1/5. Hypoglycaemia associated with the production of insulin-like growth factor ii and insulin-like growth factor binding protein 6 by a haemangiopericytoma.Non-islet-cell tumour-induced hypoglycaemia (NICTH) is, in most cases, attributable to tumour production of insulin-like growth factor ii (IGF-II). Tumour-derived IGF-II has a higher than normal molecular weight (big 'IGF-II') and an impaired ability to form the normal ternary 150 kD complex with IGF binding protein-3 (IGFBP-3) and the acid-labile subunit (ALS). Consequently, tumoral IGF-II circulates mainly in smaller binary complexes which have a higher bioavailability than the ternary complex. We had the opportunity to analyze IGFs and IGF-related factors in both pre- and post-operative blood, tumour tissue and tumour cyst fluid from a patient with a disseminated haemangiopericytoma and severe hypoglycaemia. In addition, the effect of serum and tumour cyst fluid on autophosphorylation of the insulin receptor was examined. Patient serum contained low levels of IGF-I, IGFBP-3 and ALS, while the concentrations of IGFBP-2 and IGFBP-6 were markedly elevated. The total level of circulating IGF-II was within the normal range, but Biogel P-60 gel filtration of patient serum revealed that 77% of the IGF-II was present in high molecular weight forms (normal: 10-15%), which decreased to 53% after partial removal of the tumour. Most of the IGF-II immunoreactivity in pre- and post-operative patient serum was associated with 50-60 kD complexes with only a minimal contribution (<10%) from the 150 kD complex. Tumour cyst fluid contained excessive amounts of both big IGF-II and IGFBP-6. Northern blot analysis of total mRNA isolated from the tumour demonstrated high expression of the IGF-II gene and abundant 1.1 kb IGFBP-6 transcript, while the genes encoding IGFBP-3, -4 and -5 were only weakly expressed and mRNA of IGFBP-1, -2 and IGF-I could not be detected. mRNAs for the IGF type II receptor could be easily demonstrated, whereas those for the insulin- and IGF type I receptor were hardly detectable. In contrast to patient serum tumour cyst fluid strongly stimulated the insulin receptor in vitro. The present study suggests an important role of the simultaneous production of IGF-II and IGFBP-6 in the pathophysiology of tumour-induced hypoglycaemia.- - - - - - - - - - ranking = 1keywords = hypoglycaemia (Clic here for more details about this article) |
2/5. Intraabdominal haemangiopericytoma associated with uncontrolled diabetes mellitus.Haemangiopericytoma (HPC) is a rare tumour with a predilection for the central nervous system. Though previously thought to originate from the meninges and ventricular walls, HPC's are currently accepted as distinct mesenchymal neoplasms unrelated to meningiomas. Haemangiopericytomas have been previously reported to be associated with the production of insulin like growth factor II (IGF-II) and hypoglycaemia. A case of a 61-year-old poorly controlled diabetic lady with a rare presentation of an abdominal haemangiopericytoma is discussed. A laparoscopic assisted resection of the massive lobulated tumour arising from the parietal peritoneum with dense attachment to the diaphragm and the liver was performed with an uncomplicated postoperative recovery. Control of the patient's diabetes improved dramatically following surgery and the rare association of hyperglycaemia and HPC, which has not been previously described, is elaborated upon in this report.- - - - - - - - - - ranking = 0.33333333333333keywords = hypoglycaemia (Clic here for more details about this article) |
3/5. Metabolic effects of an insulin-like factor causing hypoglycaemia in a patient with a haemangiopericytoma.We have studied a patient with fasting hypoglycaemia and skin lesions (sign of Leser-Trelat) 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.- - - - - - - - - - ranking = 3keywords = hypoglycaemia (Clic here for more details about this article) |
4/5. Paraneoplastic rhinophyma and the Leser-Trelat sign.A case of the Leser-Trelat sign associated with an underlying malignant haemangiopericytoma is described. In addition, the patient had profound hypoglycaemia and a rhinophyma-like nasal swelling which rapidly resolved post-operatively. The tumour appeared to be secreting a factor(s) which cross-reacted with both insulin receptors to induce hypoglycaemia and epidermal growth factor receptors inducing a profusion of eruptive seborrhoeic warts. It aslo had marked sebotrophic activity. The association of the Leser-Trelat sign with malignant haemangiopericytoma has not previously been described.- - - - - - - - - - ranking = 0.66666666666667keywords = hypoglycaemia (Clic here for more details about this article) |
5/5. High-molecular weight IGF-2 expression in a haemangiopericytoma associated with hypoglycaemia.Spontaneous hypoglycaemia is usually caused by an insulin-producing islet-cell tumour of the pancreas. Rarely, it can be caused by non-islet cell tumours. Most of the tumours are of mesenchymal type, large, and slowly growing. One representative is haemangiopericytoma (HAP). The present report describes a case of a large recurrent retroperitoneal HAP associated with severe hypoglycaemia. blood serum insulin and proinsulin concentrations were low. By means of acid-gel chromatography and dot-blot techniques, an increased amount of a high-molecular-weight IGF-2 peptide was found. By using antigen retrieval procedures, IGF-2-immunoreactive tumour cells were found in specimens of the recent tumour recurrence-but not in the original. When the in situ hybridization technique was used it could be shown that IGF-2 mRNA labelling had already occurred in the original tumour specimen, 11 years before the onset of hypoglycaemic symptoms. These observations confirm the hypothesized hypoglycaemic effects of high-molecular-weight (HMW) IGF-2, but also point to the presence of a prolonged compensation of this effect. A literature review, based on 17 similar cases of haemangiopericytoma with hypoglycaemia, is presented. Our observation and findings in the literature review support the idea that non-islet-cell tumour hypoglycaemia is caused by an overproduction of a HMW IGF-2 peptide. The insulin-like effect is mediated via non-specific binding to the insulin receptors. To anticipate patients at risk of developing this kind of hypoglycaemia, the histopathological investigation should include not only immunohistochemical analyses of the presence of IGF-2 peptide, but also in situ hybridization of the IGF-2 mRNA expression.- - - - - - - - - - ranking = 3keywords = hypoglycaemia (Clic here for more details about this article) |