Autoimmune Polyglandular Syndrome

Autoimmune polyglandular syndrome (APS), also called polyendocrine autoimmune syndrome, is a group of disorders defined by autoimmune destruction of multiple endocrine glands together with non-endocrine autoimmunity. APS-1 (APECED) is monogenic from AIRE mutations and presents in childhood with the triad of mucocutaneous candidiasis, hypoparathyroidism, and Addison's disease.

APS-2 (Schmidt syndrome) is polygenic with HLA-DR3/DR4 association, occurring in adults and combining Addison's disease with autoimmune thyroid disease and/or type 1 diabetes; vitiligo, pernicious anemia, celiac disease, hypogonadism, and myasthenia gravis are common associates. APS-3 includes thyroid autoimmunity plus another autoimmunity without adrenal involvement, and APS-4 is a residual category.

Diagnosis combines clinical recognition of multiple autoimmune endocrinopathies with autoantibody screening (21-hydroxylase, GAD65, TPO, TSH receptor, intrinsic factor, transglutaminase) and AIRE gene testing in suspected APS-1. Management is hormone replacement (hydrocortisone, fludrocortisone, levothyroxine, calcium and active vitamin D, insulin), treatment of mucocutaneous candidiasis in APS-1, and lifelong screening of unaffected glands and family members.