Recurrent Disease in Patients With Sporadic Pheochromocytoma and Paraganglioma

Supplemental Appendix for manuscript 'Recurrent disease in patients with sporadic pheochromocytoma and paraganglioma

Sympathoinhibition by atorvastatin in hypertensive patients.

Contains fulltext : 89086.pdf (publisher's version ) (Open Access)BACKGROUND: Experimental animal data suggest that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) might reduce enhanced sympathetic activity, a hallmark of hypertensive patients. This hypothesis was tested for the first time in patients with primary hypertension. METHODS AND RESULTS: Using a prospective, randomized, placebo-controlled, double-blind, cross-over design, a proof-of-principle trial was performed in 13 patients with mild to moderate primary hypertension, who were randomly assigned to a regimen of atorvastatin (80mg/day) for 3 weeks, followed by placebo for 3 weeks or to a regimen of placebo for 3 weeks, followed by atorvastatin (80mg/day) for 3 weeks. Microneurography was used at the end of each treatment period to measure sympathetic nervous system activity (muscle sympathetic nerve activity: MSNA). Heart rate variability (HRV) and plasma norepinephrine concentrations were also measured. Additionally, effects on blood pressure (BP) and heart rate (HR) were assessed by 24-h ambulatory BP measurement. Atorvastatin reduced postganglionic MSNA (atorvastatin 35.0+/-2.0 vs placebo: 39.2+/-1.5 bursts/min, P=0.008) and heart frequency corrected MSNA (atorvastatin: 58.5+/-2.0 vs placebo: 64.7+/-3.0 bursts/100 beats, P=0.02). Atorvastatin had no significant effect on plasma norepinephrine levels, HRV, BP or HR. CONCLUSIONS: In patients with mild to moderate hypertension, atorvastatin reduces postganglionic MSNA, which supports the hypothesis that HMG-CoA reductase plays a role in sympathetic nervous system activity

Скринінг ендокринної гіпертензії. Наукова заява Ендокринологічного товариства

Hypertension may be the initial clinical presentation for at least 15 endocrine disorders. An accurate diagnosis of endocrine hypertension provides clinicians with the opportunity to render a surgical cure or to achieve an optimal clinical response with specific pharmacologic therapy. It is challenging for the clinician to know when and how to perform case-detection testing for all the endocrine disorders in which hypertension may be the presenting symptom. Herein, we review the different forms of endocrine hypertension, with a focus on prevalence, clinical presentation, guidance on when to perform case detection testing, and currently available case-detection tests.Hypertension affects 28.6% of adults in United States. In most, hypertension is primary (essential or idiopathic), but a subgroup of approximately 15% has secondary hypertension. More than 50% of children who present with hypertension have a secondary cause. In young adults (< 40 years old), the prevalence of secondary hypertension is approximately 30%. The secondary causes of hypertension include renal causes (e.g., renal parenchymal disease) and endocrine causes. Hypertension may be the initial clinical presentation many endocrine disorders: pheochromocytoma and sympathetic paraganglioma, primary aldosteronism, hyperdeoxycorticosteronism (congenital adrenal hyperplasia – 11b-hydroxylase deficiency, 17a-hydroxylase deficiency, deoxycorticosterone-producing tumor, primary cortisol resistance), cushing syndrome, apparent mineralocorticoid excess / 11b-hydroxysteroid dehydrogenase deficiency, hyperparathyroidism, secondary hyperaldosteronism, renovascular hypertension, hypothyroidism, hyperthyroidism, obstructive sleep apnea and others.Clinical context is important. For example, case detection for endocrine hypertension may not be clinically important in an older patient with multiple life-limiting comorbidities. However, screening for endocrine hypertension may be key to enhancing and prolonging life in most patients with hypertension, especially younger patients.Артериальная гипертензия может быть первоначальным клиническим проявлением, по меньшей мере, 15 эндокринных расстройств. Точный диагноз эндокринной гипертензии позволяет клиницистам выполнить хирургическое лечение или добиться оптимального клинического ответа в ходе специфической фармакологической терапии. Клиницисту важно знать, когда и как следует проводить исследование по выявлению случаев всех эндокринных нарушений, при которых гипертензия может являться симптомом. В данной статье рассмотрены различные формы эндокринной гипертензии с акцентом на распространенность и клиническую картину, а также даны рекомендации относительно того, когда следует проводить исследования для выявления заболевания, и описаны имеющиеся в настоящее время диагностические тесты.Артериальной гипертензией страдает 28,6% взрослого населения США. В большинстве случаев она является первичной (основной или идиопатической), но приблизительно у 15% пациентов выявляется вторичная артериальная гипертензия. Более 50% детей с артериальной гипертензией имеют вторичную причину заболевания. У людей моложе 40 лет распространенность вторичной гипертензии составляет примерно 30%. Вторичные причины артериальной гипертензии включают почечные (например, паренхиматозные заболевания почек) и эндокринные. Гипертензия может быть начальным клиническим проявлением многих эндокринных расстройств: феохромоцитомы и симпатической параганглиомы, первичного альдостеронизма, гипердезоксикортикостеронизма (врожденная гиперплазия надпочечников – 11β-гидроксилазная недостаточность, 17α-гидроксилазная недостаточность, дезоксикортикостерон-продуцирующая опухоль, первичная резистентность кортизола), синдрома Кушинга, мнимого избытка минералокортикоидов/дефицита 11β-гидроксистероиддегидрогеназы, гиперпаратиреоза, вторичного гиперальдостеронизма, реноваскулярной гипертензии, гипотиреоза, гипертиреоза, обструктивного апноэ сна и др.Большое значение имеет клинический контекст заболевания. Например, выявление случаев эндокринной гипертензии может не иметь клинического значения у пожилого пациента с множественными сопутствующими заболеваниями, которые ограничивают качество жизни. Однако скрининг на эндокринную гипертензию может стать ключом к улучшению и продлению жизни большинства пациентов с артериальной гипертензией, особенно молодых.Артеріальна гіпертензія може бути первинним клінічним проявом щонайменше 15 ендокринних розладів. Точний діагноз ендокринної гіпертензії дозволяє клініцистам здійснити хірургічне лікування або досягти оптимальної клінічної відповіді під час специфічної фармакологічної терапії. Клініцисту важливо знати, коли і як слід проводити дослідження щодо виявлення випадків усіхендокринних порушень, при яких гіпертензія може бути симптомом. У даній статті розглянуті різні форми ендокринної гіпертензії з наголосом на поширеність і клінічну картину, а також представлені рекомендації щодо того, коли слід проводити дослідження для виявлення захворювання, і описані наявні діагностичні тести.На артеріальну гіпертензію страждає 28,6% дорослого населення США. У більшості випадків вона є первинною (основною або ідіопатичною), але приблизно у 15% пацієнтів виявляється вторинна артеріальна гіпертензія. Понад 50% дітей з артеріальною гіпертензією мають вторинну причину захворювання. У людей, молодших за 40 років, поширеність вторинної гіпертензії становить приблизно 30%. Вторинні причини артеріальної гіпертензії включають ниркові (наприклад, паренхіматозні захворювання нирок) та ендокринні. Гіпертензія може бути початковим клінічним проявом багатьох ендокринних розладів: феохромоцитоми і симпатичної парагангліоми, первинного альдостеронізму, гіпердезоксикортикостеронізму (вроджена гіперплазія наднирників – 11β-гідроксилазна недостатність, 17α-гідроксилазна недостатність, пухлина, що продукує дезоксикортикостерон, первинна резистентність кортизолу), синдрому Кушинга, уявного надлишку мінералокортикоїдів / дефіциту 11β-гідроксистероїддегідрогенази, гіперпаратиреозу, вторинного гіперальдостеронізму, реноваскулярної гіпертензії, гіпотиреозу, гіпертиреозу, обструктивного апное сну та ін.Велике значення має клінічний контекст захворювання. Наприклад, виявлення випадків ендокринної гіпертензії може не мати клінічного значення в літнього пацієнта з численними супутніми захворюваннями, які обмежують якість життя. Однак скринінг на ендокринну гіпертензію може стати ключем до поліпшення і продовження життя більшості пацієнтів із артеріальною гіпертензією, особливо молодих

Somatic SDHB mutation in an extraadrenal pheochromocytoma.

Contains fulltext : 52051.pdf (publisher's version ) (Open Access

Patient characteristics do not predict the individual response to antihypertensive medication: A cross-over trial

Background. International guidelines on hypertension management do not agree on whether patient characteristics can be used for the first choice of treatment of uncomplicated essential hypertension. Objective. We wanted to identify predictive patient characteristics to the response of two different classes of antihypertensive drugs in patients with newly diagnosed hypertension in primary care. Methods. We conducted a prospective, open label, blinded endpoint cross-over trial in 120 patients with a new diagnosis of hypertension from 10 family practices. Patients received 4 weeks of 12.5 mgr hydrochlorothiazide once daily and 4 weeks of 80 mgr valsartan once daily, each followed by a 4-week washout. The sequence of drugs was randomized. Age, sex and menopausal state were recorded at run in and 24 h ambulatory blood pressure, office blood pressure, plasma renin concentration, NT-proBNP, potassium, estimated glomerular filtration rate, urinary albumin, body mass index and waist circumference at each regimen change. The difference in systolic blood pressure response between both study drugs, calculated from mean daytime ambulatory blood pressures, was the main outcome measure. Results. Ninety-eight patients (52% female; median age 53 years) were eligible for per-protocolanalysis. None of the studied variables were predictive for the difference in systolic blood pressure response. Individual systolic blood pressure responses ranged from an increase by 18 mmHg to a decrease of 39 mmHg. Conclusion. In a relevant group of primary care patients with newly diagnosed hypertension, we were unable to detect predictors of treatment response. This study rather supports the United States and European guidelines than the United Kingdom and Dutch guidelines on hypertension.This study was funded by the department of Primary and Community Care, Radboud university medical center and by an unconditional grant of Novartis to cover the material costs of the stud

Interaction in COPD experiment (ICE): A hazardous combination of cigarette smoking and bronchodilation in chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a highly prevalent disease, characterised by poorly reversible, obstructive airflow limitation. Alongside other comorbidities, COPD is associated with increased morbidity and mortality resulting from cardiovascular disease - mainly heart failure and ischemic heart disease. Both diseases share an important risk factor, namely, smoking. About 50% of COPD patients are active cigarette smokers. Bronchodilation is the cornerstone of pharmaceutical treatment for COPD symptoms, and half of all COPD patients use long-acting bronchodilating agents. Discussion about these agents is currently focusing on the association with overall mortality and morbidity in COPD patients, of cardiovascular origin in particular. Bronchodilation diminishes the hyperinflated state of the lung and facilitates the pulmonary deposition of cigarette smoke by deeper inhalation into the smaller airways. Smaller particles, as in smoke, tend to penetrate and depose more in these small airways. In addition, bronchodilation indeed increases carbon monoxide uptake in the lungs, an important gaseous compound of cigarette smoke. Since the number of cigarettes smoked is positively correlated to mortality from cardiac events, we therefore hypothesise that chronic bronchodilation increases cardiovascular disease and mortality in COPD patients who continue smoking by increasing pulmonary retention of pathogenic smoke constituents. Indeed, a recent meta-analysis is suggestive that long-acting anticholinergics might increase cardiovascular disease if patients exceed a certain number of cigarettes smoked. To demonstrate the fundamental mechanism of this pathogenic interaction we will perform a randomised placebo-controlled cross-over trial to investigate the effect of maximum bronchodilation on the retention of cigarette smoke constituents. In 40 moderate to severe COPD patients we measure the inhaled and exhaled amount of tar and nicotine, as well during maximum bronchodilation as during administration of placebo. The fraction of retention of tar and nicotine is subsequently calculated for both circumstances and analysed for association with bronchodilation. Further observational cohort studies or randomised clinical trials designed to monitor cardiovascular events may well evaluate the interaction. Since many patients are at risk for this possibly hazardous interaction, its relevance to our society and healthcare is potentially great. The implication will be that the urgency to quit smoking is intensified. Besides, chronic bronchodilation - specifically long-acting bronchodilators - needs to be discouraged in smoking COPD patients that refuse to quit

Bronchodilation and smoking interaction in COPD: A cohort pilot study to assess cardiovascular risk

Background: Smoking and bronchodilator treatment are both extensively studied as key elements in patients with chronic obstructive pulmonary disease. However, little is known about whether or not these elements interact in terms of developing cardiovascular diseases in patients with COPD. Objectives: To explore to what extent the risk of developing ischemic cardiovascular disease in COPD patients is mediated by smoking status, use of bronchodilators and - specifically - their interaction. Methods: We performed an observational pilot study on a relatively healthy Dutch COPD cohort from a primary care diagnostic center database with full information on spirometry tests, smoking status, bronchodilator use and other prescribed medication. We defined first ischemic cardiovascular events as primary outcome, measured by first prescription of antiplatelet drugs and/or nitrates. Unadjusted analyses by Kaplan-Meier were followed by adjusted Cox' proportional hazards. Results: 845 COPD patients, totaling 2,169 observation years, were included in the analyses. We observed an increased risk for nonfatal ischemic cardiovascular events by smoking (adjusted HR = 3.58, p = 0.001) and a protective effect of bronchodilators (adjusted HR = 0.43, p = 0.01). Although the protective effect of bronchodilators appears to be substantially minimized in patients that persist in smoking, we could not statistically confirm a hazardous interaction between bronchodilators and smoking (HR 2.50, p = 0.21). Conclusion: Our study reveals bronchodilators may protect from ischemic cardiovascular events in a relatively 'healthy' COPD population. We did not confirm a hazardous interaction between bronchodilators and smoking, although we observed current smokers benefit substantially less from the protective effect of bronchodilators

Age at Diagnosis of Pheochromocytoma Differs According to Catecholamine Phenotype and Tumor Location

Ages at diagnosis of pheochromocytomas and paragangliomas vary according to the catecholamine phenotypes and locations of tumors