losartan-potassium and Pheochromocytoma

Topics: Adenocarcinoma; Adrenal Gland Neoplasms; Animals; Brain Neoplasms; Carcinoma; Carcinoma, Hepatocellular; Cell Transformation, Neoplastic; Cells, Cultured; Cricetinae; Cysts; Erythropoietin; Esophageal Neoplasms; Female; Growth Substances; Haplorhini; Humans; In Vitro Techniques; Kidney Neoplasms; Leiomyoma; Leukemia; Leukemia, Experimental; Liver Neoplasms; Lymphoma; Male; Mice; Neoplasm Metastasis; Neoplasm Transplantation; Pheochromocytoma; Polycythemia; Rats; Sarcoma, Experimental; Skin Neoplasms; Time Factors; Wilms Tumor

Topics: Adolescent; Adult; Aged; Animals; Blood Pressure; Cerebellar Neoplasms; Erythrocyte Count; Erythropoietin; Female; Humans; Hydronephrosis; Kidney; Kidney Diseases, Cystic; Kidney Neoplasms; Leiomyoma; Leukocytes; Liver Neoplasms; Male; Middle Aged; Pheochromocytoma; Polycythemia; Serum Globulins; Uterine Neoplasms

Topics: Adolescent; Adrenocorticotropic Hormone; Adult; Brain Neoplasms; Carcinoma; Carcinoma, Bronchogenic; Carcinoma, Hepatocellular; Carcinoma, Squamous Cell; Cerebellar Neoplasms; Child; Child, Preschool; Choriocarcinoma; Cushing Syndrome; Diagnosis, Differential; Erythropoietin; Female; Gonadotropins; Hemangiosarcoma; Hormones, Ectopic; Humans; Hypercalcemia; Hypoglycemia; Infant; Infant, Newborn; Insulin; Insulin Secretion; Kidney Neoplasms; Liver Neoplasms; Lung Neoplasms; Male; Neoplasms; Parathyroid Hormone; Pheochromocytoma; Polycythemia; Pregnancy; Teratoma; Testicular Neoplasms; Thymus Neoplasms

Mutations of genes related to Krebs cycle enzymes, kinases or to pseudohypoxic signaling pathways, including Von-Hippel-Lindau (VHL) and transmembrane-protein-127 predispose to pheochromocytoma and paraganglioma development. Homozygous loss of function mutation of VHL (VHL 598C>T) gene can associate with polycythemia because of an altered hypoxia sensing.. A 19-year-old normotensive man presented with headache, fatigue associated with severe erythrocytosis (hematocrit 76%), high hemoglobin (25.3 g/dl) in normoxic condition. Bone marrow biopsy showed marked hyperplasia of erythroid series. The Janus kinase 2 (V617F) mutation was absent. Abdominal computed tomography scan showed a 8-mm left adrenal pheochromocytoma with tracer uptake on GaDOTA-octreotate PET. Twenty-four-hour urinary metanephrine excretion was slightly increased, while normetanephrine, 3-methoxytyramine were normal. Adrenal veins sampling showed high left-side erythropoietin secretion.. Next-generation sequencing genetic analysis evidenced two concurrent heterozygous mutation of VHL598C>T and of transmembrane-protein-127 c.268G>A. Left side adrenalectomy improved symptoms, erythrocytosis, hemoglobin, and erythropoietin circulating levels. Adrenal histologic sections showed a pheochromocytoma with extensive immunostaining for erythropoietin, but also coexpression of chromogranin A, a marker of chromaffin tissue.. Congenital polycythemia was clinically diagnosed, mimicking Chuvash polycythemia. Chuvash polycythemia is an autosomal recessive disorder that usually harbors a homozygous mutation of VHL598C>T but not predispose to pheochromocytoma development; in contrast our patient showed for the first time that the concurrent heterozygous VHL and TMEM mutations, resulted in a clinical phenotype of a normotensive patient with polycythemia due to erythropoietin-secreting pheochromocytoma that improved after adrenalectomy.

Topics: Adrenal Gland Neoplasms; Erythropoietin; Genotype; Heterozygote; Humans; Male; Mutation; Phenotype; Pheochromocytoma; Polycythemia; Von Hippel-Lindau Tumor Suppressor Protein; Young Adult

Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are rare, neuroendocrine tumors derived from adrenal or extra-adrenal chromaffin cells, respectively. Metastases are discovered in 3-36% of patients at the time of diagnosis. Currently, only suboptimal treatment options exist. Therefore, new therapeutic compounds targeting metastatic PHEOs/PGLs are urgently needed. Here, we investigated if anthracyclines were able to suppress the progression of metastatic PHEO. We explored their effects on experimental mouse PHEO tumor cells using in vitro and in vivo models, and demonstrated that anthracyclines, particularly idarubicin (IDA), suppressed hypoxia signaling by preventing the binding of hypoxia-inducible factor 1 and 2 (HIF-1 and HIF-2) to the hypoxia response element (HRE) sites on DNA. This resulted in reduced transcriptional activation of HIF target genes, including erythropoietin (EPO), phosphoglycerate kinase 1 (PGK1), endothelin 1 (EDN1), glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA), and vascular endothelial growth factor (VEGFA), which consequently inhibited the growth of metastatic PHEO. Additionally, IDA downregulated hypoxia signaling by interfering with the transcriptional activation of HIF1A and HIF2A. Furthermore, our animal model demonstrated the dose-dependent suppressive effect of IDA on metastatic PHEO growth in vivo. Our results indicate that anthracyclines are prospective candidates for inclusion in metastatic PHEO/PGL therapy, especially in patients with gene mutations involved in the hypoxia signaling pathway.

Topics: Adrenal Gland Neoplasms; Animals; Antineoplastic Agents; Basic Helix-Loop-Helix Transcription Factors; Cell Growth Processes; Cell Line, Tumor; Endothelin-1; Erythropoietin; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Idarubicin; Mice; Mice, Nude; Neoplasm Metastasis; Pheochromocytoma; Phosphoglycerate Kinase; Protein Binding; Signal Transduction; Xenograft Model Antitumor Assays

A 59-year-old woman who identified as a Jehovah's Witness was diagnosed with pheochromocytoma in the left adrenal gland, measuring 11 cm in diameter, during treatment for hypertension. Given her desire to undergo transfusion-less surgery for religious reasons, we obtained fully informed consent and had the patient sign both a transfusion refusal and exemption-from-responsibility certificate and received consent to instead use plasma derivatives, preoperative diluted autologous transfusion and intraoperative salvaged autologous transfusion. To manage anemia and maintain total blood volume, we preoperatively administered erythropoiesis-stimulating agents and alpha 1 blocker, respectively. During the left adrenalectomy, the patient underwent a transfusion of 400 mL of preoperative diluted autologous blood, ultimately receiving no intraoperative salvaged autologous blood. The operation took 4 hours 42 minutes, and the total volume of blood lost was 335 mL. In conclusion, to complete transfusion-less surgery for pheochromocytoma, it is necessary to have the patient sign a generic refusal form for transfusion and exemption-from-responsibility certificate as well as outline via another consent form exactly what sort of transfusion is permitted on a more specific basis. And doctors should become skilled in perioperative management and operative technique for pheochromocytoma and make the best effort by all alternative medical treatment in order to build trust confidence with a patient.

Topics: Adrenal Gland Neoplasms; Adrenergic alpha-1 Receptor Antagonists; Blood Transfusion; Erythropoietin; Female; Humans; Informed Consent; Jehovah's Witnesses; Middle Aged; Perioperative Care; Pheochromocytoma; Treatment Outcome; Treatment Refusal

Topics: Adrenal Gland Neoplasms; Adult; Anticoagulants; Aspirin; Biomarkers; Biopsy; DNA Mutational Analysis; Erythropoietin; Genetic Predisposition to Disease; Humans; In Situ Hybridization, Fluorescence; Male; Mutation; Pedigree; Phenotype; Pheochromocytoma; Phlebotomy; Polycythemia; Treatment Outcome; von Hippel-Lindau Disease; Von Hippel-Lindau Tumor Suppressor Protein

To explore the ischemic tolerance induced by Ginkgolides in PC12 cells and its possible molecular mechanism.. An ischemic model was developed in PC12 cell line with deprivation of oxygen-glucose (OGD). PC12 cells was randomly divided into four groups: 9 hours ischemia group, 1.5 hours ischemic preconditioning + 9 hours ischemia group, Ginkgolides preconditioning + 9 hours ischemia group and control group. Cells viability was examined by MTT assay and cellular morphology was analyzed under the phase-contrast microscope. The molecular mechanism of Ginkgolides induced ischemic tolerance was pinpointedby analyzing the expression of hypoxia-inducible factor-1 alpha (HIF-1alpha) and erythropoietin (EPO). The DNA binding activities of HIF-1 in PC12 cells were examined by electrophoretic mobility shift assay.. In ischemic model, the viability of PC12 cells was decreased (49.3 +/- 2.8)% after OGD for 9 hours. However, Ginkgolides pretreatment could remarkably increase the viability of PC12 cells (65.9 +/- 2.8)% (P < 0.01). Pretreatment of Ginkgolides for 24 hours could largely rescue the morphology of PC12 cells to the damage of subsequent exposure to 9 hours ischemia insult, many cellular bodies were intact and many neurites and network of PC12 cells were still exist. At molecular level, the expression of HIF-1alpha was greatly induced by Ginkgolides treatment after compared with the control group (P < 0.01). The DNA binding activities of HIF-1 in PC12 cells pretreated with Ginkgolides was also increased. And it activates its downstream target EPO, the protein expression (P < 0.01).. The pretreatment of Ginkgolides could induce tolerance against ischemia in PC12 cells. The molecular mechanism of this process may involve in the activation of HIF-1alpha and the DNA binding activity of HIF-1 and its downstream target EPO.

Topics: Animals; Blotting, Western; Cell Hypoxia; Cell Shape; Cell Survival; Electrophoretic Mobility Shift Assay; Erythropoietin; Ginkgolides; Hypoxia-Inducible Factor 1; Ischemia; Ischemic Preconditioning; Oligonucleotides; PC12 Cells; Pheochromocytoma; Protein Binding; Rats

Pheochromocytoma is a neuroendocrine tumor associated with a variety of genetic disorders, which include von Hippel-Lindau disease (VHL), multiple endocrine neoplasia type 2 (MEN 2), neurofibromatosis type 1, hereditary paraganglioma, and succinate dehydrogenase gene-related tumors. Previous studies of VHL-associated and MEN 2-associated pheochromocytomas suggest morphological, biochemical, and clinical differences exist among the tumors, but the process by which they develop remains unclear. Studies in other VHL-associated tumors suggest that VHL gene deficiency causes coexpression of erythropoietin (Epo) and its receptor (Epo-R), which facilitates tumor growth. The objective of this study was to understand the different process of tumorigenesis for VHL and MEN 2-associated pheochromocytomas. Ten pheochromocytomas (VHL patients n = 5, MEN 2 patients n = 5) were examined for the presence or absence of Epo and Epo-R using Western blot, immunohistochemistry, and RT-PCR analyses. Coexpression of Epo and Epo-R was found in all five VHL-associated pheochromocytomas; in contrast, expression of Epo-R, but not Epo, was documented in all five MEN 2-associated pheochromocytomas. Expression of Epo appears to be a result of VHL gene deficiency, possibly through activation of the hypoxia inducible factor-1 pathway, whereas Epo-R is an embryonal marker whose sustained expression in both VHL- and MEN 2-associated pheochromocytomas reflects an arrest or defect in development. These findings suggest an alternative process of tumorigenesis in VHL- and MEN 2-associated pheochromocytomas and implicate Epo as a clinical biomarker to differentiate these tumors.

Topics: Adrenal Gland Neoplasms; Blotting, Western; DNA Primers; Erythropoietin; Humans; Immunohistochemistry; Multiple Endocrine Neoplasia Type 2a; Multiple Endocrine Neoplasia Type 2b; Pheochromocytoma; Receptors, Erythropoietin; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; von Hippel-Lindau Disease

We carried out sacral en-bloc resection in six patients (three with chordoma; one with pheochromocytoma; one with malignant schwannoma; and one with giant cell tumor) using preoperatively collected autologous blood, to avoid homologous blood transfusion. An average of 3200 ml was collected preoperatively, with patients receiving recombinant human erythropoietin (r-HuEPO), at a total dose of 130 000 units on average. In four patients, we were able to accomplish the surgery without homologous blood transfusion. Postoperatively, the hemoglobin level in these four patients recovered to the pre-collective level in 4.5 weeks, on average. These clinical results indicate that en-bloc sacrectomy, which requires a large volume of blood transfusion, can be accomplished with preoperatively collected autologous blood alone.

Topics: Adrenal Gland Neoplasms; Aged; Blood Donors; Blood Loss, Surgical; Blood Transfusion, Autologous; Chordoma; Erythropoietin; Female; Giant Cell Tumor of Bone; Hemoglobinometry; Humans; Hypotension, Controlled; Male; Middle Aged; Neurilemmoma; Pheochromocytoma; Recombinant Proteins; Sacrum; Spinal Neoplasms

Topics: Adrenal Gland Neoplasms; Adult; Erythropoietin; Female; Humans; Hypertension; Male; Osmolar Concentration; Pheochromocytoma; Reference Values

Erythropoietin-dependent pure erythrocytosis (EDPE) is a rare disorder caused by idiopathic hypererythropoietinemia. We describe a 13-year-old girl who developed an EDPE-like erythrocytosis after removal of an adrenal pheochromocytoma.. As occurs in EDPE, this post-pheochromocytoma erythrocytosis was associated with a high serum erythropoietin (s-Epo) level that maintained physiological regulation.. Phlebotomies produced a three- to sixfold increase of s-Epo, and a 6-week course of theophylline caused a decrease of both s-Epo and hemoglobin.. We hypothesize that the intense and prolonged pheochromocytoma-induced renal ischemia before surgery could be the cause of this unique case of erythrocytosis.

Topics: Adolescent; Adrenal Gland Neoplasms; Erythropoietin; Female; Humans; Pheochromocytoma; Polycythemia

Topics: Abdominal Neoplasms; Adult; Erythropoietin; Female; Humans; Neoplasm Recurrence, Local; Pheochromocytoma

Polycythemia is rarely associated with pheochromocytoma. A patient with a 22-year history of malignant pheochromocytoma is presented in whom major complications developed as a result of long-standing polycythemia, apparently due to secretion of erythropoietin by the tumors. Despite attempts to reduce tumor burden by surgery, chemotherapy, and large doses of I-131-metaiodobenzylguanidine, polycythemia persisted. Extensive venous thrombosis developed requiring hospitalization and anticoagulation. Thus, polycythemia itself may be a cause of major morbidity in patients with pheochromocytoma, and prophylactic measures may be warranted. Review of the 130 patients with benign and malignant pheochromocytoma studied since the introduction of I-131-metaiodobenzylguanidine in 1980 revealed another six patients with hematocrits over 50 but only one had a hematocrit greater than 55 and required regular phlebotomy. In contrast, anemia (hematocrit less than 35) due to variety of causes was present in 18 cases.

Topics: Abdominal Neoplasms; Adult; Erythropoietin; Humans; Male; Pheochromocytoma; Polycythemia; Thrombophlebitis; Time Factors

The results from a biological test for erythropoietin (using the rate of iron absorption in polycythemic mice) and a commercially-available immunological test (haemagglutination-inhibition test) were compared. Of 19 batches of the immunological test which were investigated, 7 batches were completely inactive and a further 3 batches reacted only with the test serum supplied with the test. There was a poor correlation between the results from the biological and the immunological measurements, both on patients with high and those with low serum erythropoietin levels. The difficulty of the immunological erythropoietin test is that pure erythropoietin is not sufficiently available. The immunological test investigated here does not use pure erythropoietin. Aside from this, pathophysiological considerations would lead one to expect basic differences between the results from immunological and biological tests.

Topics: Adrenal Gland Neoplasms; Anemia, Aplastic; Erythropoietin; Hemagglutination Inhibition Tests; Humans; Kidney Failure, Chronic; Leukemia; Pheochromocytoma; Polycythemia Vera

Topics: Adrenal Gland Neoplasms; Adult; Erythropoietin; Female; Humans; Pheochromocytoma; Secretory Rate

A transplantable rat pheochromocytoma in New England Deaconess Hospital (NEDH) was first described by WARREN in 1972. It is characterized by the documented association with systolic hypertension and the known presence of increased urinary metanephrines and vanilmadelic acid in tumor-bearing animals. The present report describes features of the transplantable tumor, our laboratories have noted, in five tumor transplantations starting in 1974. Tumor-bearing animals survive 49 +/- 5 days and die much sooner than aging, non-tumor-bearing litter mates. Gross measurements confirm the rapid growth of the primary tumor, although at autopsy, histologically proven metastatic foci are rarely seen. Polycythemia with or without increased erythropoietin (ESF) levels were not detected. Electronmicroscopic studies confirmed the presence in tumor tissue of the previously described intracytoplasmic granules. Further studies on this endocrine-associated transplantable tumor are warranted and feasible.

Topics: Animals; Body Weight; Erythropoietin; Female; Kidney; Male; Neoplasm Transplantation; Neoplasms, Experimental; Pheochromocytoma; Rats; Transplantation, Homologous

Topics: Adrenal Gland Neoplasms; Adult; Erythropoietin; Female; Humans; Pheochromocytoma; Polycythemia

Topics: Adrenal Gland Neoplasms; Animals; Biological Assay; Cerebellar Neoplasms; Cysts; Erythrocytes; Erythropoiesis; Erythropoietin; Female; Hemangiosarcoma; Hematocrit; Humans; Iron Isotopes; Kidney Neoplasms; Male; Mucoproteins; Pheochromocytoma; Polycythemia; Rats

Topics: Adrenal Gland Neoplasms; Animals; Carcinoma; Cerebellar Neoplasms; Erythropoietin; Female; Hemangiosarcoma; Humans; Hypertension, Renal; Kidney; Kidney Diseases; Kidney Neoplasms; Liver Neoplasms; Neoplasms; Pheochromocytoma; Polycythemia; Polythiazide; Rats; Renin; Uterine Neoplasms