Genotype-Dependent Brown Adipose Tissue Activation in Patients With Pheochromocytoma and Paraganglioma

Troy Puar, Anouk van Berkel, Martin Gotthardt, Bas Havekes, Ad R M M Hermus, Jacques W M Lenders, Wouter D van Marken Lichtenbelt, Ying Xu, Boudewijn Brans, Henri J L M Timmers
Journal of Clinical Endocrinology and Metabolism 2016, 101 (1): 224-32

CONTEXT: Patients with pheochromocytomas and paragangliomas (PGLs) may have brown adipose tissue (BAT) activation induced by catecholamine excess. (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography (PET)/computed tomography (CT) can be used for the localization of both PGLs and BAT. It is unknown whether BAT is specifically affected by altered cellular energy metabolism in patients with SDHx- and VHL-related PGLs.

OBJECTIVE: The objective of the study was to determine endocrine and paracrine effects of catecholamine excess on BAT activation in patients with PGLs as detected by (18)F-FDG PET/CT, taking into account genetic variation.

DESIGN: Patients with PGLs who were fully genetically characterized underwent presurgical (18)F-FDG PET/CT imaging for tumor localization and to quantify BAT activation.

SETTING: The study was conducted at a single Dutch tertiary referral center.

PATIENTS AND INTERVENTION: Seventy-three patients, aged 52.4 ± 15.4 years, with a body mass index of 25.2 ± 4.1 kg/m(2), mean ± SD, were grouped into sporadic, cluster 1 (SDHx, VHL) and cluster 2 (RET, NF1, MAX) mutations.

MAIN OUTCOME MEASURES: (18)F-FDG mean standard uptake values were assessed in predefined BAT locations, including perirenal fat.

RESULTS: Twenty-one of 73 patients (28.8%) exhibited BAT activation. BAT activation was absent in all six patients with nonsecreting PGLs. No difference in (18)F-FDG uptake by perirenal fat on the side of the pheochromocytoma and the contralateral side was observed (mean standard uptake value of 0.80 vs 0.78, respectively, P = .42). The prevalence of BAT activation did not differ between sporadic (28.9%), cluster 1 (40.0%), and cluster 2 patients (15.4%, P= .36).

CONCLUSION: Patients with PGLs exhibit a high prevalence of BAT activation on (18)F-FDG PET/CT. This is likely due to systemic catecholamine excess. BAT activation is not associated with specific germline mutations.

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