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Context: Inflammation and adipogenesis are two parallel processes with increased activity in severe Graves' ophthalmopathy., Objective: The aim of this work was to define target genes for therapeutic intervention in adipogenesis and inflammation in Graves' ophthalmopathy., Design: Orbital tissue was obtained from patients with ophthalmopathy in acute or chronic phase undergoing orbital surgery to study gene expression followed by the study of potential intervention mechanisms in preadipocytes., Setting: Clinic of Endocrinology, University Hospital, Malmö, Sweden., Participants: Patients in acute severe or in chronic phase of ophthalmopathy., Interventions: Lateral orbital decompression in acute phase and restorative surgery in chronic phase. In vitro treatment of preadipocytes with rosiglitazone and diclofenac., Main Outcome Measure: Gene expression in intraorbital tissue or preadipocytes and differentiation of preadipocytes., Results: A marker of adipose tissue, stearoyl-coenzyme A desaturase (SCD), and the proinflammatory gene, cyclooxygenase-2 (COX-2), were overexpressed in patients in active phase compared to the chronic phase of ophthalmopathy. In growth-arrested preadipocytes stimulated with rosiglitazone, COX-2 expression increased temporarily within 1 hour and decreased to undetectable levels after 48 hours. In contrast, SCD and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) expression increased continuously from day 2 to day 7 during adipogenesis. Diclofenac, an inhibitor of cyclooxygenases with antagonistic effects on PPAR-gamma, reduced the number of mature adipocytes by approximately 50%., Conclusion: We conclude that inflammation and adipogenesis decrease with a decrease in activity of ophthalmopathy and that the nonsteroidal antiinflammatory drug diclofenac inhibits adipogenesis. This may represent a putative future treatment of endocrine ophthalmopathy.

Objective: To investigate gene expression of thyrostimulin in orbital and thyroid tissue from patients with and without Graves' disease., Design: Real-time reverse transcriptase polymerase chain reaction (RT-PCR) was used for detection of thyrostimulin gene expression in intraorbital adipose tissue from patients with severe ophthalmopathy and thyroid healthy controls in addition to thyrostimulin expression in normal thyroid tissue, multinodular goiter tissue, and Graves' thyroid tissue., Main Outcome: In intraorbital tissue, thyrostimulin expression was identified in both patients and controls with fluorescence intensities varying between 0.23 and 0.88 in patients and 0.29 and 8.9 in controls before treatment with DNase. The signal of thyrostimulin was weak or absent in intraorbital adipose tissue from patients with ophthalmopathy and thyroid healthy controls after treatment of samples with DNase. This was in contrast to the expression of the thyroid-stimulating hormone (TSH) receptor and the housekeeping gene cyclophilin A that were detected both before and after DNase treatment. Similar results were found when analyzing human and rat thyroid tissue., Conclusions: Neither did we demonstrate gene expression of thyrostimulin in intraorbital adipose tissue or in thyroid tissue, nor could we confirm earlier findings in rat thyroid tissue. Whether thyrostimulin is a regulator of thyroid function has to be further investigated in future studies.