Metabolically active brown adipose tissue in PPGL: an observational cohort study

Brown adipose tissue (BAT) activity, identifiable through fluorodeoxyglucose positron emission tomography (FDG-PET), has gained interest due to its potential link with metabolic disorders and tumour pathophysiology. This study aims to explore the activation of BAT in patients with phaeochromocytoma/paraganglioma (PPGL) and its clinical relevance. This retrospective observational study, conducted in a large academic centre in London, reviewed FDG-PET images of 62 confirmed PPGL patients, collected between 2013 and 2021. We assessed patient demographics, biochemistry, radiological features, mutational status and outcomes, focussing on activated BAT detection. Of the 62 patients, 13% demonstrated active brown adipose tissue (aBAT) on FDG-PET imaging. Histopathological confirmation of BAT from one patient was used to validate BAT activation observed during imaging. Multivariate analysis indicated that elevated plasma normetanephrine concentrations were directly proportional to aBAT presence, suggesting their strong association with BAT activation. Despite identifying aBAT, no significant differences were found in BMI, sex, age or mutational status between aBAT-positive and aBAT-negative groups. Kaplan-Meier survival plots assessing overall and progression-free survival did not reach statistical significance. This study underscores the complex interaction between catecholamine excess and BAT activation in patients with PPGLs. The findings suggest that aBAT activity might be an indicator of severe catecholamine excess (especially normetanephrine), potentially influencing patient outcomes. Our study adds to the limited pool of knowledge and offers novel insights into BAT activation in patients with PPGLs, highlighting its potential link with metabolic derangements and patient outcomes.