Autoimmune polyglandular syndromes in adults: immunogenetic insights, risk stratification, and screening considerations

Autoimmune polyglandular syndromes (APS) comprise a heterogeneous group of disorders characterized by the coexistence of multiple autoimmune endocrine diseases and, frequently, additional non-endocrine autoimmune manifestations. Adult-onset APS (types 2–4) often evolves over years through sequential glandular involvement, creating a prolonged preclinical phase during which predictive biomarkers may facilitate earlier recognition and individualized surveillance. This narrative review examines the immunogenetic mechanisms underlying adult APS, evaluates the diagnostic and predictive roles of autoantibodies, and discusses emerging risk-stratified screening considerations. The review was informed by a targeted PubMed literature search of English-language publications, with emphasis on recent clinical guidelines, systematic reviews, cohort studies, landmark investigations, and key original studies relevant to adult APS, immunogenetics, autoantibody biomarkers, and screening strategies. Current evidence indicates that organ-specific autoantibodies are among the earliest detectable markers of endocrine autoimmunity and may precede clinical disease by several years. Among the available biomarkers, 21-hydroxylase autoantibodies remain the most informative marker of autoimmune adrenal insufficiency, while glutamic acid decarboxylase (GAD65) and thyroid peroxidase antibodies contribute to identifying individuals at increased risk of autoimmune diabetes and thyroid disease. Multiplex autoantibody platforms further demonstrate the potential to integrate multiple biomarkers within a single assay, supporting comprehensive immunological profiling and future risk-stratified surveillance. However, evidence supporting routine predictive screening in adults remains limited by the absence of validated risk models, standardized surveillance intervals, and prospective outcome studies. Current evidence supports targeted, phenotype-guided surveillance in selected high-risk adults rather than universal screening. Emerging multiplex autoantibody approaches may enhance individualized risk stratification and targeted monitoring but require prospective validation, cost-effectiveness evaluation, and standardized implementation before broad clinical adoption.