1. Differences of adrenal‐derived androgens in 5α‐reductase deficiency versus androgen insensitivity syndrome
- Author
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Wenjiao Zhu, Hai-Jun Yao, Jianwei Ren, Patrick O’Day, Jie Qiao, Tong Cheng, Richard J. Auchus, Bing Han, Hui Zhu, and Hao Wang
- Subjects
Male ,Steroid Metabolism, Inborn Errors ,medicine.medical_specialty ,medicine.drug_class ,medicine.medical_treatment ,5α-Reductase deficiency ,General Biochemistry, Genetics and Molecular Biology ,Steroid ,3-Oxo-5-alpha-Steroid 4-Dehydrogenase ,Tandem Mass Spectrometry ,Internal medicine ,medicine ,Humans ,In patient ,General Pharmacology, Toxicology and Pharmaceutics ,Testosterone ,Hypospadias ,Disorder of Sex Development, 46,XY ,business.industry ,General Neuroscience ,General Medicine ,Androgen-Insensitivity Syndrome ,medicine.disease ,Androgen ,Endocrinology ,Dihydrotestosterone ,Androgens ,Female ,Androgen insensitivity syndrome ,business ,Chromatography, Liquid ,medicine.drug - Abstract
Steroid 5α-reductase type 2 deficiency (5α-RD2) and androgen insensitivity syndrome (AIS) are difficult to distinguish clinically and biochemically, and adrenal-derived androgens have not been investigated in these conditions using modern methods. The objective of the study was to compare Chinese patients with 5α-RD2, AIS, and healthy men. Sixteen patients with 5α-RD2, 10 patients with AIS, and 39 healthy men were included. Serum androgen profiles were compared in these subjects using liquid chromatography/tandem mass spectrometry (LC-MS/MS). Based on clinical features and laboratory tests, 5α-RD2 and AIS were diagnosed and confirmed by genotyping. Dihydrotestosterone (DHT) and testosterone (T) were both significantly lower in patients with 5α-RD2 than AIS (p < 0.0001). The T/DHT ratio was higher in 5α-RD2 (4.5-88.6) than AIS (13.4-26.7) or healthy men (7.6-40.5). Using LC-MS/MS, a cutoff T/DHT value of 27.3 correctly diagnosed 5α-RD2 versus AIS with sensitivity 93.8% and specificity 100%. Among the adrenal-derived 11-oxygenated androgens, 11β-hydroxyandrostenedione (11OHA4) and 11-ketoandrostenedione (11KA4) were also lower in patients with 5α-RD2 than those of patients with AIS. In contrast, 11β-hydroxytestosterone (11OHT) was higher in 5α-RD2 than AIS. Furthermore, a 11OHT/11OHA4 cutoff value of 0.048 could also distinguish 5α-RD2 from AIS. Thus, both elevated T/DHT values above 27.3 and the unexpected 11-oxygenated androgen profile, with a 11OHT/11OHA4 ratio greater than 0.048, distinguished 5α-RD2 from AIS. These data suggest that the metabolism of both gonadal and adrenal-derived androgens is altered in 5α-RD2.
- Published
- 2021
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