RESUMO
Among the most interesting manifestations of neoplasms is the production of functional peptides and hormones that may induce unique clinical syndromes. It has become obvious in the last decades that a wide range of endocrine tumors secrete hormones not normally associated with the tissue in which the neoplasm arises. The resultant syndromes, some of which resemble other endocrine entities, can be the first clinical manifestation of malignant disease or a harbinger of cancer recurrence. The development of these disorders does not necessarily correlate with cancer stage or unfavorable prognosis. Early recognition of paraneoplastic endocrine syndromes is clinically important as it might lead to the detection of underlying malignancy and might prevent delay in treatment. Because paraneoplastic endocrine syndromes often cause considerable morbidity and mortality, effective treatment can improve patient quality and length of life. The aim of this study was to review the most common and the most specific paraneoplastic syndromes associated with the presence of ectopic hormone production. We emphasize the importance of considering the ectopic hormone production in the differential diagnosis of various endocrine entities.
Assuntos
Síndromes Endócrinas Paraneoplásicas/fisiopatologia , Diagnóstico Diferencial , Humanos , Síndromes Endócrinas Paraneoplásicas/diagnósticoRESUMO
Los síndromes paraneoplásicos endocrinos constituyen manifestaciones a distancia de algunas neoplasias. Una forma infrecuente, pero cada vez más descrita, es la osteomalacia tumoral (OT), un trastorno hipofosfatémico secundario a la pérdida renal de fosfatos inducida por la secreción tumoral del factor de crecimiento fibroblástico 23 (FGF-23). Sus principales manifestaciones bioquímicas son la hipofosfatemia, la reabsorción tubular de fosfatos inadecuadamente normal o baja, los niveles bajos de calcitriol, la fosfatasa alcalina elevada y el FGF-23 sérico elevado o normal. Los tumores asociados a la OT suelen ser pequeños, benignos, de lento crecimiento, de difícil localización y con predominio en las partes blandas de los miembros. La histología más frecuente son los tumores mesenquimales fosfatúricos tipo tejido conectivo mixto. Se han propuesto varias técnicas de imagen para su identificación con resultados variables. El tratamiento de elección es la resección quirúrgica completa de la lesión. Otras alternativas terapéuticas son las sales de fósforo, el calcitriol, la octreótida, el cinacalcet y los anticuerpos monoclonales (AU)
Endocrine paraneoplastic syndromes are distant manifestations of some tumours. An uncommon but increasingly reported form is tumour-induced osteomalacia, a hypophosphatemic disorder associated to fibroblast growth factor 23 (FGF-23) secretion by tumours. The main biochemical manifestations of this disorder include hypophosphatemia, inappropriately low or normal tubular reabsorption of phosphate, low serum calcitriol levels, increased serum alkaline phosphatase levels, and elevated or normal serum FGF-23 levels. These tumours, usually small, benign, slow growing and difficult to discover, are mainly localized in soft tissues of the limbs. Histologically, phosphaturic mesenchymal tumours of the mixed connective tissue type are most common. Various imaging techniques have been suggested with variable results. Treatment of choice is total surgical resection of the tumour. Medical treatment includes oral phosphorus and calcitriol supplements, octreotide, cinacalcet, and monoclonal antibodies (AU)
Assuntos
Humanos , Osteomalacia/epidemiologia , Síndromes Endócrinas Paraneoplásicas/fisiopatologia , Hipofosfatemia/etiologia , Fatores de Crescimento de Fibroblastos/análise , Mesenquimoma/patologia , Fósforo/uso terapêutico , Calcitriol/uso terapêutico , Antineoplásicos/uso terapêuticoRESUMO
A 41-year-old man was diagnosed with a solitary fibrous tumor (SFT) of the pleura in the posterior mediastinum. Despite two surgeries for excision, the SFT recurred and progressed with direct invasion of the chest wall and bone metastases. He was hospitalized because of cerebral infarction and presented with recurrent severe hypoglycemia fourteen years later. High-molecular-weight (HMW) insulin-like growth factor II (IGF-II) was identified in the serum and tumor using Western blotting and immunohistochemistry. These findings suggested that the cause of the recurrent severe hypoglycemia was SFT production of HMW IGF-II, a mediator of non-islet cell tumor-induced hypoglycemia (NICTH).
Assuntos
Hipoglicemia/etiologia , Fator de Crescimento Insulin-Like II/metabolismo , Recidiva Local de Neoplasia/metabolismo , Síndromes Endócrinas Paraneoplásicas/fisiopatologia , Tumor Fibroso Solitário Pleural/metabolismo , Adulto , Humanos , Fator de Crescimento Insulin-Like II/química , Masculino , Peso Molecular , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Síndromes Endócrinas Paraneoplásicas/patologia , Tumor Fibroso Solitário Pleural/patologiaRESUMO
Thymoma and thymic carcinoma are the representative tumors arising from the thymic epithelium. Thymoma is well known for association with autoimmune diseases including myasthenia gravis, suggesting its biological activity. Herein, recent progress in research of thymoma is reviewed with reference to its immunological function. Myasthenia gravis is frequently associated with WHO type B1 and B2 thymomas. These types of thymomas hold a significant number of CD4(+)CD8(+) double-positive T cells, and at the same time, the neoplastic epithelial cells express HLA-DR molecules at a slightly reduced level compared with the normal thymus. The impaired expression of HLA-DR molecules in neoplastic epithelial cells of thymomas possibly affects positive selection of CD4(+)CD8(-) single-positive T cells and may result in alteration of its repertoire. The function of thymoma neoplastic cells as the cortical epithelium of the thymus and the morphological resemblance of thymomas to the cortex suggest that thymoma is of cortical epithelial origin; this might imply that thymoma lacks the functional medulla where professional antigen-presenting cells are engaged in negative selection. These findings suggest that thymoma generates autoreactive T cells causing autoimmunity. Further investigation on immunological function of thymoma is supposed to elucidate the pathogenesis of thymoma-related autoimmunity and the high affinity of thymoma with myasthenia gravis. In addition, studying the biology of thymoma is also expected to contribute to further understanding of T-cell development and immunological tolerance in the human, because thymoma can be considered an acquired thymus.
Assuntos
Miastenia Gravis/fisiopatologia , Síndromes Endócrinas Paraneoplásicas/fisiopatologia , Timoma/imunologia , Neoplasias do Timo/imunologia , Relação CD4-CD8 , Humanos , Miastenia Gravis/etiologia , Síndromes Endócrinas Paraneoplásicas/etiologia , Linfócitos T/imunologiaAssuntos
Hormônio Liberador de Hormônio do Crescimento/metabolismo , Síndromes Endócrinas Paraneoplásicas , Acromegalia/etiologia , Animais , Diagnóstico Diferencial , Hormônio Liberador de Hormônio do Crescimento/genética , Hormônio Liberador de Hormônio do Crescimento/fisiologia , Humanos , Síndromes Endócrinas Paraneoplásicas/diagnóstico , Síndromes Endócrinas Paraneoplásicas/etiologia , Síndromes Endócrinas Paraneoplásicas/fisiopatologia , Síndromes Endócrinas Paraneoplásicas/terapia , Prognóstico , Regiões Promotoras GenéticasAssuntos
Eritropoetina/metabolismo , Síndromes Endócrinas Paraneoplásicas , Feminino , Humanos , Histerectomia , Leiomioma/diagnóstico , Leiomioma/metabolismo , Leiomioma/terapia , Pessoa de Meia-Idade , Síndromes Endócrinas Paraneoplásicas/diagnóstico , Síndromes Endócrinas Paraneoplásicas/etiologia , Síndromes Endócrinas Paraneoplásicas/fisiopatologia , Síndromes Endócrinas Paraneoplásicas/terapia , Policitemia/etiologia , Neoplasias Uterinas/diagnóstico , Neoplasias Uterinas/metabolismo , Neoplasias Uterinas/terapiaAssuntos
Calcitonina/metabolismo , Síndromes Endócrinas Paraneoplásicas , Animais , Calcitonina/fisiologia , Cálcio , Diagnóstico Diferencial , Humanos , Síndromes Endócrinas Paraneoplásicas/diagnóstico , Síndromes Endócrinas Paraneoplásicas/etiologia , Síndromes Endócrinas Paraneoplásicas/fisiopatologia , Síndromes Endócrinas Paraneoplásicas/terapia , Prognóstico , Precursores de ProteínasAssuntos
Arginina Vasopressina/metabolismo , Síndromes Endócrinas Paraneoplásicas , Carcinoma de Células Pequenas/diagnóstico , Carcinoma de Células Pequenas/metabolismo , Carcinoma de Células Pequenas/terapia , Diagnóstico Diferencial , Humanos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/terapia , Síndromes Endócrinas Paraneoplásicas/diagnóstico , Síndromes Endócrinas Paraneoplásicas/etiologia , Síndromes Endócrinas Paraneoplásicas/fisiopatologia , Síndromes Endócrinas Paraneoplásicas/terapiaAssuntos
Hormônio do Crescimento Humano/metabolismo , Síndromes Endócrinas Paraneoplásicas , Acromegalia/diagnóstico , Acromegalia/etiologia , Carcinoma de Células das Ilhotas Pancreáticas/metabolismo , Diagnóstico Diferencial , Humanos , Neoplasias Pulmonares/metabolismo , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/metabolismo , Síndromes Endócrinas Paraneoplásicas/diagnóstico , Síndromes Endócrinas Paraneoplásicas/etiologia , Síndromes Endócrinas Paraneoplásicas/fisiopatologia , Síndromes Endócrinas Paraneoplásicas/terapia , PrognósticoAssuntos
Síndromes Endócrinas Paraneoplásicas , Prolactina/metabolismo , Diagnóstico Diferencial , Técnicas de Diagnóstico Endócrino , Humanos , Hiperprolactinemia/etiologia , Neoplasias Renais/metabolismo , Neoplasias Pulmonares/metabolismo , Síndromes Endócrinas Paraneoplásicas/diagnóstico , Síndromes Endócrinas Paraneoplásicas/etiologia , Síndromes Endócrinas Paraneoplásicas/fisiopatologia , Síndromes Endócrinas Paraneoplásicas/terapia , PrognósticoAssuntos
Neoplasias Renais/metabolismo , Síndromes Endócrinas Paraneoplásicas , Renina/metabolismo , Humanos , Hiperaldosteronismo/etiologia , Sistema Justaglomerular , Neoplasias Renais/diagnóstico , Neoplasias Renais/etiologia , Neoplasias Renais/terapia , Síndromes Endócrinas Paraneoplásicas/diagnóstico , Síndromes Endócrinas Paraneoplásicas/etiologia , Síndromes Endócrinas Paraneoplásicas/fisiopatologia , Síndromes Endócrinas Paraneoplásicas/terapia , PrognósticoAssuntos
Síndromes Endócrinas Paraneoplásicas , Proteína Relacionada ao Hormônio Paratireóideo/metabolismo , Animais , Anticorpos/uso terapêutico , Colecalciferol/metabolismo , Diagnóstico Diferencial , Humanos , Hipercalcemia/etiologia , Osteoprotegerina/uso terapêutico , Cuidados Paliativos , Síndromes Endócrinas Paraneoplásicas/diagnóstico , Síndromes Endócrinas Paraneoplásicas/etiologia , Síndromes Endócrinas Paraneoplásicas/fisiopatologia , Síndromes Endócrinas Paraneoplásicas/terapia , Proteína Relacionada ao Hormônio Paratireóideo/imunologia , PrognósticoAssuntos
Síndromes Endócrinas Paraneoplásicas , Diagnóstico Diferencial , Humanos , Octreotida/uso terapêutico , Síndromes Endócrinas Paraneoplásicas/diagnóstico , Síndromes Endócrinas Paraneoplásicas/etiologia , Síndromes Endócrinas Paraneoplásicas/fisiopatologia , Síndromes Endócrinas Paraneoplásicas/terapia , Hormônios Peptídicos/metabolismo , Prognóstico , Receptores de Somatostatina/agonistas , Receptores de Somatostatina/fisiologiaRESUMO
Cushing's syndrome (CS) in medullary thyroid carcinoma (MTC) is rare. Only 50 cases have been reported. We report 10 cases of MTC with ectopic adrenocorticotropic hormone (ACTH)-dependent syndrome (EAS), analyzed retrospectively. Among 1640 patients with MTC, 13 developed EAS (0.7%). In 10 patients CS could unequivoqually be related to MTC (0.6%). CS was always clinically obvious. It revealed MTC in 3 cases and followed diagnosis by an average of 34.5 months in the others. Metastases were often present at diagnosis. Immunohistochemistry with ACTH antibodies was positive in one case. Diagnosis of ectopic CS was established according to clinical and biologic features, and absence of corticotropic adenoma as well as parallel evolution between tumor and CS. Therapy was medical and surgical: anticortisolic drugs alone or in association with somatostatin analogue, somatostatin analogue alone, and bilateral adrenalectomy. Eight patients died within 2 to 30 months, 4 of hypercortisolism complications (3 peritonitis and 1 hypokalaemia), 4 of MTC progression. EAS is a rare complication of MTC. The prognosis is poor because of frequency of metastasis at diagnosis. Persistent hypercortisolism can, by itself, lead to death, and has to be treated specifically.
Assuntos
Hormônio Adrenocorticotrópico/metabolismo , Carcinoma Medular/patologia , Síndromes Endócrinas Paraneoplásicas/patologia , Neoplasias da Glândula Tireoide/patologia , Adulto , Idoso , Carcinoma Medular/fisiopatologia , Evolução Fatal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Endócrinas Paraneoplásicas/fisiopatologia , Prognóstico , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/fisiopatologiaAssuntos
Glucagonoma , Neoplasias Pancreáticas , Síndromes Endócrinas Paraneoplásicas , Diagnóstico Diferencial , Glucagonoma/diagnóstico , Glucagonoma/metabolismo , Glucagonoma/fisiopatologia , Glucagonoma/terapia , Humanos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/fisiopatologia , Neoplasias Pancreáticas/terapia , Síndromes Endócrinas Paraneoplásicas/diagnóstico , Síndromes Endócrinas Paraneoplásicas/fisiopatologia , Síndromes Endócrinas Paraneoplásicas/terapia , Fatores de RiscoRESUMO
Lung tumors are capable of synthesizing and secreting peptide proteins (hormones) that lead to a variety of endocrine paraneoplastic syndromes. Knowledge about the clinical manifestations, pathophysiology, and treatment of these syndromes has evolved over time. This article provides an up-to-date overview of this knowledge.
Assuntos
Hormônio Adrenocorticotrópico/metabolismo , Neoplasias Pulmonares/diagnóstico , Síndromes Endócrinas Paraneoplásicas/diagnóstico , Proteína Relacionada ao Hormônio Paratireóideo/metabolismo , Vasopressinas/metabolismo , Biomarcadores Tumorais/análise , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/fisiopatologia , Neoplasias Pulmonares/terapia , Síndromes Endócrinas Paraneoplásicas/metabolismo , Síndromes Endócrinas Paraneoplásicas/fisiopatologia , Síndromes Endócrinas Paraneoplásicas/terapiaRESUMO
A case of erythrocytosis caused by gastric cancer that produced erythropoietin is described. To the authors' knowledge, no case of erythropoietin-producing gastric cancer has been reported until now. A 73-year-old man with a 4-year history of maintenance hemodialysis for diabetic nephropathy required phlebotomy. Serum erythropoietin level was 181 mU/mL (181 IU/L). Gastroscopy results showed rough mucosa with hemorrhaging caused by gastric cancer. The patient underwent distal gastrectomy, and serum erythropoietin level decreased to 27.1 mU/mL (27.1 IU/L) by postoperative day 8. Existence of erythropoietin in the tumor tissue was confirmed immunohistochemically. The presence of severe acquired cystic disease of the kidney, renal cell carcinoma, and other malignant tumors should be investigated in hemodialysis patients displaying erythrocytosis.
Assuntos
Adenocarcinoma/metabolismo , Eritropoetina/metabolismo , Hormônios Ectópicos/metabolismo , Síndromes Endócrinas Paraneoplásicas/etiologia , Policitemia/etiologia , Neoplasias Gástricas/metabolismo , Adenocarcinoma/sangue , Adenocarcinoma/complicações , Adenocarcinoma/cirurgia , Idoso , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/terapia , Gastrectomia , Hemorragia Gastrointestinal/etiologia , Humanos , Masculino , Síndromes Endócrinas Paraneoplásicas/sangue , Síndromes Endócrinas Paraneoplásicas/fisiopatologia , Policitemia/fisiopatologia , Diálise Renal , Neoplasias Gástricas/sangue , Neoplasias Gástricas/complicações , Neoplasias Gástricas/cirurgiaRESUMO
Adrenomedullin (AM) is a recently discovered potent vasodilatory peptide, originally isolated in extracts of human pheochromocytoma, with activities including maintenance of cardiovascular and renal homeostasis through vasodilatation, diuresis and natriuresis. Human AM consists of 52 amino acids with a 6-member ring structure linked by a disulfide bond and amidated COOH terminal, which belongs to calcitonin gene-related peptide (CGRP) and amylin. The main sites of AM production are the lungs, vascular tissues (both endothelial and smooth muscle cells), heart, kidney, adrenal glands, pancreatic islets, placenta, anterior pituitary gland and gastrointestinal neuroendocrine system. Intravenous injection of AM increases blood flow predominantly in the tissues with the highest AM expression, suggesting that AM functions primarily as a paracrine/autocrine hormone, but it is also important as circulating hormone. The objective of this review is to analyze the evidence that AM may play a role in some endocrine disorders.