Endocrine Abstracts

A 45-year-old woman was diagnosed with hypothyroidism at 26, Addison’s disease at 35 and primary ovarian insufficiency at 42. She is positive for adrenal and thyroid microsomal antibodies but negative for ovarian antibodies. She has a strong family history of autoimmunity. Interestingly, her mother has pernicious anaemia and hypothyroidism and her sister has hypothyroidism. A diagnosis of autoimmune polyglandular syndrome (APS) type 2 has been supported by the HLA haplotype B8 DR3, and DR4.

The APS syndromes types 1 and 2 have dissimilar characteristics and there is emerging evidence to suggest that the genetics and pathogeneses of these two entities are different. The genotype for a particular syndrome does not always correlate with the phenotype hence clinical presentations are variable. The syndromes are characterised by multiple endocrine organ dysfunction associated with circulating organ specific antibodies. A family history of autoimmunity is characteristic and the syndromes show specific patterns of disease associations.

There are 2 main types. Autoimmune polyendocrinopathy–candidiasis– ectodermal dystrophy (APECED) syndrome is a rare autosomal recessive disorder with an onset primarily in childhood or early adulthood. APECED has been linked to mutations in the autoimmune regulator gene on chromosome 21q22.3 and may produce different phenotypes. Adrenal insufficiency and hypoparathyroidism are the main endocrinopathies. These may coexist with non-endocrine disorders such as chronic active hepatitis, pernicious anaemia and malabsorption. APS type 2 is far more common than the type 1 syndrome. About 50% of cases are familial in origin and the mode of transmission is variable. There is a striking female preponderance and the onset occurs mainly in the middle aged. Adrenal sufficiency is the main manifestation and autoimmune thyroid disease and type 1 diabetes mellitus are common associations.

The HLA DR 3 and DR4 haplotype is significantly associated with Type 2 APS and helps with genetic screening and counselling.