Endocrine Abstracts

Autoimmune Polyglandular Syndromes (APS) are rare disorders characterised by immune-mediated multi-organ dysfunctions. The three main subtypes, APS-1, APS-2, and APS-3 are distinguished by different patterns of endocrine involvement. Mutations in the autoimmune regulator (AIRE) gene on chromosome 21q22.3 that impair thymic immune tolerance causes APS-1, which is strongly associated with autoimmune hypoparathyroidism (90% of cases), chronic mucocutaneous candidiasis and adrenal insufficiency. It can also involve type 1 diabetes, hypothyroidism, pernicious anaemia, vitiligo, hepatitis, oophoritis and keratitis. Recent evidence suggests that existing diagnostic criteria may be inadequate, as not all patients with APS-1 exhibit classical features. We present a woman (index case) with chronic hypocalcaemia due to hypoparathyroidism since birth, type 1 diabetes from age 10 years and autoimmune hypothyroidism in her forties. Her younger sister also has chronic hypoparathyroidism with hypocalcaemia, and hypothyroidism. There is a family history of thyroid dysfunction in another sister, a brother, and their mother. These findings suggest a potential hereditary polyglandular deficiency pattern that does not fully fit the diagnosis of APS-1. It raises the possibility of either a non-classical/variant form of the syndrome, an unidentified gene mutation or a different type of polyglandular syndrome which is yet to be classified. It underscores the heterogeneity of APS, revealing gaps in our understanding of its genetic and phenotypic spectrum.