Mixed gonadal dysgenesis: clinical, cytogenetic, endocrinological, and histopathological findings in 16 patients

We describe clinical, cytogenetic, endocrine, and histopathological findings in 16 patients with mixed gonadal dysgenesis (MGD). All patients except 1 presented genital ambiguity and 10 of them had Ullrich-Turner manifestations. The 45,X/46,XY karyotype was the most frequent with a predominance of 45,X cells in both peripheral lymphocytes and gonads. In all cases Müllerian and Wolffian remnants and/or derivatives were found and in some patients both Wolffian- and Müllerian-derived structures were identified on the streak or testicular side. Postpubertal patients exhibited variable degrees of virilization and all of them had hypergonadotropism coexisting with low to normal baseline serum levels of testosterone; their testicular response to human chorionic gonadotropin (HCG) in terms of testosterone secretion was also variable, ranging from minimal to almost a normal response. All prepubertal patients but 1 had normal baseline levels of pituitary gonadotropins and testosterone and their gonadal response to the HCG challenge was highly variable. With the exception of 1 case, who had a 45,X/46,XY(p-) karyotype, no correlation between the cytogenetic data and degree of external genital ambiguity and the hormonal findings was observed. Additional information on the specific structural abnormalities involving the testis-determining gene of the Y chromosome in patients with MGD is needed in order to further understand the mechanisms responsible for the wide variability characteristic of this disorder.