When performing MRI / CT / ultrasound of the orbital room 98 % of the patients with Graves´ thyrotoxicosis exhibit changes of ophthalmopathy without clinical symptoms of endocrine ophthalmopathy (Burch 1993). Thus, almost all patients with Graves´ disease are at risk to develop clinical ophthalmopathy. Tobacco exposition and treatment with radioiodine ar known factors that trigger ophthalmopathy but other factors are poorly defined. However it is well known that both environmental and genetic factors is of importance because monozygotic twins show a concordance of 20 - 50 %. One interesting observation is a patient with inactive and stable Graves´ ophthalmopathy who developed clinical ophthalmopathy when treated with pioglitazone due to type 2 diabetes (Starkey 2003). One pathogenic mechanism in Graves´ ophthalmopathy is increased orbital adipogenesis and glitazones are known to increase the volume of subcutaneous adipose tissue. Orbital fibroblasts from patients with ophthalmopathy have been shown to differentiate to adipocytes in response to rosiglitazone (Valyasevi 2002). Glitazones are PPAR-gamma agonists and it could be of interest to study effects of PPARgamma antagonists in endocrine ophthalmopathy. Diclofenac has been shown to interact with PPAR-gamma in physiological concentrations and to antagonise PPAR-gamma mediated effects like adipogenesis of the preadipocyte cell line 3T3-L1(Adamsson 2002, Vondrichova 2007). In addition diclofenac is a well-known inhibitor of cyclooxygenases with effects on the synthesis of prostaglandins in for example fibroblasts, lymphocytes and monocytes. The natural ligand for PPAR-gamma is prostaglandin J (Forman 1995). To conclude, NSAID like diclofenac may affect both synthesis of prostaglandins and concomittantly antagonise the effects of the natural ligand to PPAR-gamma, prostaglandin J2. We have recently demonstrated upregulation of immediate early genes, including COX-2, with important functions in adipogenesis in patients with severe ophthalmopathy (Lantz 2005). Previously there is only one study published on treatment of ophthalmopathy with NSAID ,indometacin (Amemia 1982). Although only 7 patients were studied there were effects on soft tissue symptoms, eye protrusion and eye muscle symptoms. Due to the knowledge of retrobulbar morphological changes in patients with Graves´ thyrotoxicosis without clinical ophthalmopathy it may be of importance to interact as early as possible. We therefore plan to start a randomised single-blind study where patients will receive diclofenac for 12 months in parallel with the standard treatment for thyrotoxicosis.