Seeking optimization of LT4 treatment in patients with differentiated thyroid cancer

Hormones (Athens). 2022 Dec;21(4):537-543. doi: 10.1007/s42000-022-00376-9. Epub 2022 Jun 2.


Levothyroxine sodium (LT4) is the mainstay treatment to replace thyroid hormonal production in thyroidectomized patients, but, depending on the aggressiveness of the cancer and on the risk of recurrence, patients with differentiated thyroid cancer may also be treated in a TSH-suppressive or semi-suppressive mode. The pathophysiological rationale for this LT4 treatment stems from the role of TSH, considered to be a growth factor for follicular cells, potentially inducing initiation or progression of follicular cell-derived thyroid cancer. Therefore, accurate tailoring of treatment, taking into account both patient characteristics (age and comorbidities) and risk of persistent/recurrent disease, is highly recommended. Furthermore, adjustments to traditional LT4 treatment should be made in thyroidectomized patients due to the lack of thyroidal contribution to whole body triiodothyronine (T3) concentration. Since LT4 exhibits a narrow therapeutic index and the side effects of over- and under-treatment could be deleterious, particularly in this category of patients, caution is required in dose individualization, in the mode of ingestion, and in potential pharmacological and other types of interference as well. Our aim was to analyze the current knowledge concerning LT4 dose requirements in patients with thyroid cancer according to different therapeutic approaches, taking into account a number of factors causing interference with LT4 efficacy. Specific mention is also made about the use of the novel LT4 formulations.

Keywords: Differentiated thyroid cancer; Dissolution; Hypothyroidism; LT4; Liquid LT4; Softgel LT4.

Publication types

  • Review

MeSH terms

  • Humans
  • Hypothyroidism* / drug therapy
  • Thyroid Neoplasms* / complications
  • Thyroid Neoplasms* / drug therapy
  • Thyrotropin
  • Thyroxine / therapeutic use
  • Triiodothyronine / therapeutic use


  • Thyrotropin
  • Thyroxine
  • Triiodothyronine

Supplementary concepts

  • Thyroid cancer, follicular