Induction of Painless Thyroiditis in Patients Receiving Programmed Death 1 Receptor Immunotherapy for Metastatic Malignancies

Abstract

Patients receiving anti-PD-1 mAb therapy should be monitored for signs and symptoms of PTS which may require supportive treatment with beta-blockers or thyroid hormone replacement. The anti-PD-1 mAb is a novel exogenous cause of PTS and provides new insight into the possible perturbations of the immune network that may modulate the development of endogenous PTS, including cases of sporadic and postpartum thyroiditis.

Endocrine side effects of cancer immunotherapy

“…The spectrum of thyroid disturbances associated with immune checkpoint inhibitors include painless thyroiditis with transient thyrotoxicosis, transient or long-standing hypothyroidism, thyroid eye disease and occasionally severe forms of thyroid disease such as thyroid storm (Borodic et al 2011, Hamnvik et al 2011, Min et al 2011, McElnea et al 2014, Min & Hodi 2014, Carl et al 2015, Orlov et al 2015, Yu et al 2015, Joshi et al 2016. Rare cases of Graves' ophtalmopathy have been reported with elevation of TSH-receptor antibodies but normal thyroid function (Borodic et al 2011, Min et al 2011.…”

“…Orlov and coworkers reported 10 cases of painless thyroiditis syndrome following anti-PD1 therapy (Orlov et al 2015). Six patients presented with an initial thyrotoxic phase from which 4 (67%) were positive for anti-thyroid peroxidase (anti-TPO) and positive for antithyroglobulin (anti-Tg), whereas all were negative for thyrotropin binding inhibitory immunoglobulins (TBII).…”

“…Thyrotoxicosis resolved spontaneously in all patients and was followed by hypothyroidism. There were 4 patients who presented with hypothyroidism without previously detected thyrotoxic phase and had serological evidence of positive anti-Tg and anti-TPO antibodies (Orlov et al 2015).…”

Nivolumab causing painless thyroiditis in a patient with adenocarcinoma of the lung

“…Management of the thyrotoxic phase includes achieving a temporary β-blockade 6. This provides relief from the adrenergic symptoms.…”

Thyroid-Induced Toxicity of Check-Point Inhibitors Immunotherapy in the Treatment of Advanced Non-Small Cell Lung Cancer

“…Four patients presented with hypothyroidism, without a previously documented thyrotoxic phase, occurring 6-8 weeks after initial drug exposure. All of these patients had positive antithyroid antibodies and required thyroid hormone replacement therapy for a minimum of 6 months [42]. It has been hypothesized that, as thyroid autoimmunity stimulated during treatment with anti-CTLA-4 antibodies could be linked to polymorphic variations of the CTLA-4 receptor gene [18], so a similar condition of polymorphic variants of the PD-1 receptor gene, may account for the occurrence of thyroiditis in a subgroup of patients treated with anti-PD-1 antibodies [42].…”