Hypothyroidism related to tyrosine kinase inhibitors: An emerging toxic effect of targeted therapy

Francesco Torino, Salvatore Maria Corsello, Raffaele Longo, Agnese Barnabei, Giampietro Gasparini

Research output: Contribution to journalArticle

Abstract

Despite their inherent selectivity, targeted therapies such as tyrosine kinase inhibitors (TKIs) can cause unusual adverse effects. Sunitinib and sorafenib are multitargeted TKIs that have been demonstrated to induce hypothyroidism and thyroid dysfunction. Retrospective studies indicate that sunitinib can induce hypothyroidism in 53-85% of patients, and in prospective studies this complication has been reported in 36-71% of patients. Sorafenib has been reported to be responsible for hypothyroidism in 18% of patients with metastatic renal-cell carcinoma. Furthermore, imatinib and sunitinib seem to increase the requirement of levothyroxine in hypothyroid patients. The management of thyroid dysfunction and possible related symptoms, such as fatigue, represents a challenge to oncologists. We propose a diagnostic and therapeutic algorithm for the management of TKI-related hypothyroidism. Prospective trials are needed to define the incidence of overt and subclinical hypothyroidism and thyroid dysfunction during therapy with sunitinib, sorafenib and potentially other TKIs. The safety and efficacy, and optimal dosing and timing of starting replacement therapy in patients affected by TKI-related hypothyroidism need accurate appraisal and should be evaluated prospectively in appropriately designed trials.

Original languageEnglish
Pages (from-to)219-228
Number of pages10
JournalNature Reviews Clinical Oncology
Volume6
Issue number4
DOIs
Publication statusPublished - 2009

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Poisons
Hypothyroidism
Protein-Tyrosine Kinases
Thyroid Gland
Therapeutics
Thyroxine
Renal Cell Carcinoma
Fatigue
Retrospective Studies
Prospective Studies
Safety
sunitinib
Incidence
sorafenib

ASJC Scopus subject areas

  • Oncology
  • Medicine(all)

Cite this

Hypothyroidism related to tyrosine kinase inhibitors : An emerging toxic effect of targeted therapy. / Torino, Francesco; Corsello, Salvatore Maria; Longo, Raffaele; Barnabei, Agnese; Gasparini, Giampietro.

In: Nature Reviews Clinical Oncology, Vol. 6, No. 4, 2009, p. 219-228.

Research output: Contribution to journalArticle

Torino, Francesco ; Corsello, Salvatore Maria ; Longo, Raffaele ; Barnabei, Agnese ; Gasparini, Giampietro. / Hypothyroidism related to tyrosine kinase inhibitors : An emerging toxic effect of targeted therapy. In: Nature Reviews Clinical Oncology. 2009 ; Vol. 6, No. 4. pp. 219-228.
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