- Email: [email protected]
P-37 Effect of GH therapy on coronary flow reserve, diastolic filling and cardiovascular risk factors in adult GHD
S38
Growth Hormone & IGF Research 18 (2008) Suppl S1
polymorphisms (SNPs) in nine genes with important metabolic functions were studied using TaqMan allelic discrimination. Results: Using a mixed model for statistical analysis, gender turned out as the strongest predictor of response to GH replacement. Therefore, all further statistic analyses were separated by gender. We found that the b3-adrenergic receptor Trp64Arg SNP was associated with IGF1-response in women (p = 0.0352) and baseline levels of IGF1 in both women and men (p < 0.0001 in both cases). There was also an association between IGF1-response and the b2-adrenergic receptor SNPs Gln27Glu and Gly16Arg in men (p = 0.0156 and 0.0145, respectively). These SNPs were also associated with baseline levels of IGF1 in men and women (p < 0.001 in all cases). Lastly, the glucocorticoid receptor N363S SNP was associated with IGF1-response in women (p = 0.0008). No associations were found with BF-response. Conclusions: Our results indicate that genetic variants in metabolic genes predict the response to GH replacement therapy in GHD adults. However, gender remains the stronger predictor of response. P-37 Effect of GH therapy on coronary flow reserve, diastolic filling and cardiovascular risk factors in adult GHD M. Boschetti1,2 ° , S. Agosti3 , L. Casalino3 , V. Albanese1 , C. Teti1,2 , G. Bezante3 , C. Brunelli3 , F. Minuto1,2 , D. Ferone1,2 . 1 DISEM, 2 CEBR, University of Genova, Italy, 3 Dept. Cardiology, University of Genova, Italy It has been suggested that GH deficiency (GHD) may contribute to increase morbidity and mortality by negatively influencing cardiovascular function both directly and indirectly. For these reasons it is believed that GHD accounts for most of the reduced life expectancy in hypopituitarism. We investigated the cardiac and endothelial function in adult onset GHD patients during the first year of GH replacement therapy in comparison with age and sex matched control group. We studied 13 (7 males, 6 females; age 56.43±4.49 years) adult patients with adult-onset hypopituitarism and GHD before and after 1 year of GH replacement therapy. In all patients (nonsmokers, non diabetics, without hypertension or vascular disease) we measured the Coronary Flow Reserve (CFR) and evaluated LV systolic and diastolic function before and after 12 months GH replacement therapy (mean starting dose 1.2 mg/week±0.19 mg titrated with IGF-I every 8–10 weeks). IGF-I plasma levels, lipid profile, HbA1c, blood pressure and anthropometric data were also recorded. CFR was low at baseline (2.34±0.20) and increased significantly after treatment (2.93±0.22; P). In conclusion, our data confirm that GH therapy reduces cardiovascular risk factors and evidence that one year of treatment improves microvascular and cardiovascular function. By consequence, GH replacement therapy could enhance life expectancy by reducing cardiovascular morbility in GHD patients. P-38 Prospective comparison of the Glucagon Stimulation Test (GST) with the Insulin Tolerance Test (ITT) in patients following pituitary surgery C. Berg ° , T. Meinel, A. Y¨uce, H. Lahner, K. Mann, S. Petersenn. University of Duisburg, Essen, Germany The ITT is the gold-standard for assessment of GH and ACTH reserve but has certain contraindications. GH and cortisol responses of <3 ng/ml and <500 nmol/l, respectively, have been defined as evidence of deficiency. The GST stimulates both the ACTH and GH secretion and is suggested to be a good alternative in terms of efficiacy. However, there are limited prospective data with modern assays on sensitivity and specificity for the GST compared to ITT. Aim of this study was to evaluate the diagnostic utility of the GST in patients with hypothalamo-hypopituitary disease following pituitary
Abstracts, 4th Int. Congress of GRS & IGF Society surgery. ITT and GST were performed within 7 days in 50 patients (26 men, age 28–64) at least 3 months after transsphenoidal surgery. Serum GH /cortisol were measured by Immulite 2000 assay (Siemens AG). ROC analysis was performed to identify optimal thresholds for GST; for cortisol deficiency analysis was adjusted to achieve a sensitivity >95%. By ITT, 19/50 cases were classified as cortisol insufficient. For cortisol sufficiency in GST, ROC analysis revealed a cut-off of 599 nmol/l with 100% sensitivity and 32.3% specificity. Using that cut-off, 14/50 (28%) cases showed conflicting values compared to ITT and were discordant in terms of defining cortisol deficiency. For cortisol deficiency in GST, ROC analysis revealed a cut-off of 278 nmol/l with >95% specifity and 74% sensitivity. Regarding GHD, 22/50 cases were classified as insufficient by ITT. ROC analysis revealed a cut-off of 2.5 ng/ml with 95% sensitivity and 79% specificity. Only 6/50 (12%) cases showed conflicting values in relation to the cut off and were discordant in terms of defining GHD. In our prospective series of patients with pituitary disease, GST is a good alternative test for assessment of GH reserve, but poor for ACTH reserve, as demonstrated by comparison with the ITT. Testspecific cut-offs should be applied to avoid misinterpretation. P-39 GH Deficiency following traumatic brain injury (TBI) as a cause of female infertility A. Giampietro, D. Milardi ° , A. Bianchi, A. Fusco, L. Tilaro, T. Porcelli, A. Pontecorvi, L. de Marinis. Division of Endocrinology, Department of Medical Pathology, Catholic University, Rome, Italy Growth hormone (GH) and IGF-I play significant roles in pubertal development, menarche, the menstrual cycle, fertility, and reproduction. The close association between reproductive status and the somatotrophic axis supports the physiological importance of GH in reproductive function. GH-deficient (GHD) women require assisted reproductive technologies to conceive and GHD children suffer from delayed pubertal development which can be overcome via GH substitution; moreover in adulthood they presented a condition of subfertility. Recent studies have demonstrated that Growth Hormone Deficiency (GHD) is very common in TBI. We report four cases of patients, two women, aged 30 and 34 ys respectively, with long standing unexplained infertility and two, aged 27 and 33 ys respectively, which presented oligoamenorrhoea. They were tested for GH-IGFI axis after several years following head trauma. All of them showed low stimulated GH values (mean GH peak SE 7.38±1.8 ng/ml after GHRH+arginine test; BMI = 27.07±1.9 kg/m2 ). LH and FSH responses to Gn-RH were normal in all patients. Two had secondary hypoadrenalism and hypothyroidism. All patients started receiving r-hGH replacement therapy (0.9 to 1.8 mg/week) for eight to twelve months. Two patients conceived without the need for ovulation induction. GH therapy was discontinued after confirmation of pregnancy. The other two patients cycled normally after six moths of GH-replacement therapy. Infertility and alteration of menstrual cycle may be represent subtle clinical manifestation of GHD as complication of traumatic head injury. Since GH, directly or indirectly via IGF-I, regulates reproductive functions at all levels of the hyophyseal-pituitary-gonadal axis, it should be always be tested in women with brain injury history as possible cause of unexplained infertility in order to identify a subgroup of patients with occult GH deficiency.
Growth Hormone & IGF Research 18 (2008) Suppl S1
polymorphisms (SNPs) in nine genes with important metabolic functions were studied using TaqMan allelic discrimination. Results: Using a mixed model for statistical analysis, gender turned out as the strongest predictor of response to GH replacement. Therefore, all further statistic analyses were separated by gender. We found that the b3-adrenergic receptor Trp64Arg SNP was associated with IGF1-response in women (p = 0.0352) and baseline levels of IGF1 in both women and men (p < 0.0001 in both cases). There was also an association between IGF1-response and the b2-adrenergic receptor SNPs Gln27Glu and Gly16Arg in men (p = 0.0156 and 0.0145, respectively). These SNPs were also associated with baseline levels of IGF1 in men and women (p < 0.001 in all cases). Lastly, the glucocorticoid receptor N363S SNP was associated with IGF1-response in women (p = 0.0008). No associations were found with BF-response. Conclusions: Our results indicate that genetic variants in metabolic genes predict the response to GH replacement therapy in GHD adults. However, gender remains the stronger predictor of response. P-37 Effect of GH therapy on coronary flow reserve, diastolic filling and cardiovascular risk factors in adult GHD M. Boschetti1,2 ° , S. Agosti3 , L. Casalino3 , V. Albanese1 , C. Teti1,2 , G. Bezante3 , C. Brunelli3 , F. Minuto1,2 , D. Ferone1,2 . 1 DISEM, 2 CEBR, University of Genova, Italy, 3 Dept. Cardiology, University of Genova, Italy It has been suggested that GH deficiency (GHD) may contribute to increase morbidity and mortality by negatively influencing cardiovascular function both directly and indirectly. For these reasons it is believed that GHD accounts for most of the reduced life expectancy in hypopituitarism. We investigated the cardiac and endothelial function in adult onset GHD patients during the first year of GH replacement therapy in comparison with age and sex matched control group. We studied 13 (7 males, 6 females; age 56.43±4.49 years) adult patients with adult-onset hypopituitarism and GHD before and after 1 year of GH replacement therapy. In all patients (nonsmokers, non diabetics, without hypertension or vascular disease) we measured the Coronary Flow Reserve (CFR) and evaluated LV systolic and diastolic function before and after 12 months GH replacement therapy (mean starting dose 1.2 mg/week±0.19 mg titrated with IGF-I every 8–10 weeks). IGF-I plasma levels, lipid profile, HbA1c, blood pressure and anthropometric data were also recorded. CFR was low at baseline (2.34±0.20) and increased significantly after treatment (2.93±0.22; P). In conclusion, our data confirm that GH therapy reduces cardiovascular risk factors and evidence that one year of treatment improves microvascular and cardiovascular function. By consequence, GH replacement therapy could enhance life expectancy by reducing cardiovascular morbility in GHD patients. P-38 Prospective comparison of the Glucagon Stimulation Test (GST) with the Insulin Tolerance Test (ITT) in patients following pituitary surgery C. Berg ° , T. Meinel, A. Y¨uce, H. Lahner, K. Mann, S. Petersenn. University of Duisburg, Essen, Germany The ITT is the gold-standard for assessment of GH and ACTH reserve but has certain contraindications. GH and cortisol responses of <3 ng/ml and <500 nmol/l, respectively, have been defined as evidence of deficiency. The GST stimulates both the ACTH and GH secretion and is suggested to be a good alternative in terms of efficiacy. However, there are limited prospective data with modern assays on sensitivity and specificity for the GST compared to ITT. Aim of this study was to evaluate the diagnostic utility of the GST in patients with hypothalamo-hypopituitary disease following pituitary
Abstracts, 4th Int. Congress of GRS & IGF Society surgery. ITT and GST were performed within 7 days in 50 patients (26 men, age 28–64) at least 3 months after transsphenoidal surgery. Serum GH /cortisol were measured by Immulite 2000 assay (Siemens AG). ROC analysis was performed to identify optimal thresholds for GST; for cortisol deficiency analysis was adjusted to achieve a sensitivity >95%. By ITT, 19/50 cases were classified as cortisol insufficient. For cortisol sufficiency in GST, ROC analysis revealed a cut-off of 599 nmol/l with 100% sensitivity and 32.3% specificity. Using that cut-off, 14/50 (28%) cases showed conflicting values compared to ITT and were discordant in terms of defining cortisol deficiency. For cortisol deficiency in GST, ROC analysis revealed a cut-off of 278 nmol/l with >95% specifity and 74% sensitivity. Regarding GHD, 22/50 cases were classified as insufficient by ITT. ROC analysis revealed a cut-off of 2.5 ng/ml with 95% sensitivity and 79% specificity. Only 6/50 (12%) cases showed conflicting values in relation to the cut off and were discordant in terms of defining GHD. In our prospective series of patients with pituitary disease, GST is a good alternative test for assessment of GH reserve, but poor for ACTH reserve, as demonstrated by comparison with the ITT. Testspecific cut-offs should be applied to avoid misinterpretation. P-39 GH Deficiency following traumatic brain injury (TBI) as a cause of female infertility A. Giampietro, D. Milardi ° , A. Bianchi, A. Fusco, L. Tilaro, T. Porcelli, A. Pontecorvi, L. de Marinis. Division of Endocrinology, Department of Medical Pathology, Catholic University, Rome, Italy Growth hormone (GH) and IGF-I play significant roles in pubertal development, menarche, the menstrual cycle, fertility, and reproduction. The close association between reproductive status and the somatotrophic axis supports the physiological importance of GH in reproductive function. GH-deficient (GHD) women require assisted reproductive technologies to conceive and GHD children suffer from delayed pubertal development which can be overcome via GH substitution; moreover in adulthood they presented a condition of subfertility. Recent studies have demonstrated that Growth Hormone Deficiency (GHD) is very common in TBI. We report four cases of patients, two women, aged 30 and 34 ys respectively, with long standing unexplained infertility and two, aged 27 and 33 ys respectively, which presented oligoamenorrhoea. They were tested for GH-IGFI axis after several years following head trauma. All of them showed low stimulated GH values (mean GH peak SE 7.38±1.8 ng/ml after GHRH+arginine test; BMI = 27.07±1.9 kg/m2 ). LH and FSH responses to Gn-RH were normal in all patients. Two had secondary hypoadrenalism and hypothyroidism. All patients started receiving r-hGH replacement therapy (0.9 to 1.8 mg/week) for eight to twelve months. Two patients conceived without the need for ovulation induction. GH therapy was discontinued after confirmation of pregnancy. The other two patients cycled normally after six moths of GH-replacement therapy. Infertility and alteration of menstrual cycle may be represent subtle clinical manifestation of GHD as complication of traumatic head injury. Since GH, directly or indirectly via IGF-I, regulates reproductive functions at all levels of the hyophyseal-pituitary-gonadal axis, it should be always be tested in women with brain injury history as possible cause of unexplained infertility in order to identify a subgroup of patients with occult GH deficiency.