COX-2 and SCD, Markers of Inflammation and Adipogenesis, Are Related to Disease Activity in Graves' Ophthalmopathy

Vondrichova, Tereza; Capretz, Annika de; Parikh, Hemang; Frenander, Christofer; Åsman, Peter; Åberg, Magnus; Groop, Leif; Hallengren, Bengt; Lantz, Mikael

doi:10.1089/thy.2007.0028

Cited by 27 publications

(23 citation statements)

References 31 publications

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“…This is supported by an observation in COX-2 knockout mice where the concentrations of IgM and IgG were reduced by 64 and 35%, respectively, or less as compared to normal controls [19]. We have previously shown that COX-2 is upregulated in orbital tissue of patients with active GO and decreased in the chronic phase [12,14]. COX-2 is an immediate early gene upregulated in response to mitogens, and among this group of genes, regulating inflammation and adipogenesis, CYR61 and EGR-1 have been found to be strongly overexpressed in patients with GO.…”

Section: Discussionmentioning

confidence: 64%

“…We have previously shown an overexpression of COX-2 in orbital tissue from GO patients [12]. Approximately one third of the patients with GD will develop clinical GO, but markers for patients at risk are lacking.…”

Section: Discussionmentioning

confidence: 99%

“…Glitazones are peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists and it is therefore of interest to study if PPAR-γ antagonists have preventive effects on the development of GO. Diclofenac has been shown to interact with PPAR-γ in physiological concentrations and to antagonize PPAR-γ-mediated effects like adipogenesis of the preadipocyte cell line 3T3-L1 [11,12]. The natural ligand of PPAR-γ is prostaglandin J [13].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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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 L-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.

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2016

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“…In contrast, diclofenac reduced the number of mature adipocytes by 50%. This study indicates that diclofenac has potential in the treatment of TED [20]. …”

Section: Clinical Treatmentmentioning

confidence: 92%

Thyroid Eye Disease: Pathogenesis and Treatment

Sikder

Weinberg²

2009

Ophthalmologica

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“…Otherwise, the gene of proinflammatory cyclooxigenase-2 (COX-2), another partner of the disease, was found overexpressed in severe and active phase of Graves' ophthalmopathy (5,6). According to these data, the use of a PPAR-gamma and COX-2 antagonist could theoretically be useful in the treatment of the orbital disease.…”

Section: Introductionmentioning

confidence: 99%

Treatment of mild to moderate Graves' ophthalmopathy with sodium diclofenac: a pilot study

Bloise

Mimura

Moura

et al. 2011

Arq Bras Endocrinol Metab

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Objective: To report the use of sodium diclofenac, an antagonist of PPAR-gamma and cyclooxigenase-2 (COX-2) inhibitor in the treatment of mild to moderate Graves' ophthalmopathy. Subjects and methods: Thirteen patients with clinical activity score (CAS) 2 to 7 were treated during a period ranging from 3 to 12 months (mean 7.8 ± 3.4) with oral sodium diclofenac, 50 mg every 12 hours. Results: Extra-ocular muscle restriction and CAS improved significantly, p = 0.003 and = 0.004, respectively. Ocular pain and diplopia disappeared, except for one patient who reported improvement of these symptoms. No recurrence was found after interruption of treatment. Conclusions: Treatment of moderate Graves' ophthalmopathy with oral sodium diclofenac is a good, safe and less expensive therapeutic option. Like others new treatment trials, findings must be confirmed in a greater number of patients in a controlled study. Arq Bras Endocrinol Metab. 2011;55(9):692-5

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COX-2 and SCD, Markers of Inflammation and Adipogenesis, Are Related to Disease Activity in Graves' Ophthalmopathy

Abstract: 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.

Cited by 27 publications

References 31 publications

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

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

Thyroid Eye Disease: Pathogenesis and Treatment

Treatment of mild to moderate Graves' ophthalmopathy with sodium diclofenac: a pilot study

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