Pembrolizumab-Induced Thyroiditis: Comprehensive Clinical Review and Insights Into Underlying Involved Mechanisms

Abstract

Thyroid dysfunction is common in cancer patients treated with pembrolizumab. Reversible destructive thyroiditis and overt hypothyroidism are the most common clinical presentations. The mechanism of thyroid destruction appears independent of thyroid autoantibodies and may include T cell, NK cell, and/or monocyte-mediated pathways. Because the thyroid is a frequent target of anti-PD-1 therapies, patients with therapeutically refractory thyroid cancer may be ideal candidates for this treatment.

Thyroid dysfunctions secondary to cancer immunotherapy

“…To get a better understanding of the development of the thyroid dysfunction after treatment with ipilimumab [52, 55], pembrolizumab [48, 49, 51, 56] or nivolumab [57, 58], investigators measured serum levels of thyroid stimulating hormone (TSH), free thyroxine (FT 4 ), and/or triiodothyronine (T 3 ) at baseline and during the treatment, as well as thyroperoxidase and thyroglobulin antibodies [48, 49, 51]. For example, Osorio et al reported that 10 of 48 (21%) patients who were euthyroid at baseline developed hypothyroidism during pembrolizumab treatment requiring thyroid hormone replacement.…”

Thyroid disorders in programmed death 1 inhibitor‐treated patients: Is previous therapy with tyrosine kinase inhibitors a predisposing factor?

“…According to the literature, while thyrotoxicosis could be transient, all patients developing hypothyroidism should usually continue hormone replacement therapy throughout the observation period, as hypothyroidism is likely to be permanent …”

Endocrine sequelae of immune checkpoint inhibitors

“…Delivanis et al reported recovery of pembrolizumab-induced thyroiditis in 4/7 (57%) patients. 33 It is noteworthy that two cases with hyperthyroidism who required high-dose systemic corticosteroids for the management of other immunerelated toxicities did not become hypothyroid. 31 The authors assumed that immunosuppressive therapy may prevent the development of hypothyroidism in those with ICIs-related thyroiditis.…”

“…The authors noticed an increased number of circulating CD56+CD16+ NK cells and an elevated surface expression of HLA-DR in the inflammatory intermediate CD14+CD16+ monocytes and assumed that this may explain the destruction of the thyroid. 33 The onset of thyroid disease usually occurs after 2-4 cycles of therapy. Aggravation of existing autoimmunity has been reported; [33][34][35] however, whether individual genetic susceptibility plays a role has not yet been established.…”

“…33 The onset of thyroid disease usually occurs after 2-4 cycles of therapy. Aggravation of existing autoimmunity has been reported; [33][34][35] however, whether individual genetic susceptibility plays a role has not yet been established. Delivanis et al reported recovery of pembrolizumab-induced thyroiditis in 4/7 (57%) patients.…”