Lenvatinib-induced thyroid abnormalities in unresectable hepatocellular carcinoma

Endocr J. 2019 Sep 28;66(9):787-792. doi: 10.1507/endocrj.EJ19-0140. Epub 2019 May 30.


Lenvatinib has anti-tumor activity against advanced hepatocellular carcinoma (HCC). Hypothyroidism is also a frequent complication in patients treated with lenvatinib. However, studies on lenvatinib-induced thyroid toxicity and destructive thyroiditis are limited. Therefore, this study aimed to clarify the frequency and timing of thyroid abnormalities in lenvatinib for unresectable HCC. This retrospective study enrolled 50 patients with advanced HCC treated with lenvatinib. Patients were classified to have euthyroid, subclinical hypothyroidism, overt hypothyroidism, and thyrotoxicosis. The timing of thyroid dysfunction was assessed, and risk factors for incident hypothyroidism or thyrotoxicosis were evaluated using multivariate models. Subclinical hypothyroidism, overt hypothyroidism, and thyrotoxicosis occurred in 7 (14.0%), 26 (52.0%), and 5 (10.0%) patients, respectively. In the 33 patients with hypothyroidism, 27 (84.4%) developed the condition within 2 weeks of starting lenvatinib treatment. Of the 5 patients with thyrotoxicosis, 3 developed the condition within 8 weeks of starting lenvatinib administration. One patient developed thyrotoxicosis in only 1 week of the initiation of treatment. No correlation between the presence of antibodies and the incidence and severity of thyroid dysfunction due to the autoimmune mechanism was observed. The progression-free survival was significantly better in the hypothyroidism group. Lenvatinib treatment for unresectable HCC not only causes hypothyroidism, but also thyrotoxicosis. Moreover, these thyroid conditions develop within the early period of treatment at a higher prevalence. Patients with thyroid dysfunction had better prognosis. Based on these results, in patients administered with lenvatinib, there is need for careful assessment for the possibility of thyroid dysfunction from the onset of treatment.

Keywords: Destructive thyroiditis; Hepatocellular carcinoma; Hyperthyroidism; Hypothyroidism; Lenvatinib.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / pathology
  • Female
  • Follow-Up Studies
  • Humans
  • Hypothyroidism / chemically induced
  • Hypothyroidism / epidemiology
  • Incidence
  • Japan / epidemiology
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Phenylurea Compounds / adverse effects*
  • Quinolines / adverse effects*
  • Retrospective Studies
  • Thyroid Diseases / chemically induced*
  • Thyroid Diseases / epidemiology
  • Thyroid Function Tests
  • Thyroid Gland / drug effects*
  • Thyroid Gland / physiopathology
  • Thyroiditis / chemically induced
  • Thyroiditis / epidemiology
  • Thyrotoxicosis / chemically induced
  • Thyrotoxicosis / epidemiology


  • Phenylurea Compounds
  • Quinolines
  • lenvatinib