Nejvíce citovaný článek - PubMed ID 32222768
Pheochromocytoma With Adrenergic Biochemical Phenotype Shows Decreased GLP-1 Secretion and Impaired Glucose Tolerance
CONTEXT: Pheochromocytomas and paragangliomas (PPGLs) are rare endocrine tumors that frequently produce catecholamines. Catecholamine-induced cardiometabolic complications substantially contribute to increased morbidity and mortality in PPGL patients prior to surgical resection. OBJECTIVE: To determine whether markers of elevated cardiometabolic risk persist in patients following PPGL resection. METHODS: In this retrospective analysis of a multicenter cohort of patients with PPGLs participating in the prospective ProsPheo study and the ENS@T registry, cardiometabolic risk factors, including glycemic status, dyslipidemia, and body mass index (BMI), were assessed in patients with PPGL at diagnosis and during follow-up. Patients with a history of resected PPGL were compared to a control group with nonfunctioning adrenal adenomas from the ENS@T registry. RESULTS: Patients with a present PPGL or a history of PPGL (n = 188), a metastatic PPGL (n = 27), or a known susceptibility gene pathogenic variant (PV) for the development of PPGL without a history of PPGL (n = 44) were included. We compared the asymptomatic PV carriers to patients with a history of PPGL: those with a history of PPGL showed a significantly higher prevalence of hyperglycemic disorders (P = .013) compared with asymptomatic PV carriers. In patients with a history of PPGL and at least 12 months of follow-up post surgery (n = 113), the prevalence of hyperglycemic disorders (P < .001), as well as the mean HbA1c (5.63%, SD 0.43%), were significantly higher, compared to a control group with nonfunctioning adrenal adenomas (n = 76) of similar age and BMI (HbA1c 5.45%, SD 0.40%; P = .004). CONCLUSION: Glycemic disturbances persist long-term after the resection of PPGL.
- Klíčová slova
- HbA1c, cardiometabolic risk, diabetes, glucose intolerance, paraganglioma, pheochromocytoma,
- MeSH
- dospělí MeSH
- feochromocytom * chirurgie komplikace epidemiologie patologie MeSH
- kardiometabolické riziko MeSH
- krevní glukóza analýza MeSH
- lidé středního věku MeSH
- lidé MeSH
- nádory nadledvin * chirurgie komplikace epidemiologie patologie MeSH
- následné studie MeSH
- paragangliom * chirurgie komplikace epidemiologie patologie MeSH
- prospektivní studie MeSH
- retrospektivní studie MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- Názvy látek
- krevní glukóza MeSH
The overproduction of catecholamines in pheochromocytoma/paraganglioma (PPGL) induces a hypermetabolic state. The aim of this study was to evaluate the incidence of a hypermetabolic state and differences in substrate metabolism in consecutive PPGL patients divided by catecholamine phenotype. Resting energy expenditure (REE) and respiratory quotient (RQ) were measured in 108 consecutive PPGL patients and 70 controls by indirect calorimetry. Hypermetabolic state was defined according to the Mifflin St. Jeor Equation as a ratio above 110%. Hypermetabolic state was confirmed in 70% of PPGL patients, regardless of phenotype. Older age, prevalence of diabetes mellitus and arterial hypertension were correlated with hypermetabolic PPGL as compared to normometabolic form. Analysis according to overproduced catecholamine showed differences in VCO2 (p < 0.05) and RQ (p < 0.01) and thus different substate metabolism between phenotypes in hypermetabolic form of PPGL. Lipid utilization was higher in the adrenergic phenotype (p = 0.001) and positively associated with the percentage of REE ratio (R = 0.48, p < 0.001), whereas the noradrenergic phenotype preferentially oxidizes carbohydrates (P = 0.001) and is correlated with the percentage of REE ratio (R = 0.60, p < 0.001). Hypermetabolic state in PPGL is a common finding in both catecholamine phenotypes. Hypermetabolic PPGL patients are older and suffer more from diabetes mellitus and arterial hypertension. Under basal conditions, the noradrenergic type preferentially metabolizes carbohydrates, whereas the adrenergic phenotype preferentially metabolizes lipids.
- Klíčová slova
- catecholamines, functional paraganglioma, indirect calorimetry, metanephrines, pheochromocytoma, respiratory quotient, resting energy expenditure, substrate metabolism,
- Publikační typ
- časopisecké články MeSH
Background: Brown adipose tissue (BAT) is a therapeutic target to combat obesity and related disorders. Pheochromocytoma and functional paraganglioma (PPGL) are associated with activated BAT due to catecholamine excess. Our aim was to evaluate BAT activity by gene profile and assess its relation to clinical characteristics and overproduced catecholamine. Methods: mRNA expression of 15 genes in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) was measured via RT-PCR in 25 patients with PPGL and 14 controls undergoing cholecystectomy. Results: We found in VAT of PPGL higher expression of UCP1 (p < 0.001), CEBPB, PPARGC1A (both p < 0.001), PRDM16 (p = 0.069) and DIO2 (p = 0.005). UCP1 expression correlated only with norepinephrine levels and its metabolite. UCP1 expression, among others, correlated negatively with BMI, age and positively with HDLc levels. Dominance of BAT or BeAT markers was not assessed in PPGL. In SAT of PPGL, we found higher expression of ADRB3, CIDEA (both p < 0.05), and PPARGC1A (p = 0.001), but not UCP1. Conclusion: We demonstrate signs of UCP1-dependent norepinephrine-induced thermogenesis connected with higher expression of DIO2, PPARGC1A, CEBPB and PRDM16 in retroperitoneal VAT of PPGL and its relations to circulating HDLc and triglycerides levels. However, no direct relationship with increased basal energy metabolism measured by calorimetry was found.
- Klíčová slova
- beige adipose tissue, brown adipose tissue, energy metabolism, functional paraganglioma, gene expression, lipids, metabolism, pheochromocytoma,
- Publikační typ
- časopisecké články MeSH