Inherited male pseudohermaphroditism due to gonadotrophin unresponsiveness

An inherited form of incomplete male pseudohermaphroditism was studied in two post-pubertal and one pre-pubertal sibling. All patients presented a 46XY karyotype infantile female external genitalia, lack of breast development and sexual hair. Persistently elevated serum levels of gonadotrophins with normal pituitary responsiveness to LRH were found. Serum 17-OH progesterone, androstenedione, and testosterone levels were extremely low before and after gonadal stimulation with hCG. Laparotomy revealed absence of Wolffian and Mullerian derivatives. Testes were small and cryptorchidic. Microscopic and ultrastructural examination revealed seminiferous tubules with absence of spermatogenesis and normal Sertoli cells. The interstitial spaces were mainly occupied by poorly differentiated cells although in the post-pubertal patients there were small and randomly distributed nodules of Leydig cells without crystaloids. Incubation of testicular tissue from one post-pubertal patient with [14C]acetate showed lack of 14C-incorporation into appropriate steroid carriers. These data were interpreted as demonstrating that gonadotrophin resistance was the underlying abnormality of this syndrome, representing the human counter part of the "vet" pseudohermaphroditic rat.