Vol 5 Issue 5 p.3-4 | American Thyroid Association

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CLINICAL THYROIDOLOGY FOR PATIENTS
A publication of the American Thyroid Association

Summaries for Patients from Clinical Thyroidology (February 2012)
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HYPOTHYROIDISM
Should patients with no functional thyroid gland be treated with both thyroxine (T₄) and triiodothyronine (T₃)?

ABBREVIATIONS & DEFINITIONS

Hypothyroidism: a condition where the thyroid gland is underactive and doesn’t produce enough thyroid hormone. Treatment requires taking thyroid hormone pills.

Thyroidectomy: surgery to remove the entire thyroid gland. When the entire thyroid is removed it is termed a total thyroidectomy. When less is removed, such as in removal of a lobe, it is termed a partial thyroidectomy.

Thyroid hormone therapy: patients with hypothyroidism are most often treated with Levothyroxine in order to return their thyroid hormone levels to normal. Replacement therapy means the goal is a TSH in the normal range and is the usual therapy. Suppressive therapy means that the goal is a TSH below the normal range and is used in thyroid cancer patients to prevent growth of any remaining cancer cells.

Thyroxine (T₄): the major hormone secreted by the thyroid gland. Thyroxine is broken down to produce Triiodothyronine which causes most of the effects of the thyroid hormones.

Triiodothyronine (T₃): the active thyroid hormone, usually produced from thyroxine, available in pill form as Cytomel™ or liothyronine.

BACKGROUND
Thyroxine (T₄) is the main hormone secreted by the thyroid gland. It is converted to the active hormone T₃ in other cells in the body, most commonly in the liver, kidney and in the cells where thyroid hormone works. Both T₄ and T₃ are important in maintaining normal metabolic function. In individuals with normal thyroid function, ~10-15% of the daily T₃ production comes from the thyroid gland. In patients who have no functioning thyroid (ie are hypothyroid), the absence of T₃ production by the thyroid can be overcome by maintaining higher circulating T₄ levels, resulting in normal circulating levels of T₃. This is why T₄ in the form of levothyroxine is the main treatment for hypothyroid patients. However, a longstanding question by both physicians and patients remains whether some hypothyroid patients could benefit from a mixture of T₄and T₃ rather than replacing T₄ alone. Recent studies have generally found that there is no clinical advantage in adding T₃ to the usual T₄ replacement regimen. One condition that the studies suggest may have some benefit to replacing both hormones are those who had their thyroid removed surgically (surgical hypothyroidism). The present study examines whether T₄ alone is sufficient to maintain normal levels both T₄ and T₃ in patients with surgical hypothyroidism.

THE FULL ARTICLE TITLE:
Gullo D et al. Levothyroxine monotherapy cannot guarantee euthyroidism in all athyreotic patients. PLoS One 2011:6:e22552. Epub August 1, 2011.

SUMMARY OF THE STUDY
This was a study of 1811 patients (1530 women and 281 men) who became hypothyroid following a total thyroidectomy for thyroid cancer and were receiving hormone replacement with T₄ alone. Subjects were free of thyroid cancer and had no evidence of any residual thyroid function. These patients were compared to a group of 3875 patients with normal thyroid function despite benign thyroid nodules less than 2 cm in size. Free T₄ (FT₄) and free T₃ (FT₃) levels were examined in both groups.

In these T₄-treated patients, FT₄ levels were 7.2% lower and FT3 levels 15.2% lower than in the nodule patients with normal thyroid function. Moreover, there was a wide range of variability in the T₃/T₄ ratios in T4-treated patients suggesting a wide range in peripheral T₃ levels in different individuals. In fact, more than 20% of the T₄-treated patients did not maintain FT₃ and FT₄ levels in normal range despite normal TSH levels.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
Hypothyroid patients are typically treated with T₄ alone. A number of studies have demonstrated that T₄ alone is sufficient for the majority of hypothyroid patients. The present study identifies a subgroup of hypothyroid patients, namely those whose thyroid was surgically removed who do not have normal FT₄ and FT₃ levels despite normal TSH levels on T₄ alone. What is not shown by this study is whether or not combination therapy (T₄ plus T₃) is beneficial in these patients. Further studies are needed to sort this out.

—Frank Crantz, MD