The incidence and clinical significance of metabolically active brown adipose tissue in patients with pheochromocytomas and paragangliomas: A retrospective cohort study, systematic review and meta-analysis

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Abstract
There is limited research into the impact of active brown adipose tissue (aBAT) in patients with phaeochromocytomas and paragangliomas (PPGLs). A small body of evidence has shown that patients with PPGL patients can exhibit a high prevalence for aBAT recognized as ranging between 8 - 28% without specific correlation to germline mutations. Furthermore, it has been suggested that aBAT may be linked to increased mortality. Systematic searches of the Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica (EMBASE), Cochrane Central Register of Controlled Trials (CENTRAL), EudraCT, ClinicalTrials.gov, medRvix CINAHL and Scopus databases were conducted. Our study was registered with PROSPERO international registry for systematic reviews with ID: CRD42021276073. Furthermore, we conducted a retrospective cohort study evaluating our records for patients between 2013-2021 with PPGLs who had an 18F-FDG PET/CT and metabolically aBAT. Meta-analytical calculations were performed using R software and SPSS was used for analyses of variables from our retrospective cohort study. Our systematic search produced 4 studies, the data of which were pooled into a meta-analysis including the data from our study. Our meta-analysis demonstrated a significant correlation between 18F-FDG PET/CT avidity and concentration of plasma metanephrines and normetanephrines using a random effect model (Pr=0.822, P=0.012) was observed. A statistically significant difference in metadrenaline levels between mutational status clusters (Kruskal-Wallis statistic = 11.435, df = 2, P=0.003) with post-hoc analysis suggesting significant difference between clusters 1 (SDH/VHL) and 2 (MEN/RET), as well as between cluster 1 and control group. Patients with PPGLs exhibit a high prevalence of BAT activation on 18F-FDG PET/CT.