RESUMO
The purpose of this study was to analyse the characteristics of 6 patients managed in a university hospital between 1996 and 2016 for non-islet cell tumor hypoglycemia (NICTH), a form of hypoglycaemia due to the paraneoplastic secretion of IGF-2 or its related substances. RESULTS: Three of these 6 patients (50%), aged over 69 years, including 2 with acromegaloid phenotype, presented with a pleural solitary fibrous tumor (SFT), with median diameter 20 cm (interquartile range, 12.5-20.5) with a low median SUV (3.3 g/mL (QR, 2-7.5)) on 18F-FDG PET. The other 3 patients presented respectively neuroendocrine carcinoma (NEC) of the palate (70-year-old woman), retroperitoneal myxofibrosarcoma (66-year-old man) and meningeal hemangiopericytoma (36-year-old woman). All 3 were inoperable and did not respond to any therapy other than glucose solution. Corticosteroid therapy was effective in the 3 SFTs and the NEC. One of the SFTs recurred 10 years later with asymptomatic hypoglycemia, which resolved after reintervention. Median (IQR) blood glucose levels of the 6 patients was 0.4g/L (QR, 0.31-0.41), with hypoinsulinemia at 0.7mIU/L (QR 0.7-2.0), undetectable GH, low IGF-1, normal IGF-2 level in 5/6 cases, a high IGF-2:IGF-1 ratio at 26.9 (QR, 20.8-37.8), hypokalemia and hypomagnesemia. CONCLUSION: NICTH is a rare syndrome, which should be considered in the presence of hypoinsulinemic hypoglycemia with low GH and IGF-1, and a IGF-2:IGF-1 ratio>10. Corticosteroid therapy was effective in elderly subjects, particularly with solitary fibrous tumor, which was generally operable. Hemangiopericytoma and myxofibrosarcoma had poor prognosis in younger patients.
Assuntos
Hipoglicemia/etiologia , Tumores Neuroendócrinos/complicações , Tumor Fibroso Solitário Pleural/complicações , Adulto , Idoso , Glicemia/análise , Feminino , Fibroma , Fibrossarcoma/sangue , Fibrossarcoma/complicações , Hemangiopericitoma/sangue , Hemangiopericitoma/complicações , Hospitais Universitários , Hormônio do Crescimento Humano/sangue , Humanos , Hipoglicemia/sangue , Hipoglicemia/tratamento farmacológico , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like II/análise , Magnésio/sangue , Masculino , Neoplasias Meníngeas/sangue , Neoplasias Meníngeas/complicações , Tumores Neuroendócrinos/sangue , Potássio/sangue , Prognóstico , Neoplasias Retroperitoneais/sangue , Neoplasias Retroperitoneais/complicações , Tumor Fibroso Solitário Pleural/sangueRESUMO
HISTORY AND ADMISSION FINDINGS: A seventy-seven year-old woman with an unclear tumor of the liver suffered from recurrent hypoglycemia and was therefore admitted to our hospital. As diabetes mellitus, hyperinsulinism and reactive forms of hypoglycemia could be excluded, the presumptive diagnosis was non-islet-cell tumor hypoglycemia (NICTH). INVESTIGATIONS: Postprandial glucose levels were normal. Fasting glucose levels were 30 - 50 mg/dl. Plasma insulin-like growth factor (IGF)-I was below the normal range, IGF-II was not elevated, although 34 % of plasma IGF-II was present as "big"-IGF-II. IGF-binding protein (IGFBP)-2 was extremely elevated, whereas IGFBP-3 was within the normal range. Histological examinations of the tumor revealed a hemangiopericytoma of the liver. TREATMENT AND COURSE: : After a 2-month treatment with steroids and an experimental antiangiogenetic therapy, the glucose metabolism became stable. The tumour did not grow. Simultaneously, plasma IGF-II and "big"-IGF-II remained constant and plasma IGF-I level improved slightly. IGFBP-2, which is presumable produced by the tumor, increased, IGFBP-3 fell below the normal range. CONCLUSION: NICTH is a rare but important differential diagnosis of recurrent hypoglycemia. The tumor derived IGF-II has a higher than normal molecular weight ("big"-IGF-II) and shows different interactions with binding proteins, thus resulting in an increased bioavailability. An increased glucose uptake in different tissues as well as inhibition of hepatic gluconeogenesis and lipolysis lead to severe hypoglycemia. If surgical therapy of the tumor is not possible, symptomatic treatment with steroids may represent an effective alternative to control severe hypoglycemia.
Assuntos
Ciclofosfamida/análogos & derivados , Hemangiopericitoma/complicações , Hipoglicemia/etiologia , Fator de Crescimento Insulin-Like II/análise , Neoplasias Hepáticas/complicações , Tiazolidinedionas , Idoso , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/uso terapêutico , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/uso terapêutico , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/uso terapêutico , Antineoplásicos Hormonais/administração & dosagem , Antineoplásicos Hormonais/uso terapêutico , Ciclofosfamida/administração & dosagem , Ciclofosfamida/uso terapêutico , Feminino , Hemangiopericitoma/sangue , Hemangiopericitoma/tratamento farmacológico , Hemangiopericitoma/fisiopatologia , Humanos , Hipoglicemia/sangue , Hipoglicemia/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Proteína 2 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like I/biossíntese , Fator de Crescimento Insulin-Like II/biossíntese , Lactonas/administração & dosagem , Lactonas/uso terapêutico , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/fisiopatologia , Pioglitazona , Prednisolona/administração & dosagem , Prednisolona/uso terapêutico , Recidiva , Sulfonas , Tiazóis/administração & dosagem , Tiazóis/uso terapêutico , Fatores de TempoRESUMO
A 47-year-old woman suffered from gait disturbance due to back pain and muscle weakness. Laboratory data showed serum hypophosphatemia, elevated alkaline phosphatase, and a normal level of ionized calcium. Radiological examinations revealed multiple pathologic fractures in the ribs and pubic rami. She had had no episode of familial or any other notable disorder, and so she was initially treated with medication for adult-onset osteomalacia. However, 19 years later (when she was 66 years old), she noticed a soft-tissue tumor in her buttock. The tumor was excised. The histological features were those of glomangiopericytoma characterized by both glomus tumor-like and hemangiopericytoma-like structures. After removal of the tumor, her symptoms disappeared immediately. Laboratory data normalized 8 months later. To our knowledge, this is the first report of oncogenic osteomalacia caused by glomangiopericytoma.
Assuntos
Nádegas , Fraturas Espontâneas/diagnóstico por imagem , Fraturas Espontâneas/etiologia , Tumor Glômico/complicações , Tumor Glômico/patologia , Hemangiopericitoma/complicações , Hemangiopericitoma/patologia , Osteomalacia/diagnóstico , Osteomalacia/etiologia , Osso Púbico/lesões , Fraturas das Costelas/diagnóstico por imagem , Fraturas das Costelas/etiologia , Neoplasias de Tecidos Moles/complicações , Neoplasias de Tecidos Moles/patologia , Idoso , Fosfatase Alcalina/sangue , Dor nas Costas/etiologia , Biópsia , Cálcio/sangue , Feminino , Tumor Glômico/sangue , Tumor Glômico/cirurgia , Hemangiopericitoma/sangue , Hemangiopericitoma/cirurgia , Humanos , Imuno-Histoquímica , Debilidade Muscular/etiologia , Fósforo/sangue , Radiografia , Neoplasias de Tecidos Moles/sangue , Neoplasias de Tecidos Moles/cirurgiaRESUMO
We report a patient with insulin-like growth factor (IGF)-II-producing hemangiopericytoma with hypoglycemia in whom repeated intra-abdominal recurrences developed over a period of about 10 years and tumor resection was performed four times. A 67-year-old woman was admitted to our hospital in 1995 because of hypoglycemic attacks. In 1985, partial resection of the small bowel had been performed for a 17-cm abdominal tumor of the transverse mesocolon, and the pathological diagnosis was hemangiopericytoma. In 1991, left hemicolectomy had been performed for a mesosigmoidal tumor associated with hypoglycemia. In 1994, hysterectomy, bilateral adnexectomy, and resection of an intrapelvic tumor were performed. The fourth operation was performed in 1996, about 10 years after the first operation. The spleen was removed, together with more than 1500 tumors having a total weight of 1,660 g. The hypoglycemia was ameliorated after each operation. Before this operation, her serum IGF-I level was low, but her IGF-II level was within the normal range; however, the Western immunoblot method showed that most of the IGF-II was high-molecular-weight IGF-II. The tissue IGF-I level was also low, and the IGF-II level was high, suggesting an IGF-II-producing tumor. We suspect that the mechanism of the hypoglycemia in this patient was related to the high-molecular-weight IGF-II produced by the tumor. The patient died in 1997 because of tumor recurrence.
Assuntos
Neoplasias Abdominais/complicações , Neoplasias Abdominais/metabolismo , Hemangiopericitoma/complicações , Hemangiopericitoma/metabolismo , Hipoglicemia/etiologia , Fator de Crescimento Insulin-Like II/efeitos adversos , Fator de Crescimento Insulin-Like II/metabolismo , Recidiva Local de Neoplasia/complicações , Recidiva Local de Neoplasia/metabolismo , Neoplasias Abdominais/sangue , Idoso , Feminino , Hemangiopericitoma/sangue , Humanos , Hipoglicemia/sangue , Fator de Crescimento Insulin-Like II/análise , Masculino , Recidiva Local de Neoplasia/sangueRESUMO
Haemangiopericytoma is a rare soft tissue tumour originating from the contractile pericapillary cells. Relatively little is known about its molecular pathogenesis. To address this issue, the insulin-like growth factor family (IGFs) was analysed in 19 tumours collected from a human tumour bank network. Seven of the tumours were associated with severe hypoglycaemia. Of these, six were retroperitoneal and one was located in the leg. 3 out of the 19 tumours (15.8 per cent) were positive for insulin-like growth factor I (IGF I) mRNA and 11 were positive for IGF II mRNA (57.9 per cent). Almost 90 per cent of haemangiopericytomas expressed IGF I receptor (IGF IR) mRNA (17 out of 19), five (26.3 per cent) expressed IGF binding protein 1 (IGF BP1), three (15.8 per cent) expressed IGF BP2, and four (21 per cent) exhibited IGF BP3 mRNA. All of the 14 haemangiopericytomas examined with regard to specific receptor binding were IGF IR positive, ranging from 1.2 to 16.2 per cent. Binding was much higher in IGF I/IGF IR positive tumours (15.3+/-0. 7) than in IGF I negative/IGF IR positive tumours (5.1+/-3.3). The potential role of IGF IR as a growth promoting factor in malignant haemangiopericytoma was studied using antisense oligonucleotides and monoclonal antibody alphaIR3 that specifically inhibit IGF IR synthesis or activity. 10 microM IGF IR antisense oligonucleotides significantly inhibited the growth of haemangiopericytoma cells in culture, by around 50 per cent; monoclonal antibody against IGF IR (alphaIR3) also significantly inhibited proliferation. The data suggest that IGF IR may play an important role in the genesis and progression of malignant haemangiopericytomas.
Assuntos
Hemangiopericitoma/química , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/genética , RNA Mensageiro/análise , Receptor IGF Tipo 1/genética , Neoplasias Retroperitoneais/química , Somatomedinas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia/análise , Peptídeo C/análise , Divisão Celular , Pré-Escolar , Feminino , Hemangiopericitoma/sangue , Hemangiopericitoma/patologia , Humanos , Hipoglicemia/metabolismo , Hipoglicemia/patologia , Insulina/sangue , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like II/análise , Fator de Crescimento Insulin-Like II/genética , Neoplasias Pulmonares/química , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Pélvicas/química , Neoplasias Pélvicas/patologia , Neoplasias Retroperitoneais/sangue , Neoplasias Retroperitoneais/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Somatomedinas/análise , Células Tumorais CultivadasRESUMO
Hemangiopericytoma is a rare soft tissue tumor originating from contractile pericapillary pericytes. To address the issue of molecular genetic events that participate in genesis and progression of hemangiopericytoma we analyzed insulin-like growth factor (IGF) II and IGF I receptor in 29 tumors collected from a human tumor bank network. Seven of these tumors were associated with severe hypoglycemia; six were retroperitoneal and one was located in the leg. Of 22 tumors tested 12 (54.5%) exhibited IGF II mRNA, while almost 90% (17 of 19) of hemangiopericytomas exhibited IGF I receptor mRNA. Sera from some patients whose tumors expressed IGF II mRNA contained elevated levels of IGF II. Removal of the tumor eliminated most of the IGF II immunoreactivity from the sera. The potential role of IGF II as a growth-promoting factor was examined on three malignant primary hemangiopericytoma cell cultures. Extracellular addition of IGF II significantly enhanced cell proliferation in a dose-dependent manner. Antisense oligodeoxynucleotides that specifically inhibit IGF II mRNA, at a concentration of 40 or 80 micrograms/ml, inhibited the growth of hemangiopericytoma cells significantly, by 40%. Simultaneous administration of antisense deoxyoligonucleotides to both IGF II and IGF I receptor inhibited tumor cell proliferation by even 80%. Our data suggest that tumor cells produce IGF II, and that this in turn stimulates their proliferation by autocrine mechanisms.
Assuntos
Hemangiopericitoma/metabolismo , Fator de Crescimento Insulin-Like II/metabolismo , Receptor IGF Tipo 1/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Divisão Celular , Criança , Pré-Escolar , Feminino , Hemangiopericitoma/sangue , Humanos , Imuno-Histoquímica , Fator de Crescimento Insulin-Like II/química , Masculino , Pessoa de Meia-Idade , Peso Molecular , Oligorribonucleotídeos Antissenso , Radioimunoensaio , Células Tumorais CultivadasRESUMO
BACKGROUND: Tumor hypoglycemia can be recurrent and severe enough to interfere with definitive antineoplastic treatment. Therefore, rapid commencement of effective therapy is essential. This is best accomplished by identifying which of the hypoglycemic processes is involved, as treatments differ. Some patients present with hypoglycemia and liver metastases; among them, only a few develop hypoglycemia as a result of a failure of hepatic glucose production. Most develop hypoglycemia as a result of an insulin-mediated process--either the secretion of insulin by an islet-cell tumor or the secretion of insulin-like growth factor-II by an extrapancreatic tumor. Administration of glucagon can rapidly make the two groups distinguishable, thus allowing institution of therapy and prompt symptomatic control of hypoglycemia. METHODS: The charts of seven patients with tumor hypoglycemia and liver metastases who had a glucagon stimulation test (serial glucose measurements after a 1 mg infusion of glucagon) as part of the workup for hypoglycemia were retrospectively reviewed. Those patients whose test revealed a rise in serum glucose of >30 mg/ dL were subsequently treated as outpatients, with a continuous glucagon infusion delivered by a portable pump. RESULTS: Three patients had an insulinoma and four had non-islet cell tumor hypoglycemia (NICTH) due to hepatocellular carcinoma, colon carcinoma, meningeal sarcoma, and hemangiopericytoma, respectively. All of the patients had liver metastases. Evaluation of these patients included a glucagon stimulation test (1 mg intravenous push), which quickly provided information about the mechanism of tumor hypoglycemia and the direction towards therapy. All patients with insulinoma responded to glucagon with a rise in blood serum glucose levels, indicating adequate glycogen stores. The four patients with NICTH had mixed responses: in two patients, the response suggested that hypoglycemia was due to an insulin-like tumor product; glucose levels did not rise in the other two cases, indicating that hypoglycemia was due to poor hepatic glycogen reserve/liver failure. In all cases, a glycemic response to glucagon predicted good response to long term treatment with glucagon (0.06-0.3 mg/hour, via intravenous infusion pump). CONCLUSIONS: The glucagon stimulation test is a simple and fast approach that serves to clarify the etiology of hypoglycemia (diagnostic use) and guide effective long term strategies for its control (therapeutic use) in patients with neoplastic diseases and liver metastases.
Assuntos
Glucagon/uso terapêutico , Hipoglicemia/diagnóstico , Hipoglicemia/tratamento farmacológico , Neoplasias Hepáticas/sangue , Adulto , Idoso , Glicemia/análise , Carcinoma/sangue , Carcinoma/tratamento farmacológico , Carcinoma/patologia , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/patologia , Neoplasias do Colo/sangue , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Feminino , Hemangiopericitoma/sangue , Hemangiopericitoma/tratamento farmacológico , Hemangiopericitoma/patologia , Humanos , Bombas de Infusão , Insulinoma/sangue , Insulinoma/tratamento farmacológico , Insulinoma/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Neoplasias Meníngeas/sangue , Neoplasias Meníngeas/tratamento farmacológico , Neoplasias Meníngeas/patologia , Pessoa de Meia-Idade , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Sarcoma/sangue , Sarcoma/tratamento farmacológico , Sarcoma/patologiaAssuntos
Hemangiopericitoma/sangue , Hipoglicemia/sangue , Fator de Crescimento Insulin-Like II/análise , Fator de Crescimento Insulin-Like I/análise , Neoplasias Pélvicas/sangue , Adulto , Hemangiopericitoma/diagnóstico , Hemangiopericitoma/cirurgia , Humanos , Hipoglicemia/etiologia , Hipoglicemia/metabolismo , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/sangue , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like II/metabolismo , Masculino , Pessoa de Meia-Idade , Neoplasias Pélvicas/diagnóstico , Neoplasias Pélvicas/cirurgia , Valores de ReferênciaRESUMO
The authors report on a case that during its 9-year-long history has repeatedly been misdiagnosed due to the misleading clinical and histopathological findings. The patient has been treated, in chronological order, for cerebrovascular disease, acoustic Schwannoma, glomus tympanicum tumor (chemodectoma) and finally turned out to have an intracranial hemangiopericytoma that originated from the area of the glomus tympanicum and eventually widely metastatized within and outside the intracranial compartment. The proper diagnosis was reached with the help of detailed immunohistochemical analysis. The subunit A of Factor XIII (FXIIIa) can be demonstrated on formaldehyde-fixed paraffin embedded sections. It has recently been shown that FXIIIa reactivity is characteristic and hence diagnostic of a subpopulation of cells within systemic and intracranial (central) hemangiopericytomas (HPCs). Since it is consistently missing from all cell components of ordinary meningiomas, glomus tumors (chemodectomas) and a host of other soft tissue tumors, its presence or absence is a helpful sign in various differential diagnostic dilemmas.
Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Cerebelares/diagnóstico , Ângulo Cerebelopontino , Fator XIII/análise , Hemangiopericitoma/diagnóstico , Fragmentos de Peptídeos/sangue , Neoplasias Cerebelares/sangue , Neoplasias Cerebelares/cirurgia , Ângulo Cerebelopontino/diagnóstico por imagem , Ângulo Cerebelopontino/patologia , Ângulo Cerebelopontino/cirurgia , Erros de Diagnóstico , Feminino , Hemangiopericitoma/sangue , Hemangiopericitoma/cirurgia , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios XRESUMO
The insulin-like growth factor II (IGF-II) gene is overexpressed in many mesenchymal tumors and can lead to non-islet-cell tumor hypoglycemia (NICTH). ProIGF-II consists of the 67 aa of IGF-II with a carboxyl 89-aa extension, the E domain. A derivative of proIGF-II containing only the first 21 aa of the E domain [proIGF-II-(E1-21)] has been isolated by others from normal serum and has O-linked glycosylation. We found that the "big IGF-II" of normal serum, as detected by an RIA directed against residues 1-21 of the E domain of proIGF-II, was reduced in size by treatment with neuraminidase and O-glycosidase. The big IGF-II, which is greatly increased in NICTH sera, was unaffected by neuraminidase and O-glycosidase treatment. We have also shown that big IGF-II from normal serum is retained by jacalin lectin columns and that big IGF-II from NICTH serum was not retained, indicating that it lacked O-glycosylation. Normal O-linked glycosylation may be required for proper peptidase processing of proIGF-II. The lack of normal O-linked glycosylation by tumors may explain the predominance of big IGF-II in NICTH sera. In normal serum, most of the IGF-II is present in a 150-kDa ternary complex with IGF-II binding protein (IGFBP) 3 and alpha subunit. In NICTH serum, however, the complexes carrying big IGF-II are < 50 kDa. We investigated whether big IGF-II of NICTH was responsible for this abnormality. Tumor big IGF-II and IGF-II were equally effective in forming the 150-kDa complex with purified IGFBP-3 and 125I-labeled alpha subunit. Both 125I-labeled IGF-II and 125I-labeled proIGF-II-(E1-21), when incubated with normal serum, formed the 150-kDa complex as detected by Superose 12 exclusion chromatography. We conclude that the nonglycosylated big IGF-II of NICTH serum can form normal complexes with serum IGFBPs. The defective binding in NICTH is attributable to defective IGFBP-3 binding.
Assuntos
Fibrossarcoma/sangue , Hemangiopericitoma/sangue , Hipoglicemia/sangue , Fator de Crescimento Insulin-Like II/metabolismo , Precursores de Proteínas/metabolismo , Processamento de Proteína Pós-Traducional , Adulto , Ligação Competitiva , Proteínas de Transporte/metabolismo , Humanos , Hipoglicemia/etiologia , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina , Fator de Crescimento Insulin-Like II/biossíntese , Fator de Crescimento Insulin-Like II/isolamento & purificação , Precursores de Proteínas/biossíntese , Precursores de Proteínas/isolamento & purificação , Radioimunoensaio , Proteínas Recombinantes/metabolismo , Valores de ReferênciaRESUMO
Non-islet-cell tumours which induce hypoglycaemia are rare. Insulin-like growth factor-II (IGF-II) produced by some tumours is thought to be responsible for the hypoglycaemia and other systemic effects, despite normal or even low serum IGF-II levels. We studied a 44-year-old woman presenting with symptomatic hypoglycaemia associated with a large intraabdominal haemangiopericytoma. The serum IGF-II level was 455 micrograms/l when measured after acid-ethanol extraction (normal range (NR) 450-750 micrograms/l) and 1063 micrograms/l after acid chromatography (normal human serum pool 1068 micrograms/l). Levels of fasting plasma insulin, C-peptide, glucose and serum IGF-I levels were low before the operation (less than 2 mU/l (NR less than 2-14), 0.23 nmol/l (NR 0.4-1.2), 3.1 mmol/l, (NR 3.7-5.9) and 0.02 U/ml respectively). After tumour removal, the symptoms resolved rapidly and the patient made a full recovery. Secretion of both insulin and growth hormone was suppressed before the operation in response to a 75 g glucose meal and to an infusion of 100 micrograms GH-releasing hormone (GHRH) respectively in comparison with studies after the operation. Serum IGF-II levels 6 weeks and 12 weeks after the operation fell to 385 micrograms/l (777 micrograms/l; acid chromatography) and 280 micrograms/l (647 micrograms/l; acid chromatography) and serum IGF-I levels increased to 0.35 U/ml and 0.26 U/ml. Serum before the operation and tumour extract contained chiefly a large molecular weight precursor IGF-II (molecular weight 15,000-20,000) which disappeared from the serum after the operation. The IGF-binding proteins (IGFBP-1, IGFBP-2, IGFBP-3 and IGFBP-4) were examined.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Proteínas de Transporte/sangue , Hemangiopericitoma/sangue , Neoplasias Intestinais/sangue , Somatomedinas/metabolismo , Adulto , Western Blotting , Feminino , Humanos , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like II/metabolismoRESUMO
We have studied a patient with fasting hypoglycaemia and skin lesions (sign of Leser-Trélat) related to a retroperitoneal haemangiopericytoma in whom removal of the tumour resulted in immediate cure of hypoglycaemia. Before removal of the tumour, severe fasting hypoglycaemia was associated with undetectable insulin and C-peptide levels. She required 16.9 mumol/kg/min (10.4 g/h) of glucose intravenously to prevent hypoglycaemia and endogenous glucose production (measured using tritiated glucose) was suppressed to 1.3 mumol/kg/min while the whole-body glucose utilization rate was elevated at 18.2 mumol/kg/min. After removal of the tumour both endogenous glucose production rate and utilization rate returned to normal (11.5 mumol/kg/min). Resting energy expenditure, measured by indirect calorimetry, was markedly elevated at 2109 kcal/day (161% of predicted) and fell to 1205 (97% of predicted) after the tumour was removed. Glucose oxidation was also enhanced at 8.5 mumol/kg/min and fell to 3.3 mumol/kg/min after removal of the tumour. Other metabolites and hormones measured, and their response to oral glucose, were all consistent with the presence of a circulating substance with similar properties to insulin. We conclude that her hypoglycaemia resulted primarily from suppression of endogenous glucose production but also from enhanced glucose utilization. These effects were the result of a circulating growth factor sharing many metabolic effects with insulin, but with a much greater effect on resting energy expenditure and glucose oxidation.
Assuntos
Hemangiopericitoma/sangue , Hipoglicemia/etiologia , Insulina/sangue , Neoplasias Peritoneais/sangue , Adulto , Glicemia/metabolismo , Peptídeo C/sangue , Calorimetria , Dióxido de Carbono/metabolismo , Feminino , Hemangiopericitoma/metabolismo , Humanos , Hipoglicemia/sangue , Hipoglicemia/metabolismo , Consumo de Oxigênio , Neoplasias Peritoneais/metabolismoRESUMO
We reported that serum and tumor from a hypoglycemic patient with a fibrosarcoma contained insulin-like growth factor II (IGF-II), mostly in a large molecular form designated "big IGF-II." We now describe two additional patients with non-islet-cell tumor with hypoglycemia (NICTH) whose sera contained big IGF-II. Removal of the tumor eliminated most of the big IGF-II from the sera of two patients. Because specific IGF-binding proteins modify the bioactivity of IGFs, the sizes of the endogenous IGF-binding protein complexes were determined after neutral gel filtration through Saphadex G-200. Normally about 75% of IGFs are carried as a ternary complex of 150 kDa consisting of IGF, a growth hormone (GH)-dependent IGF-binding protein, and an acid-labile complexing component. The three patients with NICTH completely lacked the 150-kDa complex. IGF-II was present as a 60-kDa complex with variable contributions of smaller complexes. In the immediate postoperative period, a 110-kDa complex appeared rather than the expected 150-kDa complex. Abnormal IGF-II binding may be important in NICTH because the 150-kDa complexes cross the capillary membrane poorly. The smaller complexes present in our patients' sera would be expected to enter interstitial fluid readily, and a 4- to 5-fold increase in the fraction of IGFs reaching the target cells would result.
Assuntos
Biomarcadores/sangue , Fibrossarcoma/sangue , Hemangiopericitoma/sangue , Hipoglicemia/etiologia , Fator de Crescimento Insulin-Like II/sangue , Leiomiossarcoma/sangue , Somatomedinas/sangue , Neoplasias Torácicas/sangue , Adulto , Idoso , Cromatografia em Gel , Feminino , Humanos , Hipoglicemia/sangue , Fator de Crescimento Insulin-Like I/sangue , Masculino , Ligação ProteicaRESUMO
Childhood hypophosphatemic rickets (HR) is most often caused by a defect in renal tubular resorption of filtered phosphorus. However, HR can also be caused by secretion of a phosphaturetic factor from a tumor. The presentation of patients with the different HR syndromes may be identical. Distinguishing between the HR syndromes is essential, however, because HR caused by renal defect requires life-long therapy with Vitamin D and phosphate replacement, but tumor-associated HR is cured by removal of the tumor. A case of hemangiopericytoma occurring in bone and causing HR is reported. Children with HR typically have normal levels of serum calcium and parathyroid hormone but very low levels of serum phosphorus. In a child with HR, the following features should prompt a thorough evaluation for a causative tumor: lack of other family members who have hypophosphatemia; presence of aminoaciduria, particularly glycinuria. Causative lesions are most commonly found in the bone or skin.
Assuntos
Neoplasias Femorais/cirurgia , Hemangiopericitoma/cirurgia , Hipofosfatemia Familiar/cirurgia , Fósforo/sangue , Raquitismo/cirurgia , Criança , Neoplasias Femorais/sangue , Neoplasias Femorais/complicações , Hemangiopericitoma/sangue , Hemangiopericitoma/complicações , Humanos , Hipofosfatemia Familiar/diagnóstico , Masculino , Raquitismo/diagnóstico , Raquitismo/etiologiaRESUMO
Although more than 50 patients with the tumor-induced osteomalacia syndrome, characterized by remission of unexplained osteomalacia after resection of a coexisting tumor, have been reported, the pathogenesis of this syndrome is still not clear. We investigated the cause of biopsy-confirmed osteomalacia which was resistant to treatment with 1 alpha-hydroxyvitamin D3 in a 54-yr-old man. He had severe hypophosphatemia, a high serum alkaline phosphatase level, a low plasma 1,25-dihydroxyvitamin D level, and remarkably increased urinary phosphorus excretion. A tumor, with histological characteristics of a hemangiopericytoma, was found on his left thigh. After surgical removal of this tumor, his plasma 1,25-dihydroxyvitamin D and serum phosphorus levels increased to normal levels, and his bone pain subsided. The tumor was transplanted to athymic nude mice. A nodule formed in each mouse, with histological features identical to those of the original tumor, and the tumor-bearing mice had hypophosphatemia, high serum alkaline phosphatase levels, and increased urinary phosphorus excretion. When extracts of the original tumor were added to primary cultures of renal tubular cells, renal cAMP levels did not change, but 25-hydroxyvitamin D-1 alpha-hydroxylase activity was significantly inhibited. These data indicate tumoral production of some humoral factor(s) inhibiting 25-hydroxyvitamin D-1 alpha-hydroxylase activity and phosphorus reabsorption unrelated to adenylate cyclase-cAMP production in proximal renal tubules.
Assuntos
25-Hidroxivitamina D3 1-alfa-Hidroxilase/antagonistas & inibidores , Neoplasias Femorais/complicações , Hemangiopericitoma/complicações , Rim/enzimologia , Osteomalacia/etiologia , Fosfatos/sangue , Esteroide Hidroxilases/antagonistas & inibidores , Extratos de Tecidos/farmacologia , Animais , Osso e Ossos/patologia , Células Cultivadas , Terapia Combinada , AMP Cíclico/metabolismo , Neoplasias Femorais/sangue , Neoplasias Femorais/patologia , Neoplasias Femorais/terapia , Hemangiopericitoma/sangue , Hemangiopericitoma/patologia , Hemangiopericitoma/terapia , Humanos , Rim/efeitos dos fármacos , Masculino , Camundongos , Camundongos Nus , Pessoa de Meia-Idade , Transplante de Neoplasias , Osteomalacia/sangue , Osteomalacia/patologia , Osteomalacia/terapiaAssuntos
Adenoma de Células das Ilhotas Pancreáticas/sangue , Hemangiopericitoma/sangue , Hipoglicemia/sangue , Insulinoma/sangue , Neoplasias Renais/sangue , Neoplasias Pancreáticas/sangue , Síndromes Paraneoplásicas/sangue , Adulto , Aminoácidos/sangue , Glicemia/metabolismo , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/sangueRESUMO
The relationship between malignant vascular meningeal tumours and typical meningiomas remains controversial, despite the need for accurate diagnostic distinction between the two, and some forms of vascular meningioma may be more closely allied to haemangioblastomas or extracranial haemangiopericytomas than to true meningiomas. In order to try to clarify the diagnostic characteristics and origins of the entity known as haemangiopericytic meningioma, 10 histologically typical cases were stained by the immunoperoxidase technique with a panel of seven antibodies. The results were compared with those obtained from typical and angiomatous meningiomas, haemangioblastomas and haemangiopericytomas from extracranial sites. Both the haemangiopericytic meningiomas and the extracranial haemangiopericytomas showed a similar staining pattern, which differed from that of the typical and angiomatous meningiomas in the strikingly focal nature of the vimentin staining and the lack of reactivity with antibodies to epithelial elements. The haemangioblastomas were less consistent in their individual staining characteristics, but had a quite different overall pattern from all the other tumour types. It is, therefore, suggested that so-called haemangiopericytic meningiomas are in fact primary haemangiopericytomas of the meninges, antigenically distinct from true meningiomas and displaying a malignant potential appropriate to haemangiopericytomas arising in any other sites.
Assuntos
Hemangiopericitoma/sangue , Hemangiossarcoma/irrigação sanguínea , Neoplasias Meníngeas/irrigação sanguínea , Meningioma/irrigação sanguínea , Anticorpos Monoclonais , Antígenos/análise , Desmina/análise , Fator VIII/análise , Fator VIII/imunologia , Proteína Glial Fibrilar Ácida/análise , Hemangiopericitoma/análise , Hemangiopericitoma/classificação , Hemangiossarcoma/análise , Hemangiossarcoma/classificação , Humanos , Imuno-Histoquímica , Queratinas/análise , Neoplasias Meníngeas/análise , Neoplasias Meníngeas/classificação , Meningioma/análise , Meningioma/classificação , Proteínas S100/análise , Fator de von WillebrandAssuntos
Neoplasias Femorais/diagnóstico por imagem , Hemangiopericitoma/diagnóstico por imagem , Osteomalacia/diagnóstico por imagem , Fosfatos/sangue , Feminino , Neoplasias Femorais/complicações , Hemangiopericitoma/sangue , Hemangiopericitoma/complicações , Humanos , Pessoa de Meia-Idade , Osteomalacia/sangue , Osteomalacia/etiologia , RadiografiaRESUMO
The authors undertake a general review of the association between hypophosphoraemia and connective tissue tumour, based upon three personal cases and 27 cases of benign connective tissue tumours, as well as cases of hypophosphoraemia related to malignant tumours or to diffuse dysplasia of connective tissue origin, collected from the literature. This syndrome is distinguished from hypophosphoraemia induced by other tumours (myeloma, carcinoma of the prostate) which are based upon different mechanisms. Hypophosphoraemia, associated with a fall in plasma levels of 1-25 (OH)2 D3 by inhibition of renal 1 alpha hydroxylase, suggests the existence of a complex tubular deficit. Removal of the tumour, most often vascular and intra- or para-osseous, results in rapid normalisation of laboratory then radiological and clinical abnormalities. The physiopathology of the syndrome remains very mysterious. It may be likened to certain tubulotoxic syndromes due to cadmium and in particular to maleic acid. However no precise data yet exists regarding any possible abnormal tumour secretion. In practice, any case of hypophosphoraemic osteomalacia requires investigation to locate a possible tumour of connective tissue, and this all the more so when it is accompanied by very low plasma levels of 1-25(OH)2 D2.