The Current Understanding of the Endocrine Effects From Immune Checkpoint Inhibitors and Recommendations for Management

Abstract

Clinical trials in the past decade have established the antitumor effects of immune checkpoint inhibition as a revolutionary treatment for cancer. Namely, blocking antibodies to cytotoxic T-lymphocyte antigen 4 and programmed death 1 or its ligand have reached routine clinical use. Manipulation of the immune system is not without side effects, and autoimmune toxicities often known as immune-related adverse events (IRAEs) are observed. Endocrine IRAEs, such as hypophysitis, thyroid dysfunction, and insulin-dependent diabetes mellitus, can present with unique profiles that are not seen with the use of traditional chemotherapeutics. In this Review, we discuss the current hypotheses regarding the mechanism of these endocrinopathies and their clinical presentations. Further, we suggest guidelines and algorithms for patient management and future clinical trials to optimize the detection and treatment of immune checkpoint–related endocrinopathies.

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, 22 all patients developing hypothyroidism should usually continue hormone replacement therapy throughout the observation period, as hypothyroidism is likely to be permanent. 27 Given the relatively short time to onset of thyroid disorders after the initiation of anti-PD-1 treatment and the paucity of symptoms at diagnosis, we recommend TSH and FT4 testing before starting anti-PD-1 drugs and prior to each administration for the first 3 months of therapy. Subsequently, TSH measurement could be done less frequently, guided by clinical assessment and a careful evaluation of signs and/or symptoms of thyroid disorders.…”

Development of a Functional Assessment of Chronic Illness Therapy item library and primary symptom list for the assessment of patient-reported adverse events associated with immune checkpoint modulators

“…Our literature review yielded 25 articles documenting irAE incidence, management guidelines, toxicity profiles, and associated symptomatology [4,9,[11][12][13][14][15][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57] . From these, we identified 75 possible inflammatory reactions/immune conditions across 11 organ systems, ranging from very common to rare.…”

Papillary Thyroid Carcinoma Intertwined with Hashimoto’s Thyroiditis: An Intriguing Correlation

“…With the advent of the era of cancer immunotherapy, new light on the coexistence of HT with PTC is shed by the increasingly reported development of HT as an adverse event of the monoclonal antibodies blocking programmed cell death (PD) protein 1 (PD-1) and PD ligand 1 (PD-L1). This revolutionary anticancer treatment unleashes the antitumor immunity at the expense of abrogating the self-tolerance, exemplifying the "tumor defense-induced" immunity [94]. For instance, a loss of circulatory PD1+ CD4+ and CD8+ T cells, an increase in peripheral CD56+CD16+ NK cells and an increase in activated monocytes have been implicated in pembrolizumab (anti-PD1 monoclonal antibody)-induced thyroiditis [94].…”

“…This revolutionary anticancer treatment unleashes the antitumor immunity at the expense of abrogating the self-tolerance, exemplifying the "tumor defense-induced" immunity [94]. For instance, a loss of circulatory PD1+ CD4+ and CD8+ T cells, an increase in peripheral CD56+CD16+ NK cells and an increase in activated monocytes have been implicated in pembrolizumab (anti-PD1 monoclonal antibody)-induced thyroiditis [94].…”