Pheochromocytoma and paraganglioma patients with poor survival often show brown adipose tissue activation

Zahraa Abdul Sater, Abhishek Jha, Ahmed Hamimi, Adel Mandl, Iris R. Hartle, Sriram Gubbi, Mayank Patel, Melissa Gonzales, David Taïeb, Ali Cahid Civelek, Ahmed M. Ghari, Sungyoung Auh, Alana E. O'Mara, Karel Pacak, Aaron M. Cypess

Research output: Contribution to journalArticlepeer-review

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-fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography (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 2 blinded nuclear medicine physicians; 16 patients had BAT activation on 18F-FDG PET/CT [7.80%; age 27.50 (15.00-45.50) years; 10 female/6 male; body mass index [BMI] 24.90 [19.60-25.35] kg/m2). From the remaining 189 patients, we selected 36 matched controls (age 34.4 [25.4-45.5] years; 21 female/15 male; BMI 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 with the control group (HRz 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: 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.

Original languageEnglish (US)
Pages (from-to)1176-1185
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Volume105
Issue number4
DOIs
StatePublished - Apr 1 2020

Keywords

  • Brown adipose tissue
  • Cancer
  • F-FDG
  • Norepinephrine
  • PET/CT
  • Paraganglioma
  • Pheochromocytoma
  • Succinate dehydrogenase
  • Survival.

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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