Higher BMI tied to immune checkpoint inhibitor-induced thyroid dysfunction

Treatment with PD-1/L1 inhibitors is associated with the development of thyroid immune-related adverse events (irAEs), particularly overt thyrotoxicosis, with increasing body mass index (BMI), a recent study has found.

“Overt thyrotoxicosis occurred earlier in obese versus leaner patients,” the authors said. “These data highlight the complex interplay between obesity and immune response in immune checkpoint inhibitor-treated patients.”

A single-centre, retrospective analysis was performed on 185 cancer patients treated with PD-1/L1 inhibitors from January 2014 to December 2018 to assess the relationship between BMI and thyroid irAEs. Those with normal thyroid function at baseline and available BMI were included.

The difference in BMI in patients who developed overt thyroid dysfunction compared to those who remained euthyroid following anti-PD-1/L1 initiation was the primary endpoint. Secondary endpoints included any thyroid dysfunction, overt thyrotoxicosis or overt hypothyroidism, and time to development of dysfunction according to BMI.

Seventy-two (38.9 percent) patients developed any thyroid dysfunction and 41 (22.1 percent) developed overt thyroid dysfunction. Those with overt thyroid dysfunction vs euthyroid had higher mean BMI (27.3±6.0 vs 24.9±4.5; p=0.03).

Development of overt thyrotoxicosis compared with remaining euthyroid correlated with higher BMI (28.9±5.9 vs 24.9±4.5; p<0.01), but overt hypothyroidism did not (26.7±5.5 vs 24.9±4.5; p=0.10). Overt thyrotoxicosis developed within 57.5 (interquartile range [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 group, and 23.0 (IQR, 21.0–28.0) days in the obese group (p=0.02).

“Obesity is a proinflammatory metabolic state that may play a role in the development of irAEs associated with immune checkpoint inhibitor therapy,” the authors said.