Adjuvant Treatment of Graves' Disease with Diclofenac: Safety, Effects on Ophthalmopathy and Antibody Concentrations

Abstract

Background: Orbital morphological changes are often present in patients with Graves' disease (GD) already at diagnosis, and cyclooxygenase type 2 (COX-2) is overexpressed in active Graves' ophthalmopathy (GO). Objective: To investigate if adjuvant treatment of GD with the COX inhibitor and peroxisome proliferator-activated receptor-γ (PPAR-γ) antagonist diclofenac decreases the development of ophthalmopathy and if laboratory parameters are affected. Methods: This is a multicenter trial where 61 subjects were randomized to methimazole (block and replace with <smlcap>L</smlcap>-thyroxine) either with or without diclofenac 50 mg 1 × 2 for 12 months. The primary end point development of GO after 24 months was evaluated. Smoking habits were registered and the thyroid parameters TSH, free T₄, free T₃, TSH receptor antibodies (TRAb) and anti-TPO were followed. Safety parameters (kidney, liver and blood) and adverse events were regularly registered. Results: GO developed in 11% (n = 3) of the patients treated with diclofenac and in 21% (n = 6) of the controls (p = 0.273). The adverse event profile was acceptable without any severe events related to diclofenac. Both TRAb and anti-TPO concentrations decreased during treatment with methimazole, but the anti-TPO concentrations were lower in patients treated with diclofenac after 15 months (p = 0.031). The TRAb concentrations were not significantly changed between groups. Smokers had higher concentrations of TRAb than nonsmokers both at diagnosis of GD (p = 0.048) and after 15 months (p = 0.042). Conclusions: Treatment with diclofenac had no significant influence on development of GO. Diclofenac reduces anti-TPO concentrations and seems to be safe to use in GD patients.

The Effect of Radioiodine Treatment on TRAb, Anti-TPO, and Anti-TG in Graves’ Disease

“…However, in anti-TG, only half of the patients showed an increase. Tobacco smoking has previously been shown to result in higher concentrations of TRAb [4, 5], but this was not the case because the proportion of smokers was similar in the group of patients with increased values compared to the group with unchanged or decreased values. Neither were there any differences depending on sex or age nor was there an overrepresentation of patients born outside Sweden (not significant).…”

“…The triggering of the autoimmune response depends on the interplay of genetic [1, 2] and environmental factors [3]. One strong risk factor is tobacco smoking, which results in higher TRAb at diagnosis of GD and during treatment with thiamazole than in nonsmokers [4]. It has also been shown that smokers treated with carbimazole had a much slower reduction of stimulating TRAb compared to nonsmokers with GD [5].…”

Percentage and function of CD4+CD25+ regulatory T cells in patients with hyperthyroidism

“…Peripheral blood (10 ml) was extracted from the hyperthyroidism patients and healthy control subjects in the morning for subsequent experiments. The diagnostic criteria or the patients with hyperthyroidism were as previously described ( 11 ). The inclusion criteria were as follows: Patients diagnosed with hyperthyroidism who had not received anti-thyroid medication and were aged 20–60 years-old.…”

Spontaneous resolution of euthyroid optic neuropathy

“…16 However, a randomized study failed to demonstrate a suppressive effect on the development of Graves' orbitopathy. 17 It is possible that the loxoprofen affected the clinical course of this patient.…”