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Serum IGF-I (serum + igf-i)
Terms modified by Serum IGF-I Selected AbstractsSerum Insulin-Like Growth Factor-I Concentration in Cats with Diabetes Mellitus and AcromegalyJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 5 2007Rebecca I.M. Berg Background: Serum insulin-like growth factor-I (IGF-I) has been used in place of serum growth hormone quantification for identifying acromegaly in diabetic cats. The utility of IGF-I as a screening test for acromegaly has not been critically evaluated. This retrospective study was performed to evaluate the usefulness of serum IGF-I concentration for identifying acromegaly. Hypothesis: Serum IGF-I is a useful screening test for acromegaly in diabetic cats. Animals: A review was made of the medical records of 74 diabetic cats that had serum IGF-I quantified. The diabetes was classified as well controlled (15 cats), poorly controlled because of problems with the insulin treatment regimen, concurrent disease, or both (40), or poorly controlled with clinical findings consistent with acromegaly (19). Methods: A review of medical records was made. Results: Serum IGF-I concentration was significantly (P < .0001) increased in acromegalic diabetic cats, compared with well-controlled and poorly controlled diabetic cats. Sensitivity and specificity for serum IGF-I concentration were 84% (95% confidence interval [CI] = 60.4,96.6%) and 92% (95% CI = 81.3,97.2%), respectively. There was no significant correlation between serum IGF-I concentration and duration of insulin treatment (r = 0.23, P= .089), insulin dosage (r = 0.14, P= .30), age (r = 0.16, P= .12), and pituitary volume (r = 0.40, P= .11), but a modest correlation was found between serum IGF-I concentration and body weight (r = 0.48, P < .0001). Conclusions and Clinical Importance: Results support the use of serum IGF-I concentration as a screening test for acromegaly in diabetic cats that have clinical findings supportive of the disease. [source] SERUM INSULIN-LIKE GROWTH FACTOR-I AND INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN-3 FOLLOWING CHEMOTHERAPY FOR ADVANCED BREAST CANCERANZ JOURNAL OF SURGERY, Issue 11 2003Ian M. Holdaway Background: Insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP-3) appear to influence the growth of breast cancer cells in vitro, and epidemiological studies suggest higher serum IGF-I levels increase the risk of breast cancer. IGF-I and IGFBP-3 have therefore been measured in women with advanced breast cancer to determine if changes in serum levels predict the response to treatment by chemotherapy. Methods: Serum IGF-I and IGFBP-3 levels were measured in 14 patients before and after 1 week of chemotherapy. Changes in serum levels were compared with duration of survival. Results: Mean basal serum levels of IGF-I and IGFBP-3 were not significantly different between patients with advanced breast cancer and controls or women with early breast cancer. Serum IGFBP-3 fell significantly 1 week after initiation of chemotherapy. Patient survival was not significantly related to baseline IGF-I or IGFBP-3 levels, but when the fall in serum levels 1 week after starting treatment was expressed either as absolute change or as a percentage of baseline, those individuals with a decrease in IGFBP-3 greater than the median had significantly poorer survival (median survival 5.5 months vs 18 months). These results were independent of other prognostic variables such as previous disease-free survival, and were also unaffected by the change in serum albumin with treatment. The fall in IGF-I and IGFBP-3 with chemotherapy mainly occurred in those with hepatic metastases, but prediction of survival was explained solely by the extent of the fall in IGFBP-3. Conclusions: This preliminary study has shown that serum IGFBP-3 falls significantly following initiation of chemotherapy and the extent of reduction significantly predicts the response to treatment. [source] Autocrine/paracrine involvement of insulin-like growth factor-I and its receptor in chronic lymphocytic leukaemiaBRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2005Roxana Schillaci Summary Chronic lymphocytic leukaemia (CLL) is characterized by the accumulation of long-lived B lymphocytes blocked in G0/1 by impaired apoptosis. As insulin-like growth factor-I (IGF-I) is known for its antiapoptotic effects in different cell types, we investigated whether IGF-I and its receptor (IGF-IR) participate in autocrine/paracrine loops affecting the survival of CLL cells. IGF-IR protein and mRNA was present in CLL cells in 44% and 59% of patients respectively. IGF-IR expression in CLL patients was positively correlated with the expression of the antiapoptotic protein Bcl-2 and was involved in CLL cell survival in vitro. Serum IGF-I was elevated in CLL patients, but growth hormone (GH) was normal. CLL cells expressed IGF-I mRNA and secreted the growth factor in vitro. Therefore, local production of IGF-I can account for the increased levels of serum IGF-I, independently of GH, and may be related to autocrine/paracrine control of lymphocyte survival acting at IGF-IR. This is the first demonstration of IGF-IR expression in a subgroup of CLL patients and of its antiapoptotic effects in vitro, highlighting the importance of this growth factor receptor as a possible therapeutic target in CLL. [source] Increased levels of insulin-like growth factor binding protein-2 in sera and tumours from patients with colonic neoplasia with and without acromegalyCLINICAL ENDOCRINOLOGY, Issue 4 2001F. Miraki-Moud OBJECTIVE Patients with acromegaly are at increased risk of developing colorectal carcinoma and premalignant tubulovillous adenoma. The pathogenesis of these neoplasms could involve a stimulatory effect of serum growth factors on colonic epithelial cell proliferation. The aim of this study was to evaluate changes in (1) serum IGF-I, IGF-II, IGFBP-3 and IGFBP-2 and (2) changes in local expression of IGFBPs and p53 in colonic epithelium in patients with colonic neoplasia with and without acromegaly. DESIGN A cross-sectional retrospective study was performed. Fasting serum samples were obtained at the time of colonoscopy for patients with acromegaly and at the time of surgery for patients with colonic neoplasia without acromegaly. MEASUREMENTS Serum IGF-I, IGF-II, IGFBP-2 and IGFBP,3 were measured using specific immunoassays. Tissue expression of IGFBP-2, IGFBP-3 and p53 status were determined by immunohistochemistry. PATIENTS Group 1: 26 age- and sex-matched control subjects (range 40,69 years); group 2: 18 patients with acromegaly without colonic neoplasia (range 39,68 years); group 3: 18 patients with acromegaly and colonic neoplasia (range 41,74 years, 11 = adenoma, seven = carcinoma); group 4: 19 patients with colonic neoplasia without endocrine disease (range 43,91 years, four = adenoma, 15 = carcinoma). Immunohistochemical staining of colonic biopsies was performed for IGFBP-2, IGFBP-3 and p53 in groups 3 and 4. RESULTS Mean serum IGF-I and IGFBP-3 levels were significantly elevated in group 2 (371 ± 131 µg/l and 6·5 ± 1·8 mg/l, respectively) and group 3 (379 ± 174 µg/l and 5·8 ± 1·6 mg/l, respectively), and significantly reduced in group 4 (103 ± 36 µg/l and 2·4 ± 1 mg/l) compared to controls (165 ± 40 µg/l and 4·7 ± 1 mg/l; P < 0·0001, P < 0·001, respectively). However, median serum IGFBP-2 levels were significantly elevated in group 3 (P < 0·01) and group 4 (P < 0·0001). Immunostaining for IGFBP-2 showed strong areas of immunoreactivity in the cytoplasm of malignant colonic epithelium compared to benign epithelium. IGFBP-3 immunostaining showed strong areas of immunoreactivity in the cytoplasm and in the nucleus of malignant and benign colonic epithelium compared to the normal epithelium. Nuclear staining for p53 was observed in three patients from group 3 (two carcinoma, one adenoma) and four patients from group 4 (all carcinoma). CONCLUSION Our results describe changes in IGFBP-2 expression in colonic neoplasia in patients with and without acromegaly, which suggest that this binding protein may regulate local bioavailability of IGF, which in turn could modulate colonic cell proliferation and/or differentiation. [source] Additional dietary zinc for weaning piglets is associated with elevated concentrations of serum IGF-IJOURNAL OF ANIMAL PHYSIOLOGY AND NUTRITION, Issue 9-10 2004D. Carlson Summary Two experiments were performed in order to study how weaning and post-weaning dietary zinc level affect serum IGF-I. Further, whether the growth-enhancing effect of 2500 ppm of dietary zinc (Zn2500) and/or 175 ppm of dietary copper (Cu175) in post-weaning diets is associated with elevated serum IGF-I levels in piglets was studied. Experiment 1 included 54 piglets (six litters of nine piglets). One piglet from every litter was assigned to a control group (blood sampled 1 day before weaning). At weaning the remaining eight piglets from every litter were allocated randomly to four dietary treatments with increasing zinc inclusions (Zn100, Zn250, Zn1000, Zn2500). In exp. 2, 48 piglets (six litters of eight piglets) were allocated to four dietary treatments (Zn100, Zn100Cu175, Zn2500, Zn2500Cu175). All piglets in exp. 1 were blood sampled at ,1, 1,2, 5,6 or 14,15 days after weaning and in exp. 2 blood samples were taken from all pigs 5,7 days after weaning. Feed intake was recorded per pen (two piglets) and weight gain was recorded for every piglet. Just after weaning feed intake was very low, piglets lost weight and serum IGF-I decreased in exp. 1. However, the piglets fed 2500 ppm of zinc reached pre-weaning levels of serum IGF-I at 14,15 days post-weaning, whereas piglets receiving lower zinc levels showed no changes in serum IGF-I. In exp. 2, additional dietary zinc in weaning diets for piglets was found to be associated with increased feed intake, improved growth rate and increased serum IGF-I. High levels of dietary copper did not affect any of these measurements. Zinc-induced rise in serum IGF-I was partly due to increased feed intake. After correcting for differences in feed intake, zinc significantly increased serum IGF-I. However, to completely separate effects of feed intake from effects of zinc status, pair-feeding should be considered in future studies. [source] The Inhibition of Inducible Nitric Oxide Synthase Reverts Arthritic-Induced Decrease in Pituitary Growth Hormone mRNA But Not in Liver Insulin-Like Growth Factor I mRNA ExpressionJOURNAL OF NEUROENDOCRINOLOGY, Issue 12 2003I. Ibáñez De Cáceres Abstract Experimental arthritis induced by Freund-adjuvant administration is a model of chronic inflammation and rheumatoid arthritis associated with a decrease in pituitary growth hormone (GH) and hepatic insulin-like growth factor I (IGF-I) gene expression. Excessive nitric oxide (NO) synthesis by inducible NO synthase (iNOS) has been implicated in the pathogenesis of inflammatory illness. Moreover, NO participates in the regulation of GH secretion at both the hypothalamus and the pituitary. We have examined the role of iNOS activation in producing the changes in the GH-IGF-I axis in arthritic rats. Adult male Wistar rats received aminoguanidine or vehicle from day 20, after adjuvant or vehicle injection, until day 28. Two hours and 30 min after the last aminoguanidine injection, all rats were killed by decapitation. Arthritis increased hypothalamic expression of somatostatin mRNA while it decreased pituitary GH mRNA expression, and both effects were prevented by aminoguanidine administration. In arthritic rats, the parallel decrease in serum IGF-I, and in hepatic IGF-I content and mRNA expression, correlates with the decrease in circulating GH concentrations. Aminoguanidine administration to arthritic rats did not modify either serum GH or serum IGF-I concentrations, or hepatic IGF-I mRNA expression. However, aminoguanidine administration to control rats resulted in a decrease in serum GH concentrations and in a decrease in both hepatic IGF-I mRNA expression and serum IGF-I concentrations. These data suggest that NO mediates the arthritis-induced decrease in GH mRNA expression by acting at a hypothalamic level, but it is not involved in the decrease in hepatic IGF-I mRNA expression. [source] Serum Insulin-Like Growth Factor-I Concentration in Cats with Diabetes Mellitus and AcromegalyJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 5 2007Rebecca I.M. Berg Background: Serum insulin-like growth factor-I (IGF-I) has been used in place of serum growth hormone quantification for identifying acromegaly in diabetic cats. The utility of IGF-I as a screening test for acromegaly has not been critically evaluated. This retrospective study was performed to evaluate the usefulness of serum IGF-I concentration for identifying acromegaly. Hypothesis: Serum IGF-I is a useful screening test for acromegaly in diabetic cats. Animals: A review was made of the medical records of 74 diabetic cats that had serum IGF-I quantified. The diabetes was classified as well controlled (15 cats), poorly controlled because of problems with the insulin treatment regimen, concurrent disease, or both (40), or poorly controlled with clinical findings consistent with acromegaly (19). Methods: A review of medical records was made. Results: Serum IGF-I concentration was significantly (P < .0001) increased in acromegalic diabetic cats, compared with well-controlled and poorly controlled diabetic cats. Sensitivity and specificity for serum IGF-I concentration were 84% (95% confidence interval [CI] = 60.4,96.6%) and 92% (95% CI = 81.3,97.2%), respectively. There was no significant correlation between serum IGF-I concentration and duration of insulin treatment (r = 0.23, P= .089), insulin dosage (r = 0.14, P= .30), age (r = 0.16, P= .12), and pituitary volume (r = 0.40, P= .11), but a modest correlation was found between serum IGF-I concentration and body weight (r = 0.48, P < .0001). Conclusions and Clinical Importance: Results support the use of serum IGF-I concentration as a screening test for acromegaly in diabetic cats that have clinical findings supportive of the disease. [source] Autocrine/paracrine involvement of insulin-like growth factor-I and its receptor in chronic lymphocytic leukaemiaBRITISH JOURNAL OF HAEMATOLOGY, Issue 1 2005Roxana Schillaci Summary Chronic lymphocytic leukaemia (CLL) is characterized by the accumulation of long-lived B lymphocytes blocked in G0/1 by impaired apoptosis. As insulin-like growth factor-I (IGF-I) is known for its antiapoptotic effects in different cell types, we investigated whether IGF-I and its receptor (IGF-IR) participate in autocrine/paracrine loops affecting the survival of CLL cells. IGF-IR protein and mRNA was present in CLL cells in 44% and 59% of patients respectively. IGF-IR expression in CLL patients was positively correlated with the expression of the antiapoptotic protein Bcl-2 and was involved in CLL cell survival in vitro. Serum IGF-I was elevated in CLL patients, but growth hormone (GH) was normal. CLL cells expressed IGF-I mRNA and secreted the growth factor in vitro. Therefore, local production of IGF-I can account for the increased levels of serum IGF-I, independently of GH, and may be related to autocrine/paracrine control of lymphocyte survival acting at IGF-IR. This is the first demonstration of IGF-IR expression in a subgroup of CLL patients and of its antiapoptotic effects in vitro, highlighting the importance of this growth factor receptor as a possible therapeutic target in CLL. [source] High-risk colorectal adenomas and serum insulin-like growth factorsBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 1 2001A. G. Renehan Background: This study investigated the hypothesis that circulating levels of insulin-like growth factor (IGF) I and its main binding protein (IGFBP-3) predict for the presence of colorectal adenomas, surrogate markers of colorectal cancer risk. Methods: Within the Flexi-Scope Trial (healthy volunteers aged 55,64 years), at one study centre, IGF-I and IGFBP-3 levels in serum samples collected prospectively from 442 attendants were measured. Of these, 100 individuals underwent a complete screening colonoscopy. There were 47 normal examinations, while in 11 examinations low-risk adenomas and in 42 examinations high-risk adenomas were identified. Estimates of relative risk (RR) for the adenomatous stages were calculated by means of unconditional logistic regression, adjusting for known risk factors. Results: Mean serum IGF-I and IGFBP-3 levels were similar in individuals with a normal colonoscopy finding and in those with low-risk adenomas. By contrast, the mean(s.d.) serum IGF-I level was increased (190(53) versus 169(54) µg/l; P = 0·06) and the serum IGFBP-3 concentration was significantly decreased (3·22(0·60) versus 3·47(0·62) mg/l; P = 0·05) in individuals with high-risk adenomas compared with levels in those with normal colonoscopy and low-risk adenomas combined. Levels were unaffected by removal of the adenomas. With high-risk adenoma as the dependent factor, regression models demonstrated a significant positive association with IGF-I after controlling for IGFBP-3 (RR per one standard deviation (1s.d.) change 4·39 (95 per cent confidence interval (c.i.) 1·31,14·7); P = 0·02) and, independently, an inverse association with IGFBP-3 after adjustment for IGF-I (RR per 1s.d. change 0·41 (95 per cent c.i. 0·20,0·82); P = 0·01). Conclusion: These findings suggest that circulating IGF-I and IGFBP-3 levels are related to future colorectal cancer risk and, specifically, may predict adenoma progression. © 2001 British Journal of Surgery Society Ltd [source] Serum Insulin-like Growth Factors, Insulin-like Growth Factor-binding Protein-3, and Risk of Lung Cancer Death: A Case-control Study Nested in the Japan Collaborative Cohort (JACC) StudyCANCER SCIENCE, Issue 12 2002Kenji Wakai To elucidate the roles of insulin-like growth factors (IGFs) in the development of lung cancer, we conducted a case-control study nested within the Japan Collaborative Cohort Study. Serum samples were collected at baseline from 39 140 men and women between 1988 and 1990. We measured serum IGF-I, IGF-II, and IGF-binding protein-3 (IGFBP-3) in 194 case subjects who subsequently died from lung cancer during an 8-year follow-up and in 9351 controls. The odds ratios (ORs), adjusted for smoking and other covariates, were smaller with higher levels of IGF-II and IGFBP-3. The ORs across quartiles were 0.41 (95% confidence interval [CI], 0.27,0.63), 0.47 (0.31,0.71), and 0.67 (0.46,0.98) for IGF-II (trend P=0.018), and 0.55 (95% CI, 0.37,0.81), 0.54 (0.36,0.82), and 0.67 (0.45,1.01) for IGFBP-3 (trend P=0.037). These peptides were not independently related to lung cancer risk when mutually adjusted. The risk was increased in the highest vs. the lowest quartile of IGF-I only after controlling for IGFBP-3 (OR, 1.74; 95% CI, 1.08,2.81). Limiting subjects to those followed for ,3 years strengthened the negative associations of IGF-II and IGFBP-3, whereas the ORs for IGF-I generally decreased. A higher level of circulating IGFBP-3 and/or IGF-II may decrease lung cancer risk. Elevated serum IGF-I may increase the risk, but this could partly be attributable to latent tumors. [source] Circulating IGF-I levels are associated with increased biventricular contractility in top-level rowersCLINICAL ENDOCRINOLOGY, Issue 2 2008Giovanni Vitale Summary Background, The intensive physical activity is often associated with cardiac changes. Objectives, (i) To evaluate the IGF-I system and myocardial structure and function by standard Doppler echocardiography and Tissue Doppler in athletes and sedentary controls; and (ii) to determine any relationship between IGF-I system and echocardiographic parameters. Methods, Nineteen male top-level rowers and 19 age-matched healthy sedentary male controls underwent blood determination of fasting serum IGF-I, IGFBP-3 and acid-labile subunit levels and standard Doppler echocardiography combined with pulsed Tissue Doppler of posterior septal wall, left ventricular (LV) lateral mitral annulus and right ventricular (RV) tricuspid annulus. Myocardial presystolic (PSm), systolic (Sm), the ratio of early diastolic (Em) to atrial (Am) velocities as well as myocardial time intervals were calculated. Results, Rowers had higher serum IGF-I levels (P = 0·04), higher biventricular cavity dimensions and wall thicknesses compared to controls. They also had better LV and RV myocardial function than controls. In the rowers, IGF-I was associated with LV ejection fraction (r = 0·50, P = 0·03), RV PSm velocity (r = 0·55, P = 0·01) and with RV myocardial precontraction time (r = ,0·57, P = 0·01). These associations remained significant after adjusting for age and heart rate. Conclusions, Top-level athletes showed higher IGF-I levels and a better myocardial performance than controls, particularly for the RV systolic activity. The independent correlations between IGF-I and systolic parameters of the left (ejection fraction) and right (PSm velocity and precontraction time) ventricles may possibly indicate a role of IGF-I system in the modulation of myocardial inotropism in athletes. Further studies are needed to confirm this hypothesis. [source] The impact of idiopathic childhood-onset growth hormone deficiency (GHD) on bone mass in subjects without adult GHDCLINICAL ENDOCRINOLOGY, Issue 1 2005Martin Lange Summary objective, Despite seemingly adequate growth hormone (GH) treatment during childhood, children with GH deficiency (GHD) have reduced bone mineral density (BMD) at final height. The aim was to evaluate BMD and bone mineral content (BMC) in adults treated for idiopathic childhood-onset (CO) GHD, 18 years after stopping GH treatment. subjects and methods, Twenty-six (11 females) patients with idiopathic CO GHD participated. All patients but two had been treated for isolated GHD in childhood. The childhood diagnosis was established by an insulin tolerance test (ITT) and reassessed in adulthood by an ITT (N = 21) or arginine test (n = 5), revealing that 10 patients had GHD according to adult criteria. Accordingly, the patient group was divided into (1) patients who did not have persistent GHD in adulthood and (2) patients who did have persistent adult GHD. Twenty-six healthy subjects acted as age-, gender- and body mass index (BMI)-matched controls. results, The patients who did not have persistent GHD had significantly lower IGF-I values and whole-body, femoral neck and lumbar spine BMD compared to controls [0·994 ± 0·10 vs. 1·114 ± 0·11 g/cm2 (P = 0·003), 0·842 ± 0·12 vs. 0·962 ± 0·11 g/cm2 (P = 0·006) and 1·026 ± 0·14 vs. 1·127 ± 0·13 g/cm2 (P = 0·004), respectively]. Femoral neck BMD was significantly reduced in the patients who had persistent GHD, compared to controls (0·842 ± 0·09 vs. 0·938 ± 0·11, P = 0·04). Significant correlations were observed between all bone variables and IGF-I in all subjects, whereas no correlations were observed between bone variables and GH peak levels in the 26 patients. conclusion, In conclusion, we found that (1) patients with idiopathic CO GHD, who at retest in adulthood did not have GHD according to adult criteria, had reduced serum IGF-I and BMD/BMC compared to controls. (2) This observation was also made in the patients who did have persistent GHD in adulthood. The findings may reflect the fact that the present diagnostic criteria for adult GHD (i.e. response to the ITT) do not reflect the clinical consequences of disordered GH,IGF axis in CO GHD young adults who were treated with GH in childhood. Alternatively, despite seemingly adequate GH treatment in childhood an optimal peak bone mass in adolescence may never have been reached in either of the groups. (3) IGF-I levels correlated with clinical signs of the adult GHD syndrome. We believe that further studies on the indications and diagnostic procedures for GH treatment after cessation of linear growth are necessary. [source] Serum homocysteine concentrations in children with growth hormone (GH) deficiency before and after 12 months GH replacementCLINICAL ENDOCRINOLOGY, Issue 5 2004Valentina Esposito Summary objective, This open, prospective study was designed to evaluate the effect of growth hormone deficiency (GHD) and GH replacement therapy on serum homocysteine (Hcy) concentration in children with GHD. subjects, Seventeen prepubertal children with GHD (11 boys and six girls) aged 8·6 ± 1·9 years were studied before and after 12 months of GH replacement therapy at a dose of GH of 30 µg/kg/day. Seventeen healthy children acted as controls and were matched for age, sex and body mass index (BMI). methods, At study entry, height, weight, blood pressure, serum Hcy, serum IGF-I, total-low density lipoprotein (LDL)- and high density lipoprotein (HDL) cholesterol, triglycerides, free T4, free T3, vitamin B12, folate, glucose and creatinine were measured in all subjects. The atherogenic index (AI) was also calculated as the ratio of total cholesterol/HDL cholesterol (T/HDL). In GHD children these parameters were also revaluated after 12 months of GH therapy. results, At study entry height and serum IGF-I were significantly lower, as expected, in GHD patients than in controls (P < 0·0001 and P < 0·007, respectively). Serum Hcy levels were significantly higher in GHD patients than in healthy children (8·4 ± 2·9 vs. 6·0 ± 2·9 µmol/l; P < 0·03), although the absolute values were within the normal values for age and sex. There were no significant differences at baseline with respect to blood pressure, serum vitamin B12, folate, fT3, fT4, lipid profile, creatinine and glucose levels. After 12 months of GH replacement therapy height and serum IGF-I increased significantly compared to pretreatment values (P < 0·0001); serum Hcy levels decreased significantly (6·0 ± 3·3 µmol/l; P < 0·002) compared to baseline values, becoming similar to control values. Total cholesterol (3·5 ± 0·6 mmol/l) and the AI (2·5 ± 0·8) decreased significantly with respect to both pretreatment (4·2 ± 1·0 mmol/l; P < 0·0002 and 3·4 ± 0·8; < 0·002, respectively) and control values (4·2 ± 0·4 mmol/l; P < 0·0005 and 3·3 ± 1·1; P = 0·02, respectively). conclusions GHD in children is associated with higher serum levels of Hcy compared to controls, without significantly affecting the lipid profile. GH replacement for 12 months significantly decreased the Hcy levels and improved the lipid profile with a decrease of total cholesterol and the total/HDL cholesterol ratio, compared to pretreatment values. Given the small number of patients, further larger studies are needed to clarify whether these results may have significant effects in the prevention of cardiovascular disease in adulthood. [source] Different effects of short- and long-term recombinant hGH administration on ghrelin and adiponectin levels in GH-deficient adultsCLINICAL ENDOCRINOLOGY, Issue 1 2004Claudia Giavoli Summary objective, To evaluate circulating levels of ghrelin and adiponectin (ApN) in GH-deficient (GHD) adults before and after short- and long-term recombinant human GH (rhGH) administration. patients and methods, Twenty-three patients were studied. Seventeen subjects (Group A, 12 men, five women) were evaluated at baseline and after 1 year rhGH therapy (dose mean ± SD: 0·3 ± 0·1 mg/day) with the assessment of serum IGF-I, ghrelin, ApN, leptin, insulin and glucose levels, percentage of body fat (BF%), HOMA-IR and QUICKI. Seventeen age-, sex- and body mass index (BMI)-matched healthy subjects were recruited for comparisons. Six patients (Group B, three men, three women) underwent IGF-I generation test (rhGH 0·025 mg/kg/day for 7 days), blood sampled at baseline and on day 8 for determination of IGF-I, ghrelin and ApN levels. results, Group,A: at baseline GHD patients showed low IGF-I levels and BF% significantly higher than controls (31·4 ± 2·5 vs. 26·4 ± 1·3, P < 0·05). Glucose, insulin, leptin, tryglicerides, low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels, as well as HOMA-IR and QUICKI values were similar in the two series, while total cholesterol levels were higher in GHD. In GHD, ghrelin levels were significantly lower than in controls (193·9 ± 27·1 vs. 298·1 ± 32·5 pmol/l, respectively, P = 0·02), while ApN levels were similar (10·2 ± 1·1 and 9 ± 1 mg/l, respectively, P = ns). After 1 year of rhGH therapy, BF%, BMI, serum total and LDL cholesterol significantly decreased, serum leptin levels showed a trend to decrease, while HOMA-IR and QUICKI did not change. Ghrelin and ApN levels significantly increased from 193·9 ± 27·1 to 232·4 ± 26·3 pmol/l (P < 0·01) and from 8·6 ± 0·8 to 10·3 ± 1·1 mg/l (P < 0·05), respectively. In group B, the expected increase in IGF-I levels was associated with a significant decrease in ghrelin levels, while ApN did not change. conclusion, GHD patients showed serum ghrelin lower than controls, probably due to the higher BF%. No difference in ApN was observed. Ghrelin and ApN increments induced by long-term treatment may be related to the significant BMI and BF% reduction that is the predominant metabolic effect of rhGH therapy. Conversely, the decrease in ghrelin levels observed after short-term rhGH administration may be consistent with an inhibitory feedback of GH and/or IGF-I on ghrelin release. [source] Impaired GH secretion to provocative stimuli in two families with hypocalciuric hypercalcaemiaCLINICAL ENDOCRINOLOGY, Issue 5 2003Elisabetta Cecconi Summary objective, To determine whether hypercalcemia per se might be responsible for an impairment in GH secretion. design, Prospective study. patients, Six subjects of two unrelated families with familial hypocalciuric hypercalcaemia (FHH), an autosomal dominant disorder due to inactivating mutations in the calcium receptor gene, leading to an increase in serum calcium levels and inappropriately normal serum PTH concentrations. Forty normal subjects, matched for sex and age served as controls. measurements, Serum GH concentrations were measured after GHRH-Arginine (GHRH-Arg) stimulation test; serum IGF-I, ACTH, cortisol, FT4, FT3, TSH, PRL, LH, FSH levels were measured under basal conditions. results, All subjects (two male, four female, age range 24,74 years) had increased serum ionized calcium levels (range 1·36,1·56 mmol/l) and five of six patients had normal PTH levels (range for all patients was 14,68 ng/l). Basal serum GH concentrations ranged from 0·1 to 7·0 µg/l. Mean serum GH secretory peak after GHRH-Arg stimulation test was reduced in five subjects (mean 9·3 ± 3·6 µg/l, P < 0·006 vs. Controls, mean 67·0 ± 44·0 µg/l, cut-off, 16·0 µg/l) and normal in one subject (38·7 µg/l). However, serum IGF-I levels were reduced only in two patients (29 and 57 µg/l) and normal in four subjects (range 127,208 µg/l). The basal secretion of the other anterior pituitary hormones was within their normal ranges. conclusions, The results of the present study support the concept that elevated serum calcium levels impair GH secretion. However, the clinical relevance of GH deficiency in FHH remains to be elucidated. [source] GH administration and discontinuation in healthy elderly men: effects on body composition, GH-related serum markers, resting heart rate and resting oxygen uptakeCLINICAL ENDOCRINOLOGY, Issue 1 2001Kai Henrik Wiborg Lange BACKGROUND AND OBJECTIVES GH administration results in increased lean body mass (LBM), decreased fat mass (FM) and increased energy expenditure (EE). GH therapy may therefore have potential benefits, especially in the elderly, who are known to have decreased function of the GH/IGF-I axis. Several studies have focused on effects of GH administration in the elderly in the last decade. However, very limited information is available regarding changes in body composition and EE upon GH discontinuation in the elderly. The present study therefore investigated the effects of 12 weeks of GH administration and subsequent discontinuation on body composition, resting oxygen uptake (VO2), resting heart rate (HR) and GH related serum markers in healthy elderly men. SUBJECTS AND METHODS Sixteen healthy men [age 74 ± 1 years (mean ± SEM), height 174·2 ± 1·6 cm, body weight 80·7 ± 2·6 kg, body fat 27·5 ± 1·1%] completed the study protocol. Recombinant human GH (1·80 ± 0·24 IU/day) was administered for 12 weeks in a single-blinded, placebo-controlled design. Body composition (dual energy X-ray absorptiometry), resting VO2 (indirect calorimetry), resting HR (telemetry) and serum IGF-I, IGF-II, IGFBP-3 and acid labile subunit (ALS) were measured at baseline, after 12 weeks of GH administration and, additionally in the GH group, 1, 2, 3, 4, 5 and 9 days after GH discontinuation. RESULTS Body weight was unchanged from baseline to 12 weeks in both groups. However, GH administration caused a decrease in FM (3·4 ± 1·0 kg, P < 0·012), paralleled by a similar increase in LBM (3·2 ± 0·4 kg, P < 0·0002). Resting VO2 and resting HR increased by 31 ± 3·6% and 7·3 ± 1·9 per minute, respectively, in the GH-group, where significant increases in serum IGF-I, IGFBP-3 and ALS also were noted. None of the above parameters changed in the placebo group. Within 2,3 days after GH discontinuation, the GH related serum markers and resting HR returned to baseline levels, whereas resting VO2 remained elevated even 9 days after GH discontinuation. In addition, GH discontinuation caused a significant decrease in body weight (1·86 ± 0·35 kg), derived exclusively from a decrease in LBM (1·63 ± 0·43 kg), while the decreased FM was maintained (12 weeks: 17·93 ± 1·65 kg, +9 days: 17·74 ± 1·62 kg). CONCLUSIONS The increases in serum IGF-I, IGFBP-3, ALS and resting heart rate induced by 12 weeks of GH administration in elderly men returned to baseline levels within 2,3 days after GH discontinuation. However, resting VO2 remained elevated for a longer period. GH administration reduced fat mass but maintained body weight by increasing lean body mass. In contrast, 9 days of GH discontinuation reduced body weight exclusively by reducing lean body mass. [source] Increased levels of insulin-like growth factor binding protein-2 in sera and tumours from patients with colonic neoplasia with and without acromegalyCLINICAL ENDOCRINOLOGY, Issue 4 2001F. Miraki-Moud OBJECTIVE Patients with acromegaly are at increased risk of developing colorectal carcinoma and premalignant tubulovillous adenoma. The pathogenesis of these neoplasms could involve a stimulatory effect of serum growth factors on colonic epithelial cell proliferation. The aim of this study was to evaluate changes in (1) serum IGF-I, IGF-II, IGFBP-3 and IGFBP-2 and (2) changes in local expression of IGFBPs and p53 in colonic epithelium in patients with colonic neoplasia with and without acromegaly. DESIGN A cross-sectional retrospective study was performed. Fasting serum samples were obtained at the time of colonoscopy for patients with acromegaly and at the time of surgery for patients with colonic neoplasia without acromegaly. MEASUREMENTS Serum IGF-I, IGF-II, IGFBP-2 and IGFBP,3 were measured using specific immunoassays. Tissue expression of IGFBP-2, IGFBP-3 and p53 status were determined by immunohistochemistry. PATIENTS Group 1: 26 age- and sex-matched control subjects (range 40,69 years); group 2: 18 patients with acromegaly without colonic neoplasia (range 39,68 years); group 3: 18 patients with acromegaly and colonic neoplasia (range 41,74 years, 11 = adenoma, seven = carcinoma); group 4: 19 patients with colonic neoplasia without endocrine disease (range 43,91 years, four = adenoma, 15 = carcinoma). Immunohistochemical staining of colonic biopsies was performed for IGFBP-2, IGFBP-3 and p53 in groups 3 and 4. RESULTS Mean serum IGF-I and IGFBP-3 levels were significantly elevated in group 2 (371 ± 131 µg/l and 6·5 ± 1·8 mg/l, respectively) and group 3 (379 ± 174 µg/l and 5·8 ± 1·6 mg/l, respectively), and significantly reduced in group 4 (103 ± 36 µg/l and 2·4 ± 1 mg/l) compared to controls (165 ± 40 µg/l and 4·7 ± 1 mg/l; P < 0·0001, P < 0·001, respectively). However, median serum IGFBP-2 levels were significantly elevated in group 3 (P < 0·01) and group 4 (P < 0·0001). Immunostaining for IGFBP-2 showed strong areas of immunoreactivity in the cytoplasm of malignant colonic epithelium compared to benign epithelium. IGFBP-3 immunostaining showed strong areas of immunoreactivity in the cytoplasm and in the nucleus of malignant and benign colonic epithelium compared to the normal epithelium. Nuclear staining for p53 was observed in three patients from group 3 (two carcinoma, one adenoma) and four patients from group 4 (all carcinoma). CONCLUSION Our results describe changes in IGFBP-2 expression in colonic neoplasia in patients with and without acromegaly, which suggest that this binding protein may regulate local bioavailability of IGF, which in turn could modulate colonic cell proliferation and/or differentiation. [source] |