab. |volume=87 |issue=6 |pages=2611–22 |year=2002 |pmid=12050224 |doi=10.1210/jcem.87.6.8615 |url=}}</ref>
* Neonates ≥12,600 ng/dL
* Tanner stage I children ≥5490 ng/dL
* Children with premature pubarche ≥9790 ng/dL
* Adults ≥9620 ng/dL
 
Other laboratory findings include:
* [Hyponatremia]
* [Hyperkalemia]
 
== Treatment ==
=== Medical Therapy ===
*The mainstay of therapy for 3 beta-hydroxysteroid dehydrogenase deficiency is [[hydrocortisone]] and [[fludrocortisone acetate]].
* Gender-appropriate replacement of androgens or estrogens with progestins is necessary at the puberty time.
=== Surgery ===
The reconstruction surgery for ambiguous genitalia in genetically male patients may be applied.
==References==
{{Reflist|2}}
 
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Revision as of 19:27, 8 August 2017


Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mehrian Jafarizade, M.D [2]

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Overview

Historical Perspective

3 beta-hydroxysteroid dehydrogenase deficiency first time described in 1962, a patient with ambiguous genitalia and salt wasting.[1]

Classification

There are three types of 3 beta-hydroxysteroid dehydrogenase deficiency: the salt-wasting, non-salt-wasting, and non-classic types.

Pathophysiology

  • The pathogenesis of 3 beta-hydroxysteroid dehydrogenase deficiency is characterized by impaired pathway biosynthesis of progestins, mineralocorticoids, glucocorticoids, and androgens (therefore estrogen. As a result of cortisol absence, corticotropin (ACTH) secretion increases leads to produce 3-hydroxy-delta-5-steroids pregnenolone, 17-hydroxypregnenolone, and dehydroepiandrosterone (DHEA), also their sulfates.[1]

Causes

  • 3 beta-hydroxysteroid dehydrogenase deficiency is caused by a mutation in the HSD3B2 gene.

Differentiating [disease name] from other Diseases

Epidemiology and Demographics

  • The prevalence of 3 beta-hydroxysteroid dehydrogenase deficiency is unknown. At least 60 affected individuals have been reported.[2]

Risk Factors

  • Common risk factors in the development of 3 beta-hydroxysteroid dehydrogenase deficiency is family history of this disease.

Diagnosis

Symptoms

  • Symptoms of 3 beta-hydroxysteroid dehydrogenase deficiency may include the following:[3]

Symptoms of both cortisol and aldosterone deficiency:

  • Undervirilization in newborn males.
  • Mild virilization and clitoromegaly in newborn female because of peripheral conversion of DHEA sulfate (DHEAS) to testosterone.

Physical Examination

  • Physical examination may be remarkable for:

Undervirilization in newborn males and mild virilization and clitoromegaly in newborn female.

Laboratory Findings

Hormonal criteria described for 3 beta-hydroxysteroid dehydrogenase deficiency based on delta-5-17-hydroxypregnenolone levels as following:[4]

  • Neonates ≥12,600 ng/dL
  • Tanner stage I children ≥5490 ng/dL
  • Children with premature pubarche ≥9790 ng/dL
  • Adults ≥9620 ng/dL

Other laboratory findings include:

  • [Hyponatremia]
  • [Hyperkalemia]

Treatment

Medical Therapy

  • The mainstay of therapy for 3 beta-hydroxysteroid dehydrogenase deficiency is hydrocortisone and fludrocortisone acetate.
  • Gender-appropriate replacement of androgens or estrogens with progestins is necessary at the puberty time.

Surgery

The reconstruction surgery for ambiguous genitalia in genetically male patients may be applied.

References

  1. ↑ 1.0 1.1 BONGIOVANNI AM (1962). "The adrenogenital syndrome with deficiency of 3 beta-hydroxysteroid dehydrogenase". J. Clin. Invest. 41: 2086–92. doi:10.1172/JCI104666. PMC 291138. PMID 13968789.
  2. ↑ "3-beta-hydroxysteroid dehydrogenase deficiency - Genetics Home Reference".
  3. ↑ Simard J, Rheaume E, Mebarki F, Sanchez R, New MI, Morel Y, Labrie F (1995). "Molecular basis of human 3 beta-hydroxysteroid dehydrogenase deficiency". J. Steroid Biochem. Mol. Biol. 53 (1–6): 127–38. PMID 7626445.
  4. ↑ Lutfallah C, Wang W, Mason JI, Chang YT, Haider A, Rich B, Castro-Magana M, Copeland KC, David R, Pang S (2002). "Newly proposed hormonal criteria via genotypic proof for type II 3beta-hydroxysteroid dehydrogenase deficiency". J. Clin. Endocrinol. Metab. 87 (6): 2611–22. doi:10.1210/jcem.87.6.8615. PMID 12050224.


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