Premature ovarian failure associated with autoimmune polyglandular syndrome: pathophysiological mechanisms and future...

Autoimmune polyglandular syndromes (APS) are a series of disorders characterized by autoimmunity against two or more endocrine organs. Premature ovarian failure (POF) may also have an autoimmune origin and, when accompanied by other autoimmune endocrinopathies, may be part of the APSs. Onset of autoimmune ovarian failure usually occurs in childhood, adolescence, or adulthood, and as a result, fertility may be severely compromised.

A 26-year-old women with secondary amenorrhea, Addison's disease, and autoimmune hypothyroidism requested infertility evaluation. Examination, transvaginal ultrasonography, endocrine evaluation, and ovarian biopsy were performed. 21-Hydroxylase and antithyroid antibodies were demonstrated, but ovarian steroid cell antibodies (StCA) were absent at the time of her infertility evaluation. Transvaginal sonography demonstrated only a few ovarian follicles. An ovarian biopsy revealed lymphocytic infiltration of the ovary. This presentation is consistent with APS type II accompanied by autoimmune POF.

Unlike APS types I and III, autoimmune POF is more commonly encountered with APS types I and III than with APS type II. An autoimmune response to steroidogenic enzymes and ovarian steroid cells appears to mediate destruction of ovarian function. Although immunotherapy with corticosteroids (with or without in vitro fertilization [IVF]) may be successful in limited cases where several follicles are present, oocyte donation with IVF may be the best option for the patient seeking fertility, particularly in the absence of ovarian follicles.

Advances in molecular genetics may be valuable in predicting and counseling women at risk for APS and POF, and cryopreservation of ovarian tissue may offer hope to affected unmarried young women. It is reasonable to suggest that children and reproductive aged women with one autoimmune disorder should be periodically screened for other autoimmune disorders.