Metabolic impact of pheochromocytoma/paraganglioma: targeted metabolomics in patients before and after tumor removal

in European Journal of Endocrinology

Correspondence should be addressed to M Kroiss; Email: Kroiss_m@ukw.de
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Objective

Excess catecholamine release by pheochromocytomas and paragangliomas (PPGL) leads to characteristic clinical features and increased morbidity and mortality. The influence of PPGLs on metabolism is ill described but may impact diagnosis and management. The objective of this study was to systematically and quantitatively study PPGL-induced metabolic changes at a systems level.

Design

Targeted metabolomics by liquid chromatography-tandem mass spectrometry of plasma specimens in a clinically well-characterized prospective cohort study.

Methods

Analyses of metabolic profiles of plasma specimens from 56 prospectively enrolled and clinically well-characterized patients (23 males, 33 females) with catecholamine-producing PPGL before and after surgery, as well as measurement of 24-h urinary catecholamine using LC-MS/MS.

Results

From 127 analyzed metabolites, 15 were identified with significant changes before and after surgery: five amino acids/biogenic amines (creatinine, histidine, ornithine, sarcosine, tyrosine) and one glycerophospholipid (PCaeC34:2) with increased concentrations and six glycerophospholipids (PCaaC38:1, PCaaC42:0, PCaeC40:2, PCaeC42:5, PCaeC44:5, PCaeC44:6), two sphingomyelins (SMC24:1, SMC26:1) and hexose with decreased levels after surgery. Patients with a noradrenergic tumor phenotype had more pronounced alterations compared to those with an adrenergic tumor phenotype. Weak, but significant correlations for 8 of these 15 metabolites with total urine catecholamine levels were identified.

Conclusions

This first large prospective metabolomics analysis of PPGL patients demonstrates broad metabolic consequences of catecholamine excess. Robust impact on lipid and amino acid metabolism may contribute to increased morbidity of PPGL patients.

Supplementary Materials

    • Table 1a. List of metabolites measured with the AbsoluteIDQ® p180 Kit included in statistical analyses (127 of 188)**
    • Table 1b: List of metabolites measured with the AbsoluteIDQ® p180 Kit excluded from the statistical analyses (61 of 188)
    • 2.1a Normalization Result (all 56 preoperative patients/samples):
    • Statistical analyses results for sex comparison (female/male) in PPGL patients prior surgery
    • 2.1a PLS-DA results:
    • 2.1b Normalization Result (56 preoperative patients/samples)
    • 2.1 b Statistical analyses results for tumor localization (adrenal/extraadrenal) in PPGL patients prior surgery
    • 2.1b PLS-DA results:
    • 2.1 c Normalization Result (56 preoperative patients/samples):
    • 2.1c Statistical analyses results for catecholamine phenotype (adrenergic/noradrenergic) in PPGL patients prior surgery
    • 2.1c PLS-DA results:
    • 2.1d Normalization Result (52 preoperative samples; 4 samples with BMI missing information excluded):
    • 2.1d Statistical analyses results stratified by BMI (threshold 25kg/m2) in PPGL patients prior surgery:
    • 2.1d PLS-DA results:
    • 2.1e Normalization Result (56 preoperative samples):
    • 2.1e Statistical analyses results stratified by arterial hypertension (AHT) (present/absent) in PPGL patients prior surgery
    • 2.1e PLS-DA results:
    • 2.1f Normalization Result (56 preoperative samples):
    • 2.1 f) Statistical analyses results stratified by diabetes mellitus (present/absent) in PPGL patients prior surgery
    • 2.1f PLS-DA results:
    • 2.1g Normalization Result (56 preoperative samples):
    • 2.1g Statistical analyses results stratified by age (threshold 45 years) in PPGL patients prior surgery
    • 2.1g PLS-DA results:
    • 2.2.a Normalization Result (106 samples, 53 pairs):
    • 2.2a Statistical analyses results for comparison before and after surgery in all patients with biochemical remission
    • 2.2a PLS-DA results:
    • 2.2b Normalization Result (62 samples, 31 pairs):
    • 2.2b Statistical analyses results for comparison before and after surgery in female patients with biochemical remission
    • 2.2b PLS-DA results:
    • 2.2c Normalization Result (44 samples, 22 pairs):
    • 2.2c Statistical analyses results for comparison before and after surgery in male patients with biochemical remission
    • 2.2c PLS-DA results:
    • 2.2d Normalization Result (50 samples, 25 pairs):
    • 2.2d Statistical analyses results for comparison before and after surgery in adrenergic tumor patients with biochemical remission
    • 2.2d PLS-DA results:
    • 2.2e Normalization Result (56 samples, 28 pairs):
    • 2.2e Statistical analyses results for comparison before and after surgery in noradrenergic patients with biochemical remission
    • 2.2e PLS-DA results:
    • 2.2f Normalization Result (60 samples, 30 pairs):
    • 2.2f Statistical analyses results for comparison before and after surgery in patients with preoperative BMI <25 and postoperative biochemical remission
    • 2.2f PLS-DA results:
    • 2.2g Normalization Result (40 samples, 20 pairs):
    • 2.2g Statistical analyses results for comparison before and after surgery in patients with preoperative BMI &#x2265;25 and postoperative biochemical remission
    • 2.2g PLS-DA results:
    • 2.2h Normalization Result (40 samples, 20 pairs):
    • 2.2h Statistical analysis results for comparison before and after surgery in patients with preoperative age <45 and postoperative biochemical remission
    • - PLS-DA results:
    • 2.2i Normalization Result (66 samples, 33 pairs):
    • 2.2i Statistical analyses results for comparison before and after surgery in patients with preoperative age &#x2265;45 and postoperative biochemical remission
    • 2.2i PLS-DA results:
    • REFERENCES

 

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