84th Annual Meeting of the American Thyroid Association:
Painless Thyroiditis May Occur in Patients Receiving PD-1 for Metastatic Cancer
Paul G. Walfish, CM, O. Ont, MD, FRPC from the Joseph and Mildred Sonshine Family Centre for Head and Neck Diseases at Mount Sinai Hospital in Toronto presented, Induction of Painless Thyroiditis in Patients Receiving Programmed Death 1 Receptor Immunotherapy for Metastatic Malignancies during the American Thyroid Association’s annual meeting. During his presentation, Dr. Walfish reviewed the mechanisms of human regulation by programmed death-1(PD-1 receptor) compared to the cytotoxic T-lymphocyte antigen 4 receptor. Dr. Walfish characterized 10 cases of metastatic malignancy treated with anti-PD-1 monoclonal antibody from which the patients developed a painless thyroiditis syndrome with transient thyrotoxicosis and hypothyroidism.
Dr. Walfish stated, “Painless thyroiditis may occur endogenously through a sporadic idiopathic cause, or more commonly postpartum and occasionally in patients who previously had Graves' disease but can have an attack of painless thyroiditis. And we've seen it in Addison's disease before treatment, and sometimes treatment ameliorates it. And in Cushing's disease, after remission, sometimes brings up an episode of painless thyroiditis.”
The list of exogenous causes of painless thyroiditis is growing and includes interferons, kinase inhibitors, interleukin-2, lithium, and iodine. Dr. Walfish indicated painless thyroiditis can occur after radiation or parathryoidectomy if the thyroid is palpated too much.
The study participants were 10 patients with metastatic malignancies (melanoma=7, non-small cell lung cancer=3) who received immunotherapy PD-1 receptor antibodies as part of a clinical trial.
- Mean age = 55
- Gender: 60% female
- Antithyroglobulin antibodies and TSH receptor immunoglobulins were measured.
- Transient thyrotoxicosis was first were observed in 60% of the patients (n=6), and all required temporary beta blocker therapy until the hypothyroid phase resolved (4 to 6 weeks).
- Thyrotropin binding inhibiting immunoglobulins was negative in all the patients.
- Antithyroglobulin and antithyroid peroxidase were noted in 67% of the patients (n=4).
- All patients required thyroid hormone replacement therapy for a minimum of 6 months; longer for some patients if a good response was realized through monoclonal antibody therapy.
The incidence of painless thyroiditis “had no consistent relationship to whether the oncological response to the immunotherapy caused a regression of metastases," stated Dr. Walfish. He explained that some immunotherapies applied to malignancies have a selective immunotoxic effect on the thyroid gland. Furthermore, this effect does not occur in all patients, and those affected may have an immunogenetic susceptibility to an adverse complication.
Dr. Walfish's conclusions included:
- “Immunotherapy with PD-1 receptor antibodies for metastatic malignancies can induce painless thyroiditis syndrome in a subset of susceptible patients.”
- “Given the increasing application of immunotherapy for the treatment of a variety of malignancies, clinicians should monitor such patients where clinical and biochemical signs of thyroid dysfunction and potential adverse consequences appropriately treated in the hyperthyroid phase, usually with beta blockers, and the hypothyroid phase with thyroid hormone replacement.”
January 27, 2015