Beyond glycaemic control: autoimmune polyglandular syndrome type 3 as an emerging distinct entity rather than a mere comorbidity in paediatric type 1 diabetes - 30/09/26

Doi : 10.1016/j.diabet.2026.101796

Styliani Giza, Vasiliki Rengina Tsinopoulou, Eleni P Kotanidou, Thekla Poukoulidou, Stergianna Ntouma, Kosmas Margaritis, Assimina Galli-Tsinopoulou ^⁎

Unit of Diabetes Mellitus of Children and Adolescents, Unit of Paediatric Endocrinology, and Metabolism, 2nd Department of Paediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, AHEPA University General Hospital of Thessaloniki, Stilponos Kyriakidi 1, 54636, Thessaloniki, Greece

^⁎ Corresponding author: Assimina Galli-Tsinopoulou MD PhD, Professor in Paediatrics - Paediatric Endocrinology, Head of the 2nd Department of Paediatrics, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, AHEPA University Hospital, Stilponos Kyriakidi 1, 54636 Thessaloniki, Greece Professor in Paediatrics - Paediatric Endocrinology, Head of the 2nd Department of Paediatrics, School of Medicine, Faculty of Health Sciences Aristotle University of Thessaloniki, AHEPA University Hospital Stilponos Kyriakidi 1 Thessaloniki 54636 Greece

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HIGHLIGHTS

•	Autoimmune polyglandular syndrome (APS)-3a is common in pediatric patients (23.5%).
•	Overlap of APS-3 subtypes is recorded in type 1 diabetes mellitus paediatric patients.
•	Lifelong regular screening for emerging autoimmune entities is necessary.
•	Peadiatric autoimmune thyroid disease patients should be educated on diabetes symptoms.

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AΒSTRACT

Aim

Autoimmune polyglandular syndrome type 3 (APS-3) is the coexistence of autoimmune thyroid disease (AITD) with type 1 diabetes (T1D) or other autoimmune diseases, after exclusion of adrenal insufficiency. We aimed to evaluate the prevalence, timeline and features of APS-3 in children and adolescents with T1D.

Methods

We studied 439 T1D paediatric patients who were diagnosed and followed up over 16 years using annual biochemical and autoantibody profile evaluations.

Results

The prevalence of APS-3a (T1D+AITD) was 23.5%, with significant female predominance (54.4%, P = 0.007). The vast majority had Hashimoto’s thyroiditis (96.0%), while Graves’ disease represented only 4.0%. Coincidence of T1D and AITD diagnosis was recorded in 49.5%. The frequency of diabetic ketoacidosis in patients diagnosed with AITD before the onset of T1D (63.6%) was similar to that in patients with isolated T1D (61.7%). Overlapping of APS-3 subtypes were identified, including celiac disease (n=4), autoimmune hepatitis (n=1), atrophic gastritis (n=1) (APS-3b), vitiligo (n=1), psoriasis (n=1) (APS-3c) and Sjögren’s syndrome (n=1) (APS-3d).

Conclusions

APS-3a is common in the paediatric T1D population and is often diagnosed at its clinical onset. The overlaps with gastrointestinal and connective tissue pathology highlight the unpredictable natural course of autoimmunity, underscoring the necessity for lifelong regular monitoring.

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Keywords : Autoimmune polyglandular syndrome type 3, Autoimmune thyroid disease, Diabetic ketoacidosis, Graves’ disease, Hashimoto's thyroiditis, Type 1 diabetes