D0ble-Blind Clinical Trials ! Effectiveness and safety of T3 (triiodothyronine) therapy for euthyroid fibromyalgia: a double-blind placebo-controlled response-driven crossover study. John C. Lowe, MA, DC, Richard L. Garrison, MD, Alan J. Reichman, MD, Jackie Yellin, BA, Mervianna Thompson, RN, MSN, APN, Daniel Kaufman, MD: Clinical Bulletin of Myofascial Therapy, 2(2/3):31-58, 1997. Background. Clinical features of fibromyalgia syndrome (FMS) resemble those of hypothyroidism although some patients have normal thyroid function tests results. The hypothyroid-like FMS features of these patients may result from partial cellular resistance to thyroid hormone. We treated euthyroid FMS patients with T3 to see if they would respond as do patients with peripheral thyroid hormone resistance syndrome: significant therapeutic effects with supraphysiologic dosages, without target tissue responses typical of thyrotoxicosis. Methods. Seven patients were alternately treated with T3 and placebo over an 8-month period. Phase crossover was response-driven, based on changes in measures of mean tender point sensitivity by algometry, mean symptom intensity by visual analog scales, and mean pain distribution by the percentage method and the ACR criteria. Testing for adverse responses to supraphysiologic dosages of T3 was performed for heart, bone, muscle, and liver. Results. Significant therapeutic effects were shown in T3 phases compared to placebo phases on all measures of FMS status. Effective T3 dosages were supraphysiologic, and ranged from 93.75-to-150 µg. Available patients had maintained improvement at 2-month follow-up. Tests showed no clinically significant cardiac, osseous, muscle, or hepatic adverse effects. Conclusions. In this study, supraphysiologic dosages of T3 were safe and significantly effective in the treatment of euthyroid FMS. Though these dosages produced thyroid function test results indicative of hyperthyroidism, our patients had no clinically significant adverse target tissue effects. Results suggest that euthyroid FMS is a clinical phenotype of partial peripheral resistance to thyroid hormone. We recommend that further studies be done to answer the questions: Are euthyroid FMS patients partially resistant to thyroid hormone? And if so, what are the molecular mechanisms of the resistance? Further testing is also necessary to establish the long-term safety of T3 therapy.