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

NCT06440122 | Recruiting

• 1 other identifier: GafREC-Endo203
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Pheochromocytoma; Paraganglioma

Keywords

Brown Adipose Tissue; FDG-PET; Activation; Pheochromocytoma; Paraganglioma

Outcome Measures

Primary Outcomes (2)

• Number of patients with pheochromocytoma and metabolically active brown adipose tissue on FGD-PET scan

  through study completion, an average of 1 year

• Number of patients with paraganglioma and metabolically active brown adipose tissue on FGD-PET scan

  through study completion, an average of 1 year

Secondary Outcomes (3)

• Metabolically active brown adipose tissue and presence of germ-line mutations (NHL) in patients with pheochromocytoma and paraganglioma

  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

  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

  through study completion, an average of 1 year

Study Arms (2)

Patients with pheochromocytoma or paraganglioma and positive brown adipose tissue on FDG-PET

Diagnostic Test: FDG-PET Scan

Patients with pheochromocytoma or paraganglioma and negative brown adipose tissue on FDG-PET

Diagnostic Test: FDG-PET Scan

Interventions

FDG-PET Scan DIAGNOSTIC_TEST

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; Patients with pheochromocytoma or paraganglioma and positive brown adipose tissue on FDG-PET

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

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

You may not qualify if:

• Patients with any other neoplasm other than pheochromocytoma or paraganglioma

Sponsors & Collaborators

• King's College Hospital NHS Trust: lead

Study Sites (1)

King's College Hospital NHS Foundation Trust

London, United Kingdom of Great Britain and Northern Ireland, SE5 9RS, United Kingdom

RECRUITING

Related Publications (13)

• Santhanam P, Solnes L, Hannukainen JC, Taieb D. ADIPOSITY-RELATED CANCER AND FUNCTIONAL IMAGING OF BROWN ADIPOSE TISSUE. Endocr Pract. 2015 Nov;21(11):1282-90. doi: 10.4158/EP15870.RA. Epub 2015 Aug 17.

  PMID: 26280202 BACKGROUND

• Fenzl A, Kiefer FW. Brown adipose tissue and thermogenesis. Horm Mol Biol Clin Investig. 2014 Jul;19(1):25-37. doi: 10.1515/hmbci-2014-0022.

  PMID: 25390014 BACKGROUND

• Marlatt KL, Ravussin E. Brown Adipose Tissue: an Update on Recent Findings. Curr Obes Rep. 2017 Dec;6(4):389-396. doi: 10.1007/s13679-017-0283-6.

  PMID: 29101739 BACKGROUND

• Iyer RB, Guo CC, Perrier N. Adrenal pheochromocytoma with surrounding brown fat stimulation. AJR Am J Roentgenol. 2009 Jan;192(1):300-1. doi: 10.2214/AJR.08.1166. No abstract available.

  PMID: 19098214 BACKGROUND

• Bartness TJ, Vaughan CH, Song CK. Sympathetic and sensory innervation of brown adipose tissue. Int J Obes (Lond). 2010 Oct;34 Suppl 1(0 1):S36-42. doi: 10.1038/ijo.2010.182.

  PMID: 20935665 BACKGROUND

• Nedergaard J, Bengtsson T, Cannon B. Unexpected evidence for active brown adipose tissue in adult humans. Am J Physiol Endocrinol Metab. 2007 Aug;293(2):E444-52. doi: 10.1152/ajpendo.00691.2006. Epub 2007 May 1.

  PMID: 17473055 BACKGROUND

• 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 Jun 11;7(7):1399-1403. doi: 10.1002/ccr3.2259. eCollection 2019 Jul.

  PMID: 31360497 BACKGROUND

• Blondin DP, Nielsen S, Kuipers EN, Severinsen MC, Jensen VH, Miard S, Jespersen NZ, Kooijman S, Boon MR, Fortin M, Phoenix S, Frisch F, Guerin B, Turcotte EE, Haman F, Richard D, Picard F, Rensen PCN, Scheele C, Carpentier AC. Human Brown Adipocyte Thermogenesis Is Driven by beta2-AR Stimulation. Cell Metab. 2020 Aug 4;32(2):287-300.e7. doi: 10.1016/j.cmet.2020.07.005.

  PMID: 32755608 BACKGROUND

• Wang Q, Zhang M, Ning G, Gu W, Su T, Xu M, Li B, Wang W. 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. doi: 10.1371/journal.pone.0021006. Epub 2011 Jun 20.

  PMID: 21701596 BACKGROUND

• Puar T, van Berkel A, Gotthardt M, Havekes B, Hermus AR, Lenders JW, van Marken Lichtenbelt WD, Xu Y, Brans B, Timmers HJ. Genotype-Dependent Brown Adipose Tissue Activation in Patients With Pheochromocytoma and Paraganglioma. J Clin Endocrinol Metab. 2016 Jan;101(1):224-32. doi: 10.1210/jc.2015-3205. Epub 2015 Nov 17.

  PMID: 26574955 BACKGROUND

• 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 Jul;48(7):1077-83. doi: 10.2967/jnumed.106.035915. Epub 2007 Jun 15.

  PMID: 17574980 BACKGROUND

• Abdul Sater Z, Jha A, Hamimi A, Mandl A, Hartley IR, Gubbi S, Patel M, Gonzales M, Taieb D, Civelek AC, Gharib AM, Auh S, O'Mara AE, Pacak K, Cypess AM. Pheochromocytoma and Paraganglioma Patients With Poor Survival Often Show Brown Adipose Tissue Activation. J Clin Endocrinol Metab. 2020 Apr 1;105(4):1176-85. doi: 10.1210/clinem/dgz314.

  PMID: 31903484 BACKGROUND

• Sampath SC, Sampath SC, Bredella MA, Cypess AM, Torriani M. Imaging of Brown Adipose Tissue: State of the Art. Radiology. 2016 Jul;280(1):4-19. doi: 10.1148/radiol.2016150390.

  PMID: 27322970 BACKGROUND

MeSH Terms

Conditions

Pheochromocytoma; Paraganglioma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue

Study Officials

• Georgios Dimitriadis

  King's College Hospital NHS Trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Georgios K Dimitriadis

CONTACT

0777615084; g.dimitriadis@nhs.net

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 21, 2024
• First Posted: June 3, 2024
• Study Start: May 31, 2024
• Primary Completion: September 30, 2024
• Study Completion: December 31, 2024
• Last Updated: June 3, 2024

Record last verified: 2024-05

Locations

GB (1)