Abstract
Background: Immune therapy using monoclonal antibodies against cytotoxic T-lymphocyte-associated
antigen 4 (CTLA-4) and programmed cell death 1 receptor (PD-1) for various cancers
have been reported to cause thyroid dysfunction. Little is known, however, about the
underlying pathogenic mechanisms and the course of hypothyroidism that subsequently
develops. In this report, we use the change in thyroglobulin and thyroid antibody
levels in patients on immune therapy who develop hypothyroidism to better understand
its pathogenesis as well as examine the status of hypothyroidism in the long term.
Methods: We report a case series of 10 patients who developed hypothyroidism after initiation
of immune therapy (either anti-PD-1 alone or in combination with anti-CTLA-4). Available
thyroid antibodies including anti-thyroglobulin (anti-Tg), anti-thyroid peroxidase
(anti-TPO), and thyroid stimulating immunoglobulin (TSI) were noted during the initial
thyroiditis phase as well as the hypothyroid phase. Persistence or remission of hypothyroidism
was noted at 6 months.
Summary: During the thyroiditis phase, 50% of the patients had elevated Tg titers, 40% had
elevated anti-Tg, and 40% had elevated TSI. All of these titers decreased during the
hypothyroid phase. Permanent hypothyroidism was noted in 80% of the cases.
Conclusion: Hypothyroidism following initiation of immune therapy has immunologic and non-immunologic
mediated mechanisms and is likely to be persistent.
Key words
hypothyroidism - immunotherapy - oncology - thyroiditis - immune phenomena
