Diagnosis and management of immune checkpoint inhibitor-associated adrenal insufficiency: A single-institution experience

Abstract

Background

Immune checkpoint inhibitor (ICI) therapy has revolutionized the treatment of various malignancies. Unfortunately, ICI therapy has been associated with multiple immune related adverse events (irAEs) resulting in organ damage. One rare, but potentially devastating side effect, is adrenal insufficiency.

Methods

A retrospective analysis of all patients receiving anti-PD-1/PD-L1 or anti-CTLA-4 therapy at Gundersen Health System from 2011 to 2023 was conducted.

Results

Patients (n = 684) receiving anti-PD-1/anti-PD-L1/anti-CTLA-4 therapy at Gundersen Health System were included in our retrospective analysis. There were eleven (1.6%) patients that were diagnosed with an adrenal irAE after beginning immunotherapy. The median days from first treatment to diagnosis of irAE was 304 days. Most common symptoms at the time of onset included fatigue (82%) and syncope (36%). Five patients (45%) required treatment delay or cessation and eight (73%) patients were referred to endocrinology after original diagnosis.

Discussion

Detection of adrenal insufficiency secondary to immunotherapy requires a degree of high suspicion. Given the potential significant morbidity and mortality associated with adrenalitis/adrenal insufficiency, prompt diagnosis is of the utmost importance. Liberal use of early morning/8 am cortisol screening should be implemented as a standard part of clinical work up in acute onset of fatigue, hypotension, fever, weakness, weight loss, dehydration, oral intolerance, gastrointestinal upset, hyponatremia, and hyperkalemia. Immunotherapy related adrenal insufficiency is a rare complication, with most cases being secondary adrenal insufficiency. Multidisciplinary care with oncology and endocrinology is an important aspect of comprehensive management.