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J Clin Endocrinol Metab. 2020 Jan 6. pii: dgz314. doi: 10.1210/clinem/dgz314. [Epub ahead of print]

Pheochromocytoma and Paraganglioma Patients with Poor Survival Often Show Brown Adipose Tissue Activation.

Author information

1
National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
2
Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
3
Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
4
Department of Nuclear Medicine, La Timone University Hospital, CERIMED, Aix-Marseille University, Marseille, France.
5
Nuclear Medicine Division, Radiology, and Imaging Sciences, Warren Grant Magnuson Clinical Center, National Institutes of Health, Bethesda, MD, USA.
6
Nuclear Medicine, Radiology and Radiological Science, Johns Hopkins Medicine, Baltimore, MD, USA.

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-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 two blinded nuclear medicine physicians; sixteen patients had BAT activation on 18F-FDG PET/CT [7.80%; 27.50 (15.00-45.50) y, 10F/6M, 24.90 (19.60-25.35) kg/m2]. From the remaining 189 patients, we selected 36 matched controls [34.4 (25.4-45.5) y, 21F/15M, 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 to 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:

In conclusion, 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.

KEYWORDS:

18F-FDG; Brown adipose tissue; PET/CT; cancer; norepinephrine; paraganglioma; pheochromocytoma; succinate dehydrogenase; survival

PMID:
31903484
DOI:
10.1210/clinem/dgz314

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