The Incidence and Outcomes of Metabolically Active Brown Adipose Tissue (aBAT) in Patients With Pheochromocytoma or Paraganglioma (PPGLs)

May 28, 2024 updated by: King's College Hospital NHS Trust

White adipose tissue (WAT) and brown adipose tissue (BAT) form the main adipose tissue subtypes in humans and several animals. BAT, owing to its unique metabolic function, has been of increased focus and interest in metabolic research (1). BAT forms the major organ of non-shivering thermogenesis in the body, and is dependent on the large concentration of mitochondria and increased uncoupling protein-1 (UCP-1) activity present in this type of tissue (2). There are numerous triggers for the metabolic activation of BAT including cold temperature, low body mass index (BMI), adrenergic agonists, and elevated concentration of thyroid hormones (3).

BAT is found more abundantly in fetuses and infants, with significant regression into adulthood. The main areas where BAT can be found are the neck, mediastinum, axilla, retroperitoneum, and abdominal wall (4). Clinical research suggests that activation and thermogenesis in BAT are mediated by noradrenaline release from the sympathetic nervous system (5). With the increasing use of fluorodeoxyglucose positron emission tomography (18FDG-PET) imaging, there has been an increased detection rate of activated brown adipose tissue (aBAT); this may affect diagnoses and lead to false-positive reporting (6).

Phaeochromocytomas/paragangliomas (PPGLs) are chromaffin-cell-derived endocrine tumors that emerge from the adrenal medulla or extra-adrenal ganglia. High FDG accumulation has been commonly noted in aBAT in patients with catecholamine-producing tumours, with subsequent resolution of these findings after resection of the tumour (7). This finding is likely related to the increased glucose transport related to noradrenaline excess (4). BAT has traditionally been considered to mainly express β3-adrenoreceptors; however, in vitro studies have indicated that activated β2-adrenoreceptors may be the main driving force behind thermogenesis (8).

Studies reviewing PPGLs have shown an aBAT detection rate of 7.8% to 42.8% on FDG-PET imaging, correlating with elevated catecholamine levels but without clear correlation to germline mutations (9-12). In one study, this imaging finding was associated with a statistically significant reduction in overall survival (12). Standardisation for the 'standardised uptake value' (SUV) cut-offs for aBAT on FDG-PET are lacking, but these are often reported between 1.0 and 2.0 (13); in previous studies of PPGL, a cut-off value of >1.5 has been employed (10, 12).

Research on the clinical implications of aBAT in patients with PPGL remains scarce. The main objectives of this study were to gain further insights into BAT activation rates in patients with PPGLs and how this may relate to patient demographics, biochemistry, radiological features, mutational status, and outcomes. The main hypotheses were that aBAT rates would be significantly linked to the severity of catecholamine excess and could be considered a poor prognostic feature.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

References:

  1. Santhanam P, Solnes L, Hannukainen JC, Taïeb D. Adiposity-related cancer and functional imaging of brown adipose tissue. Endocr Pract. 2015;21(11):1282-90.
  2. Fenzl A, Kiefer FW. Brown adipose tissue and thermogenesis. Horm Mol Biol Clin Investig. 2014;19(1):25-37.
  3. Marlatt KL, Ravussin E. Brown adipose tissue: An update on recent findings. Curr Obes Rep. 2017;6(4):389-96.
  4. Iyer RB, Guo CC, Perrier N. Adrenal pheochromocytoma with surrounding brown fat stimulation. AJR Am J Roentgenol. 2009;192(1):300-1.
  5. Bartness TJ, Vaughan CH, Song CK. Sympathetic and sensory innervation of brown adipose tissue. Int J Obes (Lond). 2010;34 Suppl 1(S1):S36-42.
  6. Nedergaard J, Bengtsson T, Cannon B. Unexpected evidence for active brown adipose tissue in adult humans. Am J Physiol Endocrinol Metab. 2007;293(2):E444-52.
  7. Terada E, Ashida K, Ohe K, Sakamoto S, Hasuzawa N, Nomura M. Brown adipose activation and reversible beige coloration in adipose tissue with multiple accumulations of 18F-fluorodeoxyglucose in sporadic paraganglioma: A case report. Clin Case Rep. 2019;7(7):1399-403.
  8. Blondin DP, Nielsen S, Kuipers EN, Severinsen MC, Jensen VH, Miard S, et al. Human brown adipocyte thermogenesis is driven by β2-AR stimulation. Cell Metab. 2020;32(2):287-300.e7.
  9. Wang Q, Zhang M, Ning G, Gu W, Su T, Xu M, et al. Brown adipose tissue in humans is activated by elevated plasma catecholamines levels and is inversely related to central obesity. PLoS One. 2011;6(6):e21006.
  10. Puar T, van Berkel A, Gotthardt M, Havekes B, Hermus ARMM, Lenders JWM, et al. Genotype-dependent brown adipose tissue activation in patients with pheochromocytoma and paraganglioma. J Clin Endocrinol Metab. 2016;101(1):224-32.
  11. Hadi M, Chen CC, Whatley M, Pacak K, Carrasquillo JA. Brown fat imaging with (18)F-6-fluorodopamine PET/CT, (18)F-FDG PET/CT, and (123)I-MIBG SPECT: a study of patients being evaluated for pheochromocytoma. J Nucl Med. 2007;48(7):1077-83.
  12. Abdul Sater Z, Jha A, Hamimi A, Mandl A, Hartley IR, Gubbi S, et al. Pheochromocytoma and paraganglioma patients with poor survival often show brown adipose tissue activation. J Clin Endocrinol Metab. 2020;105(4):1176-85.
  13. Sampath SC, Sampath SC, Bredella MA, Cypess AM, Torriani M. Imaging of brown adipose tissue: State of the art. Radiology. 2016;280(1):4-19.

Study Type

Observational

Enrollment (Estimated)

100

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United Kingdom
    • United Kingdom Of Great Britain And Northern Ireland
      • London, United Kingdom Of Great Britain And Northern Ireland, United Kingdom, SE5 9RS
        • Recruiting
        • King's College Hospital NHS Foundation Trust
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

N/A

Sampling Method

Probability Sample

Study Population

Any patients with confirmed pheochromocytoma or paraganglioma treated at King's College Hospital NHS Foundation Trust Endocrinology department who underwent an FDG-PET scan.

Description

Inclusion Criteria:

  • Patients with confirmed pheochromocytoma or paraganglioma who have undergone a FDG-PET as part of staging process.

Exclusion Criteria:

  • Patients with any other neoplasm other than pheochromocytoma or paraganglioma

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Patients with pheochromocytoma or paraganglioma and positive brown adipose tissue on FDG-PET
Diagnostic test: FDG-PET Scan
Positive for activated brown adipose tissue (SUVmax >1.5) FDG-PET scan
Patients with pheochromocytoma or paraganglioma and negative brown adipose tissue on FDG-PET
Diagnostic test: FDG-PET Scan
Positive for activated brown adipose tissue (SUVmax >1.5) FDG-PET scan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of patients with pheochromocytoma and metabolically active brown adipose tissue on FGD-PET scan
Time Frame: through study completion, an average of 1 year
through study completion, an average of 1 year
Number of patients with paraganglioma and metabolically active brown adipose tissue on FGD-PET scan
Time Frame: through study completion, an average of 1 year
through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Metabolically active brown adipose tissue and presence of germ-line mutations (NHL) in patients with pheochromocytoma and paraganglioma
Time Frame: through study completion, an average of 1 year
We are going to assess if patients with metabolically active adipose tissue and pheochromocytoma or paraganglioma present with germ-line mutations (VHL) or whether this occurs in patients with sporadic tumours
through study completion, an average of 1 year
Metabolically active brown adipose tissue and presence of germ-line mutations (NF-1) in patients with pheochromocytoma and paraganglioma
Time Frame: through study completion, an average of 1 year
We are going to assess if patients with metabolically active adipose tissue and pheochromocytoma or paraganglioma present with germ-line mutations (NF-1) or whether this occurs in patients with sporadic tumours
through study completion, an average of 1 year
Metabolically active brown adipose tissue and presence of germ-line mutations (MEN) in patients with pheochromocytoma and paraganglioma
Time Frame: through study completion, an average of 1 year
We are going to assess if patients with metabolically active adipose tissue and pheochromocytoma or paraganglioma present with germ-line mutations (MEN) or whether this occurs in patients with sporadic tumours
through study completion, an average of 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

King's College Hospital NHS Trust

Investigators

  • Principal Investigator: Georgios Dimitriadis, King's College Hospital NHS Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

May 31, 2024

Primary Completion (Estimated)

September 30, 2024

Study Completion (Estimated)

December 31, 2024

Study Registration Dates

First Submitted

May 21, 2024

First Submitted That Met QC Criteria

May 28, 2024

First Posted (Actual)

June 3, 2024

Study Record Updates

Last Update Posted (Actual)

June 3, 2024

Last Update Submitted That Met QC Criteria

May 28, 2024

Last Verified

May 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GafREC-Endo203

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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