Issue 145 Item 3 Pioglitazone May Worsen Autoimmune Thyroid Eye Disease

Thiazolidinediones, may worsen eye disease associated with autoimmune thyroid disease. That, according to a report in the January issue of The Journal of Clinical Endocrinology and Metabolism.

Dr. Marian Ludgate from University of Wales College of Medicine in Cardiff, UK and colleagues report the case of a 57-year-old man with a history of Graves’ disease and thyroid eye disease that was rapidly exacerbated after he began treatment with pioglitazone, a thiazolidinedione, for type 2 diabetes.

The man’s thyroid eye disease had been inactive and stable for more than 2 years, the authors report, but he developed recurrence of his thyroid eye disease symptoms with marked orbital fat expansion within 3 months of commencing pioglitazone therapy. The drug was discontinued and the patient’s condition improved substantially, but his clinical activity score (CAS) had not returned to its pre-pioglitazone level 3 months later.

Dr. Ludgate encourages physicians to maintain close supervision of patients treated with thiazolidinediones who have a previous or family history of Graves’ or thyroid eye diseases.

Dr. Ludgate did not think the results suggest that thiazolidinedione therapy should be avoided in Graves’ patients. "The exacerbation of eye disease has been found in only one patient so far and the benefits of thiazolidinediones in maintaining glycemic control currently outweigh any detrimental effect."

Thiazolidinediones activate the peroxisome proliferator-activated receptor (PPAR) gamma, Dr. Ludgate and colleagues note in their paper, which in turn regulates the differentiation of preadipocytes into mature adipocytes.

The investigators studied preadipocytes cultured in differentiation medium and found that the presence of a PPAR-gamma agonist increase differentiation a 2- to 8-fold, and pioglitazone alone induced adipogenesis in 7%-8% of preadipocytes in culture. In contrast, a PPAR-gamma antagonist significantly inhibited both hormone- and agonist-induced differentiation of preadipocytes.

The results suggest that PPAR-gamma antagonists could ameliorate thyroid eye disease by reducing orbital adipogenesis but would have to be administered when disease is active, the authors conclude, because PPAR-gamma antagonists have no effect on mature adipocytes.

J Clin Endocrinol Metab 2003;88:55-59.