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Thyroid-hormone therapy and thyroid cancer: a reassessment

Abstract

Experimental studies and clinical data have demonstrated that thyroid-cell proliferation is dependent on thyroid-stimulating hormone (TSH), thereby providing the rationale for TSH suppression as a treatment for differentiated thyroid cancer. Several reports have shown that hormone-suppressive treatment with the L-enantiomer of tetraiodothyronine (L-T4) benefits high-risk thyroid cancer patients by decreasing progression and recurrence rates, and cancer-related mortality. Evidence suggests, however, that complex regulatory mechanisms (including both TSH-dependent and TSH-independent pathways) are involved in thyroid-cell regulation. Indeed, no significant improvement has been obtained by suppressing TSH in patients with low-risk thyroid cancer. Moreover, TSH suppression implies a state of subclinical thyrotoxicosis. In low-risk patients, the goal of L-T4 treatment is therefore to obtain a TSH level in the normal range (0.5–2.5 mU/l). Only selected patients with high-risk papillary and follicular thyroid cancer require long-term TSH-suppressive doses of L-T4. In these patients, careful monitoring is necessary to avoid undesirable effects on bone and heart.

Key Points

  • Thyroid-cell proliferation is thyroid-stimulating hormone (TSH)-dependent, hence L-tetraiodothyronine (L-T4)-induced TSH suppression should be included in the treatment strategies for differentiated thyroid carcinomas

  • TSH suppression implies a state of subclinical thyrotoxicosis and becomes necessary only when there is evidence of persistent or recurrent disease; in low-risk patients, L-T4 treatment serves to return TSH level to within the normal range

  • To ensure optimal dosing, each patient must always receive the same preparation and the daily L-T4 dose should be carefully tailored

  • Adjustments of L-T4 dosage will be required under particular circumstances, for example in pregnant women, patients with significant weight gain or weight loss, those with known heart disease and older patients

  • If long-term TSH suppression is necessary because of a high-risk cancer, a cardioselective β-blocking drug can be added to reduce cardiovascular risk and to improve quality of life

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Figure 1: Regulation of the pituitary–thyroid axis: the role of tri-iodothyronine and tetraiodothyronine in the feedback regulation of thyroid-stimulating hormone secretion
Figure 2: Thyroid-stimulating hormone target level during treatment with L-tetraiodothyronine in high-risk and low-risk thyroid cancer patients

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Correspondence to Bernadette Biondi.

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Biondi, B., Filetti, S. & Schlumberger, M. Thyroid-hormone therapy and thyroid cancer: a reassessment. Nat Rev Endocrinol 1, 32–40 (2005). https://doi.org/10.1038/ncpendmet0020

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