Context: Measurements of plasma methoxytyramine, the O-methylated dopamine metabolite, are useful for detecting rare dopamine-producing pheochromocytomas and paragangliomas (PPGLs) and head and neck paragangliomas (HNPGLs), but utility for screening beyond that achieved using standard measurements of normetanephrine and metanephrine is unclear.Objective: Evaluation of the additional utility of methoxytyramine compared to plasma normetanephrine and metanephrine for diagnosis of PPGLs and HNPGLs.Design: Comparative prospective study.Methods: Comparison of mass spectrometric-based measurements of plasma methoxytyramine, normetanephrine and metanephrine in 1963 patients tested for PPGLs at six tertiary medical centers according to reference intervals verified in 423 normotensive and hypertensive volunteers.Results: Of the screened patients, 213 had PPGLs and 38 HNPGLs. Using an upper cut-off of 0.10 nmol/L for methoxytyramine, 0.45 nmol/L for metanephrine and age-specific upper cut-offs for normetanephrine, diagnostic sensitivity with the addition of methoxytyramine increased from 97.2% to 98.6% for patients with PPGLs and from 22.1% to 50.0% for patients with HNPGLs, with a small decrease in specificity from 95.9% to 95.1%. Addition of methoxytyramine did not significantly alter areas under receiver operating characteristic curves for patients with PPGLs (0.984 vs 0.991), but did increase (P < 0.05) areas for patients with HNPGLs (0.627 vs 0.801). Addition of methoxytyramine also increased the proportion of patients with PPGLs who showed highly positive predictive elevations of multiple metabolites (70.9% vs 49.3%).Conclusions: While the benefit of additional measurements of plasma methoxytyramine for the detection of PPGLs is modest, the measurements do assist with positive confirmation of disease and are useful for the detection of HNPGLs.

The association between fibromuscular dysplasia (FMD) and spontaneous cervical artery dissection (SCeAD) has been recognized, but the available evidence on this relationship is scant. Therefore, the main goal of our study was to systematically evaluate FMD frequency, clinical characteristics and vascular bed involvement in patients with SCeAD. Among 230 patients referred to the ARCADIA-POL study, 43 patients (mean age 44.1 ± 8.9 years; 15 men and 28 women) with SCeAD were referred. Also, 135 patients with FMD were compared to patients with and without SCeAD. Patients underwent: ambulatory blood pressure measurements, biochemical evaluation, echocardiographic examination, and whole body computed tomographic angiography. FMD changes were found in 39.5% of patients with SCeAD. There were no differences in clinical characteristics between patients with SCeAD and FMD and those without FMD, except for a tendency towards a higher female ratio in SCeAD patients with FMD. There were no differences in other parameters describing target organ and SCeAD characteristics. Patients with SCeAD and FMD compared to those without SCeAD were characterized by a lower frequency of hypertension and a higher frequency of hyperlipidemia and history of contraceptive hormone use. Our study indicates a high incidence (39.5%) of FMD in subjects with SCeAD. Since there are no distinctive discriminating factors between patients with SCeAD and FMD and those without FMD, FMD should be suspected in all patients with SCeAD.

Context Cross sectional imaging with computed tomography (CT) or magnetic resonance imaging (MRI) is regarded as a first-choice modality for tumor localization in patients with pheochromocytoma and paraganglioma (PPGL). ¹²³I-labeled metaiodobenzylguanidine (¹²³I-MIBG) is widely used for functional imaging but the added diagnostic value is controversial. Objective To establish the virtual impact of adding ¹²³I-MIBG scintigraphy to CT or MRI on diagnosis and treatment of PPGL. Design International multicenter retrospective study. Intervention None. Patients 236 unilateral adrenal, 18 bilateral adrenal, 48 unifocal extra-adrenal, 12 multifocal and 26 metastatic PPGL. Main Outcome Measures Patients underwent both anatomical imaging (CT and/or MRI) and ¹²³I-MIBG scintigraphy. Local imaging reports were analyzed centrally by two independent observers who were blinded to the diagnosis. Imaging-based diagnoses determined by CT/MRI only, ¹²³I-MIBG only, and CT/MRI combined with ¹²³I-MIBG scintigraphy were compared with the correct diagnoses. Results The rates of correct imaging-based diagnoses determined by CT/MRI only versus CT/MRI plus ¹²³I-MIBG scintigraphy were similar: 89.4 versus 88.8%, respectively, (P=0.50). Adding ¹²³I-MIBG scintigraphy to CT/MRI resulted in a correct change in the imaging-based diagnosis and ensuing virtual treatment in four cases (1.2%: two metastatic instead of non-metastatic, one multifocal instead of single, one unilateral instead of bilateral adrenal) at the cost of an incorrect change in seven cases (2.1%: four metastatic instead of non-metastatic, two multifocal instead of unifocal and one bilateral instead of unilateral adrenal). Conclusions For the initial localization of PPGL, the addition of ¹²³I-MIBG scintigraphy to CT/MRI rarely improves the diagnostic accuracy at the cost of incorrect interpretation in others, even when ¹²³I-MIBG scintigraphy is restricted to patients who are at risk for metastatic disease. In this setting, the impact of ¹²³I-MIBG scintigraphy on clinical decision-making appears very limited.

Objective: To provide a comprehensive assessment of left ventricle (LV) structure, and function and to detect alterations in cardiac properties in relationship to presence, subtypes and extent of fibromuscular dysplasia (FMD). Methods: We studied 144 patients with FMD. The control group consisted of 50 matched individuals. Office and ambulatory blood pressure levels were evaluated. Echocardiography was employed to assess: left ventricular mass index (LVMI), systolic function including speckle tracking echocardiography and diastolic function assessed by mitral flow and tissue Doppler imaging. Results: There were no differences in LV morphology and function between patients with FMD and the control group. Among 128 patients with renal FMD, there were no differences in LVMI and LV systolic function between patients with unifocal and multifocal FMD. The patients with multifocal FMD were characterized by lower early diastolic velocity (e′) as compared with unifocal FMD and control groups. However, in a multivariate regression model, e′ was not independently correlated with FMD. There were no associations between echocardiographic indexes and vascular involvement of FMD. Also, there were no differences in LV morphology and function in patients with significant renal artery stenosis (RAS) compared with patients with history of significant RAS and patients with nonsignificant RAS. Conclusion: Our study in contrast to those with atherosclerotic RAS, did not show differences in LV morphology and function between FMD patients and matched controls. Although FMD can result in hypertension and serious vascular complications, there is no proof that it can alter LV regardless of FMD type and its extent.

We investigated plasma fibrin clot properties in high-risk hypertensive patients with obstructive sleep apnoea (OSA) and assessed the impact of continuous positive airway pressure (CPAP) treatment on clot phenotype. We studied 50 hypertensive patients with clinically significant OSA (age 50.0 ± 8.8 years, 39 M, 11 F). In total, 38 hypertensive patients without OSA balanced for age, sex, blood pressure, cardiovascular risk factors, and metabolic status served as controls. Plasma fibrin clot properties, including clot permeability coefficient, clot lysis time (CLT), and turbidimetric parameters of clot formation were determined. Patients underwent transthoracic echocardiography, carotid ultrasonography, evaluation of endothelial function and calcium score index of coronary arteries, and Doppler imaging of renal arteries. Compared with controls, OSA patients were characterized by more compact fibrin structure (lower median clot permeability coefficient, 6.00 vs. 7.25 10−9 cm2; P < 0.001), impaired fibrinolysis (longer median CLT, 108.00 vs. 92.50 min; P < 0.001), and by faster clot formation (shorter median lag phase, 40.50 vs. 42.50 s; P = 0.041), and higher median maximum clot absorbency indicating denser fibrin networks (0.87 vs. 0.81; P = 0.028). Clot permeability coefficient and CLT correlated with apnoea–hypopnoea index (r = −0.46; P < 0.001 and r = 0.44; P < 0.001, respectively) as well with mean (r = 0.31; P = 0.003; r = −0.36; P = 0.001, respectively) and minimal oxygen saturation (r = 0.46; P < 0.001; r = −0.49; P < 0.001, respectively). After 3 months of CPAP treatment we observed an increase in clot permeability coefficient (5.95 vs. 7.60 10−9 cm2; P = 0,001), shortened CLT (107.00 vs. 87.00; P = 0.006), a longer lag phase of fibrin formation (40.00 vs. 43.50 s; P = 0.013), and a trend toward lower maximum clot absorbency (0.86 vs. 0.81; P = 0.058). In hypertensive patients at high cardiovascular risk, OSA was associated with unfavourable prothrombotic fibrin clot characteristics, including hypofibrinolysis, which significantly improve as early as after 3 months of CPAP treatment.