Endocrine complications of immunotherapies: a review

Abstract

Use of immune checkpoint inhibitors in cancer treatment has increased vastly over the past decade, as both single and combination agent therapies. While having a positive impact on survival rates, adverse effects have been noted, with endocrine effects in around 10% of patients. Thyroid disease and hypophysitis are the most commonly encountered, with diabetes mellitus and primary adrenal insufficiency also reported, as well as more rare endocrinopathies. Patient and clinician education to raise awareness of these effects, as well as regular monitoring to enable early recognition, diagnosis and prompt treatment of the immune side effects, are key. In this review, we discuss the aetiology, presentation and management of the endocrine complications of immunotherapies that are relevant to the general physician, as well as highlighting important areas where further research is still needed.

Atezolizumab-Induced Hypothyroidism in a Patient With Pre-existing Triiodothyronine (T3) Thyrotoxicosis Due to Graves’ Disease: A Case Report and Literature Review

“…The incidence rate is approximately 5%-8%: this could be as high as 14%-20% with combination therapy. Most patients developed destructive thyroiditis with an initial thyrotoxic phase followed by hypothyroidism, while very few patients developed Graves’ disease [ 7 , 8 ]. Thyroid abnormalities typically occur within one to three months after initiation of immune checkpoint inhibitor therapy.…”

“…Thyrotoxicosis may require beta-blockers for symptoms or rarely require anti-thyroid medication. Most cases of hypothyroidism require thyroid replacement therapy [ 8 , 9 ].…”

Grand Challenge in Adrenal Endocrinology: Is the Legacy of the Past a Challenge for the Future of Precision Medicine?

“…More recently, adrenals, and in particular the hypothalamicpituitary-adrenal axis (HPA) have been identified as a likely target of immune therapies and checkpoint inhibitor therapies in patients with cancers (32). Most patients present with nonspecific symptoms, such as fatigue, which can be erroneously attributed to the malignant disease itself.…”

“…or primary adrenal insufficiency (32), which are two well-known lifethreatening conditions. Therefore, in the future, screening for adrenal or HPA activity disorders should become a routine practice for oncologists using these therapies, even in the absence of specific signs and symptoms for adrenal insufficiency.…”

The Continuum of Thyroid Disorders Related to Immune Checkpoint Inhibitors: Still Many Pending Queries

“…The advent of the last decade witnessed a turning point in cancer therapeutics, signified by the incorporation of the immune checkpoint inhibitors (ICPi) in the oncologists’ arsenal [ 1 ]. Cancer cells coopt the immune checkpoints—inhibitory immune regulators credited with an assurance of immune tolerance—to escape from immune surveillance.…”