title: Genotype-Dependent Brown Adipose Tissue Activation in Patients With Pheochromocytoma and Paraganglioma.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Patients with PGLs who were fully genetically characterized underwent presurgical (18)F-FDG PET/CT imaging for tumor localization and to quantify BAT activation.
  
  
  METHODS
  The study was conducted at a single Dutch tertiary referral center.
  
  
  METHODS
  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.
  
  
  METHODS
  (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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Internal Medicine (T.P., A.v.B., A.R.M.M.H., H.J.L.M.T.), Division of Endocrinology, Department of Radiology and Nuclear Medicine (M.G.), and Department of Internal Medicine (J.W.M.L.), Division of Vascular Medicine, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands; Department of Endocrinology (T.P.), Changi General Hospital, Singapore 529889, Singapore; Department of Internal Medicine (B.H.), Division of Endocrinology, and Department of Human Biology (W.D.v.M.L.), NUTRIM School for Nutrition, Toxicology, and Metabolism, and Department of Medical Imaging (B.B.), Division of Nuclear Medicine, Maastricht University Medical Centre, 6202 AZ Maastricht, The Netherlands; Department of Medicine and Institute of Clinical Chemistry and Laboratory Medicine (J.W.M.L.), University Hospital Carl Gustav Carus, 01307 Dresden, Germany; and Centre for Quantitative Medicine (Y.X.), Duke-National University Singapore Graduate Medical School, Singapore 169856, Singapore.
authors.forename: Troy
authors.initials: T
authors.lastname: Puar
authors.affiliation: Department of Internal Medicine (T.P., A.v.B., A.R.M.M.H., H.J.L.M.T.), Division of Endocrinology, Department of Radiology and Nuclear Medicine (M.G.), and Department of Internal Medicine (J.W.M.L.), Division of Vascular Medicine, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands; Department of Endocrinology (T.P.), Changi General Hospital, Singapore 529889, Singapore; Department of Internal Medicine (B.H.), Division of Endocrinology, and Department of Human Biology (W.D.v.M.L.), NUTRIM School for Nutrition, Toxicology, and Metabolism, and Department of Medical Imaging (B.B.), Division of Nuclear Medicine, Maastricht University Medical Centre, 6202 AZ Maastricht, The Netherlands; Department of Medicine and Institute of Clinical Chemistry and Laboratory Medicine (J.W.M.L.), University Hospital Carl Gustav Carus, 01307 Dresden, Germany; and Centre for Quantitative Medicine (Y.X.), Duke-National University Singapore Graduate Medical School, Singapore 169856, Singapore.
authors.forename: Anouk
authors.initials: A
authors.lastname: van Berkel
authors.affiliation: Department of Internal Medicine (T.P., A.v.B., A.R.M.M.H., H.J.L.M.T.), Division of Endocrinology, Department of Radiology and Nuclear Medicine (M.G.), and Department of Internal Medicine (J.W.M.L.), Division of Vascular Medicine, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands; Department of Endocrinology (T.P.), Changi General Hospital, Singapore 529889, Singapore; Department of Internal Medicine (B.H.), Division of Endocrinology, and Department of Human Biology (W.D.v.M.L.), NUTRIM School for Nutrition, Toxicology, and Metabolism, and Department of Medical Imaging (B.B.), Division of Nuclear Medicine, Maastricht University Medical Centre, 6202 AZ Maastricht, The Netherlands; Department of Medicine and Institute of Clinical Chemistry and Laboratory Medicine (J.W.M.L.), University Hospital Carl Gustav Carus, 01307 Dresden, Germany; and Centre for Quantitative Medicine (Y.X.), Duke-National University Singapore Graduate Medical School, Singapore 169856, Singapore.
authors.forename: Martin
authors.initials: M
authors.lastname: Gotthardt
authors.affiliation: Department of Internal Medicine (T.P., A.v.B., A.R.M.M.H., H.J.L.M.T.), Division of Endocrinology, Department of Radiology and Nuclear Medicine (M.G.), and Department of Internal Medicine (J.W.M.L.), Division of Vascular Medicine, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands; Department of Endocrinology (T.P.), Changi General Hospital, Singapore 529889, Singapore; Department of Internal Medicine (B.H.), Division of Endocrinology, and Department of Human Biology (W.D.v.M.L.), NUTRIM School for Nutrition, Toxicology, and Metabolism, and Department of Medical Imaging (B.B.), Division of Nuclear Medicine, Maastricht University Medical Centre, 6202 AZ Maastricht, The Netherlands; Department of Medicine and Institute of Clinical Chemistry and Laboratory Medicine (J.W.M.L.), University Hospital Carl Gustav Carus, 01307 Dresden, Germany; and Centre for Quantitative Medicine (Y.X.), Duke-National University Singapore Graduate Medical School, Singapore 169856, Singapore.
authors.forename: Bas
authors.initials: B
authors.lastname: Havekes
authors.affiliation: Department of Internal Medicine (T.P., A.v.B., A.R.M.M.H., H.J.L.M.T.), Division of Endocrinology, Department of Radiology and Nuclear Medicine (M.G.), and Department of Internal Medicine (J.W.M.L.), Division of Vascular Medicine, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands; Department of Endocrinology (T.P.), Changi General Hospital, Singapore 529889, Singapore; Department of Internal Medicine (B.H.), Division of Endocrinology, and Department of Human Biology (W.D.v.M.L.), NUTRIM School for Nutrition, Toxicology, and Metabolism, and Department of Medical Imaging (B.B.), Division of Nuclear Medicine, Maastricht University Medical Centre, 6202 AZ Maastricht, The Netherlands; Department of Medicine and Institute of Clinical Chemistry and Laboratory Medicine (J.W.M.L.), University Hospital Carl Gustav Carus, 01307 Dresden, Germany; and Centre for Quantitative Medicine (Y.X.), Duke-National University Singapore Graduate Medical School, Singapore 169856, Singapore.
authors.forename: Ad R M M
authors.initials: AR
authors.lastname: Hermus
authors.affiliation: Department of Internal Medicine (T.P., A.v.B., A.R.M.M.H., H.J.L.M.T.), Division of Endocrinology, Department of Radiology and Nuclear Medicine (M.G.), and Department of Internal Medicine (J.W.M.L.), Division of Vascular Medicine, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands; Department of Endocrinology (T.P.), Changi General Hospital, Singapore 529889, Singapore; Department of Internal Medicine (B.H.), Division of Endocrinology, and Department of Human Biology (W.D.v.M.L.), NUTRIM School for Nutrition, Toxicology, and Metabolism, and Department of Medical Imaging (B.B.), Division of Nuclear Medicine, Maastricht University Medical Centre, 6202 AZ Maastricht, The Netherlands; Department of Medicine and Institute of Clinical Chemistry and Laboratory Medicine (J.W.M.L.), University Hospital Carl Gustav Carus, 01307 Dresden, Germany; and Centre for Quantitative Medicine (Y.X.), Duke-National University Singapore Graduate Medical School, Singapore 169856, Singapore.
authors.forename: Jacques W M
authors.initials: JW
authors.lastname: Lenders
authors.affiliation: Department of Internal Medicine (T.P., A.v.B., A.R.M.M.H., H.J.L.M.T.), Division of Endocrinology, Department of Radiology and Nuclear Medicine (M.G.), and Department of Internal Medicine (J.W.M.L.), Division of Vascular Medicine, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands; Department of Endocrinology (T.P.), Changi General Hospital, Singapore 529889, Singapore; Department of Internal Medicine (B.H.), Division of Endocrinology, and Department of Human Biology (W.D.v.M.L.), NUTRIM School for Nutrition, Toxicology, and Metabolism, and Department of Medical Imaging (B.B.), Division of Nuclear Medicine, Maastricht University Medical Centre, 6202 AZ Maastricht, The Netherlands; Department of Medicine and Institute of Clinical Chemistry and Laboratory Medicine (J.W.M.L.), University Hospital Carl Gustav Carus, 01307 Dresden, Germany; and Centre for Quantitative Medicine (Y.X.), Duke-National University Singapore Graduate Medical School, Singapore 169856, Singapore.
authors.forename: Wouter D
authors.initials: WD
authors.lastname: van Marken Lichtenbelt
authors.affiliation: Department of Internal Medicine (T.P., A.v.B., A.R.M.M.H., H.J.L.M.T.), Division of Endocrinology, Department of Radiology and Nuclear Medicine (M.G.), and Department of Internal Medicine (J.W.M.L.), Division of Vascular Medicine, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands; Department of Endocrinology (T.P.), Changi General Hospital, Singapore 529889, Singapore; Department of Internal Medicine (B.H.), Division of Endocrinology, and Department of Human Biology (W.D.v.M.L.), NUTRIM School for Nutrition, Toxicology, and Metabolism, and Department of Medical Imaging (B.B.), Division of Nuclear Medicine, Maastricht University Medical Centre, 6202 AZ Maastricht, The Netherlands; Department of Medicine and Institute of Clinical Chemistry and Laboratory Medicine (J.W.M.L.), University Hospital Carl Gustav Carus, 01307 Dresden, Germany; and Centre for Quantitative Medicine (Y.X.), Duke-National University Singapore Graduate Medical School, Singapore 169856, Singapore.
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Internal Medicine (T.P., A.v.B., A.R.M.M.H., H.J.L.M.T.), Division of Endocrinology, Department of Radiology and Nuclear Medicine (M.G.), and Department of Internal Medicine (J.W.M.L.), Division of Vascular Medicine, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands; Department of Endocrinology (T.P.), Changi General Hospital, Singapore 529889, Singapore; Department of Internal Medicine (B.H.), Division of Endocrinology, and Department of Human Biology (W.D.v.M.L.), NUTRIM School for Nutrition, Toxicology, and Metabolism, and Department of Medical Imaging (B.B.), Division of Nuclear Medicine, Maastricht University Medical Centre, 6202 AZ Maastricht, The Netherlands; Department of Medicine and Institute of Clinical Chemistry and Laboratory Medicine (J.W.M.L.), University Hospital Carl Gustav Carus, 01307 Dresden, Germany; and Centre for Quantitative Medicine (Y.X.), Duke-National University Singapore Graduate Medical School, Singapore 169856, Singapore.
authors.forename: Boudewijn
authors.initials: B
authors.lastname: Brans
authors.affiliation: Department of Internal Medicine (T.P., A.v.B., A.R.M.M.H., H.J.L.M.T.), Division of Endocrinology, Department of Radiology and Nuclear Medicine (M.G.), and Department of Internal Medicine (J.W.M.L.), Division of Vascular Medicine, Radboud University Medical Centre, 6500 HB Nijmegen, The Netherlands; Department of Endocrinology (T.P.), Changi General Hospital, Singapore 529889, Singapore; Department of Internal Medicine (B.H.), Division of Endocrinology, and Department of Human Biology (W.D.v.M.L.), NUTRIM School for Nutrition, Toxicology, and Metabolism, and Department of Medical Imaging (B.B.), Division of Nuclear Medicine, Maastricht University Medical Centre, 6202 AZ Maastricht, The Netherlands; Department of Medicine and Institute of Clinical Chemistry and Laboratory Medicine (J.W.M.L.), University Hospital Carl Gustav Carus, 01307 Dresden, Germany; and Centre for Quantitative Medicine (Y.X.), Duke-National University Singapore Graduate Medical School, Singapore 169856, Singapore.
authors.forename: Henri J L M
authors.initials: HJ
authors.lastname: Timmers
mesh_terms: D002001:Adipose Tissue, Brown / Q000000981:diagnostic imaging / Q000378:metabolism*; D000310:Adrenal Gland Neoplasms / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism*; D000328:Adult; D000368:Aged; D002395:Catecholamines / Q000378:metabolism; D005260:Female; D019788:Fluorodeoxyglucose F18; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D019899:Paracrine Communication / Q000235:genetics; D010235:Paraganglioma / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism*; D010673:Pheochromocytoma / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals
chemical_list: D002395:Catecholamines; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18