Background: Despite adequate presurgical management, blood pressure fluctuations are common during resection of pheochromocytoma or sympathetic paraganglioma (PPGL). To a large extent, the... Show moreBackground: Despite adequate presurgical management, blood pressure fluctuations are common during resection of pheochromocytoma or sympathetic paraganglioma (PPGL). To a large extent, the variability in blood pressure control during PPGL resection remains unexplained. Adrenomedullin and B-type natriuretic peptide, measured as MR-proADM and NT-proBNP, respectively, are circulating biomarkers of cardiovascular dysfunction. We investigated whether plasma levels of MR-proADM and NT-proBNP are associated with blood pressure fluctuations during PPGL resection. Methods: Study subjects participated in PRESCRIPT, a randomized controlled trial in patients undergoing PPGL resection. MR-proADM and NT-proBNP were determined in a single plasma sample drawn before surgery. Multivariable linear and logistic regression analyses were used to explore associations between these biomarkers and blood pressure fluctuations, use of vasoconstrictive agents during surgery as well as the occurrence of perioperative cardiovascular events. Results: A total of 126 PPGL patients were included. Median plasma concentrations of MR-proADM and NT-proBNP were 0.51 (0.41-0.63) nmol/L and 68.7 (27.9-150.4) ng/L, respectively. Neither MR-proADM nor NT-proBNP were associated with blood pressure fluctuations. There was a positive correlation between MR-proADM concentration and the cumulative dose of vasoconstrictive agents (03B2 0.44, P = 0.001). Both MR-proADM and NT-proBNP were significantly associated with perioperative cardiovascular events (OR: 5.46, P = 0.013 and OR: 1.54, P = 0.017, respectively). Conclusions: plasma MR-proADM or NT-proBNP should not be considered as biomarkers for the presurgical risk assessment of blood pressure fluctuations during PPGL resection. Future studies are needed to explore the potential influence of these biomarkers on the intraoperative requirement of vasoconstrictive agents and the perioperative cardiovascular risk. Show less
Context: Pretreatment with alpha-adrenergic receptor blockers is recommended to prevent hemodynamic instability during resection of a pheochromocytoma or sympathetic paraganglioma (PPGL).Objective:... Show moreContext: Pretreatment with alpha-adrenergic receptor blockers is recommended to prevent hemodynamic instability during resection of a pheochromocytoma or sympathetic paraganglioma (PPGL).Objective: To determine which type of alpha-adrenergic receptor blocker provides the best efficacy.Design: Randomized controlled open-label trial (PRESCRIPT; ClinicalTrials.gov NCT01379898)Setting: Multicenter study including 9 centers in The Netherlands.Patients: 134 patients with nonmetastatic PPGL.Intervention: Phenoxybenzamine or doxazosin starting 2 to 3 weeks before surgery using a blood pressure targeted titration schedule. lntraoperative hemodynamic management was standardized.Main Outcome Measures: Primary efficacy endpoint was the cumulative intraoperative time outside the blood pressure target range (ie, SBP >160 mmHg or MAP <60 mmHg) expressed as a percentage of total surgical procedure time. Secondary efficacy endpoint was the value on a hemodynamic instability score.Results: Median cumulative time outside blood pressure targets was 11.1% (interquartile range [IQR]: 4.3-20.6] in the phenoxybenzamine group compared to 12.2% (5.3-20.2)] in the doxazosin group (P = .75, r = 0.03). The hemodynamic instability score was 38.0 (28.8-58.0) and 50.0 (35.3-63.8) in the phenoxybenzamine and doxazosin group, respectively (P = .02, r = 0.20). The 30-day cardiovascular complication rate was 8.8% and 6.9% in the phenoxybenzamine and doxazosin group, respectively (P = .68). There was no mortality after 30 days.Conclusions: The duration of blood pressure outside the target range during resection of a PPGL was not different after preoperative treatment with either phenoxybenzamine or doxazosin. Phenoxybenzamine was more effective in preventing intraoperative hemodynamic instability, but it could not be established whether this was associated with a better clinical outcome. Show less
PurposeClinically non-functioning pituitary macroadenomas (NFMA) have been reported to express somatostatin receptors (SSTR), but results are inconsistent across different studies. This may be... Show morePurposeClinically non-functioning pituitary macroadenomas (NFMA) have been reported to express somatostatin receptors (SSTR), but results are inconsistent across different studies. This may be related to limited sensitivity and specificity of techniques used to date, i.e. immunohistochemistry in surgical specimens and In-111-DTPA-octreotide scintigraphy in vivo. The aim of this study was to assess SSTR expression in NFMA in vivo using Ga-68-DOTATATE PET, which offers superior sensitivity and spatial resolution as compared with planar scintigraphy or SPECT.MethodsThirty-seven patients diagnosed with NFMA underwent Ga-68-DOTATATE PET/CT of the head in the framework of a randomised controlled trial assessing the effect of the somatostatin analogue lanreotide on NFMA size. Individual co-registered T1-weighted pituitary MRIs were used to assess Ga-68-DOTATATE uptake (SUVmean) in the adenoma. An SUVmean of >2 was considered positive.Results(68)Ga-DOTATATE uptake was positive in 34/37 patients (92%), with SUVmean of positive adenomas ranging from 2.1 to 12.4 (meanSD 5.82.6).Conclusions This is the first report of Ga-68-DOTATATE PET performed in NFMA patients, demonstrating in vivo SSTR expression in the vast majority of cases. The high positivity rate when compared with results obtained with In-111-DTPA-octreotide scintigraphy probably reflects the superior sensitivity of PET imaging.Trial registrationNetherlands Trial Register, NL5136, registered on 18 August 2015; EudraCT, 2015-001234-22, registered on 10 March 2015, https://eudract.ema.europa.eu/ Show less
Introduction At present, there is no approved medical treatment option for patients with non-functioning pituitary adenoma. A number of open-label studies suggest that treatment with somatostatin... Show moreIntroduction At present, there is no approved medical treatment option for patients with non-functioning pituitary adenoma. A number of open-label studies suggest that treatment with somatostatin analogues may prevent tumour progression. In vivo somatostatin receptor imaging using(68)Ga-DOTATATE PET (PET, positron emission tomography) could help in preselecting patients potentially responsive to treatment. Our aim is to investigate the effect of the somatostatin analogue lanreotide as compared with placebo on tumour size in patients with a(68)Ga-DOTATATE PET-positive non-functioning pituitary macroadenoma (NFMA). Methods and analysis The GALANT study is a multicentre, randomised, double-blind, placebo-controlled trial in adult patients with a suprasellar extending NFMA. Included patients undergo a(68)Ga-DOTATATE PET/CT of the head and tracer uptake is assessed after coregistration with pituitary MRI. Forty-four patients with a(68)Ga-DOTATATE PET-positive NFMA are randomised in a 1:1 ratio between lanreotide 120 mg or placebo, both administered as subcutaneous injections every 28 days for 72 weeks. The primary outcome is the change in cranio-caudal tumour diameter on pituitary MRI after treatment. Secondary outcomes are change in tumour volume, time to tumour progression, change in quality of life and number of adverse events. Final results are expected in the second half of 2021. Ethics and dissemination The study protocol has been approved by the Medical Research Ethics Committee of the Academic Medical Centre (AMC) of the Amsterdam University Medical Centres and by the Dutch competent authority. It is an investigator-initiated study with financial support by Ipsen Farmaceutica BV. The AMC, as sponsor, remains owner of all data. Results will be submitted for publication in a peer-reviewed journal. Show less
