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The Journal of Clinical Endocrinology & Metabolism Vol. 89, No. 3 1487-1488
Copyright © 2004 by The Endocrine Society

Letter to the Editor

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

John P. Walsh and Bronwyn G. A. Stuckey

Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia 6009

Address correspondence to: John P. Walsh, FRACP, Ph.D., Department of Endocrinology and Diabetes, Sir Charles Gairdner Hospital, Nedlands, Western Australia 6009. E-mail: john.walsh{at}health.wa.gov.au.

To the editor:

Dr. Blanchard (1) finds that in his experience, patients are "clearly better" on combined T4/T3 therapy than on T4 alone. No clinician doubts the value of experience, but most recognize that nonspecific, subjective symptoms are unreliable guides: patients may feel better because of a placebo effect or because they are being treated by a sympathetic physician. Blanchard (1) makes several other assertions unsupported by evidence. First, the physiological ratio of T4 to T3 secreted by human thyroid under iodine-sufficient conditions is 11:1 (2), so there is no physiological basis for prescribing T4 and T3 in a ratio of 98:2 or for the various other ratios promoted by a few physicians in non-peer-reviewed publications and on the Internet. Second, the dose of T3 used in our study (3) was not supraphysiological by of a factor of 10–20. T3 secretion by the human thyroid approximates 3.3 µg/d·m2, or about 6 µg/d (4). Assuming 95% bioavailability, the dose we used was, at worst, supraphysiological by a factor of 1.5 (5). Third, the response to combined therapy described by Blanchard (1) of "spectacular improvement" initially, "followed by a gradual decline and, ultimately, no benefit" is characteristic of a placebo response, rather than reflecting some complex interplay of T4 and T3 at a tissue level.

The current balance of evidence is that combined T4/T3 treatment is not generally beneficial to hypothyroid patients compared with T4 alone. Anecdotal evidence can be useful in generating hypotheses, but combined treatment will not become more widely accepted unless benefits can be demonstrated in well-designed, double-blind clinical trials.

Received November 21, 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. Bianco AC, Salvatore D, Gereben B, Berry MJ, Larsen PR 2002 Biochemistry, cellular and molecular biology, and physiological roles of iodothyronine selenodeiodinases. Endocr Rev 23:38–89[Abstract/Free Full Text]
  3. Walsh JP, Shiels L, Lim EM, Bhagat CI, Ward LC, Stuckey BGA, Dhaliwal SS, Chew GT, Bhagat MC, Cussons AJ 2003 Combined thyroxine/liothyronine treatment does not improve well-being, quality of life, of cognitive function compared to thyroxine alone: a randomized controlled trial in patients with primary hypothyroidism. J Clin Endocrinol Metab 88:4543–4550[Abstract/Free Full Text]
  4. Pilo A, Iervasi G, Vitek F, Ferdeghini M, Cazzuola F, Bianchi R 1990 Thyroidal and peripheral production of 3,5,3'-triiodothyronine in humans by multicompartmental analysis. Am J Physiol 258:E715–E726
  5. Hays MT 1969 Absorption of triiodothyronine in man. J Clin Endocrinol 30:675–677




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