Endocrine Abstracts

Background: Immune checkpoint inhibitors (ICIs) are a rapidly expanding therapeutic class that act by restoring T-cell anti-tumour activity via PD-1/PD-L1 and CTLA-4 inhibition. Yet whilst ICIs have notably improved cancer survival, they are associated with endocrine toxicities often requiring lifelong management. Among these, immune-mediated hypogonadism remains an overlooked yet relatively common toxicity that may reflect central dysfunction. Recently, the MHRA and EMA have approved additional ICIs – atezolizumab, durvalumab, dostarlimab, tremelimumab – and a novel LAG-3 inhibitor, relatlimab. However, real-world data on incidence, onset, and associations of these newer agents are limited.

Objective(s): To investigate associations between ICI-related endocrinopathies and patient demographics, ICI regimen, and cancer type.

Methods: Following HRA approval (IRAS ID: 360494, REC reference: 25/HCRW/0013), this retrospective cohort study included adults treated with ICI at Glan Clwyd Cancer Centre between 01/01/2022 - 31/01/2025. The endocrinopathy cohort (n = 123) comprised those with persistent biochemical endocrine abnormality, or imaging suggesting gland dysfunction. Controls (n = 710) included subclinical, transient, or confirmed steroid/radiotherapy-related endocrinopathies. Binary logistic regression was performed.

Results: Cohort mean age was 64.0 (SD: 12.0); 54.5% were male. Age, sex, and ICI agent showed no significant overall associations. Breast (OR 2.51, P = 0.016*) and renal cell cancer (OR 1.989, P = 0.050*) were associated with increased odds of ICI-related endocrinopathy. The overall incidence was 14.8%; predominantly thyroid dysfunction (61%) and rarely insulin-dependent diabetes (0.8%). Thyroid toxicity also predominated among the newer agents. Longer ICI treatment increased risk (OR 1.002/day, P < 0.001). Generally, ICI-related endocrinopathies developed early (<250 days) but onset varied markedly (P < 0.001): median 26.5 days [10.5–102.5] for hypogonadism versus 208 days [78–307] for adrenal insufficiency.

Conclusions: ICI-related endocrinopathies are common, affecting 14.8% of ICI-treated patients. Longer ICI exposure confers greater risk, supporting ongoing monitoring beyond initial treatment cycles. Marked differences in endocrinopathy onset indicate distinct immune mechanisms and diagnostic windows that warrant timely detection.