Health-related quality of life in adrenocortical carcinoma:Development of the disease-specific questionnaire ACC-QOL and results from the PROFILES registry

We aimed to develop a disease-specific adrenocortical carcinoma (ACC) health-related quality of life (HRQoL) questionnaire (ACC-QOL) and assess HRQoL in a population-based cohort of patients with ACC. Development was in line with European Organization for Research and Treatment of Cancer (EORTC) guidelines, though not an EORTC product. In phase I and II, we identified 90 potential HRQoL issues using literature and focus groups, which were reduced to 39 by healthcare professionals. Pilot testing resulted in 28 questions, to be used alongside the EORTC QLQ-C30. In Phase III, 100 patients with ACC were asked to complete the questionnaires twice in the PROFILES registry (3-month interval, respondents: first 67, second 51). Confirmatory factor analysis demonstrated the structural validity of 26 questions with their scale structure (mitotane side-effects, hypercortisolism/hydrocortisone effects, emotional effects). Internal consistency and reliability were good (Cronbach's alpha 0.897, Interclass correlation coefficient 0.860). Responsiveness analysis showed good discriminative ability (AUC 0.788). Patients diagnosed more than 5 years ago reported a good HRQoL compared with the Dutch reference population, but experienced residual fatigue and emotional problems. Patients who underwent recent treatment reported a lower HRQoL and problems in several domains. In conclusion, we developed an ACC-specific HRQoL questionnaire with good psychometric properties

Efficacy of α-Blockers on Hemodynamic Control during Pheochromocytoma Resection: A Randomized Controlled Trial

CONTEXT: Pretreatment with α-adrenergic receptor blockers is recommended to prevent hemodynamic instability during resection of a pheochromocytoma or sympathetic paraganglioma (PPGL). OBJECTIVE: To determine which type of α-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. Intraoperative 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

Circulating adrenomedullin and B-type natriuretic peptide do not predict blood pressure fluctuations during pheochromocytoma resection: a cross-sectional study

Background: 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.Diabetes mellitus: pathophysiological changes and therap

Increased Mortality in SDHB but Not in SDHD Pathogenic Variant Carriers

Germline mutations in succinate dehydrogenase subunit B and D (SDHB and SDHD) are predisposed to hereditary paraganglioma (PGL) and pheochromocytoma (PHEO). The phenotype of pathogenic variants varies according to the causative gene. In this retrospective study, we estimate the mortality of a nationwide cohort of SDHB variant carriers and that of a large cohort of SDHD variant carriers and compare it to the mortality of a matched cohort of the general Dutch population. A total of 192 SDHB variant carriers and 232 SDHD variant carriers were included in this study. The Standard Mortality Ratio (SMR) for SDHB mutation carriers was 1.89, increasing to 2.88 in carriers affected by PGL. For SDHD variant carriers the SMR was 0.93 and 1.06 in affected carriers. Compared to the general population, mortality seems to be increased in SDHB variant carriers, especially in those affected by PGL. In SDHD variant carriers, the mortality is comparable to that of the general Dutch population, even if they are affected by PGL. This insight emphasizes the significance of DNA-testing in all PGL and PHEO patients, since different clinical risks may warrant gene-specific management strategies

Unenhanced CT imaging is highly sensitive to exclude pheochromocytoma: A multicenter study

Background: A substantial proportion of all pheochromocytomas is currently detected during the evaluation of an adrenal incidentaloma. Recently, it has been suggested that biochemical testing to rule out pheochromocytoma is unnecessary in case of an adrenal incidentaloma with an unenhanced attenuation value ≤10Hounsfield Units (HU) at computed tomography (CT). Objectives: We aimed to determine the sensitivity of the 10HU threshold value to exclude a pheochromocytoma. Methods: Retrospective multicenter study with systematic reassessment of preoperative unenhanced CT scans performed in patients in whom a histopathologically proven pheochromocytoma had been diagnosed. Unenhanced attenuation values were determined independently by two experienced radiologists. Sensitivity of the 10HU threshold was calculated, and interobserver consistency was assessed using the intraclass correlation coefficient (ICC). Results: 214 patients were identified harboring a total number of 222 pheochromocytomas. Maximum tumor diameter was 51 (39–74)mm. The mean attenuation value within the region of interest was 36±10HU. Only one pheochromocytoma demonstrated an attenuation value ≤10HU, resulting in a sensitivity of 99.6% (95% CI: 97.5–99.9). ICC was 0.81 (95% CI: 0.75–0.86) with a standard error of measurement of 7.3HU between observers. Conclusion: The likelihood of a pheochromocytoma with an unenhanced attenuation value ≤10HU on CT is very low. The interobserver consistency in attenuation measurement is excellent. Our study supports the recommendation that in patients with an adrenal incidentaloma biochemical testing for ruling out pheochromocytoma is only indicated in adrenal tumors with an unenhanced attenuation value >10HU

Response to Letter to the Editor: "Approach to the Patient: Perioperative Management of the Patient With Pheochromocytoma or Sympathetic Paraganglioma"

Contains fulltext : 229491.pdf (Publisher’s version ) (Open Access

Approach to the Patient: Perioperative Management of the Patient with Pheochromocytoma or Sympathetic Paraganglioma

Contains fulltext : 225527.pdf (Publisher’s version ) (Closed access)Pheochromocytomas and sympathetic paraganglioma (PPGL) are rare chromaffin cell tumors originating in the adrenal medulla and sympathetic paraganglia, respectively, which share the capacity to synthesize and release catecholamines. The incidence of PPGL has increased in recent years. Surgical resection is the only curative treatment for PPGL. Management of patients with PPGL is complex and should be done by a specialized multidisciplinary team in centers with broad expertise. Surgical resection of a PPGL is a high-risk procedure for which optimal pretreatment with antihypertensive drugs is required in combination with state-of-the-art surgical procedures and anesthesiological techniques. In this article we discuss the underlying evidence and the pros and cons of presurgical medical preparation. Finally, the areas of uncertainty and controversies in this field are addressed