3 beta-hydroxysteroid dehydrogenase deficiency: Difference between revisions
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==Pathophysiology== | ==Pathophysiology== | ||
The pathogenesis of 3 beta-hydroxysteroid dehydrogenase deficiency is characterized by impaired pathway biosynthesis of [[progestins]], [[mineralocorticoids]], [[glucocorticoids]], and [[androgens]]. As a result of [[cortisol]] absence, [[corticotropin]] ([[ACTH]]) secretion increases and leads to produce 3-hydroxy-delta-5-steroids pregnenolone, [[17-hydroxypregnenolone]], and [[dehydroepiandrosterone]] ([[DHEA]]), also their sulfates. In peripheral tissues the conversion of [[DHEA sulfate]] ([[DHEAS]]) to [[testosterone]], is responsible for [[virilization]] in [[females]].<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> | The pathogenesis of 3 beta-hydroxysteroid dehydrogenase deficiency is characterized by impaired pathway of biosynthesis of [[progestins]], [[mineralocorticoids]], [[glucocorticoids]], and [[androgens]]. As a result of [[cortisol]] absence, [[corticotropin]] ([[ACTH]]) secretion increases and leads to produce 3-hydroxy-delta-5-steroids pregnenolone, [[17-hydroxypregnenolone]], and [[dehydroepiandrosterone]] ([[DHEA]]), also their sulfates. In peripheral tissues the conversion of [[DHEA sulfate]] ([[DHEAS]]) to [[testosterone]], is responsible for [[virilization]] in [[females]].<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== | ==Causes== | ||
3 beta-hydroxysteroid dehydrogenase deficiency is caused by a [[mutation]] in the HSD3B2 [[gene]]. | 3 beta-hydroxysteroid dehydrogenase deficiency is caused by a [[mutation]] in the HSD3B2 [[gene]]. | ||
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== Diagnosis == | == Diagnosis == | ||
=== Symptoms === | === Symptoms === | ||
Symptoms of 3 beta-hydroxysteroid dehydrogenase deficiency may include symptoms of both [[cortisol]] and [[aldosterone]] deficiency such as [[feeding difficulties]], [[vomiting]], [[volume depletion]], [[muscle weakness]] | Symptoms of 3 beta-hydroxysteroid dehydrogenase deficiency may include symptoms of both [[cortisol]] and [[aldosterone]] deficiency such as [[feeding difficulties]], [[vomiting]], [[volume depletion]], [[muscle weakness]], [[undervirilization]] in male newborns, and mild [[virilization]] and [[clitoromegaly]] in newborn female. <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> | ||
=== Physical Examination === | === Physical Examination === | ||
Physical examination may be remarkable for: [[undervirilization]] in [[newborn]] [[males]] | Physical examination may be remarkable for: | ||
* [[undervirilization]] in [[newborn]] [[males]] | |||
* Mild [[virilization]] and [[clitoromegaly]] in [[newborn]] [[female]]. | |||
=== Laboratory Findings === | === Laboratory Findings === | ||
Diagnosis for 3 beta-hydroxysteroid dehydrogenase deficiency is based on delta-5-17-hydroxypregnenolone high levels. <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> Other laboratory findings include: [[hyponatremia]], [[hyperkalemia]]. | Diagnosis for 3 beta-hydroxysteroid dehydrogenase deficiency is based on delta-5-17-hydroxypregnenolone high levels. <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> Other laboratory findings include: [[hyponatremia]], [[hyperkalemia]]. | ||
== Treatment == | == Treatment == | ||
=== Medical Therapy === | === 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. | The mainstay of therapy for 3 beta-hydroxysteroid dehydrogenase deficiency is [[hydrocortisone]] and [[fludrocortisone acetate]] adiminstration. Gender-appropriate replacement of [[androgens]] or [[estrogens]] with [[progestins]] is necessary at the [[puberty]] time. | ||
=== Surgery === | === Surgery === | ||
The reconstruction surgery for [[ambiguous genitalia]] in genetically male patients may be applied.<ref name="pmid11344932">{{cite journal |vauthors=Schnitzer JJ, Donahoe PK |title=Surgical treatment of congenital adrenal hyperplasia |journal=Endocrinol. Metab. Clin. North Am. |volume=30 |issue=1 |pages=137–54 |year=2001 |pmid=11344932 |doi= |url=}}</ref> | The reconstruction surgery for [[ambiguous genitalia]] in genetically male patients may be applied.<ref name="pmid11344932">{{cite journal |vauthors=Schnitzer JJ, Donahoe PK |title=Surgical treatment of congenital adrenal hyperplasia |journal=Endocrinol. Metab. Clin. North Am. |volume=30 |issue=1 |pages=137–54 |year=2001 |pmid=11344932 |doi= |url=}}</ref> | ||
Revision as of 20:31, 5 September 2017
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mehrian Jafarizade, M.D [2]
Overview
3 beta-hydroxysteroid dehydrogenase deficiency is a rare disease due to congenital adrenal hyperplasia. It is characterized by impaired biosynthesis pathway of progestins, mineralocorticoids, glucocorticoids, and androgens. As a result of cortisol absence, corticotropin (ACTH) secretion increases and leads to produce 3-hydroxy-delta-5-steroids pregnenolone, 17-hydroxypregnenolone, and dehydroepiandrosterone (DHEA), also their sulfates. In peripheral tissues the conversion of DHEA sulfate (DHEAS) to testosterone, is responsible for virilization in females. 3 beta-hydroxysteroid dehydrogenase deficiency is caused by a mutation in the HSD3B2 gene. Symptoms of 3 beta-hydroxysteroid dehydrogenase deficiency may include symptoms of both cortisol and aldosterone deficiency such as feeding difficulties, vomiting, volume depletion, undervirilization in newborn males, and mild virilization and clitoromegaly in newborn female. Diagnosis for 3 beta-hydroxysteroid dehydrogenase deficiency is based on delta-5-17-hydroxypregnenolone high levels in serum laboratory tests. The mainstay of therapy for this disease is hydrocortisone and fludrocortisone acetate. The reconstruction surgery for ambiguous genitalia in genetically male patients may be applied.
Historical Perspective
3 beta-hydroxysteroid dehydrogenase deficiency was first time described in 1962, in a patient with ambiguous genitalia and salt wasting.[1]
Classification
There are two types of 3 beta-hydroxysteroid dehydrogenase deficiency:
- Salt-wasting
- Non-salt-wasting
Pathophysiology
The pathogenesis of 3 beta-hydroxysteroid dehydrogenase deficiency is characterized by impaired pathway of biosynthesis of progestins, mineralocorticoids, glucocorticoids, and androgens. As a result of cortisol absence, corticotropin (ACTH) secretion increases and leads to produce 3-hydroxy-delta-5-steroids pregnenolone, 17-hydroxypregnenolone, and dehydroepiandrosterone (DHEA), also their sulfates. In peripheral tissues the conversion of DHEA sulfate (DHEAS) to testosterone, is responsible for virilization in females.[1]
Causes
3 beta-hydroxysteroid dehydrogenase deficiency is caused by a mutation in the HSD3B2 gene.
Differentiating 3 beta-hydroxysteroid dehydrogenase deficiency from other Diseases
3 beta-hydroxysteroid dehydrogenase deficiency must be differentiated from diseases that cause ambiguous genitalia:[2][3]
| Disease name | Steroid status | Important clinical findings | |
|---|---|---|---|
| Increased | Decreased | ||
| Classic type of 21-hydroxylase deficiency |
|
| |
| 11-β hydroxylase deficiency |
|
| |
| 17-α hydroxylase deficiency |
| ||
| 3 beta-hydroxysteroid dehydrogenase deficiency |
| ||
| Gestational hyperandrogenism |
|
| |
3 beta-hydroxysteroid dehydrogenase deficiency must be differentiated from diseases that cause virilization and hirsutism in female:[4][3][5]
| Disease name | Steroid status | Other laboratory | Important clinical findings |
|---|---|---|---|
| Non-classic type of 21-hydroxylase deficiency | Increased:
|
|
|
| 11-β hydroxylase deficiency | Increased:
Decreased: |
|
|
| 3 beta-hydroxysteroid dehydrogenase deficiency | Increased:
Decreased: |
|
|
| Polycystic ovary syndrome |
|
|
|
| Adrenal tumors |
|
|
|
| Ovarian virilizing tumor |
|
|
|
| Cushing's syndrome |
|
||
| Hyperprolactinemia |
|
|
Epidemiology and Demographics
The prevalence of 3 beta-hydroxysteroid dehydrogenase deficiency is unknown. At least 60 affected individuals have been reported.[6]
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 symptoms of both cortisol and aldosterone deficiency such as feeding difficulties, vomiting, volume depletion, muscle weakness, undervirilization in male newborns, and mild virilization and clitoromegaly in newborn female. [7]
Physical Examination
Physical examination may be remarkable for:
- undervirilization in newborn males
- Mild virilization and clitoromegaly in newborn female.
Laboratory Findings
Diagnosis for 3 beta-hydroxysteroid dehydrogenase deficiency is based on delta-5-17-hydroxypregnenolone high levels. [8] Other laboratory findings include: hyponatremia, hyperkalemia.
Treatment
Medical Therapy
The mainstay of therapy for 3 beta-hydroxysteroid dehydrogenase deficiency is hydrocortisone and fludrocortisone acetate adiminstration. 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.[9]
References
- ↑ 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.
- ↑ Hughes IA, Nihoul-Fékété C, Thomas B, Cohen-Kettenis PT (2007). "Consequences of the ESPE/LWPES guidelines for diagnosis and treatment of disorders of sex development". Best Pract. Res. Clin. Endocrinol. Metab. 21 (3): 351–65. doi:10.1016/j.beem.2007.06.003. PMID 17875484.
- ↑ 3.0 3.1 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.
- ↑ Hohl A, Ronsoni MF, Oliveira M (2014). "Hirsutism: diagnosis and treatment". Arq Bras Endocrinol Metabol. 58 (2): 97–107. PMID 24830586. Vancouver style error: initials (help)
- ↑ Melmed, Shlomo (2016). Williams textbook of endocrinology. Philadelphia, PA: Elsevier. ISBN 978-0323297387.=
- ↑ "3-beta-hydroxysteroid dehydrogenase deficiency - Genetics Home Reference".
- ↑ 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.
- ↑ 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.
- ↑ Schnitzer JJ, Donahoe PK (2001). "Surgical treatment of congenital adrenal hyperplasia". Endocrinol. Metab. Clin. North Am. 30 (1): 137–54. PMID 11344932.