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The Journal of Clinical Endocrinology & Metabolism Vol. 89, No. 3 1486-1487
Copyright © 2004 by The Endocrine Society


Letter to the Editor

Dosage Recommendations for Combination Regimen of Thyroxine and 3,5,3'-Triiodothyronine

Kenneth R. Blanchard

Newton Lower Falls, Massachusetts 02462

Address correspondence to: Kenneth R. Blanchard, M.D., Ph.D., 200 Washington Street, Suite 565, Newton Lower Falls, Massachusetts 02462.

To the editor:

I wish to reply to two recent papers concluding that T4 plus T3 was no better than T4 alone in the treatment of hypothyroidism (1, 2). Despite the good number of subjects and elaborate scientific design, these studies are fatally flawed because of the use of grossly wrong dosages of T4 and T3. These studies were done because of the 1999 Lithuanian study (3) that concluded that the subjects receiving T4 and T3 did better than they did on T4 alone. I speak from the perspective of a physician who has used T4 and T3 together routinely since 1990 and currently has about 1000 patients on such combined treatment. Many of those patients previously were followed at eminent institutions on standard 100% T4 and are clearly much better on the combined treatment. The key to using T4 and T3 successfully is getting the right ratio between the two, approximately 98% T4 and 2% T3 (4). The old teaching that 4 or 5 µg of T4 should be eliminated for every 1 µg of T3 given is fundamentally fallacious as well. The fact that all three of these studies reduced T4 dosages according to this formula and gave 10–20 times more T3 than is physiological leads to rapid decline in T4 tissue levels over time. This means that the longer such a study is carried out, the worse people feel. One of the reasons why the 1999 study showed a positive result was that the duration was 5 wk (3). The effect of a given dose of T3 depends on the T4 saturation level of the tissue that it is going into. That is the reason why many physicians in the last 4 yr, following the protocol of the 1999 study, have noted often spectacular improvement in a few days or 1 or 2 wk, followed by a gradual decline and, ultimately, no benefit (3). Giving T3 in compounded, time-release capsules works much better than any T3 pill, partly because one can tailor the dose more precisely as well as get the better pharmacological profile due to time-release. If anything, the introduction of a physiological dose of T3 in time-release form to a patient who appears euthyroid on T4 will actually cause a small increase in the T4 requirement over time. The failure to keep the T4 tissue level up causes the beneficial effect of adding T3 to wane over time. Any physician with an open mind who follows the protocol that I have outlined (4) will now understand that all of those hypothyroid patients who have been complaining for years about their treatment were right after all.

Received November 12, 2003.

References

  1. Walsh JP, Shiels L, Lim EM, Bhagat CI, Ward LC, Stuckey BGA, Dhaliwal SS, Chew GT, Bhagat MC, Cussons AJ 2003 Combined thyroxine/liothyromine treatment does not improve well-being, quality of life, or 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]
  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? Results of a double-blind, randomized, controlled trial. J Clin Endocrinol Metab 88:4551–4555[Abstract/Free Full Text]
  3. Bunevicius R, Kazanavicius G, Zalinkevicius R, Prange Jr AJ 1999 Effects of thyroxine as compared with thyroxine plus triiodothyronine in patients with hypothyroidism. N Engl J Med 340:424–429[Abstract/Free Full Text]
  4. Blanchard K, Brill MA 2004 What your doctor may not tell you about hypothyroidism. New York: Warner Books



This article has been cited by other articles:


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J. Clin. Endocrinol. Metab.Home page
A. M. Sawka and H. C. Gerstein
Authors' Response: Dosage Recommendations for Combination Regimen of Thyroxine and 3,5,3'-Triiodothyronine
J. Clin. Endocrinol. Metab., March 1, 2004; 89(3): 1487 - 1487.
[Full Text] [PDF]


Home page
J. Clin. Endocrinol. Metab.Home page
J. P. Walsh and B. G. A. Stuckey
Authors' Response: Dosage Recommendations for Combination Regimen of Thyroxine and 3,5,3'-Triiodothyronine
J. Clin. Endocrinol. Metab., March 1, 2004; 89(3): 1487 - 1488.
[Full Text] [PDF]


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