Endocrine and Metabolic Studies in an XY Patient with Gonadal Agenesis¹

Endocrine and metabolic studies were performed in a 16-yr-old phenotypic girl with primary amenorrhea and gonadal agenesis. Sex chromatin determination and karyotype in peripheral blood leukocytes and bone marrow cells revealed a 46 XY chromosome complement. High plasma basal levels of radioimmunoassayable (RIA) pituitary gonadotropins which had a pulsatile pattern and normal pituitary responsiveness to synthetic LH-releasing hormone were demonstrated. Undetectable levels of plasma RIA testosterone and lack of response after human chorionic gonadotropin (hCG) stimulation were observed. Plasma levels of RIA pregnenolone, dehydroepiandrosterone, progesterone, 17α-OH-progesterone, androstenedione, testosterone, cortisol and estradiol were determined in: basal conditions, ACTH stimulation, dexamethasone inhibition (DI), and combined DI and hCG stimulation. The results indicated normal adrenal function and absence of gonadal function. A normal anabolic response after testosterone propionate administration was demonstrated by a significant nitrogen and phosphorus retention. No gonadal structures, i.e., Mullerian, or Wolffian derivatives, were found at laparatomy. Daily administration of ethinyl estradiol 3-methyl ether depressed plasma gonadotropins, and during sustained suppression an acute LH release in response to estradiol benzoate administration was observed, thus demonstrating negative and positive feedback mechanisms to estrogens in this patient. Our data demonstrate the functional integrity of the hypothalamus, pituitary and adrenal as well as a complete lack of hormonal testicular function in an XY male pseudohermaphrodite with gonadal agenesis. A complete testicular insufficiency with a concomitant absence of Mullerian structures or early partial testicular function resulting in Mullerian regression and subsequent resorption of the gonads may explain this syndrome.