Association of antithyroglobulin antibodies with the development of thyroid dysfunction induced by nivolumab

Cancer Sci. 2018 Nov;109(11):3583-3590. doi: 10.1111/cas.13800. Epub 2018 Oct 13.


Thyroid dysfunction (TD) induced by immune checkpoint inhibitors is not sufficiently understood. The purpose of this retrospective observational study was to identify risk factors and the clinical course of TD induced by nivolumab. Patients with advanced solid tumors who were treated with nivolumab from March 2009 through to March 2016 at the National Cancer Center Hospital (Tokyo, Japan) were included. Thyroid function and antithyroid Abs from serum samples among all patients were evaluated at baseline and during nivolumab treatment. Overt hypothyroidism was defined as low serum-free T4 together with elevated thyroid-stimulating hormone (TSH) >10 μIU/mL. Thyrotoxicosis was defined as low TSH with elevated free T4 and/or free T3. We defined thyroid autoimmunity as the presence of antithyroid Abs at baseline, including antithyroid peroxidase Abs and antithyroglobulin Abs (TgAb). Twenty-three (14%) of a total of 168 patients developed TD, including 17 cases of hypothyroidism and 20 of thyrotoxicosis. Thyrotoxicosis followed by hypothyroidism occurred in 14 cases. Fourteen of 35 patients (40%) with thyroid autoimmunity developed TD vs 9 of 133 (7%) without (odds ratio 9.19; 95% confidence interval [CI], 3.53-23.9). In multivariate analysis, elevated TSH and TgAb at baseline were significantly associated with the development of TD, with odds ratio of 7.36 (95% CI, 1.66-32.7) and 26.5 (95% CI, 8.18-85.8), respectively. Association between TD and elevated antithyroid peroxidase Abs at baseline was not significant. These results suggest that patients with pre-existing TgAb and elevated TSH at baseline are at high risk of TD.

Keywords: antithyroglobulin antibody; antithyroid peroxidase antibody; immune-related adverse event; nivolumab; thyroid dysfunction.

Publication types

  • Observational Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / adverse effects*
  • Autoantibodies / metabolism*
  • Female
  • Humans
  • Hypothyroidism / chemically induced
  • Hypothyroidism / epidemiology
  • Hypothyroidism / immunology
  • Japan / epidemiology
  • Male
  • Middle Aged
  • Nivolumab
  • Odds Ratio
  • Retrospective Studies
  • Thyroid Diseases / chemically induced
  • Thyroid Diseases / epidemiology*
  • Thyroid Diseases / immunology
  • Thyroid Gland / immunology*
  • Thyroid Gland / metabolism
  • Thyrotoxicosis / chemically induced
  • Thyrotoxicosis / epidemiology
  • Thyrotoxicosis / immunology
  • Thyrotropin / metabolism
  • Young Adult


  • Antibodies, Monoclonal
  • Autoantibodies
  • anti-thyroglobulin
  • Nivolumab
  • Thyrotropin