Thyroid-related adverse events induced by immune checkpoint inhibitors

Abstract

Immune checkpoint inhibitors, namely anti-CTLA-4, anti-PD-1 and anti-PD-L1 monoclonal antibodies, have emerged in the last decade as a novel form of cancer treatment, promoting increased survival in patients. As they tamper with the immune response in order to destroy malignant cells, a new type of adverse reactions has emerged, known as immune-related adverse events (irAEs), which frequently target the endocrine system, especially the thyroid and hypophysis. Thyroid irAEs include hyperthyroidism, thyrotoxicosis, hypothyroidism and a possibly life-threatening condition known as the “thyroid storm”. Early prediction of occurrence and detection of the thyroid irAEs should be a priority for the clinician, in order to avoid critical situations. Moreover, they are recently considered both a prognostic marker and a means of overseeing treatment response, since they indicate an efficient activation of the immune system. Therefore, a multidisciplinary approach including both oncologists and endocrinologists is recommended when immune checkpoint inhibitors are used in the clinic.

Research hot spots and trends in endocrine-related adverse events caused by immune checkpoint inhibitors: a bibliometric analysis and visualization research

“…Comprehensive studies of adverse effects at different endocrine sites have started to appear and have reached their current degree of maturity as a result of the continual development of safety studies. According to reports, thyroid and pituitary toxicity are the most common endocrine toxicities of this class of drugs ( 20 ) and are also the most studied by researchers. Diabetes and adrenocortical insufficiency are uncommon endocrine toxicities associated with ICI treatment ( 21 ), but diabetic ketoacidosis (DKA) and adrenal crisis are frequently life-threatening.…”

Combined diabetic ketoacidosis and hyperosmolar hyperglycemic state in type 1 diabetes mellitus induced by immune checkpoint inhibitors: Underrecognized and underreported emergency in ICIs-DM

“…Apart from blood glucose, acute kidney, and previous exposure to chemotherapy, none of the biochemical parameters and clinical characteristics at presentation was significantly different between the DKA and combined DKA-HHS groups. It is worth noting that the majority of these patients had primary thyroid dysfunction (hypothyroidism or thyroiditis) in the DKA group, which is the most common cooccurrence with type 1 diabetes related to ICIs ( 21 , 22 ). We recommend that blood glucose be frequently monitored for this population in that thyroid dysfunction is associated with T1DM and T2DM ( 23 – 25 ).…”

Immune-related adverse events of immune checkpoint inhibitors: a review

“…Symptoms associated with hypophysitis include fatigue, muscle weakness, headache, anorexia, nausea, weight loss, vision changes, temperature intolerance, arthralgia, and altered mental status. Hyponatremia, low adrenocorticotropic hormone (ACTH), or low thyroid stimulating hormone (TSH) may be present ( 92 ).…”