Endocrine Abstracts

Antithyroid drugs represent mainly the first choice therapy in hyperthyroid Graves’ disease. Their therapeutical ineffectiveness can lead to the onset or the severity of ophthalmopathy associated with Graves’ disease. Type 2 5’-deiodinase enzyme (DIO2) plays a crucial role besides type 1 5’-deiodinase enzyme in the development of Graves’ hyperthyroidism. Anti-thyroid drugs inhibit the activity of both type 5’-deiodinases blocking the synthesis of thyroid hormones and can induce antineutrophil cytoplasmic antibodies. In this study, the frequency of antibodies against type 2 5’-deiodinase and their effects on the inhibition of thyroid hormone synthesis were investigated during antithyroid drug therapy. Antibodies against DIO2 peptides (cys- and hom-peptides) were studied in 78 patients with Graves’ disease (58 females and 20 males, mean age of 43±14 years, 39 had ophthalmopathy) and 30 healthy controls (27 females and 3 males, mean age of 47±16 years) using ELISA. The thyroid hormone and antibody serum levels were measured with chemiluminescence immuno-assay and ELISA. In hyperthyroid patients treated by propylthiouracil (PTU), a greater frequency of antibodies against DIO2 peptides was demonstrated compared with those treated by methi-ma-zole (MMI) (3/3 vs 5/23 cases, P<0.002 for cys-peptide and 2/3 vs 2/23 cases, P<0.027 for hom-peptide antibodies). The patients, who were treated with PTU and had cys-peptide anti-body positivity, demonstrated significantly increased TSH receptor antibody levels compared with those treated with MMI (26.4±10.57 vs 6.96±4.85 IU/l, P<0.011). In hyperthyroid Graves’ ophthalmopathy, the patients were hom-peptide (0/12 vs 3/11, P<0.05) and cys-peptide (0/12 vs 5/12, P<0.012) antibody negative after MMI therapy in comparison with patients without ophthalmopathy. In hyperthyroid Graves’ ophthalmopathy, the occurrence of hom-peptide antibodies was associated with elevated FT₄ (3.08±0.86 vs 2.02±0.49 ng/dl, P<0.013) and FT₃ (10.44±6.02 vs 5.36±1.42 pg/ml, P<0.003) serum levels compared with those who were antibody negative. In summary, an increased presence of antibodies againts DIO2 peptides could be demonstrated after PTU therapy in hyperthyroid Graves’ disease. None of hyperthyroid cases with ophthalmopathy had antibodies against DIO2 peptides after MMI therapy. The presence of DIO2 peptide antibodies was associated with a prolonged hyper-thyroidism and increased TSH receptor antibody levels declining the therapeutical effective-ness of antithyroid drugs.