Isolated follicle-stimulating hormone deficiency in a woman with X chromosomal mosaicism.

Primary amenorrhea was observed in a 40-year-old woman with a proportionate female habitus. Serum levels of luteinizing hormone (LH) (71 to 97 mIU/ml) and estradiol (less than 10 pg/ml) were in the postmenopausal range, while follicle-stimulating hormone (FSH) remained at the lower limit of detection (1 to 6 mIU/ml). LH was found to be biologically active in a mouse Leydig cell testosterone production assay. Chromosomal analysis revealed three major cell lines: 5% 45,X; 83% 46,XX; and 3% 47,XXX. The remaining cells showed apparently random aneuploidy and chromosome rearrangements. Intravenous administration of 150 micrograms of gonadotropin-releasing hormone produced a threefold elevation in LH but did not alter FSH levels. Review of ovarian biopsies performed at age 22 revealed a multitude of primordial follicles and one follicle with antrum formation. There was no evidence of recent or past ovulation. An insulin tolerance test evoked normal responses in serum growth hormone, prolactin, and cortisol. This is the first reported case of an isolated deficiency of FSH associated with mosaicism of the X chromosome. This coexistence of functional and genetic aberrations suggests that the differential secretion of LH and FSH may be related to specific independent loci on the X chromosome.