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Surgical Resection of Pheochromocytomas and Paragangliomas is Associated with Lower Cholesterol Levels.

ABSTRACT: BACKGROUND:Catecholamine excess in patients with pheochromocytomas or paragangliomas (PPGLs) can lead to hypertension, diabetes and hyperlipidemia. The aim was to investigate the prevalence of hyperlipidemia and the effect of surgical resection. METHODS:One hundred and thirty-two patients with PPGLs underwent an operation at the National Institutes of Health from 2009 to 2016, of which 54 patients met the inclusion criteria. Clinical demographics, BMI, genetic mutations, tumor size, perioperative catecholamine levels and perioperative lipid panels were retrospectively reviewed. Spearman correlation between catecholamines and lipid levels was evaluated. Paired Wilcoxon and paired t test were used to analyze differences in pre- and postoperative lipid levels. RESULTS:Preoperatively, 51 patients (94.4%) had elevated catecholamines, thirteen (24.1%) had elevated total cholesterol (TC) (>200 mg/dL), nine (16.6%) had elevated LDL (>130 mg/dL) and ten (18.5%) had elevated triglycerides (>150 mg/dL). Serum and urinary metanephrine levels were positively associated with TC (r?=?0.2792, p?=?0.0372 and r?=?0.4146, p?=?0.0031, respectively) and LDL levels (r?=?0.2977, p?=?0.0259 and r?=?0.4434, p?=?0.0014, respectively). Mean TC decreased from 176.4 to 166.3 mg/dL (p?=?0.0064) and mean HDL decreased from 56.7 to 53.2 mg/dL (p?=?0.0253) after PPGL resection (median 3.1 months (range 1.3-50.2) between lipid panels). Most patients with elevated TC (76.9%) had improvement with mean TC decreasing from 225 to 200.2 mg/dL (p?=?0.0230). Of patients with elevated LDL, 66.7% had improvement with mean LDL decreasing from 149 to 131.1 mg/dL (p?=?0.0313). CONCLUSIONS:The prevalence of hyperlipidemia in patients with PPGLs is 46%. Future prospective studies are needed to determine whether surgical resection improves TC and/or LDL levels.

SUBMITTER: Good ML

PROVIDER: S-EPMC7442156 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Surgical Resection of Pheochromocytomas and Paragangliomas is Associated with Lower Cholesterol Levels.

Good Meghan L ML Malekzadeh Parisa P Ruff Samantha M SM Gupta Shreya S Copeland Amy A Pacak Karel K Nilubol Naris N Kebebew Electron E Patel Dhaval D

World journal of surgery 20200201 2

<h4>Background</h4>Catecholamine excess in patients with pheochromocytomas or paragangliomas (PPGLs) can lead to hypertension, diabetes and hyperlipidemia. The aim was to investigate the prevalence of hyperlipidemia and the effect of surgical resection.<h4>Methods</h4>One hundred and thirty-two patients with PPGLs underwent an operation at the National Institutes of Health from 2009 to 2016, of which 54 patients met the inclusion criteria. Clinical demographics, BMI, genetic mutations, tumor siz ...[more]

PMID: 31531722

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Project description:Pheochromocytomas and paragangliomas are neuroendocrine tumors shown to be responsive to multitargeted tyrosine kinase inhibitor (TKI) treatment. Despite growing knowledge regarding their genetic basis, the ability to predict behavior in these tumors remains challenging. There is also limited knowledge of their tyrosine kinase receptor expression and whether the clinical response observed to the TKI sunitinib relates only to its anti-angiogenic properties or also due to a direct effect on tumor cells. To answer these questions, an in vitro model of sunitinib treatment of a pheochromocytoma cell line was created. Sunitinib targets (VEGFRs, PDGFRs, and C-KIT), FGFRs, and cell cycle regulatory proteins were investigated in human tissue microarrays. SDHB immunohistochemistry was used as a surrogate marker for the presence of succinate dehydrogenase mutations. The FGFR4 G388R single nucleotide polymorphism was also investigated. Sunitinib treatment in vitro decreases cell proliferation mainly by targeting cell cycle, DNA metabolism, and cell organization genes. FGFR1, -2, and -4, VEGFR2, PDGFRα, and p16 were overexpressed in primary human pheochromocytomas and paragangliomas. Discordant results were observed for VEGFR1, p27, and p21 overexpressed in paragangliomas but underexpressed in pheochromocytomas; PDGFRβ, Rb, and Cyclin D1 overexpressed in paragangliomas only; and FGFR3 overexpressed in pheochromocytomas and underexpressed in paragangliomas. Low expression of C-KIT, p53, and Aurora kinase A and B was observed. Nuclear FGFR2 expression was associated with increased risk of metastasis (odds ratio (OR)=7.61, P=0.008), as was membranous PDGFRα (OR=13.71, P=0.015), membranous VEGFR1 (OR=8.01, P=0.037), nuclear MIB1 (OR=1.26, P=0.008), and cytoplasmic p27 (OR=1.037, P=0.030). FGFR3, VEGFR2, and C-KIT levels were associated with decreased risk of metastasis. We provide new insights into the mechanistic actions of sunitinib in pheochromocytomas and paragangliomas, and support current evidence that multitargeted TKIs might be a suitable treatment alternative for these tumors.

Dataset Information

Surgical Resection of Pheochromocytomas and Paragangliomas is Associated with Lower Cholesterol Levels.

Publications

Surgical Resection of Pheochromocytomas and Paragangliomas is Associated with Lower Cholesterol Levels.

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