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Serum free triiodothyronine (T3) to free thyroxine (T4) ratio in treated central hypothyroidism compared with primary hypothyroidism and euthyroidism

Sesmilo, Gemma; Simó, Olga; Choque, Lucía; Casamitjana, Roser; Puig-Domingo, Manel; Halperin, Irene

Published in Endocrinol Nutr. 2011;58:9-15. - vol.58 núm 01

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Abstract

The standard treatment of hypothyroidism (central and primary) consists of thyroxine (T4) administration alone. However, the normal thyroid gland produces a small proportion of triiodothyronine (T3) directly into the circulation.

Aim

We aimed to study the free T3 to free T4 ratio in treated central hypothyroidism compared with euthyroidism and treated primary hypothyroidism.

Methods

Eighty-three subjects were included in this cross-sectional study: 36 with central hypothyroidism, 20 with primary hypothyroidism and 27 healthy controls. A clinical history and a physical examination, including height and weight measurement, were performed and body mass index (BMI) was calculated. Fasting blood was drawn to measure T3, T4, free T3, free T4 and TSH.

Results

The free T3 to free T4 ratio was lower in treated central hypothyroidism than in euthyroidism but was similar to treated primary hypothyroidism. Free T4 was higher in treated central and primary hypothyroidism than in euthyroidism. Age, sex and BMI did not affect the free T3 to free T4 ratio.

Conclusions

Treated patients with central hypothyroidism had a lower free T3 to free T4 ratio, similar free T3 levels and higher free T4 concentrations than euthyroid controls, whereas all these parameters were similar in central and primary hypothyroid patients treated with T4. The question of whether these findings translate into adequate tissue concentrations of free thyroid hormones in all tissues remains to be answered. Further studies should aim to determine whether clinical outcomes could be improved by a treatment achieving more physiological plasma concentrations.

Key words: Central hypothyroidism. Triiodothyronine to thyroxine ratio. T3. T4.

Introduction

Introduction Triiodothyronine (T3) is the active thyroid hormone. Plasma T3 is generated by direct thyroid production (about 20%) and from peripheral conversion of thyroxine (T4) to T3, mainly in liver and kidneys (80%).¹^,²^,³^,⁴ The T3 found in the cell nucleus in distinct tissues is derived in a different proportion either from the plasma pool or from local T4 deiodination within the tissue.⁴ Patients with primary hypothyroidism correctly treated with levothyroxine (LT4) [based on normal thyroid-stimulating hormone (TSH) levels] are known to have a lower plasma T3 to T4 ratio than euthyroid individuals.⁵^,⁶ Central hypothyroidism is usually part of a complex hormonal dysfunction. This disorder is rarely found as an isolated deficiency and is frequently combined with other pituitary deficiencies. Therefore, in addition to the clinical consequences of thyroid hormone deficiency and replacement, other hormone deficiencies and their treatments come into play. Cortisol and growth hormone (GH) play a role in T4 to T3 conversion;⁷^,⁸^,⁹ non-replacement or suboptimal replacement of these hormones affect T4 deiodination¹⁰ and may alter the plasma free T3 to free T4 ratio. In addition, TSH levels are not useful to adjust the LT4 dose in central hypothyroidism and consequently a potential T3 deficiency will be more difficult to detect.¹¹ Whether the free T3 to free T4 ratio in patients with stable treated central hypothyroidism is similar to that of euthyroid individuals and to that of primary hypothyroid patients treated with T4 is unknown. Determining this issue would be the first step to evaluate the adequacy of LT4 alone in the treatment...

Sesmilo, Gemma^a; Simó, Olga^b; Choque, Lucía^c; Casamitjana, Roser^d; Puig-Domingo, Manel^c; Halperin, Irene^c