Lateralization in C-11-Metomidate PET and outcome of adrenalectomy in primary aldosteronism

Introduction Subtype classification method is essential when considering adrenalectomy as a possible treatment for primary aldosteronism. We aimed to retrospectively evaluate surgical outcomes of primary aldosteronism in patients who had undergone C-11-metomidate positron emission tomography (C-11-MTO-PET) for subtype classification. Methods Postoperative clinical and biochemical cure and histopathological diagnosis from biobank samples were retrospectively evaluated in 44 patients who had all undergone preoperative C-11-MTO-PET with or without adrenal venous sampling (AVS). We compared those operated based on C-11-MTO-PET alone and those with concordant or discordant lateralization in C-11-MTO-PET and AVS studies according to postoperative immunohistochemical findings and biochemical and clinical cure. Results Adrenalectomy side was based on C-11-MTO-PET alone in 14 cases and on AVS in 30 cases of whom 42 achieved complete and two partial biochemical cures. Among those who underwent AVS and were operated according to it, the two lateralization methods were concordant in 22 cases and discordant in 8 cases. Similar immunohistochemical profiles and cure rates were seen after C-11-MTO-PET alone or AVS-based operations. Respectively, those with concordant or discordant C-11-MTO-PET and AVS lateralization did not differ in surgical outcome. Together, we found errors of lateralization diagnostics with C-11-MTO-PET in 18% and with AVS in 3% among those eligible for adrenal surgery. Conclusions Outcomes of adrenalectomy based on clinically significant lateralization in C-11-MTO-PET alone correspond to those based on C-11-MTO-PET with concordant AVS lateralization. However, our results suggest that diagnosis of unilateral PA should be performed with caution with C-11-MTO-PET in case of discordant lateralization studies.Peer reviewe

Diminished coagulation capacity assessed by calibrated automated thrombography during acute Puumala hantavirus infection

Coagulation abnormalities are associated with Puumala-virus-induced hemorrhagic fever with renal syndrome (PUUV-HFRS). We evaluated the coagulation capacity of plasma during acute PUUV-HFRS by measuring thrombin generation using calibrated automated thrombography (CAT). The study cohort comprised 27 prospectively collected, consecutive, hospital-treated patients with acute PUUV infection. Blood samples were drawn in the acute phase and at the control visit approximately 5 weeks later. To evaluate thrombin generation, the lag time of initiation, endogenous thrombin potential (ETP), and peak and time to peak thrombin concentration were assessed by CAT in platelet poor plasma without corn trypsin inhibitor. Plasma levels of d-dimer, fibrinogen and prothrombin fragments (F1 + 2) were also evaluated. When the acute phase was compared with the control phase, ETP was decreased (median 1154 nmol/l/min, range 67-1785 vs. median 1385 nmol/l/min, range 670-1970; P <0.001), while the lag time was prolonged (median 3.8 min, range 2.1-7.7 vs. median 2.9 min, range 2.0-4.1; P <0.001). Low ETP correlated with low peak thrombin concentration (r = 0.833, P <0.001). Prolonged time to peak associated with the lag time (r = 0.78, P <0.001). ETP was associated with thrombocytopenia (r = 0.472, P = 0.015) and weakly with fibrinogen level (r = 0.386, P = 0.047). The measured CAT parameters did not associate with d-dimer and F1 + 2 levels. Decreased ETP together with low peak and prolonged lag time indicate decreased plasma potential for thrombin generation in vitro. Together with low platelet count and enhanced fibrinolysis, this further refers to altered blood coagulation and increased propensity toward bleeding in acute PUUV-HFRS. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.Peer reviewe

Disparate Information Provided by Pulse Wave Velocity versus Other Measures of Aortic Compliance in End-Stage Renal Disease

acceptedVersionPeer reviewe

Lateralization in 11C-Metomidate PET and outcome of adrenalectomy in primary aldosteronism

IntroductionSubtype classification method is essential when considering adrenalectomy as a possible treatment for primary aldosteronism. We aimed to retrospectively evaluate surgical outcomes of primary aldosteronism in patients who had undergone 11C-metomidate positron emission tomography (11C-MTO-PET) for subtype classification.MethodsPostoperative clinical and biochemical cure and histopathological diagnosis from biobank samples were retrospectively evaluated in 44 patients who had all undergone preoperative 11C-MTO-PET with or without adrenal venous sampling (AVS). We compared those operated based on 11C-MTO-PET alone and those with concordant or discordant lateralization in 11C-MTO-PET and AVS studies according to postoperative immunohistochemical findings and biochemical and clinical cure.ResultsAdrenalectomy side was based on 11C-MTO-PET alone in 14 cases and on AVS in 30 cases of whom 42 achieved complete and two partial biochemical cures. Among those who underwent AVS and were operated according to it, the two lateralization methods were concordant in 22 cases and discordant in 8 cases. Similar immunohistochemical profiles and cure rates were seen after 11C-MTO-PET alone or AVS-based operations. Respectively, those with concordant or discordant 11C-MTO-PET and AVS lateralization did not differ in surgical outcome. Together, we found errors of lateralization diagnostics with 11C-MTO-PET in 18% and with AVS in 3% among those eligible for adrenal surgery.ConclusionsOutcomes of adrenalectomy based on clinically significant lateralization in 11C-MTO-PET alone correspond to those based on 11C-MTO-PET with concordant AVS lateralization. However, our results suggest that diagnosis of unilateral PA should be performed with caution with 11C-MTO-PET in case of discordant lateralization studies.</p

Various vascular malformations are prevalent in Finnish pseudoxanthoma elasticum (PXE) patients : a national registry study

BACKGROUND: Pseudoxanthoma elasticum (PXE, OMIM# 264800) is an inborn error of metabolism causing ectopic soft tissue calcification due to low plasma pyrophosphate concentration. We aimed to assess the prevalence of PXE in Finland and to characterize the Finnish PXE population. A nationwide registry search was performed to identify patients with ICD-10 code Q82.84. Information was gathered from available medical records which were requisitioned from hospitals and health centers. Misdiagnosed patients and patients with insufficient records were excluded. RESULTS: The prevalence of PXE in Finland was 1:260,000 with equal sex distribution. Patients with high conventional cardiovascular risk had more visual and vascular complications than patients with low risk. Four patients (19%) had at least one vascular malformation. A high proportion (33%) of ABCC6 genotypes were of the common homozygous c.3421C > T, p.Arg1141Ter variant. Nine other homozygous or compound heterozygous allelic variants were found. CONCLUSIONS: The prevalence of diagnosed PXE appears to be lower in Finland than in estimates from other countries. Decreased visual acuity is the most prevalent complication. We suggest that various vascular malformations may be an unrecognized feature of PXE.publishedVersionPeer reviewe

PIM-Related Kinases Selectively Regulate Olfactory Sensations in Caenorhabditis elegans

The mammalian PIM family of serine/threonine kinases regulate several cellular functions, such as cell survival and motility. Because PIM expression is observed in sensory organs, such as olfactory epithelium, we now wanted to explore the physiological roles of PIM kinases there. As our model organism, we used the Caenorhabditis elegans nematodes, which express two PIM-related kinases, PRK-1 and PRK-2. We demonstrated PRKs to be true PIM orthologs with similar substrate specificity as well as sensitivity to PIM-inhibitory compounds. When we analyzed the effects of pan-PIM inhibitors on C. elegans sensory functions, we observed that PRK activity is selectively required to support olfactory sensations to volatile repellents and attractants sensed by AWB and AWCON neurons, respectively, but is dispensable for gustatory sensations. Analyses of prk-deficient mutant strains confirmed these findings and suggested that PRK-1, but not PRK-2 is responsible for the observed effects on olfaction. This regulatory role of PRK-1 is further supported by its observed expression in the head and tail neurons, including AWB and AWC neurons. Based on the evolutionary conservation of PIM-related kinases, our data may have implications in regulation of also mammalian olfaction.</p

Adrenal androgens versus cortisol for primary aldosteronism subtype determination in adrenal venous sampling

Objective: We examined if measurement of adrenal androgens adds to subtype diagnostics of primary aldosteronism (PA) under cosyntropin-stimulated adrenal venous sampling (AVS).Design: A prospective pre-specified secondary endpoint analysis of 49 patients with confirmed PA, of whom 29 underwent unilateral adrenalectomy with long-term follow-up.Methods: Concentrations of androstenedione, dehydroepiandrosterone (DHEA) and dehydroepiandrosterone sulphate (DHEAS) were measured during AVS in addition to aldosterone and cortisol. Subjects with lateralisation index (LI) of ≥4 were treated with unilateral adrenalectomy, and the immunohistochemical subtype was determined with CYP11B2 and CYP11B1 stains. The performance of adrenal androgens was evaluated by receiver operating characteristics (ROC) curve analyses in adrenalectomy and medical therapy groups.Results: During AVS, the correlations between cortisol and androstenedione, DHEA and DHEAS for LI and selectivity index (SI) were highly significant. The right and left side SIs for androstenedione and DHEA were higher (p Conclusions: Under cosyntropin-stimulated AVS, the measurement of androstenedione and DHEA did not improve the cannulation selectivity. The performance of cortisol and adrenal androgens are confirmatory but not superior to cortisol-based results in lateralisation diagnostics of PA.</p

Ambulatory daytime blood pressure versus tonometric blood pressure measurements in the laboratory : effect of posture

Objective To compare blood pressure (BP) in tonometric radial artery recordings during passive head-up tilt with ambulatory recordings and evaluate possible laboratory cutoff values for hypertension. Methods Laboratory BP and ambulatory BP were recorded in normotensive (n=69), unmedicated hypertensive (n=190), and medicated hypertensive (n=151) subjects. Results Mean age was 50.2 years, BMI 27.7kg/m2, ambulatory daytime BP 139/87mmHg, and 276 were male (65%). As supine-to-upright changes in SBP ranged from -52 to +30mmHg, and in DBP from -21 to +32mmHg, the mean values of BP supine and upright measurements were compared with ambulatory BP. The mean(supine+upright) systolic laboratory BP was corresponding to ambulatory level (difference +1mmHg), while mean(supine+upright) DBP was 4mmHg lower (P<0.05) than ambulatory value. Correlograms indicated that laboratory 136/82mmHg corresponded to ambulatory 135/85mmHg. When compared with ambulatory 135/85mmHg, the sensitivity and specificity of laboratory 136/82mmHg to define hypertension were 71.5% and 77.3% for SBP, and 71.7% and 72.8%, for DBP, respectively. The laboratory cutoff 136/82mmHg classified 311/410 subjects similarly to ambulatory BP as normotensive or hypertensive, 68 were hypertensive only in ambulatory, while 31 were hypertensive only in laboratory measurements. Conclusion BP responses to upright posture were variable. When compared with ambulatory BP, mean(supine+upright) laboratory cutoff 136/82mmHg classified 76% of subjects similarly as normotensive or hypertensive. In the remaining 24% the discordant results may be attributed to white-coat or masked hypertension, or higher physical activity during out-of-office recordings.Peer reviewe

Response to letter on use of functional imaging by 11C-metomidate PET for primary aldosteronism subtyping

Non peer reviewe