Adrenal steroid secretion in girls with pseudoprecocious puberty due to autonomous ovarian cysts

To evaluate the role of adrenal steroids in pseudoprecocious puberty due to large ovarian follicular cysts, we studied the serum 17-hydroxyprogesterone response to a combination of dexamethasone suppression followed by iv ACTH administration in two girls and compared the results to those in girls with premature thelarche, normal prepubertal girls, and a girl with true precocious puberty. Although basal serum 17-hydroxyprogesterone levels were normal in all subjects, there was incomplete suppression of 17-hydroxyprogesterone with dexamethasone in the two girls with pseudoprecocious puberty and large ovarian cysts. The 17-hydroxyprogesterone response to ACTH was much greater in these girls (360 and 540 ng/dl) than in the girls with other types of precocious puberty (mean +/- SD, 71 +/- 15 ng/dl) or in normal prepubertal girls (80 +/- 20 ng/dl). The girls with large ovarian cysts had decreased gonadotropin responses to GnRH, which were reversed subsequent to removal of the cyst. Removal of the ovarian cysts also restored the dexamethasone suppressibility of serum 17-hydroxyprogesterone and abolished the progression of pubertal development. However, 17-hydroxyprogesterone responses to ACTH were still elevated (160 and 350 ng/dl). Preoperatively, both girls had increased levels of dehydroepiandrosterone sulfate, 16-hydroxydehydroepiandrosterone sulfate, and another unidentified steroid sulfate. These steroid sulfates were also found in the cyst fluid from the one patient from whom the fluid was obtained. These results suggest that steroid production by the adrenal gland may stimulate the development of small ovarian cysts (which may be present in normal prepubertal girls) into large ovarian cysts capable of causing gonadotropin-independent precocious puberty.