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.