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Cited by 77Sexual Differentiation and DisordersAdrenal Hormones and DisordersMetabolism and Genetic Disorders

Clinical perspectives in congenital adrenal hyperplasia due to 3β-hydroxysteroid dehydrogenase type 2 deficiency

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Al Alawi, Abdullah M., Nordenström, Anna, Falhammar, Henrik·2019·Endocrine
DOI 10.1007/s12020-018-01835-3PMC PMC6420607
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Abstract

PURPOSE: 3β-hydroxysteroid dehydrogenase type 2 deficiency (3βHSD2D) is a very rare variant of congenital adrenal hyperplasia (CAH) causing less than 0.5% of all CAH. The aim was to review the literature. METHODS: PubMed was searched for relevant articles. RESULTS: 3βHSD2D is caused by HSD3B2 gene mutations and characterized by impaired steroid synthesis in the gonads and the adrenal glands and subsequent increased dehydroepiandrosterone (DHEA) concentrations. The main hormonal changes observed in patients with 3βHSD2D are elevated ratios of the Δ5-steroids over Δ4-steroids but molecular genetic testing is recommended to confirm the diagnosis. Several deleterious mutations in the HSD3B2 gene have been associated with salt-wasting (SW) crisis in the neonatal period, while missense mutations have been associated with a non-SW phenotype. Boys may have ambiguous genitalia, whereas girls present with mild or no virilization at birth. The existence of non-classic 3βHSD2D is controversial. In an acute SW crisis, the treatment includes prompt rehydration, correction of hypoglycemia, and parenteral hydrocortisone. Similar to other forms of CAH, glucocorticoid and mineralocorticoid replacement is needed for long-term management. In addition, sex hormone replacement therapy may be required if normal progress through puberty is failing. Little is known regarding possible negative long-term consequences of 3βHSD2D and its treatments, e.g., fertility, final height, osteoporosis and fractures, adrenal and testicular tumor risk, and mortality. CONCLUSION: Knowledge is mainly based on case reports but many long-term outcomes could be presumed to be similar to other types of CAH, mainly 21-hydroxylase deficiency, although in 3βHSD2D it seems to be more difficult to suppress the androgens.

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  • The reported prevalence of TARTs in CAH ranges from 14% to 86%, with an average of 25% in adolescents, and 46% in men.

    “The reported prevalence of TARTs in CAH ranges from 14% to 86% (437,634), with an average of 25% in adolescents, and 46% in men (378).”

    From Congenital Adrenal Hyperplasia—Current Insights in Pathophysiology, Diagnostics, and Management (2022) · cites this paper as [634]

    Citation (378) is attached to the averages of 25% in adolescents and 46% in men, not to the preceding range. The “Testicular adrenal rest tumors” section reports a 34–94% range in males with CAH due to 21-hydroxylase deficiency, but gives neither cited average; searches for those figures and age groups found no supporting passage in our copy. (LLM, conf=0.75)

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Authors
Al Alawi, A. M., Nordenström, A., & Falhammar, H.
Affiliations
Karolinska University Hospital (SE)
Corresponding author
Falhammar, Henrik
ORCID
Venue
Endocrine
Publisher
Springer Science and Business Media LLC
Published
2019-02-04
Volume
63
Issue
3
Pages
407-421
ISSN
  • 0969-711X (ISSN-L)
  • 1355-008X
  • 1559-0100
DOI
10.1007/s12020-018-01835-3
PMC
PMC6420607
OpenAlex
W2911382434
Cited by
77
References
143
Citations by year
2026: 6 · 2025: 10 · 2024: 10 · 2023: 14 · 2022: 8 · 2021: 12 · 2020: 13 · 2019: 4
FWCI
0.82
Type
journal article
Language
en
Open access
Licence
Locations
  • Endocrine (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
Magnus Bergvalls Stiftelse (2017-02138)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
Keywords
congenital adrenal hyperplasia, salt-wasting crisis, dehydroepiandrosterone, ambiguous genitalia, non-classical congenital adrenal hyperplasia, glucocorticoid replacement therapy, mineralocorticoid replacement, sex hormone replacement therapy, long-term outcomes, fertility, osteoporosis
MeSH terms
Adrenal Hyperplasia, Congenital, Humans, 3-Hydroxysteroid Dehydrogenases

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