Beyond glycaemic control: autoimmune polyglandular syndrome type 3 as an emerging distinct entity rather than a mere comorbidity in paediatric type 1 diabetes.

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.