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T4/T3 Combination Therapy and Euthyroidism: Medical Journals and Conferences

Purpose of this compilation

To show that treating hypothyroidism with T3 (triiodothyronine) in addition to T4 (thyroxine) has a scientific as well as a clinical basis, and that for many hypothyroid patients, supplementing with T4 alone does not constitute adequate treatment. These findings come from various parts of the world.

A. T3 and euthyroidism
B. T3 and clinical status

A. T3 and euthyroidism

1. "T3/T4 Combination Therapy" (UK, 2002)

Studies in hypothyroid rats suggest that it is only possible to restore universal tissue euthyroidism using a combination of T3 and T4. In patients in whom long-term T4 therapy was substituted by the equivalent combination of T3 and T4 scored better in a variety of neuropsychological tests. It would appear that the treatment of hypothyroidism is about to come full circle.

Toft AD. T3/T4 combination therapy. (Abtract of presentation presented at the 21st Joint Meeting of the British Endocrine Societies in April 2002).

Abstract online at <www.endocrine-abstracts.org/ea/0003/ea0003s40.htm>.

2. "Narrow individual variations in serum T(4) and T(3) in normal subjects: a clue to the understanding of subclinical thyroid disease" (Denmark, 2002)

High individuality causes laboratory reference ranges to be insensitive to changes in test results that are significant for the individual....Our data indicate that each individual had a unique thyroid function. The individual reference ranges for test results were narrow, compared with group reference ranges used to develop laboratory reference ranges. Accordingly, a test result within laboratory reference limits is not necessarily normal for an individual.

Andersen S, Pedersen KM, Bruun NH, Laurberg P. Narrow individual variations in serum T(4) and T(3) in normal subjects: a clue to the understanding of subclinical thyroid disease. J Clin Endocrinol Metab 2002 Mar;87(3):1068-72.

Online at <http://jcem.endojournals.org/cgi/content/full/87/3/1068>.

3. "Only the combined treatment with thyroxine and triiodothyronine ensures euthyroidism in all tissues of the thyroidectomized rat" (Spain, 1996)

We have recently shown that it is not possible to restore euthyroidism completely in all tissues of thyroidectomized rats infused with T4 alone. The present study was undertaken to determine whether this is achieved when T3 is added to the continuous sc infusion of T4....Combined replacement therapy with T4 and T3 (in proportions similar to those secreted by the normal rat thyroid) completely restored euthyroidism in thyroidectomized rats at much lower doses of T4 than those needed to normalize T3 in most tissues when T4 alone was used.

Escobar-Morreale HF, del Rey FE, Obregon MJ, de Escobar GM. Only the combined treatment with thyroxine and triiodothyronine ensures euthyroidism in all tissues of the thyroidectomized rat. Endocrinology 1996 Jun;137(6):2490-502.

Abstract online at <www.ncbi.nlm.nih.gov>.

4. "Replacement therapy for hypothyroidism with thyroxine alone does not ensure euthyroidism in all tissues, as studied in thyroidectomized rats" (Spain, 1995)

...euthyroidism is not restored in plasma and all tissues of thyroidectomized rats on T4 alone. These results may well be pertinent to patients on T4 replacement therapy.

Escobar-Morreale HF, Obregon MJ, Escobar del Rey F, Morreale de Escobar G. Replacement therapy for hypothyroidism with thyroxine alone does not ensure euthyroidism in all tissues, as studied in thyroidectomized rats. J Clin Invest 1995 Dec;96(6):2828-38.

Abstract online at <www.ncbi.nlm.nih.gov>.

B. T3 and clinical status

1. "[Treatment of hypothyroidism]" [Article in Norwegian; abstract in English] (Norway, 2002)

In patients not satisfactorily treated with thyroxine alone, treatment with thyroxine combined with triiodothyronine may be tried.

Haug E. [Treatment of hypothyroidism.]Tidsskr Nor Laegeforen. 2002 Apr 10;122(9):935-7.

Abstract online at <www.ncbi.nlm.nih.gov>.

2. "Thyroid insufficiency. Is Thyroxine the only valuable drug?" (Belgium, 2001)

Having prescribed for many years a natural thyroid hormone (Thyranon), containing both liothyronine (T3) and thyroxine (T4), as well as a combined T3 + T4 drug (Novothyral, containing 20 µg T3 and 100 µg T4), we had the opportunity in 1974 to prescribe a new T4-only drug (Euthyrox, commercially available in Belgium since August 1978). After less than six months, we ascertained the inability of this new T4 alone drug to produce clinically the same results as the previously used combined drugs. [ p. 159]

In the 89 T4 treated hypothyroid patients the prevalence of symptoms was comparable with that of the main group of 832 untreated hypothyroid patients....[p. 161]

This study does not preclude the possibility that T4 can cure certain patients with hypothyroidism. Indeed, patients who are able to convert the inactive prohormone T4 into the active hormone T3 by liver- and kidney-produced 5' -deiodase can be cured by T4 alone. [pp. 162-3]

It is necessary to stress that the clinical evaluation of a patient's condition must precede interpretation of laboratory tests and not follow it....The patient's thyroid insufficiency has in each case to be treated with the most appropriate drug, to restore the patient to the euthyroid state, i.e. with the lowest possible number of symptoms. [p. 164]

Basier VW, Hertoghe J, Eeekhaut W. Thyroid insufficiency. Is Thyroxine the only valuable drug? J Nutr Envir Med 2001;11,159-166.