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The Journal of Clinical Endocrinology & Metabolism Vol. 88, No. 1 55-59
Copyright © 2003 by The Endocrine Society

Original Article

Peroxisome Proliferator-Activated Receptor-{gamma} in Thyroid Eye Disease: Contraindication for Thiazolidinedione Use?

Kerry Starkey, Armin Heufelder, Glynn Baker, Werner Joba, Marc Evans, Stephen Davies and Marian Ludgate

Departments of Medicine (K.S., G.B., M.E., D.D., M.L.) and Ophthalmology (G.B.), University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, United Kingdom; and Endocrinology and Molecular Medicine (A.H., W.J.), Clinical Research Centre, D80336 Munich, Germany

Address all correspondence and requests for reprints to: Marian Ludgate, Ph.D., Department of Medicine, Endocrinology, Metabolism & Diabetes Section, University of Wales College of Medicine, Heath Park, Cardiff CF14 4XN, United Kingdom. E-mail: ludgate{at}cf.ac.uk.

A male type-2 diabetic, treated with the peroxisome proliferator-activated receptor (PPAR) agonist, Pioglitazone, experienced exacerbation of his thyroid eye disease (TED), which had been stable and inactive for more then 2 yr. Expansion of the orbital fat developed, and we have investigated the effects of PPAR{gamma} agonists, including Pioglitazone and, subsequently, an antagonist on the adipogenesis of preadipocytes from TED orbits and Graves’ neck fats.

The percentage of differentiating cells, assessed by oil red O staining, morphological changes, and PPAR{gamma} transcript levels, was determined for preadipocytes in hormone/agonist-induced models of adipogenesis, supplemented or not with PPAR{gamma} agonists or antagonist. The PPAR{gamma} agonists resulted in a 2- to 13-fold increase, and a PPAR{gamma} antagonist produced a 2- to 7-fold reduction in adipogenesis in vitro. Effects were dose dependent and maximal at 1 or 10 µM.

We suggest that care should be exercised when selecting patients for treatment with PPAR{gamma} agonists and that such agonists may be contraindicated in individuals with a previous history of autoimmune thyroid or eye diseases. Our work also suggests that PPAR{gamma} antagonists could provide a novel therapy for TED patients in the active stage of disease.

This work was supported by grants from the University of Wales College of Medicine and the Wales Office for Research and Development.

Abbreviations: APRT, Adenine phosphoribosyltransferase; CAS, clinical activity score; GD, Graves’ disease; PD, pretibial dermopathy; PPAR, peroxisome proliferator-activated receptor; TED, thyroid eye disease; TSHR, TSH receptor; TZD, thiazolidinedione.




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