Anna Paola Savoldi

Introduction Autoimmune polyglandular syndromes (APS) encompass a broad spectrum of disorders. APS III is characterized by autoimmune thyroiditis (AT) plus any autoimmune disorder, excluding Addison's disease. Methods and results This study explores the link between GAD65 related-temporal lobe epilepsy (GAD-TLE) and APS III. We retrospectively analyzed 29 GAD-TLE patients. Eighteen patients (62%) experienced at least one autoimmune disease, and ten patients (56%) fulfilled diagnostic criteria for APS III. In addition to AT and GAD-TLE, five patients had type 1 diabetes mellitus, one patient had latent autoimmune diabetes in adulthood, one autoimmune alopecia, one pernicious anemia, one had celiac disease and one patient had autoimmune alopecia, vitiligo, autoimmune atrophic gastritis and psoriasis. Approximately 35 years after the onset of the first disease, the probability of having the second disorder is over 80%. In our cohort, GAD65 antibodies are more frequently linked to AT than to type 1 diabetes mellitus, despite their well-known association. Conclusion Our data suggests that GAD65-TLE may share a common pathophysiology and should be included among APS-III diagnostic criteria. These insights support the need for rigorous, multidisciplinary monitoring to prevent delays in diagnosis and treatment. This work enhances understanding of APS complexity and informs targeted management strategies for patients with overlapping endocrine and neurological autoimmune disorders.