Immune checkpoint inhibitor (ICI) therapy is an efficacious cancer treatment, often resulting in autoimmune off-target effects. Magnetic resonance imaging (MRI) has been a recommended investigation for ICI-related hypophysitis. We sought to identify the frequency of identifiable MRI changes.

A retrospective case-control audit was performed of individuals who received one or more ICI between January 2018 and December 2023 at a single tertiary referral centre in Melbourne, Australia.

Individuals requiring hormone supplementation were screened for hypophysitis. A randomly selected control group receiving ICI demonstrated normal pituitary function at the time of MRI.

Fifty-four (6.9%) of 778 individuals who received ICI therapy were diagnosed with ICI-related hypophysitis. 43 had an MRI examining the pituitary gland within 2 months. Four (9.3%) had initial reporting consistent with hypophysitis. Upon re-examination by an MRI-Fellowship trained radiologist, a further 6 (total 10, 23%) had acute hypophysitis changes. Among the control group, 45 of 46 individuals had an MRI within 2 months of normal pituitary biochemistry. All initial MRI reports were normal, but upon review 1 (2.2%) had acute hypophysitis abnormalities, with a significant difference between groups (10/43 vs 1/45, p = 0.003). Within the control group, a further 10 (22%) individuals had an atrophic pituitary and/or empty sella. No other significant pituitary pathology, including pituitary metastasis, was identified.

Although changes were observed in a minority of patients with hypophysitis, MRI provides minimal additional clinically meaningful information, so it could be reserved for atypical cases or those with persisting symptoms despite adequate supplementation.

This case report presents a 57-year-old male with hepatocellular carcinoma who developed Type 1 Diabetes Mellitus (T1DM) and diabetic ketoacidosis (DKA) following treatment with Envafolimab, a PD-L1 immune checkpoint inhibitor. The patient experienced a rapid onset of hyperglycemia and DKA after several cycles of Envafolimab, consistent with the pattern of diabetes induced by immune checkpoint inhibitors (ICIs). Notably, the absence of diabetes-related autoantibodies suggests that the diabetes was induced by the immune-modulating effects of Envafolimab rather than a pre-existing autoimmune condition. Management required intensive insulin therapy and a multidisciplinary approach to stabilize the patient's health. This case underscores the critical need for heightened clinical awareness and early intervention in managing severe immune-related adverse events (irAEs) associated with novel ICIs like Envafolimab. The complexity of autoimmune-related adverse events, such as the negative autoimmune profiles observed in our patient, emphasizes the importance of multidisciplinary collaboration to optimize patient outcomes. We advocate for the establishment of long-term follow-up plans, including regular monitoring for potential irAEs and endocrine function assessments, to address the chronicity of conditions post-ICI treatment. Recognizing the limitations of current understanding, there is a clear call for further research, particularly on identifying biomarkers that may predict adverse reactions to immunotherapy, to guide precision medicine and improve patient safety.

Recent genome-wide association studies of European populations have identified rs16906115, a single-nucleotide polymorphism in the interleukin-7 gene, as a predictor of immune-related adverse events (irAEs) and the therapeutic efficacy of immune checkpoint inhibitors. We evaluated this single-nucleotide polymorphism in a Japanese population.

From January 2021, we stored host DNA from individuals who received various types of immune checkpoint inhibitors. From this population, we categorized 510 participants into cases (grade ≥2 irAEs) and controls (received ≥3 immune checkpoint inhibitor doses, follow-up ≥12 weeks, no irAEs), and divided 339 hepatocellular carcinoma patients treated with atezolizumab/bevacizumab into responders and non-responders, evaluated using the modified response evaluation criteria in solid tumors. We compared the minor allele frequencies of rs16906115 between cases and controls, and responders and non-responders.

In the irAE prediction analysis of 234 cases and 276 controls, the minor allele frequency was 0.244 in the case group and 0.265 in the control group. This difference is not significant. In the analysis predicting the therapeutic efficacy for hepatocellular carcinoma patients, the responders had a significantly lower minor allele frequency of 0.220, compared with 0.300 for the non-responders (p = 0.022). Univariate and multivariate analyses identified the minor allele homozygosity as a significant predictor of treatment response, with odds ratios of 0.292 (p = 0.015) in the univariate analysis and 0.315 (p = 0.023) in the multivariate analysis.

In our Japanese cohort, no association was found between the rs16906115 minor allele and irAEs or treatment efficacy. The minor allele homozygosity may be associated with a negative therapeutic outcome.

UMIN Clinical Trials Registry with the number UMIN000043798.

With the increasing application of immune checkpoint inhibitors (ICI) in cancer therapy, the occurrence of isolated adrenocorticotropic hormone deficiency (IAD), as an adverse effect, is also on the rise. Nevertheless, there are only a few studies regarding IAD induced by ICI. This study aimed at investigating the characteristics of IAD induced by ICI and its relationship with other endocrine adverse events.

A retrospective study was conducted in the Endocrinology Department from January 2019 to August 2022 to investigate characteristics of patients with IAD. Clinical features, laboratory findings and treatment information were collected. All patients underwent a follow-up of 3-6-month.

28 patients with IAD were enrolled. All patients received treatment with anti-PD-1/ PD-L1. The median occurrence time of IAD was 24 (18-39) weeks after initiation of ICI treatment. Over half of the patients (53.5%) had an additional endocrinopathy, including primary hypothyroidism and fulminant type 1 diabetes mellitus (FT1DM), while other types of endocrinopathies were not identified. The interval between the occurrences of two gland damages was between 4 and 21 weeks or simultaneous. Primary hypothyroidism (46.4%) was more prevalent than FT1DM (7.1%). Fatigue and nausea were common symptoms, with a frequent occurrence of hyponatremia. All patients continued on oral glucocorticoids during follow-up.

IAD induced by ICI could manifest independently, or more frequently in combination with hypothyroidism or FT1DM. This damage could happen at any point of ICI treatment. Given that IAD can be life-threatening, it is critical to evaluate pituitary function dynamically in patients undergoing immunotherapy.

Immune checkpoint inhibitors (ICIs) have increasingly been the mainstay of treatment for numerous malignancies. However, due to their association with autoimmunity, ICIs have resulted in a variety of side effects that involve multiple organs including the endocrine system. In this review article, we describe our current understanding of the autoimmune endocrinopathies as a result of the use of ICIs. We will review the epidemiology, pathophysiology, clinical presentation, diagnosis, and management of the most commonly encountered endocrinopathies, including thyroiditis, hypophysitis, Type 1 diabetes, adrenalitis, and central diabetes insipidus.

Immune-checkpoint inhibitors (ICIs) are antagonists of inhibitory receptors in the immune system, such as the cytotoxic T-lymphocyte-associated antigen-4, the programmed cell death protein-1 and its ligand PD-L1, and they are increasingly used in cancer treatment. By blocking certain suppressive pathways, ICIs promote T-cell activation and antitumor activity but may induce so-called immune-related adverse events (irAEs), which mimic traditional autoimmune disorders. With the approval of more ICIs, irAE prediction has become a key factor in improving patient survival and quality of life. Several biomarkers have been described as potential irAE predictors, some of them are already available for clinical use and others are under development; examples include circulating blood cell counts and ratios, T-cell expansion and diversification, cytokines, autoantibodies and autoantigens, serum and other biological fluid proteins, human leucocyte antigen genotypes, genetic variations and gene profiles, microRNAs, and the gastrointestinal microbiome. Nevertheless, it is difficult to generalize the application of irAE biomarkers based on the current evidence because most studies have been retrospective, time-limited and restricted to a specific type of cancer, irAE or ICI. Long-term prospective cohorts and real-life studies are needed to assess the predictive capacity of different potential irAE biomarkers, regardless of the ICI type, organ involved or cancer site.

Immune checkpoint inhibitors (ICI) are cancer therapies that are approved in at least 19 different cancers. They function by stimulating immune cell responses against cancer, and their toxicities comprise a host of autoinflammatory syndromes that may impact any organ system. Endocrine toxicities occur in as high as 25-50% of ICI recipients, depending on the treatment regimen used. These toxicities vary in severity from mild, asymptomatic cases of subclinical hypothyroidism to severe, fatal cases of adrenal crisis, thyroid dysfunction, or diabetic ketoacidosis. Thus, timely recognition and treatment is critical. Herein, we present clinical cases of ICI-induced thyroid dysfunction, hypophysitis, and insulin-dependent diabetes mellitus. We use these cases to discuss the screening, diagnosis, and management of ICI-associated endocrine dysfunction.

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.