Insulin autoantibodies in Graves' disease--before and after carbimazole therapy

Insulin autoantibodies (IAA) are well documented in patients with insulin-dependent diabetes (IDDM) prior to the administration of insulin and in patients with reactive hypoglycaemia--the insulin autoimmune syndrome (IAS). It has been suggested that IAA can be induced by the administration of drugs containing sulphydryl groups, such as carbimazole, and they have been frequently described in Graves' disease. An alternative explanation is the clustering of autoantibodies in autoimmune disease. We studied 39 patients (37 females, two males, age range 14 to 61 years; mean 33.8 years) with proven Graves' disease and no previous treatment with carbimazole. Fifteen of the 39 patients had a family history of other autoimmune diseases. IAA and thyroid autoantibodies were assayed at diagnosis and monthly thereafter while on treatment with carbimazole, for up to 6 months. IAA were measured using a direct-binding solid-phase ELISA and specificity was confirmed by absorption studies using insulin covalently coupled to Sepharose beads. At diagnosis 33 of the 39 patients (85%) were positive for thyroid microsomal antibodies, 13 (33%) were positive for thyroglobulin antibodies, and 4 (10%) were positive for IAA. All IAA-positive patients had microsomal antibodies at diagnosis, and two had thyroglobulin antibodies in addition. After 4 months on carbimazole, the frequency of thyroid microsomal autoantibodies was unchanged (83%), while that of anti-thyroglobulin antibodies had fallen (8.6%). All four IAA-positive patients remained positive, and studies of binding to human, porcine and bovine insulin demonstrated that one serum, initially human insulin specific, later became cross-reactive with all three. We conclude that low titres of IAA are found in Graves' disease, and are associated with the presence of autoimmunity rather than the carbimazole. Symptomatic hypoglycaemia, however, is rare in Caucasian patients.