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1.
Intern Med ; 59(14): 1741-1744, 2020 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-32295999

RESUMO

TEMPI syndrome, a disease entity comprising telangiectasia, erythrocytosis with high erythropoietin, monoclonal gammopathy, perinephric fluid collection, and intrapulmonary shunting, was first described by Sykes et al. in 2011. To our knowledge, only 15 cases have been reported worldwide, none of which were in Japan. We herein report a 47-year-old man who had intractable ascites for 2 and a half years and was referred to our department for a peritoneovenous shunt. In addition to ascites, he had telangiectasia, high erythropoietin, monoclonal gammopathy, and perinephric fluid collection. Thus, this is the first case of TEMPI syndrome in Japan.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Bortezomib/uso terapêutico , Gamopatia Monoclonal de Significância Indeterminada/tratamento farmacológico , Policitemia/tratamento farmacológico , Telangiectasia/tratamento farmacológico , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Gamopatia Monoclonal de Significância Indeterminada/diagnóstico , Gamopatia Monoclonal de Significância Indeterminada/epidemiologia , Policitemia/diagnóstico , Policitemia/epidemiologia , Telangiectasia/diagnóstico , Telangiectasia/epidemiologia , Resultado do Tratamento
2.
Acta Haematol ; 143(1): 69-72, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31167179

RESUMO

This original report describes the management of a pregnant woman with congenital erythrocytosis (Chuvash polycythaemia) and reviews the scarce data available in the literature. Therapy consisted of low-dose aspirin and phlebotomies to maintain haematocrit <50% while monitoring iron stores to avoid severe deficiency detrimental to the foetus. Despite normal initial foetal growth, the pregnancy was complicated by preterm birth due to chorioamnionitis. The placenta showed no signs of thrombotic events. The published reports cover 13 pregnancies in 8 patients, showing 1 first-trimester miscarriage, 5 infants with intrauterine growth restriction and/or preterm birth and 1 maternal thrombotic event. These cases were managed with phlebotomies, low-dose aspirin and/or low-molecular-weight heparin, although inconsistently.


Assuntos
Policitemia/congênito , Adulto , Aspirina/uso terapêutico , Feminino , Ferritinas/análise , Heparina de Baixo Peso Molecular/uso terapêutico , Homozigoto , Humanos , Ferro/administração & dosagem , Policitemia/diagnóstico , Policitemia/tratamento farmacológico , Polimorfismo de Nucleotídeo Único , Gravidez , Nascimento Prematuro , Proteína Supressora de Tumor Von Hippel-Lindau/genética
4.
Transplant Proc ; 50(6): 1842-1846, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30056912

RESUMO

Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are the cornerstone treatment in chronic kidney disease patients. Despite facilitating a reduction in blood pressure and albuminuria, there are insufficient data in kidney transplant recipients (KTRs). They are often administered for hypertension and polycythemia treatment. The aim of this study was to investigate the frequency and route of administration of ACEIs and ARBs and their early clinical effects in the KTR population. In a cross-sectional, retrospective study we analyzed 874 medical records of all KTRs treated in our unit in 2014. A total of 391 KTRs (44.7%) using ARBs or ACEIs were qualified for the study. The primary reasons for renin-angiotensin-aldosterone system antagonist administration were hypertension (59.1%), polycythemia (19.2%), and proteinuria (18.2%). Among the studied KTRs, 86.7% of patients were treated with ACEIs and 12.2% were treated with ARBs. The majority of patients treated with ACEIs and ARBs received these agents in a dose range below 25% and between 25% and 49% of their maximal dose, respectively. Both the mean serum creatinine level and estimated glomerular filtration rate (chronic kidney disease epidemiology collaboration) remained fairly stable and urine protein excretion (g/24 hours) was significantly reduced after 3 months of ACEI and ARB therapy. The serum potassium level increased significantly, while hemoglobin concentration dropped significantly. In KTRs, renin-angiotensin-aldosterone system antagonists were applied mainly due to hypertension, proteinuria, and polycythemia. ACEIs and ARBs were effective in the reduction of proteinuria and hemoglobin, but graft function was stable and the increase of serum potassium was not of clinical significance.


Assuntos
Antagonistas de Receptores de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Transplante de Rim , Estudos Transversais , Feminino , Humanos , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Policitemia/tratamento farmacológico , Proteinúria/tratamento farmacológico , Sistema Renina-Angiotensina/efeitos dos fármacos , Estudos Retrospectivos
5.
BMJ Case Rep ; 20182018 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-29954763

RESUMO

Post-transplant erythrocytosis (PTE) is a condition with elevated haematocrit (hct) in renal allograft recipients. The mainstay of treatment is ACE inhibitors (ACEi) or angiotensin II receptor blockers (ARB), but seldom phlebotomy. PTE must be recognised early to prevent major thromboembolic events. We present a case of PTE that was refractory to blockade of renin-angiotensin system (RAS) by ACEi and ARB and required phlebotomy for control of hct. Our review of medical literature about prevalence and pathophysiology of PTE suggests that approximately 22% of patients with PTE are refractory to ACEi/ARB treatment. There are four plausible pathways that appear to play a role in causing PTE: disruption of erythropoietin regulation, mitogenic effect of the RAS on erythroid lineage, insulin-like growth factor 1 and androgenic stimulation. Presently, there is no unifying hypothesis involving these factors, but refractoriness to ACEi/ARB may represent a distinct subcategory of PTE.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Aspirina/uso terapêutico , Transplante de Rim/efeitos adversos , Losartan/uso terapêutico , Transplante de Pâncreas/efeitos adversos , Policitemia/sangue , Hematócrito , Humanos , Masculino , Pessoa de Meia-Idade , Flebotomia/métodos , Policitemia/tratamento farmacológico , Policitemia/etiologia , Resultado do Tratamento
7.
J Clin Invest ; 128(4): 1317-1325, 2018 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-29480820

RESUMO

Chuvash polycythemia is an inherited disease caused by a homozygous germline VHLR200W mutation, which leads to impaired degradation of HIF2α, elevated levels of serum erythropoietin, and erythrocytosis/polycythemia. This phenotype is recapitulated by a mouse model bearing a homozygous VhlR200W mutation. We previously showed that iron-regulatory protein 1-knockout (Irp1-knockout) mice developed erythrocytosis/polycythemia through translational derepression of Hif2α, suggesting that IRP1 could be a therapeutic target to treat Chuvash polycythemia. Here, we fed VhlR200W mice supplemented with Tempol, a small, stable nitroxide molecule and observed that Tempol decreased erythropoietin production, corrected splenomegaly, normalized hematocrit levels, and increased the lifespans of these mice. We attribute the reversal of erythrocytosis/polycythemia to translational repression of Hif2α expression by Tempol-mediated increases in the IRE-binding activity of Irp1, as reversal of polycythemia was abrogated in VhlR200W mice in which Irp1 was genetically ablated. Thus, a new approach to the treatment of patients with Chuvash polycythemia may include dietary supplementation of Tempol, which decreased Hif2α expression and markedly reduced life-threatening erythrocytosis/polycythemia in the VhlR200W mice.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/biossíntese , Óxidos N-Cíclicos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Proteína 1 Reguladora do Ferro/metabolismo , Policitemia/tratamento farmacológico , Biossíntese de Proteínas/efeitos dos fármacos , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Humanos , Proteína 1 Reguladora do Ferro/genética , Camundongos , Camundongos Mutantes , Policitemia/genética , Policitemia/metabolismo , Policitemia/patologia , Marcadores de Spin
8.
High Alt Med Biol ; 19(1): 69-80, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29077517

RESUMO

Zhang, Zhiqing, Zhonghai Xiao, Bingnan Deng, Xiaohua Liu, Wei Liu, Hongjing Nie, Xi Li, Zhaoli Chen, Danfeng Yang, and Ruifeng Duan. Therapeutic efficacy of methazolamide against intermittent hypoxia-induced excessive erythrocytosis in rats. High Alt Med Biol 19:69-80, 2018.-This study aimed to determine whether methazolamide is effective for the treatment of chronic mountain sickness. Forty-eight male Wistar rats were randomly divided into eight groups: normoxia control, hypoxia control, hypoxia + acetazolamide (30 mg·kg-1·d-1), and five hypoxia + methazolamide groups (5, 10, 30, 90, and 120 mg·kg-1·d-1). Excessive erythrocytosis was induced through 4 weeks of hypobaric hypoxia (8 hours O2 10%/16 hours O2 21%). Rats were then treated for 4 weeks, and their body weight was measured. Hematological, hemorheological, and biochemical parameters were analyzed. Renal hypoxia-inducible factor-1alpha (HIF-1α) and vascular endothelial growth factor (VEGF) levels were detected by immunohistochemistry. Proteomic analysis of plasma was conducted to determine the most differentially expressed proteins. Methazolamide with doses lower than 30 mg·kg-1·d-1 had no significant effects on body weight compared with the hypoxia control group (p > 0.05). Methazolamide dose-dependently reduced the hemoglobin concentration, hematocrit (Hct), and blood viscosity. Hct/blood viscosity, an oxygen delivery index, dose-dependently increased after methazolamide treatment. A methazolamide dose of 10 mg·kg-1·d-1 showed similar efficacy to an acetazolamide dose of 30 mg·kg-1·d-1 for all the above parameters. Plasma levels of low-density lipoprotein cholesterol, total cholesterol, creatinine, and hemoglobin increased substantially after long-term hypoxia, but decreased after methazolamide treatment. HIF-1α and VEGF both increased substantially after long-term hypoxia and decreased in the kidney after methazolamide treatment. The most differentially expressed protein was haptoglobin, an endogenous protective factor, which was depleted in rats with excessive erythrocytosis and increased substantially after methazolamide treatment. In summary, methazolamide exhibits dose-dependent efficacy for the treatment of excessive erythrocytosis induced by long-term hypoxia. It also has beneficial effects on oxygen transport and lipid metabolism, which are encouraging with regard to the development of methazolamide-based chronic mountain sickness therapies.


Assuntos
Inibidores da Anidrase Carbônica/uso terapêutico , Hipóxia/sangue , Metazolamida/uso terapêutico , Policitemia/sangue , Policitemia/tratamento farmacológico , Acetazolamida/uso terapêutico , Animais , Viscosidade Sanguínea/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Inibidores da Anidrase Carbônica/administração & dosagem , LDL-Colesterol/sangue , Creatinina/sangue , Relação Dose-Resposta a Droga , Haptoglobinas/metabolismo , Hematócrito , Hemoglobinas/metabolismo , Hipóxia/complicações , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Rim/metabolismo , Masculino , Metazolamida/administração & dosagem , Policitemia/etiologia , Ratos , Ratos Wistar , Fator A de Crescimento do Endotélio Vascular/metabolismo
10.
Chin J Integr Med ; 23(12): 908-915, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27145942

RESUMO

OBJECTIVE: To explore the protective effects of Tibetan medicine Zuo-Mu-A Decoction (, ZMAD) on the blood parameters and myocardium of high altitude polycythemia (HAPC) model rats. METHODS: Forty male Wistar rats were randomly divided into 4 groups by a random number table, including the normal, model, Rhodiola rosea L. (RRL) and ZMAD groups (10 in each group). Every group was raised in Lhasa to create a HAPC model except the normal group. After modeling, rats in the RRL and the ZMAD groups were administered intragastrically with RRL (20 mL/kg) and ZMAD (7.5 mL/kg) once a day for 2 months, respectively; for the normal and the model groups, 5 mL of distilled water was administered intragastrically instead of decoction. Then routine blood and hematologic rheology parameters were taken, levels of erythropoietin and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were tested, and ultrastructural change in the left ventricular myocardium was observed using transmission electron microscopy. RESULTS: Compared with the model group, ZMAD significantly reduced the red blood cell count, hemoglobin levels, whole blood viscosity at low/middle shear rates, plasma viscosity, erythrocyte electrophoretic time, erythropoietin and 8-OHdG levels, and also increased the erythrocyte deformation index (P<0.05). There was no difference in all results between the RRL and the ZMAD groups. The cardiac muscle fibers were well-protected, mitochondrial matrix swelled mildly and ultrastructure changes were less prominent in the ZMAD group compared with the model group. CONCLUSION: ZMAD has significant protective effects on the blood parameters against HAPC, and also has the beneficial effect in protecting against myocardial injury.


Assuntos
Doença da Altitude/sangue , Doença da Altitude/tratamento farmacológico , Medicina Tradicional Tibetana , Miocárdio/patologia , Policitemia/sangue , Policitemia/tratamento farmacológico , Substâncias Protetoras/uso terapêutico , 8-Hidroxi-2'-Desoxiguanosina , Doença da Altitude/complicações , Animais , Desoxiguanosina/análogos & derivados , Desoxiguanosina/sangue , Modelos Animais de Doenças , Eritropoetina/sangue , Miocárdio/ultraestrutura , Policitemia/complicações , Substâncias Protetoras/farmacologia , Reologia/efeitos dos fármacos
12.
BMJ Case Rep ; 20162016 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-27651406

RESUMO

In contrast to anaemia, polycythaemia is a distinctly uncommon finding in patients with multiple myeloma. We describe the presence of otherwise unexplained polycythaemia in a 57-year-old Caucasian man who was found to have IgG κ multiple myeloma. After treatment of myeloma, the polycythaemia resolved. We reviewed previous reports of polycythaemia associated with multiple myeloma and discuss potential pathophysiological mechanisms that link these 2 conditions.


Assuntos
Antineoplásicos/uso terapêutico , Bortezomib/uso terapêutico , Mieloma Múltiplo/complicações , Síndromes Paraneoplásicas/tratamento farmacológico , Policitemia/etiologia , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/patologia , Policitemia/tratamento farmacológico , Policitemia/patologia , Resultado do Tratamento
14.
Eksp Klin Farmakol ; 79(2): 24-8, 2016.
Artigo em Russo | MEDLINE | ID: mdl-27416679

RESUMO

The study performed on erythroblastic island cultures and rats with experimental polycythemia showed that recormon and epokrin stimulated erythropoiesis in erythroblastic islands both in vitro and in vivo. In cell cultures, recormon activates the formation of erythroblastic islands de novo and de repeto 1.3 times better than epokrin (p < 0.05). Erythroid cells exbhibited same reaction to epokrin and recormon in vivo: the number of erythroblastic islands in the bone marrow increased 3.4 times (p < 0.05) and the number of reticulocytes in the blood increased 2.2 times (p < 0.05).


Assuntos
Eritroblastos/efeitos dos fármacos , Eritropoese/efeitos dos fármacos , Eritropoetina/farmacologia , Hematínicos/farmacologia , Policitemia/tratamento farmacológico , Animais , Animais não Endogâmicos , Medula Óssea/efeitos dos fármacos , Medula Óssea/patologia , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Eritroblastos/patologia , Feminino , Policitemia/patologia , Cultura Primária de Células , Isoformas de Proteínas/farmacologia , Ratos , Proteínas Recombinantes/farmacologia
15.
Intern Med ; 55(3): 285-7, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26831025

RESUMO

A 65-year-old Japanese man presented with acute myocardial infarction (AMI) and polycythemia. Biochemical studies of the patient's hemoglobin (Hb) and the sequencing of his globin genes revealed that the polycythemia was secondary to a high oxygen affinity Hb variant, Hb Fuchu-II. Hb variants with high oxygen affinity can be an additional thrombotic risk factor in older patients and/or those with other risk factors. The patient was diagnosed with hemoglobinopathy after the development of AMI and exemplifies the importance of recognizing such conditions and of taking appropriate prophylactic interventions.


Assuntos
Anticoagulantes/administração & dosagem , Aspirina/administração & dosagem , Dor no Peito/diagnóstico por imagem , Hemoglobinas Anormais/metabolismo , Infarto do Miocárdio/diagnóstico , Oxigênio/metabolismo , Inibidores da Agregação de Plaquetas/administração & dosagem , Policitemia/diagnóstico , Varfarina/administração & dosagem , Idoso , Dor no Peito/etiologia , Angiografia Coronária , Hemoglobinas Anormais/isolamento & purificação , Humanos , Masculino , Infarto do Miocárdio/complicações , Infarto do Miocárdio/tratamento farmacológico , Policitemia/complicações , Policitemia/tratamento farmacológico , Resultado do Tratamento
16.
Am J Med ; 129(6): 568-72, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-26714210

RESUMO

The success of organ transplantation allows many transplant recipients to return to life similar to nontransplant patients. Their need for regular health care, including preventive medicine, has switched the majority of responsibilities for their health care from transplant specialists to primary care physicians. To take care of transplant recipients, it is critical for primary care physicians to be familiar with immunosuppressive medications, their side effects, and common complications in transplant recipients. Ten subjects are reviewed here in order to assist primary care physicians in providing optimal care for transplant recipients.


Assuntos
Monitoramento de Medicamentos/normas , Rejeição de Enxerto/tratamento farmacológico , Imunossupressores/uso terapêutico , Transplante de Órgãos/efeitos adversos , Atenção Primária à Saúde/normas , Transplantados , Corticosteroides/efeitos adversos , Corticosteroides/imunologia , Corticosteroides/uso terapêutico , Anticoncepcionais Femininos/administração & dosagem , Anticoncepcionais Femininos/normas , Ciclosporina/efeitos adversos , Ciclosporina/imunologia , Ciclosporina/uso terapêutico , Diarreia/induzido quimicamente , Diarreia/complicações , Diarreia/imunologia , Interações Medicamentosas/imunologia , Monitoramento de Medicamentos/métodos , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Procedimentos Cirúrgicos Eletivos/normas , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/imunologia , Masculino , Adesão à Medicação , Ácido Micofenólico/efeitos adversos , Ácido Micofenólico/imunologia , Ácido Micofenólico/uso terapêutico , Osteonecrose/induzido quimicamente , Osteonecrose/tratamento farmacológico , Policitemia/tratamento farmacológico , Policitemia/etiologia , Gravidez , Complicações na Gravidez/induzido quimicamente , Complicações na Gravidez/imunologia , Complicações na Gravidez/prevenção & controle , Atenção Primária à Saúde/métodos , Sirolimo/efeitos adversos , Sirolimo/imunologia , Sirolimo/uso terapêutico , Tacrolimo/efeitos adversos , Tacrolimo/imunologia , Tacrolimo/uso terapêutico , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/etiologia , Infecções Urinárias/imunologia
17.
J Med Case Rep ; 9: 30, 2015 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-26187587

RESUMO

INTRODUCTION: The World Health Organization classification of chronic myeloproliferative disease encompasses eight entities of bone marrow neoplasms, among them Breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1-positive chronic myeloid leukemia and polycythemia vera. Polycythemia vera requires, in the majority of cases (95%), the negativity of Breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1 rearrangement and the presence of the Janus kinase 2 mutation. We report a case of erythrocytosis as the primary manifestation of a chronic myeloid leukemia, with the presence of the Philadelphia chromosome and the Breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1 fusion gene, and in the absence of any Janus kinase 2 mutation. CASE PRESENTATION: A 68-year-old Caucasian woman, with a history of cigarette consumption and obstructive sleep apnoea syndrome (undergoing continuous positive airway pressure treatment) had presented to our institution with fatigue and a hemoglobin level of 18.6g/L, with slight leukocytosis at 16G/L, and no other anomalies on her complete blood cell count. Examination of her arterial blood gases found only a slight hypoxemia; erythropoietin and ferritin levels were very low and could not explain a secondary erythrocytosis. Further analyses revealed the absence of any Janus kinase 2 mutation, thus excluding polycythemia vera. Taken together with a high vitamin B12 level, we conducted a Breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1 gene analysis and bone marrow cytogenetic analysis, both of which returned positive, leading to the diagnosis of chronic myeloid leukemia. CONCLUSIONS: To date, this case is the first description of a Breakpoint cluster region-Abelson murine leukemia viral oncogene homolog 1-positive chronic myeloid leukemia, presenting with erythrocytosis as the initial manifestation, and mimicking a Janus kinase 2 V617F-negative polycythemia vera. Her impressive response to imatinib therapy underscores the importance of not missing this diagnosis.


Assuntos
Proteínas de Fusão bcr-abl , Leucemia Mielogênica Crônica BCR-ABL Positiva/complicações , Policitemia Vera/complicações , Policitemia/complicações , Idoso , Doença Crônica , Diagnóstico Diferencial , Feminino , Humanos , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Policitemia/tratamento farmacológico , Policitemia Vera/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico
19.
J Clin Invest ; 125(5): 1987-97, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25866969

RESUMO

Patients with a germline mutation in von Hippel-Lindau (VHL) develop renal cell cancers and hypervascular tumors of the brain, adrenal glands, and pancreas as well as erythrocytosis. These phenotypes are driven by aberrant expression of HIF2α, which induces expression of genes involved in cell proliferation, angiogenesis, and red blood cell production. Currently, there are no effective treatments available for VHL disease. Here, using an animal model of VHL, we report a marked improvement of VHL-associated phenotypes following treatment with HIF2α inhibitors. Inactivation of vhl in zebrafish led to constitutive activation of HIF2α orthologs and modeled several aspects of the human disease, including erythrocytosis, pathologic angiogenesis in the brain and retina, and aberrant kidney and liver proliferation. Treatment of vhl(-/-) mutant embryos with HIF2α-specific inhibitors downregulated Hif target gene expression in a dose-dependent manner, improved abnormal hematopoiesis, and substantially suppressed erythrocytosis and angiogenic sprouting. Moreover, pharmacologic inhibition of HIF2α reversed the compromised cardiac contractility of vhl(-/-) embryos and partially rescued early lethality. This study demonstrates that small-molecule targeting of HIF2α improves VHL-related phenotypes in a vertebrate animal model and supports further exploration of this strategy for treating VHL disease.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/antagonistas & inibidores , Hidrazonas/uso terapêutico , Sulfonas/uso terapêutico , Doença de von Hippel-Lindau/tratamento farmacológico , Regiões 5' não Traduzidas , Aminoácidos Dicarboxílicos/toxicidade , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/deficiência , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Encéfalo/irrigação sanguínea , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Embrião não Mamífero , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Hidrazonas/farmacologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/deficiência , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Rim/patologia , Fígado/patologia , Contração Miocárdica/efeitos dos fármacos , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/genética , Fenótipo , Policitemia/tratamento farmacológico , Policitemia/genética , Vasos Retinianos/patologia , Sulfonas/farmacologia , Proteínas Supressoras de Tumor/deficiência , Proteínas Supressoras de Tumor/genética , Peixe-Zebra/embriologia , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/deficiência , Proteínas de Peixe-Zebra/genética , Doença de von Hippel-Lindau/genética , Doença de von Hippel-Lindau/patologia , Doença de von Hippel-Lindau/fisiopatologia
20.
Endocr Res ; 40(4): 177-80, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25775381

RESUMO

PURPOSE: To report a rare case of erythrocytosis that occurred in close association with Graves' hyperthyroidism. In order to explore the role of altered erythropoiesis in hyperthyroidism, factors related to erythropoiesis were studied in 30 patients with Graves' hyperthyroidism. METHOD: The relationship between thyroid hormone level and erythrocytosis was studied in a patient with Graves' hyperthyroidism and erythrocytosis. Later, 30 consecutive patients with proven untreated Graves' hyperthyroidism and 30 age- and sex-matched healthy controls were recruited. All patients received methimazole therapy. Erythrocyte indices, thyroid function, serum erythropoietin (EPO), and hypoxia-inducible factor-1α (HIF-1α) concentrations were measured before and after eight weeks of therapy. RESULTS: In our case study, erythrocytosis relapsed with elevation of thyroid hormones. Methimazole or subsequent radioiodine therapy reduced the conditions of erythrocytosis and thyroid function returned to normal. In the clinical study, erythrocyte counts, serum erythropoietin, and HIF-1α levels in the hyperthyroid group were significantly higher than those in the control subjects. All subjects were grouped together for correlation analyses and HIF-1α was shown to correlate with total triiodothyronine (TT(3)), total thyroxine (TT(4)), and EPO levels. The correlation between EPO and TT(3) or TT(4) approached significance. After eight weeks of anti-thyroid drug therapy, a small but statistically significant increase in hemoglobin and erythrocyte count with a significant decrease in HIF-1α and EPO level was seen in hyperthyroid subjects. CONCLUSION: Erythrocytosis may appear in patients with hyperthyroidism, and one possible mechanism is thyroid hormone-induced augmentation of HIF-1α, resulting in increased EPO levels.


Assuntos
Antitireóideos/farmacologia , Eritropoetina/sangue , Doença de Graves , Subunidade alfa do Fator 1 Induzível por Hipóxia/sangue , Metimazol/farmacologia , Policitemia , Adolescente , Adulto , Antitireóideos/administração & dosagem , Feminino , Doença de Graves/sangue , Doença de Graves/complicações , Doença de Graves/tratamento farmacológico , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/efeitos dos fármacos , Masculino , Metimazol/administração & dosagem , Pessoa de Meia-Idade , Policitemia/sangue , Policitemia/tratamento farmacológico , Policitemia/etiologia , Adulto Jovem
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