CLINICAL THYROIDOLOGY FOR PATIENTS
A publication of the American Thyroid Association

Summaries for Patients from Clinical Thyroidology by Ernest Mazzaferri, MD MACP
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HYPOTHYROIDISM

Abbreviations & Definitions

TSH is thyroid stimulating hormone (thyrotropin)

T4 is levothyroxine, a molecule that contains 4 iodine atoms. This is the main hormone secreted by the thyroid gland and the main hormone used for replacement therapy in patients with hypothyroidism.

T3 is triiodothyronine, a molecule that contains 3 iodine atoms and is the most potent form of thyroid hormone. Liothyronine (Cytomel) is a potent short acting form of T3 that is not ordinarily used for replacement therapy.

This is the most potent form of thyroid hormone that is mainly derived from enzymes that remove one iodine atom from T4

Conversion of T4 to T3 The thyroid gland secretes considerably more T4 than T3 which is biologically much more potent than T4. Deiodinases The conversion of T4 to T3 is made by several enzymes (deiodinases) expressed in the liver, kidney, thyroid gland and other tissues which provide 80% of circulating serum T3 levels.

What is the study about? Does levothyroxine (L-T4) therapy restore serum T3 levels in patients
with hypothyroidism?

The full article title: “Triiodothyronine levels in athyreotic individuals during levothyroxine therapy.” It is in the February 2008 Issue of the Journal of the American Medical Association (Volume 299, Issue 7, pages 769-777). The authors are J Jonklaas, B Davidson, S Bhagat, and SJ Soldin, The abstract can be obtained from: http://www.ncbi.nlm.nih.gov/pubmed/
18285588?dopt=Citation

What is known about the problem being studied? Clinical trials have demonstrated that adding liothyronine (T3) to levothyroxine (L-T4) confers no consistent benefit to patients being treated for hypothyroidism. However, there is no direct evidence that T3 deficiency is avoided by using L-T4 alone. As 80% of circulating serum T3 is derived from the peripheral conversion of L-T4 to T3, thyroidectomy theoretically deprives the individual of the 20% contribution of direct T3 secretion from the thyroid.

What was the aim of the study? The study is designed to compare preoperative serum T3 levels in patients with normally functioning thyroid glands with the T3 levels in the same patients after their thyroid was surgically removed and were being treated with L-T4 alone.

Who was studied? The study subjects were 50 patients with normal thyroid function (euthyroid) aged 18 to 65 years who were scheduled for total thyroidectomy for suspected or known thyroid cancer, goiter, or benign nodular thyroid disease.

How was the study done? Thyroid hormone levels were measured before thyroidectomy in individuals not receiving thyroid hormone therapy, and again after surgery when they were being treated with L-T4 alone. Postoperatively, patients with benign thyroid disease were given L-T4 (1.7 μg/kg daily) replacement therapy aimed at keeping the serum TSH levels in the normal range, and others were given L-T4 (2.2 μg/kg daily) to maintain the serum TSH level below normal for the treatment of thyroid cancer. The L-T4 doses were adjusted during the two postoperative (third and fourth) thyroid profiles to achieve the treatment goals. Patients underwent a complete history and physical examination and had two separate thyroid profiles before and two after thyroidectomy when they were taking L-T4 and had achieved stable serum thyrotropin (TSH) levels. At the end of the study, the medication history and physical examination were repeated.

What were the results of the study? By the end of the study, there were no significant decreases in serum T3 levels in patients receiving L-T4 therapy as compared with their prethyroidectomy T3 levels.

How does this compare with other studies? This is the first study to assess serum T3 levels in patients taking L-T4. Other studies published to date compare patients with hypothyroidism already taking L-T4 who were either continued on L-T4 therapy or switched to T4/T3 combination therapy.

What are the Limitations of this study? One potential limitation is that the patients with benign thyroid disease had varying amounts of remnant thyroid tissue. It is unlikely that this accounted for the results.

What are the implications of this study? This unique study provides clear evidence that adding liothyronine (T3) to levothyroxine replacement therapy is not necessary to achieve normal serum T3 levels and euthyroidism..

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