Autoimmune hypogonadism as part of an autoimmune polyglandular syndrome

The most compelling case for autoimmune mediated hypogonadism occurs when o varian failure is part of an autoimmune polyglandular syndrome (APS). In pa tients with the rare, recessively inherited type 1 APS (APS-1), characteriz ed by the triad of chronic mucocutaneous moniliasis, hypoparathyroidism, an d Addison's disease, primary amenorrhea (elevated pituitary gonadotropins) or oligomenorrhea and infertility are constant features. Ovarian failure is associated with autoantibodies to steroid hormone secreting cells in the a drenal cortex, Leydig cells of the testes, granulosa/thecal cells of the Gr affian follicles, corpus luteum, and the syncytiotrophoblast of the placent a. These autoantibodies react with 3 P450 enzymes involved with steroidogen esis, namely, 21-hydroxylase (adrenal specific), 17 alpha -hydroxylase, and the side chain cleavage enzyme. Recently the 14 exon, APS-1 (autoimmune re gulator or AIRE) gene has been cloned (chr. 21p22.3), and multiple mutants discovered. Parents who are obligatory heterozygotes for a single mutant ge ne lack clinical features of APS-1. They also do not develop APS-1 autoanti bodies. Thus, hypogonadal patients without features of APS-1 are unlikely t o have AIRE gene mutations. In the more common APS-2/3, characterized by co mbinations of autoimmune thyroid disease, immune mediated type 1 diabetes, vitiligo, pernicious anemia, and Addison's disease (type 2, not type 3), ov arian disease may be seen. In primary hypogonadism outside of the context o f an APS, these autoantibodies are rare. (J Soc Gynecol Investig 2001;8:S52 -S54) Copyright (C) 2001 by the Society for Gynecologic Investigation.