The testosterone:androstenedione ratio in male undermasculinization

Ahmed, SF; Iqbal, Asma; Hughes, Ieuan A.

doi:10.1046/j.1365-2265.2000.01166.x

Cited by 67 publications

(19 citation statements)

References 27 publications

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“…1). From this figure, it can be observed that one subject with normal gene sequence for both HSD17B3 and AR was found to have a T/A ratio below 0.8, possibly reflecting a degree of testicular failure as reported by other authors (23). Therefore, with the stipulation of including only subjects with normal serum FSH concentrations, an unstimulated T/A ratio below 0.8 in post-pubertal patients before gonadectomy is 100% sensitive and specific in identifying those with HSD17B3 deficiency and can be used to guide mutational analysis.…”

Section: European Journal Of Endocrinologysupporting

confidence: 54%

Screening for mutations in 17β-hydroxysteroid dehydrogenase and androgen receptor in women presenting with partially virilised 46,XY disorders of sex development

Phelan

Williams

Cardamone

et al. 2015

European Journal of Endocrinology

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Context and objective: The precise diagnosis of partially virilised women with 46,XY disorders of sex development (DSD) is often obscure. In practice, this group often comes under the poorly defined, clinically based label of partial androgen insensitivity syndrome (PAIS). In a previous study, we found that 5a-reductase 2 (SRD5A2) mutations occurred in 43% of women in this subgroup. We expand this work to include biochemical and genetic screening for 17b-hydroxysteroid dehydrogenase (HSD17B3) and androgen receptor (AR) mutations. Methods: Analysis of serum androgens (androstenedione and testosterone) and genetic analyses for HSD17B3 and AR were performed in 42 women from 36 pedigrees with partially virilised 46,XY DSD in whom SRD5A2 deficiency had been excluded by urine steroid profiling. Results: Out of 36 unrelated women, 14 (38%) were found to have HSD17B3 mutations and one (2.7%) to have an AR defect. Six novel pathogenic HSD17B3 mutations were identified: three splice site mutations and three missense changes.Seven patients with HSD17B3 deficiency tested before gonadectomy had basal testosterone/androstenedione (T/A) ratio !0.8 (sensitivity 100% and specificity 91%). Conclusions: HSD17B3 deficiency is prevalent in the adolescent and adult 46,XY female DSD population and is often associated with lesser degrees of virilisation compared with those with 5a-reductase deficiency. This diagnosis should be considered for individuals labelled as PAIS, particularly, but not exclusively, those who present with virilisation at puberty or primary amenorrhoea. Before gondadectomy, T/A ratio is useful to aid diagnosis, but after gonadectomy sequencing of HSD17B3 must be performed to confirm the diagnosis.

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Section: European Journal Of Endocrinologysupporting

confidence: 54%

Screening for mutations in 17β-hydroxysteroid dehydrogenase and androgen receptor in women presenting with partially virilised 46,XY disorders of sex development

Phelan

Williams

Cardamone

et al. 2015

European Journal of Endocrinology

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“…We are unsure whether 17βHSD-3 deficiency is truly rare in the United States or whether it is frequently missed. In one study, patients who were later confirmed to have 17βHSD-3 deficiency were initially misdiagnosed with androgen insensitivity syndrome (AIS), and the rate of misdiagnosis was calculated to be as high as 67% [29]. The risk of misdiagnosis is especially problematic because the clinical findings in 17βHSD-3 deficiency may mimic AIS in childhood and 5α-reductase deficiency in puberty [30].…”

Section: Epidemiology and Demographicsmentioning

confidence: 99%

“…The characteristic hormonal profile of 17βHSD-3 deficiency is of increased concentrations of Δ4-androstenedione and reduced levels of testosterone [29]. The basal levels can be quite variable at different ages [29]. At baseline in adults, the precursor Δ4-androstenedione is usually elevated with a borderline low or normal testosterone [11].…”

Section: Diagnosis Of 17βhsd-3 Deficiency: Endocrine Imaging and Molmentioning

confidence: 99%

“…At baseline in adults, the precursor Δ4-androstenedione is usually elevated with a borderline low or normal testosterone [11]. This translates to a low T/Δ4 ratio of <0.8 [29] (table 3). The DHT levels in 17βHSD-3 deficiency can be decreased, normal or high, while the dehydroepiandrosterone (DHEA) levels are typically high [11].…”

Section: Diagnosis Of 17βhsd-3 Deficiency: Endocrine Imaging and Molmentioning

confidence: 99%

“…2). The characteristic hormonal profile of 17βHSD-3 deficiency is of increased concentrations of Δ4-androstenedione and reduced levels of testosterone [29]. The basal levels can be quite variable at different ages [29].…”

Section: Diagnosis Of 17βhsd-3 Deficiency: Endocrine Imaging and Molmentioning

confidence: 99%

See 2 more Smart Citations

The Clinical and Molecular Heterogeneity of 17βHSD-3 Enzyme Deficiency

et al. 2010

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17-β-hydroxysteroid dehydrogenase type 3 (17βHSD-3) deficiency is a rare, but frequently misdiagnosed autosomal recessive cause of 46,XY disorder of sex development (DSD). 17βHSD-3 enzyme is present almost exclusively in the testes and converts Δ4-androstenedione (Δ4) to testosterone (T). The diagnosis can be easily missed in early childhood as the clinical presentation may be subtle. Any young girl with an inguinal hernia, mild clitoromegaly, single urethral opening or urogenital sinus should raise suspicion. If not diagnosed early, patients present with severe virilization and primary amenorrhea in adolescence and may undergo a change from a female to male gender role. A low T/Δ4 ratio on baseline or hCG (human chorionic gonadotropin)-stimulated testing is suggestive of 17βHSD-3 deficiency. The diagnosis can be confirmed with molecular genetic studies. This review summarizes the clinical presentations, reported mutations, diagnosis, treatment and clinical course of this disorder. The Arg80 site in exon 3 is the most common location of repeated mutations and can be considered a hot spot in certain Arab populations.

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Ambiguous Genitalia

Hughes¹

2005

Clinical Pediatric Endocrinology

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The testosterone:androstenedione ratio in male undermasculinization

Cited by 67 publications

References 27 publications

Screening for mutations in 17β-hydroxysteroid dehydrogenase and androgen receptor in women presenting with partially virilised 46,XY disorders of sex development

Screening for mutations in 17β-hydroxysteroid dehydrogenase and androgen receptor in women presenting with partially virilised 46,XY disorders of sex development

The Clinical and Molecular Heterogeneity of 17βHSD-3 Enzyme Deficiency

Ambiguous Genitalia

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