MON-374 - Autoimmune Polyglandular Syndrome Type 3 with Type 1 Diabetes, Graves' Disease, and Alopecia Universalis: A Case Report

Introduction: Autoimmune Polyglandular Syndrome (APS) Type 3 is defined by autoimmune thyroid disease (AITD) with another organ-specific autoimmune disorder, excluding adrenal insufficiency. The combination of Type 1 Diabetes Mellitus (T1DM), Graves’ disease, and Alopecia Universalis (AU) is extremely rare, representing < 1% of APS-3 cases in large registries. We report a case of APS-3 with sequential onset of pancreatic, follicular, and thyroid autoimmunity over four years, illustrating the natural history of this aggressive “triple hit” phenotype and its surveillance and treatment challenges.

Clinical

Case: A 24-year-old woman developed progressive autoimmunity over four years. In 2021, she tested positive for thyroid peroxidase antibodies (TPO-Ab) while euthyroid. In 2023, she presented with acute-onset T1DM, confirmed by absolute insulin deficiency (C-peptide 0.1 ng/mL) and hyperglycemia, and simultaneously developed AU with complete scalp and body hair loss.

By early 2025, her thyroid status progressed to overt hyperthyroidism. Labs showed severe thyrotoxicosis: TSH < 0.01 mIU/L, Free T4 4.12 ng/dL (ref 0.8–1.8), Total T3 383 ng/dL (ref 80–200), and elevated TSI (2.72 IU/L), confirming Graves’ disease. Despite high T4, she remained afebrile with normal mental status and a Burch-Wartofsky score < 25, excluding thyroid storm. Immunology revealed hypogammaglobulinemia (IgG 3.4 g/L), prompting evaluation for primary immunodeficiencies (e.g., CVID, CTLA-4 haploinsufficiency, LRBA deficiency) and secondary causes, given infection risk and implications for immunomodulatory therapy.

Clinical Lessons:
Triple Hit Phenotype: This rare APS-3 variant involves pancreatic (T1DM), follicular (AU), and thyroid (Graves’) autoimmunity. Management extends beyond hormone replacement to dermatologic and metabolic care, requiring multidisciplinary coordination.
Surveillance: Progression from TPO-Ab positivity to Graves’ disease reinforces guidelines for TSH and TPO-Ab screening at diabetes diagnosis, with repeat TSH every 1–2 years in antibody-positive patients or sooner if symptomatic. Screening for additional autoimmune conditions is essential.
Therapeutic Nuance: AU occurs in APS-1 and APS-3, but mechanisms differ. APS-3 is polygenic, unlike interferon-driven APS-1. While JAK inhibitors (e.g., baricitinib) are FDA-approved for alopecia areata, their role in T1DM or Graves’, or as unified APS-3 therapy, remains investigational.

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