Type 1 diabetes is associated with other autoimmune diseases. Many diabetes centers routinely screen patients with type 1 diabetes for autoimmune thyroid disease (ATD). The presence of two autoimmune diseases raises the possibility of polyendocrine autoimmune disease. The association of autoimmune adrenal insufficiency, or Addison’s disease, with type 1 diabetes is described in case reports dating back more than a century (1,2). Studies have illustrated shared HLA alleles (DQA1*0501, for example) among patients with type 1 diabetes, ATD, and Addison’s disease (3,4). Pancreatic islet cell antibodies have been detected in 6.2% of patients with Addison’s disease (5). Yet, it is unclear whether patients with type 1 diabetes should be routinely screened for Addison’s disease.
Our study’s objective was to determine whether routine screening for Addison’s disease is warranted in children with both type 1 diabetes and ATD. Children were diagnosed with thyroid disease if they had thyroid peroxidase antibodies (TPOs >50 Ku/l) and/or were receiving thyroid hormone replacement for primary hypothyroidism. A population of children with type 1 diabetes but without thyroid disease was also screened. The study population consisted of 114 children with type 1 diabetes, 35 (25 girls and 10 boys) with thyroid disease (28 on l-thyroxine) and 79 (42 girls and 37 boys) without thyroid disease (normal thyroid-stimulating hormone and TPO <50 Ku/l). Adrenal antibodies were measured by standard immunofluorescent technique (Nova Century Scientific-Immco anti-adrenal slides), and TPOs were measured by an automated electrochemiluminescence immunoassay (Roche Elecsys 2010).
None of the children had signs or symptoms suggestive of Addison’s disease. No adrenal antibodies were detected in the group with thyroid disease. In the group without thyroid disease, a teenage boy presenting with new-onset type 1 diabetes tested positive for adrenal antibodies. There was a known history of Addison’s disease in the child’s deceased mother. The child continues to be followed and has shown no clinical or biochemical evidence of adrenal insufficiency. The mean age of the children was 11.2 ± 3.7 years in the group with thyroid disease and 11.1 ± 3.7 years in the group without thyroid disease. The mean diabetes duration was 3.5 ± 2.5 and 4.2 ± 3.5 years in the groups with and without thyroid disease, respectively. The median TPOs in the group with thyroid disease was 331 (interquartile range 109–997) Ku/l.
We detected adrenal antibodies in only one of our children with type 1 diabetes, a child with a known family history of Addison’s disease. The previous literature shows contradicting data in this regard. Although some studies have shown increased prevalence of adrenal antibodies and biochemical adrenal insufficiency in patients with type 1 diabetes (4,6–8), others have not shown any statistically significant increase in prevalence compared with healthy control subjects (9–11). Although most of these previous studies tend not to differentiate the patients with or without thyroid disease, one study of patients with type 1 diabetes did show an increased prevalence of adrenal antibodies (5.1 vs. 0.6%) in patients with thyroid antibodies compared with those without (7).
Measurement of the more specific and sensitive 21-hydroxylase antibody may have resulted in more positive results in our patients (4,12). However, Peterson et al. (12) found good correlation between the conventional immunofluorescent adrenal autoantibody and 21-hydroxylase antibody techniques.
We conclude that routine screening for Addison’s disease in children with type 1 diabetes, regardless of thyroid status, does not appear warranted unless there is a strong clinical suspicion or family history of Addison’s disease.