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Observational Study
. 2025 Mar 7;32(4):e240200.
doi: 10.1530/ERC-24-0200. Print 2025 Apr 1.

Metabolically active brown adipose tissue in PPGL: an observational cohort study

Eduard Oštarijaš, Michael C Onyema, Zoulikha Zair, David R Taylor, Fannie Lajeunesse-Trempe, Saira Reynolds, Nicola Mulholland, Ben Corcoran, Mohamed Halim, Eftychia E Drakou, Ashley B Grossman, Royce P Vincent, Simon J B Aylwin, Georgios K Dimitriadis, Silvija Canecki-Varžić
Observational Study

Metabolically active brown adipose tissue in PPGL: an observational cohort study

Eduard Oštarijaš et al. Endocr Relat Cancer. .

Abstract

Brown adipose tissue (BAT) activity, identifiable through fluorodeoxyglucose positron emission tomography (FDG-PET), has gained interest due to its potential link with metabolic disorders and tumour pathophysiology. This study aims to explore the activation of BAT in patients with phaeochromocytoma/paraganglioma (PPGL) and its clinical relevance. This retrospective observational study, conducted in a large academic centre in London, reviewed FDG-PET images of 62 confirmed PPGL patients, collected between 2013 and 2021. We assessed patient demographics, biochemistry, radiological features, mutational status and outcomes, focussing on activated BAT detection. Of the 62 patients, 13% demonstrated active brown adipose tissue (aBAT) on FDG-PET imaging. Histopathological confirmation of BAT from one patient was used to validate BAT activation observed during imaging. Multivariate analysis indicated that elevated plasma normetanephrine concentrations were directly proportional to aBAT presence, suggesting their strong association with BAT activation. Despite identifying aBAT, no significant differences were found in BMI, sex, age or mutational status between aBAT-positive and aBAT-negative groups. Kaplan-Meier survival plots assessing overall and progression-free survival did not reach statistical significance. This study underscores the complex interaction between catecholamine excess and BAT activation in patients with PPGLs. The findings suggest that aBAT activity might be an indicator of severe catecholamine excess (especially normetanephrine), potentially influencing patient outcomes. Our study adds to the limited pool of knowledge and offers novel insights into BAT activation in patients with PPGLs, highlighting its potential link with metabolic derangements and patient outcomes.

Keywords: BAT; FDG-PET; PPGL; brown adipose tissue; catecholamines; paraganglioma; phaeochromocytoma.

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Conflict of interest statement

EO received an honorarium from Krka. GKD received research grants from NIHR, Novo Nordisk, UK Research Foundation and DDM, and payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Novo Nordisk, Rhythm Pharmaceuticals, J&J/Ethicon and Medtronic. SCV received research grants, payment or honoraria for lectures, presentations or educational events from Novo Nordisk, Eli Lilly, Medtronic and Krka. GKD, EO and SCV report that there is no conflict of interest that could be perceived as prejudicing the impartiality of the work reported. Other authors did not report conflicts of interest.

Figures

Figure 1
Figure 1
Enrolment and analysis flowchart.
Figure 2
Figure 2
Low magnification image shows phaeochromocytoma to the far right of the image in an aBAT patient from our cohort in a retrospective post-surgical specimen. BAT adjacent to the phaeochromocytoma is seen occupying the left two-thirds of the field.
Figure 3
Figure 3
At higher magnification (from Fig. 2), the adipocytes in brown fat show multivacuolated cytoplasm resulting from numerous small lipid droplets. The cytoplasm is acidophilic and granular due to large number of mitochondria. Small number of white fat adipocytes are present in this field for comparison. These have a single intracytoplasmic large fat droplet only.
Figure 4
Figure 4
Low magnification shows thyroid tissue on the left-hand side of the field and brown fat in the adjacent right-hand side of the field.
Figure 5
Figure 5
Forest plot showing multivariate adjusted and unadjusted odds ratios of aBAT presence associated with multiple covariates.
Figure 6
Figure 6
Kaplan–Meier survival plots: (A) OS, (B) PFS.
See this image and copyright information in PMC

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