Background: Fetal-derived androgen excess, such as 21-hydroxylase deficiency (21-OHD), is a major cause of 46,XX disorders of sex development (DSD), but there are rarely is due to maternal androgen excess such as that caused by adrenal tumors or luteoma.Recently, in addition to the classical androgen synthesis pathway, the alternative androgen synthesis by backdoor pathway and 11-oxygenated steroids has been reported for virilization of female patients with 21-OHD. We have reported 46,XX DSD due to maternal androgen-producing adrenal tumors with mild masculinization signs in the Journal of the Japan Pediatric Society.The purpose of this study was to examine the relationship between maternal androgen levels and fetal external genitalia in our patients.
Patients and Methods: The female patient was diagnosed as 46,XX DSD with degree of virilization with Prader grade 3-4. Her mother was 30 years old and had noticed hirsutism before and during pregnancy, without other masculinization signs. She developed gestational diabetes mellitus and pregnancy-associated hypertension and gave birth via emergency cesarean section at 30 weeks of gestation. She was diagnosed with an androgen-producing adrenal tumor and Cushing syndrome at 8 months after delivery because of the virilization of her female infant's external genitalia and continuing her hirsutism.The tumor was removed by laparoscopic surgery, and the histology indicated an adrenal adenoma. With the use of gas chromatography/mass spectrometry (GC/MS), urinary steroid profiles were measured in maternal urine before tumor resection.
Results: Maternal serum DHEA-S, androstenedione and testosterone levels were only slightly high at 571 µ/dL, 2.26 ng/mL, and 81 ng/dL, respectively. Analysis of urinary steroid profiles revealed high DHEA metabolite values, and 11-OH androstenedione metabolite levels, which were 4 times higher than the upper limit, and androstenedione metabolite levels which were remained at 1.5 times higher than the upper limit.
Discussion & Conclusion: Maternal serum androstenedione and testosterone levels could not explain the severe virilization of the female infant's genitalia. According to the results of maternal urinary steroid profiles, virilization of the external genitalia may be caused by the alternative pathway via 11-oxygenated steroids. Although we were unable to measure maternal serum 11-oxygenated steroids, 11-oxygenated androgens may be related to the virilization of female external genitalia due to the maternal androgen-producing adrenal tumor.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology