Clinical Characteristics, Management, and Potential Biomarkers of Endocrine Dysfunction Induced by Immune Checkpoint Inhibitors

Abstract

Immune-related adverse events (irAEs) affecting the endocrine glands are among the most frequent irAEs induced by immune checkpoint inhibitors (ICIs) and include hypopituitarism, primary adrenal insufficiency, thyrotoxicosis, hypothyroidism, hypoparathyroidism, and type 1 diabetes mellitus. Since the incidence and clinical features of endocrine irAEs vary according to the ICI used, it is important to understand the characteristics of these irAEs and to manage each one appropriately. Since some endocrine irAEs, including adrenal crisis and diabetic ketoacidosis, are potentially life-threatening, predicting the risk of endocrine irAEs before their onset is critical. Several autoantibodies have been detected in patients who develop endocrine irAEs, among which anti-thyroid antibodies may be predictive biomarkers of thyroid dysfunction. In this review, we describe the clinical features of each endocrine irAE induced by ICIs and discuss their potential biomarkers, including autoantibodies.

Preconditioning of the immune system modulates the response of papillary thyroid cancer to immune checkpoint inhibitors

“…Our study was not sufficiently powered to account for a more detailed classification of tumor burden or aggressiveness. However, the analysis of PTC focality reported in table 1 corroborates the findings from the analysis of PTC presence, and our findings are in line with clinical observations showing that the effect of ICIs on PTC [17][18][19][20][21][22][23] and other forms of cancer 8-10 24 is stronger in patients Open access with thyroiditis. In this respect, it should be noted that, as reported in our prior study with the NOD.H2 h4 TPO-CRE-ER BRAF v600E model, 11 animals with pre-existing IET developed PTC with lower frequency than animals without IET or with concomitant IET (figure 2) and they developed mostly unifocal PTC (table 1).…”

Immune Checkpoint Inhibitors as a Threat to the Hypothalamus–Pituitary Axis: A Completed Puzzle

“…Finally, it has been suggested that the development of the pituitary [ 82 , 83 ] or thyroid [ 84 , 85 ] dysfunction is associated with better outcomes after ICI treatment [ 86 , 87 ]. However, the paucity of cases and the absence of data regarding their follow-up preclude any prognostic correlation in patients who are diagnosed with ICI-induced posterior pituitary or hypothalamic dysfunction.…”

Recovery from insulin dependence in immune checkpoint inhibitor‐associated diabetes mellitus: A case report

“…Patients with ICI‐DM generally require lifelong insulin therapy, which adversely affects their quality of life. However, patients with endocrine irAEs have been reported to have a favorable prognosis 7 . The present patient's primary and metastatic cancer lesions were reduced using ICI and they did not progress further.…”

“…Predictors and markers of ICI‐DM are important for an early diagnosis. Some relevant predictors include the presence of baseline levels of diabetes‐related autoantibodies 7 , human leukocyte antigen susceptibility alleles 9 and complications of multiple irAEs 9 . Diagnostic markers include the presence of specific autoantibodies 7 , and elevation of serum amylase and lipase levels 8 , in addition to symptoms and quantitative estimations of blood glucose and ketone bodies.…”