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Background: Androgen insensitivity syndrome (AIS) is the most frequent etiology of 46,XY disorders of sex development (DSDs), and it is an X-linked disorder caused by mutations in the androgen receptor (AR) gene. AIS patients present a broad phenotypic spectrum and individuals with a partial phenotype present with different degrees of undervirilized external genitalia. There are more than 500 different AR gene allelic variants reported to be linked to AIS, but the presence of somatic mosaicisms has been rarely identified. In the presence of a wild-type AR gene, a significant degree of spontaneous virilization at puberty can be observed, and it could influence the gender assignment, genetic counseling and the clinical and psychological management of these patients and the psychosexual outcomes of these patients are not known., Case Presentation: In this study, we report two patients with AR allelic variants in heterozygous (c.382G>T and c.1769-1G>C) causing a partial AIS (PAIS) phenotype. The first patient was raised as female and she had undergone a gonadectomy at puberty. In both patients there was congruency between gender of rearing and gender identity and gender role., Conclusions: Somatic mosaicism is rare in AIS and nonsense AR variant allelic can cause partial AIS phenotype in this situation. Despite the risk of virilization and prenatal androgen exposure, the gender identity and gender role was concordant with sex of rearing in both cases. A better testosterone response can be expected in male individuals and this should be considered in the clinical management.

Background: Inhibin B is a hormone produced by the Sertoli cells that can provide important information for the investigation of disorders of sex development (DSD) with 46,XY karyotype. The aim of this study is to compare two enzyme-linked immunosorbent assay (ELISA) assays for dosage of serum inhibin B in patients with 46,XY DSD with normal testosterone secretion., Methods: Twenty-nine patients with 46,XY DSD and normal testosterone secretion (partial androgen insensitivity syndrome [PAIS] [n=8]; 5α-reductase deficiency [n=7] and idiopathic 46,XY DSD [n=14]) were included. Molecular analysis of the AR and SRD5A2 genes were performed in all patients and the NR5A1 gene analysis in the idiopathic group. Measurements of inhibin B were performed by two second-generation ELISA assays (Beckman-Coulter and AnshLabs). Assays were compared using the interclass correlation coefficient (ICC) and the Bland-Altman method., Results: ICC was 0.915 [95% confidence interval (CI): 0.828-0.959], however, a discrepancy was observed between trials, which is more evident among higher values when analyzed by the Bland-Altman method., Conclusions: It is recommended to perform the inhibin B measurement always using the same ELISA kit when several evaluations are required for a specific patient.

There are few reports of adults with disorders of sexual development (DSD). Here we describe the clinical profile and results of psychological assessment of three siblings with 46, XY DSD caused by partial androgen insensitivity syndrome (PAIS). The elder sibling (aged 22 years) was reared as female, while the middle and youngest siblings (17 and 18 years of age), were reared as males. The gender identity was concordant with the sex of rearing. There was no gender dysphoria. The psychological distress that our patients experienced was due to the limitations placed on them by their medical condition. It did not permit them to experience various facets of being either male or female completely. The younger siblings reared as males had additional problems of gynecomastia and lack of male secondary sexual development.

The hypothesis that human male and female amative orientation, arousal and courtship are sex-hormone dependent had as its precursor John Hunter's recorded but unpublished 18th century experiments of cross-sexed gonadal transplants in chicks. The hypothesis gained momentum in the 20th century after the discovery and eventual marketing of the sex hormones, and after the experimental demonstration by William C. Young that, in guinea-pigs, cross-sexed hormone administered prenatally influenced their subsequent male/female courtship and mating behavior. Comparatively and in review, human clinical syndromes of hypermasculinization and hypomasculinization do not disconfirm the hormonal hypothesis, but they do not adequately confirm it, either. They are compatible with the idea of a cofactor that governs whether amative orientation in practice, ideation and imagery is homosexual, heterosexual or bisexual.

Investigation of the origin of sexual ambiguity is complex. Although testicular function has traditionally been assessed only by examining the steroidogenic capacity of Leydig cells and spermatogenesis, it has recently been shown that the measurement of serum anti-Müllerian hormone (AMH) as a marker of Sertoli cell function may also help clinicians. The aim of this study was to evaluate both Leydig and Sertoli cell functions in 46,XY patients with intersex states in order to establish biochemical patterns that would help to reach an etiologic diagnosis. We measured serum androgens, AMH and gonadotropins in 24 patients with sexual ambiguity and XY karyotype: 8 with gonadal dysgenesis (GD), 3 with 3beta-hydroxysteroid dehydrogenase deficiency (3betaHSD), 5 with androgen insensitivity syndrome (AIS), 4 with 5alpha-reductase 2 (SRD5A2) deficiency, and 4 were of unknown origin or idiopathic. Our results showed that while testosterone was low and gonadotropins elevated in patients with either GD or 3betaHSD, AMH was low in the former and high in the latter. Serum AMH and gonadotropins were normal or high in patients with 3betaHSD or AIS, but these could be distinguished by testosterone levels. Serum testosterone and gonadotropins were normal or high in AIS and SRD5A2 deficiency patients; however, while AMH was elevated in AIS, it was not the case in SRD5A2 deficiency patients, indicating that testosterone is sufficient to inhibit AMH within the testis. In idiopathic cases gonadotropins and testosterone were normal, and AMH was normal or low. We conclude that the combined measurement of androgens, AMH and gonadotropins helps to establish the diagnosis in intersex patients.