| 1. |
- Eisenhofer, G., et al.
(författare)
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Plasma methoxytyramine: A novel biomarker of metastatic pheochromocytoma and paraganglioma in relation to established risk factors of tumour size, location and SDHB mutation status
- 2012
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 0959-8049. ; 48:11, s. 1739-1749
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Tidskriftsartikel (refereegranskat)abstract
- Background: There are currently no reliable biomarkers for malignant pheochromocytomas and paragangliomas (PPGLs). This study examined whether measurements of catecholamines and their metabolites might offer utility for this purpose. Methods: Subjects included 365 patients with PPGLs, including 105 with metastases, and a reference population of 846 without the tumour. Eighteen catecholamine-related analytes were examined in relation to tumour location, size and mutations of succinate dehydrogenase subunit B (SDHB). Results: Receiver-operating characteristic curves indicated that plasma methoxytyramine, the O-methylated metabolite of dopamine, provided the most accurate biomarker for discriminating patients with and without metastases. Plasma methoxytyramine was 4.7-fold higher in patients with than without metastases, a difference independent of tumour burden and the associated 1.6- to 1.8-fold higher concentrations of norepinephrine and normetanephrine. Increased plasma methoxytyramine was associated with SDHB mutations and extra-adrenal disease, but was also present in patients with metastases without SDHB mutations or those with metastases secondary to adrenal tumours. High risk of malignancy associated with SDHB mutations reflected large size and extra-adrenal locations of tumours, both independent predictors of metastatic disease. A plasma methoxytyramine above 0.2 nmol/L or a tumour diameter above 5 cm indicated increased likelihood of metastatic spread, particularly when associated with an extra-adrenal location. Conclusion: Plasma methoxytyramine is a novel biomarker for metastatic PPGLs that together with SDHB mutation status, tumour size and location provide useful information to assess the likelihood of malignancy and manage affected patients. (C) 2011 Elsevier Ltd. All rights reserved.
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| 2. |
- Petersson, Magnus, 1965, et al.
(författare)
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Long-term outcome in relation to renal sympathetic activity in patients with chronic heart failure
- 2005
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Ingår i: Eur Heart J. - 0195-668X. ; 26:9, s. 906-13
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Although cardiac sympathetic activation is associated with adverse outcome in patients with chronic heart failure (CHF), the influence of renal sympathetic activity on outcome is unknown. We assessed the hypothesis that renal noradrenaline (NA) spillover is a predictor of the combined endpoint of all-cause mortality and heart transplantation in CHF. METHODS AND RESULTS: Sixty-one patients with CHF, New York Heart Association (NYHA) I-IV (66% NYHA III-IV), and left ventricular ejection fraction (LVEF) 26+/-9% (mean+/-SD) were studied with cardiac and renal catheterizations at baseline and followed for 5.5+/-3.7 years (median 5.5 years, range 12 days to 11.6 years). Nineteen deaths and 13 cases of heart transplantation were registered. Only renal NA spillover above median, 1.19 (interquartile range 0.77-1.43) nmol/min, was independently associated with an increased relative risk (RR) of the combined endpoint (RR 3.1, 95% CI 1.2-7.6, P=0.01) in a model also including total body NA spillover, LVEF, glomerular filtration rate (GFR), renal blood flow, cardiac index, aetiology, and age. CONCLUSION: Renal noradrenergic activation has a strong negative predictive value on outcome independent of overall sympathetic activity, GFR, and LVEF. These findings suggest that treatment regimens that further reduce renal noradrenergic stimulation could be advantageous by improving survival in patients with CHF.
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| 3. |
- Pacak, K., et al.
(författare)
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Pheochromocytoma: recommendations for clinical practice from the First International Symposium. October 2005
- 2007
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Ingår i: Nature clinical practice. - : Springer Science and Business Media LLC. - 1745-8366. ; 3:2, s. 92-102
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Tidskriftsartikel (refereegranskat)abstract
- The First International Symposium on Pheochromocytoma, held in October 2005, included discussions about developments concerning these rare catecholamine-producing tumors. Recommendations were made during the symposium for biochemical diagnosis, localization, genetics, and treatment. Measurement of plasma or urinary fractionated metanephrines, the most accurate screening approach, was recommended as the first-line test for diagnosis; reference intervals should favor sensitivity over specificity. Localization studies should only follow reasonable clinical evidence of a tumor. Preoperative pharmacologic blockade of circulatory responses to catecholamines is mandatory. Because approximately a quarter of tumors develop secondary to germ-line mutations in any one of five genes, mutation testing should be considered; however, it is not currently cost effective to test every gene in every patient. Consideration of tumor location, presence of multiple tumors, presence of metastases, and type of catecholamine produced is useful in deciding which genes to test. Inadequate methods to distinguish malignant from benign tumors and a lack of effective treatments for malignancy are important problems requiring further resolution.
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| 4. |
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| 5. |
- Taïeb, David, et al.
(författare)
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Management of phaeochromocytoma and paraganglioma in patients with germline SDHB pathogenic variants : an international expert Consensus statement
- 2024
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Ingår i: Nature Reviews Endocrinology. - : Springer Nature. - 1759-5029 .- 1759-5037. ; 20:3, s. 168-184
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Forskningsöversikt (refereegranskat)abstract
- Adult and paediatric patients with pathogenic variants in the gene encoding succinate dehydrogenase (SDH) subunit B (SDHB) often have locally aggressive, recurrent or metastatic phaeochromocytomas and paragangliomas (PPGLs). Furthermore, SDHB PPGLs have the highest rates of disease-specific morbidity and mortality compared with other hereditary PPGLs. PPGLs with SDHB pathogenic variants are often less differentiated and do not produce substantial amounts of catecholamines (in some patients, they produce only dopamine) compared with other hereditary subtypes, which enables these tumours to grow subclinically for a long time. In addition, SDHB pathogenic variants support tumour growth through high levels of the oncometabolite succinate and other mechanisms related to cancer initiation and progression. As a result, pseudohypoxia and upregulation of genes related to the hypoxia signalling pathway occur, promoting the growth, migration, invasiveness and metastasis of cancer cells. These factors, along with a high rate of metastasis, support early surgical intervention and total resection of PPGLs, regardless of the tumour size. The treatment of metastases is challenging and relies on either local or systemic therapies, or sometimes both. This Consensus statement should help guide clinicians in the diagnosis and management of patients with SDHB PPGLs.
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