Pheochromocytoma and Paraganglioma Patients With Poor Survival Often Show Brown Adipose Tissue Activation

Abstract

Context Pheochromocytomas/paragangliomas (PPGLs) are neuroendocrine tumors that can secrete norepinephrine (NE). Brown adipose tissue (BAT) activation is mediated through the action of NE on β-adrenoceptors (β-ARs). In some malignancies BAT activation is associated with higher cancer activity. Objective To study the relationship between BAT activation and PPGL clinical outcomes. Design A retrospective case-control study that included 342 patients with PPGLs who underwent ¹⁸F-FDG PET/CT imaging at the National Institutes of Health (NIH). We excluded all patients with parasympathetic tumors and those who underwent ¹⁸F-FDG PET/CT after PPGL resection. Scans of 205 patients were reviewed by two blinded nuclear medicine physicians; sixteen patients had BAT activation on ¹⁸F-FDG PET/CT [7.80%; 27.50 (15.00-45.50) y, 10F/6M, 24.90 (19.60-25.35) kg/m²]. From the remaining 189 patients, we selected 36 matched controls [34.4 (25.4-45.5) y, 21F/15M, 25.0 (22.0-26.0) kg/m²]. Primary Outcome Measure Overall survival Results The presence of active BAT on ¹⁸F-FDG PET/CT was associated with decreased overall survival when compared to the control group (HR_z: 5.80, 95% CI:1.05-32.05; p=0.02). This association remained significant after adjusting for the SDHB mutation. Median plasma NE in the BAT group was higher than the control group [4.65 vs. 0.55 times above the upper limit of normal; p<0.01]. There was a significant association between higher plasma NE levels and mortality in PPGLs in both groups. Conclusions In conclusion, our findings suggest that the detection of BAT activity in PPGL patients is associated with higher mortality. We suggest that BAT activation could either be reflecting or contributing to a state of increased host stress that may predict poor outcome in metastatic PPGL.