losartan-potassium and Paraganglioma

We report the case of a 22-year-old woman with onset of erythrocytosis at the age of 9 years. Endocrinological and radiological examinations revealed an elevated catecholamine level and the presence of multiple abdominal tumors. After the removal of the tumors, the catecholamine level normalized, whereas erythropoietin remained at the same level and erythrocytosis persisted. The tumor lysate contained considerable amounts of catecholamine but not erythropoietin. Moreover, no erythropoietin mRNA was detected in the tumor by in situ hybridization. These data suggest that this paraganglioma did not produce erythropoietin. A review of the literature showed the existence of patients with early-onset erythrocytosis complicated with paraganglioma, whose erythrocytosis was not relieved even after the resection of paraganglioma.

Topics: Abdominal Neoplasms; Adult; Chronic Disease; Cyclic AMP; Epinephrine; Erythropoietin; Female; Humans; Norepinephrine; Paraganglioma; Polycythemia

Topics: Adenocarcinoma; Adrenocorticotropic Hormone; Arginine; Biliary Tract Diseases; Bronchial Neoplasms; Carcinoma; Chorionic Gonadotropin; Colonic Neoplasms; Cushing Syndrome; Erythropoietin; Female; Follicle Stimulating Hormone; Growth Hormone; Gynecomastia; Hormones, Ectopic; Humans; Hypercalcemia; Lactation Disorders; Lung Neoplasms; Luteinizing Hormone; Models, Biological; Neoplasms; Paraganglioma; Paraneoplastic Endocrine Syndromes; Polycythemia; Pregnancy; Prolactin; Thyroid Neoplasms; Vasopressins

Recently, a new syndrome of paraganglioma, somatostatinoma, and polycythemia has been discovered (known as Pacak-Zhuang syndrome). This new syndrome, with somatic HIF2A gain-of-function mutations, has never been reported in male patients. We describe a male patient with Pacak-Zhuang syndrome who carries a newly discovered HIF2A mutation. Congenital polycythemias have diverse etiologies, including germline mutations in the oxygen-sensing pathway. These include von Hippel-Lindau (Chuvash polycythemia), prolyl hydroxylase domain-containing protein-2, and hypoxia-inducible factor-2α (HIF-2α). Somatic gain-of-function mutations in the gene encoding HIF-2α were reported in patients with paraganglioma and polycythemia and have been found exclusively in female patients. Through sequencing of the HIF2A using DNA from paraganglioma in 15-year-old male patient, we identified a novel mutation of HIF2A: a heterozygous C to A substitution at base 1589 in exon 12 of HIF2A. The mutation was not found in germline DNA from leukocytes. The C1589A mutations resulted in substitution of alanine 530 in the HIF-2α protein with glutamic acid. This mutation is undoubtedly associated with increased HIF-2α activity and increased protein half-life, because it affects the vicinity of the prolyl hydroxylase target residue, proline 531. To our knowledge, this is the first report describing Pacak-Zhuang syndrome with somatic gain-of-function mutation in HIF2A in a male patient. Congenital polycythemia of unknown origin should raise suspicion for the novel disorder Pacak-Zhuang syndrome, even in male patients.

Topics: Abdominal Neoplasms; Adolescent; Basic Helix-Loop-Helix Transcription Factors; Diagnosis, Differential; Diagnostic Imaging; Erythrocyte Count; Erythropoietin; Follow-Up Studies; Genetic Carrier Screening; Hemoglobinometry; Humans; Male; Neoplasms, Multiple Primary; Norepinephrine; Paraganglioma; Polycythemia; Syndrome

Topics: Abdominal Neoplasms; Adolescent; Adult; Basic Helix-Loop-Helix Transcription Factors; Child; DNA Mutational Analysis; Erythropoietin; Exudates and Transudates; Female; Fibrosis; Fluorescein Angiography; Humans; Male; Optic Disk; Pancreatic Neoplasms; Paraganglioma; Polycythemia; Retinal Neovascularization; Somatostatinoma

Paragangliomas are tumors arising from the extra-adrenal paragangliar neural crest cells. The sympathoadrenal neuroendocrine system consists of extra-adrenal paragangliar cellular layer along the paravertebral and para-aortic axis, and the adrenal medullae. Paraganglioma should be included in the differential diagnosis of secondary erythrocytosis due to its possible ectopic erythropoietin (EPO) secretion. Thus, in this report we present a 24-year-old female patient with onset of unregulated ectopic EPO secretion, and consecutive erythrocytosis followed by hypertension, secondary to paraganglioma of multifocal retroperitoneal localization. Clinical, laboratory, and radiological investigations confirmed both an elevated EPO level and the presence of multiple paraganglioma. This paraneoplastic-mediated medical condition with high risk of cellular hyperviscosity syndrome (CHVS) requires prompt diagnosis and rapid therapeutic interventions. Initially, simple phlebotomy procedures were used; following that, tumors were surgically removed. In the course of the disease, this tumor relapsed, and urgent apheresis, as a treatment of life-threatening state, was used. The therapy performed resulted in a rapid blood viscosity depletion and a significant (P < 0.01) serum EPO reduction, as well as the general clinical benefit. Therefore, we conclude that the use of our own "multi-manner" apheresis (erythrocythapheresis plus plasma exchange), for long-time interval (until further causative therapy), effectively cross-bridged the possible hazards of EPO-dependent CHVS.

Topics: Adult; Blood Component Removal; Combined Modality Therapy; Erythropoietin; Female; Humans; Paraganglioma; Polycythemia; Viscosity