Abstract

Hypophysitis occurs in up to 10% of patients treated with immune-checkpoint inhibitors (ICIs). MRI shows no abnormalities of the pituitary gland in one third of patients. A delayed diagnosis increases the risk for life-threatening adrenal crisis, underscoring the need for early detection. This study evaluates the diagnostic accuracy FDG PET/CT in detecting ICI-induced hypophysitis in a cohort of melanoma patients. Patients with metastatic melanoma and ICI-induced hypophysitis, who underwent FDG PET/CT 90 days before to 10 days after diagnosis, were compared with an age- and sex-matched control group of patients undergoing ICI treatment without signs of hypophysitis. The ratio of SUVmax of the pituitary gland to the SUVmean of the blood pool (target-to-background ratio [TBR]) was calculated. Diagnostic accuracy of the TBR was assessed using area under the receiver operating characteristics curve analysis. A total of 28 patients was included. The majority of patients with hypophysitis received ipilimumab/nivolumab (64.3%, 9/14). Visual assessment of the TBR distribution demonstrated a positive correlation with decreasing time to diagnosis. To evaluate diagnostic performance, only patients with FDG PET/CT 50 days before to 8 days after diagnosis (11/14) were included. TBR was significantly higher in these compared with the control group (median [interquartile range], 2.78 [2.41] vs 1.59 [0.70], respectively; P = 0.034). A sensitivity of 72.7% and a specificity of 90.9% were achieved at a TBR threshold of 2.41 (area under the receiver operating characteristics curve = 0.769). Our findings suggest that, in patients undergoing ICI treatment for metastatic melanoma, a pituitary TBR of approximately 2.4 may indicate impending ICI-induced hypophysitis.

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