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Journal of Nuclear Medicine : Official... Aug 2017Pheochromocytoma/paraganglioma (PPGL) syndromes associated with polycythemia have previously been described in association with mutations in the von Hippel-Lindau gene....
Pheochromocytoma/paraganglioma (PPGL) syndromes associated with polycythemia have previously been described in association with mutations in the von Hippel-Lindau gene. Recently, mutations in the prolyl hydroxylase gene () 1 and 2 and in the hypoxia-inducible factor 2 α () were also found to be associated with multiple and recurrent PPGL. Such patients also presented with PPGL and polycythemia, and later on, some presented with duodenal somatostatinoma. In additional patients presenting with PPGL and polycythemia, no further mutations have been discovered. Because the functional imaging signature of patients with PPGL-polycythemia syndromes is still unknown, and because these tumors (in most patients) are multiple, recurrent, and metastatic, the goal of our study was to assess the optimal imaging approach using 4 different PET radiopharmaceuticals and CT/MRI in these patients. Fourteen patients (10 women, 4 men) with confirmed PPGL and polycythemia prospectively underwent Ga-DOTATATE (13 patients), F-FDG (13 patients), F-fluorodihydroxyphenylalanine (F-FDOPA) (14 patients), F-fluorodopamine (F-FDA) (11 patients), and CT/MRI (14 patients). Detection rates of PPGL lesions were compared between all imaging studies and stratified between the underlying mutations. F-FDOPA and F-FDA PET/CT showed similar combined lesion-based detection rates of 98.7% (95% confidence interval [CI], 92.7%-99.8%) and 98.3% (95% CI, 90.9%-99.7%), respectively. The detection rates for Ga-DOTATATE (35.3%; 95% CI, 25.0%-47.2%), F-FDG (42.3; 95% CI, 29.9%-55.8%), and CT/MRI (60.3%; 95% CI, 48.8%-70.7%) were significantly lower ( < 0.01), irrespective of the mutation status. F-FDOPA and F-FDA are superior to F-FDG, Ga-DOTATATE, and CT/MRI and should be the radiopharmaceuticals of choice in this rare group of patients.
Topics: Adolescent; Adult; Child; Female; Humans; Male; Middle Aged; Multimodal Imaging; Paraganglioma; Polycythemia; Young Adult
PubMed: 28336782
DOI: 10.2967/jnumed.116.187690 -
Blood May 2021Polycythemia and pulmonary hypertension are 2 human diseases for which better therapies are needed. Upregulation of hypoxia-inducible factor-2α (HIF-2α) and its target...
Polycythemia and pulmonary hypertension are 2 human diseases for which better therapies are needed. Upregulation of hypoxia-inducible factor-2α (HIF-2α) and its target genes, erythropoietin (EPO) and endothelin-1, causes polycythemia and pulmonary hypertension in patients with Chuvash polycythemia who are homozygous for the R200W mutation in the von Hippel Lindau (VHL) gene and in a murine mouse model of Chuvash polycythemia that bears the same homozygous VhlR200W mutation. Moreover, the aged VhlR200W mice developed pulmonary fibrosis, most likely due to the increased expression of Cxcl-12, another Hif-2α target. Patients with mutations in iron regulatory protein 1 (IRP1) also develop polycythemia, and Irp1-knockout (Irp1-KO) mice exhibit polycythemia, pulmonary hypertension, and cardiac fibrosis attributable to translational derepression of Hif-2α, and the resultant high expression of the Hif-2α targets EPO, endothelin-1, and Cxcl-12. In this study, we inactivated Hif-2α with the second-generation allosteric HIF-2α inhibitor MK-6482 in VhlR200W, Irp1-KO, and double-mutant VhlR200W;Irp1-KO mice. MK-6482 treatment decreased EPO production and reversed polycythemia in all 3 mouse models. Drug treatment also decreased right ventricular pressure and mitigated pulmonary hypertension in VhlR200W, Irp1-KO, and VhlR200W;Irp1-KO mice to near normal wild-type levels and normalized the movement of the cardiac interventricular septum in VhlR200Wmice. MK-6482 treatment reduced the increased expression of Cxcl-12, which, in association with CXCR4, mediates fibrocyte influx into the lungs, potentially causing pulmonary fibrosis. Our results suggest that oral intake of MK-6482 could represent a new approach to treatment of patients with polycythemia, pulmonary hypertension, pulmonary fibrosis, and complications caused by elevated expression of HIF-2α.
Topics: Animals; Basic Helix-Loop-Helix Transcription Factors; Endothelin-1; Erythropoietin; Female; Gene Expression Regulation; Hypertension, Pulmonary; Iron Regulatory Protein 1; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Polycythemia; Sulfones; Von Hippel-Lindau Tumor Suppressor Protein
PubMed: 33512384
DOI: 10.1182/blood.2020009138 -
Deutsche Medizinische Wochenschrift... Jan 2019Due to its rare incidence, erythrocytosis frequently represents a challenge for the treating doctors. The erythropoiesis (= production of erythrocytes) is located in... (Review)
Review
Due to its rare incidence, erythrocytosis frequently represents a challenge for the treating doctors. The erythropoiesis (= production of erythrocytes) is located in the bone marrow, and the hormone erythropoietin (EPO) takes control in its regulation. Therefore, measurement of EPO in serum is one of the main diagnostic steps. In erythrocytosis, congenital causes have to be distinguished from acquired ones. Furthermore, there are primary and secondary forms. Congenital causes of erythrocytoses occur very infrequently, are mainly diagnosed in young age and should be treated in specialized centers. Polycythemia vera (PV), a clonal disorder and one of the main myeloproliferative neoplasms (beside essential thrombocythemia and primary myelofibrosis), represents the most frequent primary acquired cause of erythrocytosis. Clinically, increased thrombophilia and microvascular disturbance occur. The first-line treatment in patients with PV includes administration of aspirin and phlebotomies. Secondary acquired forms of erythrocytosis mainly occur due to hypoxia triggered by nicotine abuse or chronic heart and lung diseases. Regarding other differential diagnoses, a cancer-associated EPO production, kidney diseases or exogenous supply with EPO (= EPO doping) have to be considered.
Topics: Diagnosis, Differential; Humans; Polycythemia
PubMed: 30674061
DOI: 10.1055/a-0739-8340 -
Clinical Obstetrics and Gynecology Sep 2015Twin-twin transfusion syndrome (TTTS) affects 10% to 15% of monochorionic pregnancies. In the absences of timely diagnosis and intervention perinatal loss or long term... (Review)
Review
Twin-twin transfusion syndrome (TTTS) affects 10% to 15% of monochorionic pregnancies. In the absences of timely diagnosis and intervention perinatal loss or long term developmental delay can be expected in over 90% of cases. Establishing chorionicity in the first trimester followed by serial ultrasounds beginning at 16 weeks of gestation and intervention with placental laser ablation before the development of advance disease overall survival rates can be expected in 70% to 80% of cases.
Topics: Anemia; Arteriovenous Anastomosis; Female; Fetal Therapies; Fetofetal Transfusion; Humans; Laser Therapy; Placenta; Polycythemia; Pregnancy; Pregnancy, Twin; Ultrasonography, Doppler; Ultrasonography, Prenatal; Umbilical Veins
PubMed: 26165181
DOI: 10.1097/GRF.0000000000000128 -
BMC Ophthalmology Jan 2023To assess retinal structural parameters in high-altitude (HA) residents with and without high altitude polycythemia (HAPC) and to elucidate the relationship between...
BACKGROUND
To assess retinal structural parameters in high-altitude (HA) residents with and without high altitude polycythemia (HAPC) and to elucidate the relationship between retinal structural parameters and hemoglobin (HGB).
METHODS
This cross-sectional study included 55 HAPC patients and 52 healthy HA residents. Retinal structural parameters included retinal nerve fiber layer (RNFL) thickness, optic nerve head (ONH) parameters and retinal vessel diameter. RNFL thickness were acquired from spectral domain optical coherence tomography (SD-OCT) built-in software. ONH parameters including neuroretina rim height, cup area, disc area and vertical cup/disc ratio were obtained by OCT built-in software and ImageJ software. Retinal vessel measurements including central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE) and AVR (artery/vein ratio) were calculated by revised formulas for summarizing retinal vessel diameters. All parameters were compared between HAPC group versus healthy HA group. The associations between retinal parameters and HGB were assessed by Pearson correlation analyses.
RESULTS
In comparison of HAPC group versus healthy HA group, RNFL thickness was thicker in the nasal quadrant of the optic disc in HAPC group (74.82 ± 14.4 VS. 66.06 ± 13.71 μm, P = 0.002). Bigger disc area and bigger cup area were also observed in HAPC group (all P < 0.05). Meanwhile, the value of CRVE was higher in HAPC group which suggested that retinal veins dilated significantly in HAPC patients (P < 0.001), however, CRAE and AVR were comparable between groups. Pearson analyses revealed that HGB was positive correlated with CRVE in HAPC group (r = 0.469, P = 0.003).
CONCLUSIONS
long-term HA exposure secondary HAPC could result in thickened RNFL, enlarged ONH and dilated retinal veins. Moreover, increased blood viscosity caused by HGB should be responsible for dilated veins, but not for thickened RNFL and enlarged ONH. This study deepens the understanding of the impact of HA environment on retina.
Topics: Humans; Altitude; Cross-Sectional Studies; Nerve Fibers; Polycythemia; Retina; Retinal Ganglion Cells; Tomography, Optical Coherence
PubMed: 36597056
DOI: 10.1186/s12886-022-02674-7 -
Journal of Veterinary Internal Medicine Jul 2022Prolonged tissue hypoxia caused by chronic pulmonary disease is commonly regarded as an important mechanism in the development of secondary polycythemia, but little...
BACKGROUND
Prolonged tissue hypoxia caused by chronic pulmonary disease is commonly regarded as an important mechanism in the development of secondary polycythemia, but little clinical data are available to support this hypothesis.
OBJECTIVE
To study the prevalence and severity of erythrocytosis accompanying chronic hypoxic pulmonary disease in dogs.
ANIMALS
Forty-seven dogs with hypoxic chronic pulmonary disease, 27 dogs with nonhypoxic chronic pulmonary disease, and 60 healthy controls.
METHODS
Dogs with chronic pulmonary disease and chronic hypoxemia (partial pressure of arterial oxygen [PaO ] < 80 mm Hg on at least 2 arterial blood gas measurements a minimum of 1 month apart) were identified retrospectively from patient records. Association between arterial oxygen and red blood cell parameters was analyzed using Pearson's correlation coefficients and multivariable linear regression analysis.
RESULTS
Red blood cell parameters measured at the end of the hypoxemia period were within the laboratory reference range in most dogs. In chronically hypoxemic dogs, hematocrit (Hct) was increased in 4/47 (8.5%; 95% confidence interval [CI], 0-17) dogs, erythrocyte count (Erytr) was increased in 12/47 (26%; 95%CI, 13-38) dogs and hemoglobin concentration (Hb) was increased in 3/47 (6.4%; 95%CI, 0-14) dogs. No marked polycythemia (Hct ≥65%) was noted in any of the dogs. Red blood cell parameters were not associated with the severity of hypoxemia (correlation to PaO : Erytr, r = -.14; Hb, r = -.21; Hct, r = -.14; P > .05 for all).
CONCLUSIONS AND CLINICAL IMPORTANCE
Polycythemia is uncommon, and usually mild if present, in dogs with chronic hypoxia caused by pulmonary disease.
Topics: Animals; Dog Diseases; Dogs; Hypoxia; Lung Diseases; Oxygen; Polycythemia; Retrospective Studies
PubMed: 35702817
DOI: 10.1111/jvim.16466 -
Acta Diabetologica Jan 2024Sodium glucose transporter inhibitors (SGLT2i) therapy is associated with an increase in hematocrit as a class effect. There is a lack of information regarding the...
AIMS
Sodium glucose transporter inhibitors (SGLT2i) therapy is associated with an increase in hematocrit as a class effect. There is a lack of information regarding the clinical magnitude and significance of hematocrit elevation, especially cardiovascular outcomes in patients with polycythemia and possible masking of lower hemoglobin levels as a sign of potential severe disease.
METHODS
A retrospective study utilizing large community healthcare provider electronic database. Hematocrit levels and variables with potential effect on hematocrit change were compared before and during SGLT2i treatment in adults with type 2 diabetes mellitus.
RESULTS
Study population included 9646 patients treated with Dapagliflozin or Empagliflozin between 01.2015 and 06.2019. Hematocrit levels were significantly higher after treatment initiation (2.1%), with higher median elevation among male vs female (2.3% vs. 1.8%). Anemia prevalence was significantly lower under treatment (20% vs. 31.6%). In multivariable model, gender, smoking status, SGLT2i type, pretreatment hematocrit, diabetes duration, body mass index and estimated glomerular filtration rate change significantly effected hematocrit change.
CONCLUSIONS
In the current study SGLT2i treatment was associated with significant hematocrit elevation, polycythemia and lower anemia prevalence. Further studies are needed to determine the clinical significance and approach to patients with pretreatment or on treatment polycythemia and the approach to patients with lower-normal hemoglobin levels under SGLT2i treatment.
Topics: Adult; Humans; Male; Female; Diabetes Mellitus, Type 2; Sodium-Glucose Transporter 2 Inhibitors; Retrospective Studies; Hematocrit; Polycythemia; Anemia; Sodium-Glucose Transport Proteins; Hemoglobins; Glucose
PubMed: 37698758
DOI: 10.1007/s00592-023-02174-0 -
Consensus diagnostic criteria and monitoring of twin anemia-polycythemia sequence: Delphi procedure.Ultrasound in Obstetrics & Gynecology :... Sep 2020Twin anemia-polycythemia sequence (TAPS) is associated with increased perinatal morbidity and mortality. Inconsistencies in the diagnostic criteria for TAPS exist, which...
OBJECTIVES
Twin anemia-polycythemia sequence (TAPS) is associated with increased perinatal morbidity and mortality. Inconsistencies in the diagnostic criteria for TAPS exist, which hinder the ability to establish robust evidence-based management or monitoring protocols. The main aim of this study was to determine, by expert consensus using a Delphi procedure, the key diagnostic features and optimal monitoring approach for TAPS.
METHODS
A Delphi process was conducted among an international panel of experts on TAPS. Panel members were provided with a list of literature-based parameters for diagnosing and monitoring TAPS. They were asked to rate the importance of the parameters on a five-point Likert scale. Consensus was sought to determine the cut-off values for accepted parameters, as well as parameters used in the monitoring of and assessment of outcome in twin pregnancy complicated by TAPS.
RESULTS
A total of 132 experts were approached. Fifty experts joined the first round, of whom 33 (66%) completed all three rounds. There was agreement that the monitoring interval for the development of TAPS should be every 2 weeks and that the severity should be assessed antenatally using a classification system based on middle cerebral artery (MCA) peak systolic velocity (PSV), but there was no agreement on the gestational age at which to start monitoring. Once the diagnosis of TAPS is made, monitoring should be scheduled weekly. For the antenatal diagnosis of TAPS, the combination of MCA-PSV ≥ 1.5 MoM in the anemic twin and ≤ 0.8 MoM in the polycythemic twin was agreed. Alternatively, MCA-PSV discordance ≥ 1 MoM can be used to diagnose TAPS. Postnatally, hemoglobin difference ≥ 8 g/dL and intertwin reticulocyte ratio ≥ 1.7 were agreed criteria for diagnosis of TAPS. There was no agreement on the cut-off of MCA-PSV or its discordance for prenatal intervention. The panel agreed on prioritizing perinatal and long-term survival outcomes in follow-up studies.
CONCLUSIONS
Consensus-based diagnostic features of TAPS, as well as cut-off values for the parameters involved, were agreed upon by a panel of experts. Future studies are needed to validate these diagnostic features before they can be used in clinical trials of interventions. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Adult; Anemia; Delphi Technique; Female; Fetofetal Transfusion; Gestational Age; Humans; Polycythemia; Pregnancy; Pregnancy, Twin; Prenatal Diagnosis
PubMed: 31605505
DOI: 10.1002/uog.21882 -
Combinatorial Chemistry & High... 2021Hyperviscosity of blood secondary to polycythemia results in increased resistance to blood flow and decrease in delivery of oxygen.
BACKGROUND
Hyperviscosity of blood secondary to polycythemia results in increased resistance to blood flow and decrease in delivery of oxygen.
OBJECTIVE
To evaluate whether serum endocan, NSE and IMA levels can be compared in terms of endothelial injury/ dysfunction and neuronal damage in term neonates with polycythemia who underwent PET.
METHODS
38 symptomatic polycythemic newborns having PET and 38 healthy newborns were included in the study. Blood samples for endocan, NSE and IMA were taken at only postnatal 24 hours of age in the control group and in polycytemia group just before PET, at 24 and 72 hours after PET.
RESULTS
The polycythemia group had higher serum endocan(1073,4 ± 644,8 vs. 378,8 ± 95,9ng/ml; p<0.05), IMA(1,32 ± 0,34 vs.0,601 ± 0,095absorbance unit; p<0.05) and NSE(44,7 ± 4,3 vs. 26,91 ± 7,12μg/l; p<0.05) levels than control group before the PET procedure. At 24 hours after PET, IMA(0,656 ± 0,07 vs. 0,601 ± 0,095absorbance unit; p<0.05) and endocan(510,9 ± 228,6 vs. 378,8 ± 95,9ng/ml; p<0.05) levels were closer to the control group, being still statistically significant higher. NSE levels decreased to control group levels having no difference between the PET and control groups at 24 hours after PET (28,98 ± 6,5 vs. 26,91 ± 7,12μg/l; p>0.05). At 72 hours after PET the polycythemia and control groups did not differ statistically for IMA, endocan and NSE levels (p>0.05).
CONCLUSION
Serum endocan and IMA levels can be used as a biomarker for endothelial damage/ dysfunction and tissue hypoxia in infants with symptomatic polycytemia.
Topics: Biomarkers; Exchange Transfusion, Whole Blood; Humans; Infant, Newborn; Neoplasm Proteins; Phosphopyruvate Hydratase; Polycythemia; Proteoglycans; Serum Albumin, Human
PubMed: 33109054
DOI: 10.2174/1386207323999200820163525 -
Acta Neurologica Belgica Jun 2016
Topics: Child; Demyelinating Diseases; Female; Humans; Paraganglioma; Polycythemia
PubMed: 26085379
DOI: 10.1007/s13760-015-0498-9