Hyperthyroidism in Patients with Graves’ Ophthalmopathy, and Thyroidal, Skeletal and Eye Muscle Specific Type 2 Deiodinase Enzyme Activities

Abstract

AbstractGraves’ ophthalmopathy is characterized by hyperthyroidism, which is associated with higher serum T3 levels than T4 due to deiodinase enzymes.The effect of Graves’ patient’s sera (n=52) with elevated thyroid hormone and TSH receptor or thyroid peroxidase antibody (anti-TPO) levels was investigated on thyroidal, skeletal and eye muscle type 2 deiodinase enzyme (DII) activities. DII activities were measured with 125I-T4 substrate, while thyroid hormone and antibody levels with immunoassays.In Graves’ ophthalmopathy, sera with elevated FT4 or FT3 levels reduced DII activites remarkably in all tissue fractions. Thyroidal DII activities were lower than those using eye muscle fraction (0.6±0.22 vs 1.14±0.43 pmol/mg/min, P<0.006). Effect of sera with increased FT3 levels demonstrated also reduced DII activities in patients with Graves’ ophthalmopathy after methimazole therapy compared to those who had no ophthalmopathy (2.88±2 vs 20.42±11.82 pmol/mg/min, P<0.006 for thyroidal fraction, 4.07±2.72 vs 29.22±15.46 pmol/mg/min, P<0.004 for skeletal muscle, 5.3±3.47 vs 37.87±18.82 pmol/mg/min, P<0.003 for eye muscle). Hyperthyroid sera with TSH receptor antibodies resulted in increased DII activities, while sera with anti-TPO antibodies were connected to lower DII activities in Graves’ ophthalmopathy.In summary, the actions of hyperthyroid sera derived from patients with Graves’ disease were tested on tissue-specific DII activities. Elevated FT4 level-induced DII inactivation is present in Graves’ ophthalmopathy, which seems to be also present at the beginning of methimazole therapy. Stimulating TSH receptor antibiodies increased DII activities via their nongenomic effects using sera of hyperthyroid Graves’ ophthalmopathy, but anti-TPO antibodies could influence DII activities via altering FT4 levels.