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Authors’ Response: Dosage Recommendations for Combination Regimen of Thyroxine and 3,5,3'-Triiodothyronine

Division of Endocrinology and Metabolism, McMaster University, Hamilton, Ontario, Canada L8N 1G6

Address correspondence to: Anna M. Sawka, M.D., Center for Evaluation of Medicines, 105 Main Street East, Level P1, Ontario, Canada L8N 1G6. E-mail: sawkaam{at}yahoo.com.

To the editor:

Dr. Blanchard commented (1) that our comparison of therapy with T₄ to combination therapy with T₃ and T₄ (2) may have tested an inappropriate dosage of T₄ and T₃. This is based on his anecdotal experience with 1000 patients on combination therapy of T₄ and T₃ for whom the ratio of T₄:T₃ was 98%:2%. His patients were apparently "much better" (1) on combination therapy than on their previous therapy.

We agree with Dr. Blanchard that our findings may not be generalizable to other dosing regimens of combination T₄/T₃ therapy or to a sustained release of T₃ preparation. However, if it is possible that different combination therapies are superior, this should be rigorously tested within a double-blinded, randomized, controlled trial setting. Of note, the psychological scores [Symptom Checklist-90 (SCL-90) and Center for Epidemiological Studies-Depression Scale (CES-D)] in our study improved in both treatment groups with repeated testing; this observation suggests that there was a substantial placebo effect (2). It is well established that anecdotal experience, without a control group, may be subject to various biases that may overestimate benefits (3). In this light, a multicenter, randomized, controlled trial that explicitly tests the benefits and risks of alternative dosing regimens of combination T₃/T₄ therapy would clearly be appropriate. In the meantime, the best controlled evidence does not support changing the way that hypothyroidism is routinely treated.

Received November 27, 2003.

References

1. Blanchard KR 2004 Letter: dosage recommendations for combination regimen of thyroxine and 3,5,3'-triiodothyronine J Clin Endocrinol Metab 89:1486–1487[Free Full Text]
2. Sawka AM, Gerstein HC, Marriott MJ, MacQueen GM, Joffe RT 2003 Does a combination regimen of thyroxine (T₄) and 3,5,3'-triiodothyronine improve depressive symptoms better than T₄ alone in patients with hypothyroidism? J Clin Endocrinol Metab 88:4551–4555[Abstract/Free Full Text]
3. Guyatt GH, Sackett DL, Cook DJ 1993 Users’ guides to the medical literature. II. How to use an article about therapy or prevention. A. Are the results of the study valid? Evidence-Based Medicine Working Group. JAMA 270:2598–2601[Free Full Text]

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