Genetic and endocrinological evaluations of three 46,XX patients with congenital lipoid adrenal hyperplasia previously reported as having presented spontaneous puberty

Congenital lipoid adrenal hyperplasia (CLAH) is an autosomal recessive diso rder characterized by impaired synthesis of adrenal and gonadal steroids. I t was demonstrated that loss-of-function mutations in the steroidogenic acu te regulatory protein (StAR) gene cause CLAH and that 46,XX patients with C LAH develop spontaneous puberty. We had reported that three 46,XX patients with CLAH had presented spontaneous puberty and one of the patients had dev eloped life-threatening ovarian cysts, before the etiology of CLAH had been clarified. In the present study, we analyzed their StAR gene and demonstra ted mutations. Endocrinological examinations of the patients revealed that serum LH and FSH levels and their responses to the LHRH stimulation were no t exaggerated before the onset of puberty. Serum LH levels and its response to LHRH were increased during puberty, whereas serum FSH levels remained w ithin the normal range. Serum estradiol increased after the administration of human menopausal gonadotropins in the pubertal patient, suggesting that the ovary might have another system than StAR to facilitate cholesterol tra nsport into the mitochondria. Although the patients had menstrual cycles, t hey remained anovulatory, and the resultant increased secretion of LH was s peculated to be responsible for the development of ovarian cysts.