Endocrine Abstracts

Objective: This study aimed to characterise the relationship between immune checkpoint inhibitors (ICIs), which are commonly used to treat cancer, and thyroid dysfunction in terms of the proportions affected, timing of onset, sequalae and risk factors.

Design: Retrospective cohort study

Methods: Patients with normal baseline thyroid function who received an ICI were included. Proportions of incident hyperthyroidism or hypothyroidism (subclinical, overt or isolated hyperthyroxinemia/hypothyroxinemia) were determined along with median times to onset and subsequent thyroid function statuses. Hazard ratios (HRs) and 95% confidence intervals for associations between baseline factors and abnormal T4 were estimated using Fine and Grey regression.

Results: 1364 patients were included. Lung cancer and pembrolizumab, respectively, were the most common diagnosis and ICI. Hyperthyroidism was observed in 43.1% of patients, including in 73.5% receiving ipilimumab with nivolumab. In melanoma, hyperthyroidism was more common with adjuvant compared to palliative ICIs (45.2% vs. 26.9%). Hypothyroidism was observed in 36.9% of patients. Around half with subclinical thyroid dysfunction returned to normal, while 44.2% of overt hyperthyroidism led to overt hypothyroidism in a median time of 1.6 months. Raised T4 was associated with reduced estimated glomerular filtration rate (eGFR) (HR=1.73, 1.26-2.38), body mass index (BMI) ≥40kg/m2 (HR=2.96, 1.66-5.29) and, inversely, with raised aspartate aminotransferase (HR=0.62, 0.41-0.96).

Conclusion: Thyroid dysfunction affects up to three quarters of patients receiving ICIs. Clinical courses vary from temporary dysfunction to rapid progression from hyperthyroidism to hypothyroidism. Further investigation is merited given increasing ICI use and the effect of thyroid dysfunction on mortality and quality of life.