Immune Checkpoint Inhibitor-Induced Thyroid Dysfunction is Associated with Higher Body Mass Index.

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Obesity is a pro-inflammatory metabolic state that may play a role in the development of immune-related adverse events (irAEs) associated with immune checkpoint inhibitor therapy.To characterize the association between body mass index (BMI) and thyroid irAEs.We performed a single center, retrospective analysis of 185 cancer patients treated with anti-PD-1/L1 from January 2014 to December 2018. Patients with normal thyroid function at baseline and available BMI were included.The primary endpoint was difference in BMI in patients who developed overt thyroid dysfunction vs. remained euthyroid following anti-PD-1/L1 initiation. Additional endpoints included any (overt or subclinical) thyroid dysfunction, overt thyrotoxicosis or overt hypothyroidism, and time to development of dysfunction according to BMI.Any thyroid dysfunction developed in 72 (38.9%) patients and 41 (22.1%) developed overt thyroid dysfunction. Mean BMI was higher in those with overt thyroid dysfunction vs. euthyroid (27.3±6.0 vs. 24.9±4.5, p=0.03). Development of overt thyrotoxicosis vs. remaining euthyroid was associated with higher BMI (28.9±5.9 vs. 24.9±4.5; p<0.01), whereas overt hypothyroidism was not (26.7±5.5 vs. 24.9±4.5, p=0.10). Overt thyrotoxicosis developed within 57.5 (IQR 31.8-78.8) days of treatment in the low-normal BMI group, 38.0 (IQR 26.8-40.5) days in the overweight and 23.0 (IQR 21.0-28.0) days in the obese group (p=0.02).Patients treated with PD-1/L1 inhibitors were more likely to develop thyroid irAEs, specifically overt thyrotoxicosis, with increasing BMI. Overt thyrotoxicosis occurred earlier in obese vs. leaner patients. These data highlight the complex interplay between obesity and immune response in ICI-treated patients.

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