Growth hormone (GH) replacement decreases serum total and LDL-cholesterol in hypopituitary patients on maintenance HMG CoA reductase inhibitor (statin) therapy Effects of GH on lipid peroxidation and neutrophil superoxide anion‐generating capacity in hypopituitary adults with GH deficiency Moderate doses of hGH (0.64 mg/d) improve lipids but not cardiovascular function in GH-deficient adults with normal baseline cardiac function. Baseline characteristics and effects of growth hormone therapy over two years in younger and elderly adults with adult onset GH deficiency. Does a gender-related effect of growth hormone (GH) replacement exist on cardiovascular risk factors, cardiac morphology, and performance and atherosclerosis? Results of a two-year open, prospective study in young adult men and women with severe GH deficiency. Increased lipid peroxidation in adult GH-deficient patients: Effects of short-term GH administration Atherogenic lipoprotein phenotype and low-density lipoprotein size and subclasses in patients with growth hormone deficiency before and after short-term replacement therapy. The influence of growth hormone replacement on peripheral inflammatory and cardiovascular risk markers in adults with severe growth hormone deficiency. Fifteen years of GH replacement improves body composition and cardiovascular risk factors Adolescents with partial growth hormone (GH) deficiency develop alterations of body composition after GH discontinuation and require follow-up. Limited effects of growth hormone replacement in patients with GH deficiency during long-term cure of acromegaly Correction of cortisol overreplacement ameliorates morbidities in patients with hypopituitarism: a pilot study The effect of low dose recombinant human growth hormone replacement on regional fat distribution, insulin sensitivity, and cardiovascular risk factors in hypopituitary adults. Evaluation of coagulation and fibrinolytic parameters in adult onset GH deficiency and the effects of GH replacement therapy: a placebo controlled study. OPPORTUNITY™: a large-scale randomized clinical trial of growth hormone in hemodialysis patients. Effects of GH treatment in GH-deficient adults on adiponectin, leptin and pregnancy-associated plasma protein-A. One year of GH replacement therapy with a fixed low-dose regimen improves body composition, bone mineral density and lipid profile of GH-deficient adults.
Objective Adult onset GH deficiency ( GHD ) is characterized by abnormalities of serum lipoprotein profiles and GH replacement results in favourable alterations in serum total and low density lipoprotein (LDL)‐cholesterol . Preliminary evidence has indicated that the effect of GH replacement in this respect may be additive to that of HMG CoA reductase inhibitor ( statin ) therapy . We have examined this possibility during prospect i ve follow‐up of adult onset hypopituitary patients enrolled in KIMS ( Pfizer International Metabolic Data base ) , a pharmacoepidemiological study of GH replacement in adult hypopituitary patients objectives  Untreated growth hormone deficiency ( GHD ) is implicated in the increased cardiovascular risk associated with adult hypopituitarism . Oxidative stress , predisposing to lipid peroxidation , may be an important mediator of endothelial dysfunction , a pro‐atherogenic state associated with adult GHD CONTEXT Data regarding effects of lower-dose GH on cardiopulmonary function in GH-deficient ( GHD ) adults are limited . OBJECTIVES The objective was to assess effects of lower-dose GH on exercise capacity and echocardiographic parameters in GHD adults . DESIGN The study was a 6-month double-blind , placebo-controlled r and omized trial . SETTING The study was conducted at the General Clinical Research Center . PARTICIPANTS Thirty hypopituitary adults with GHD were studied . INTERVENTION Subjects were r and omized to recombinant human GH or placebo for 6 months , followed by open-label recombinant human GH for 12 months . MAIN OUTCOME MEASURES Primary endpoints were exercise duration , maximal oxygen consumption , and left ventricular ejection fraction . Secondary endpoints were echocardiographic indices of systolic and diastolic function , left ventricular mass , lipids , and body composition . RESULTS In the 6-month double-blind phase , mean GH dose was 0.64 mg/d . Mean IGF-I sd score increased from -4.5 to -1.0 . Exercise duration , maximal oxygen consumption , left ventricular ejection fraction , and other echocardiographic parameters were normal at baseline and did not change . GH decreased total and low-density lipoprotein cholesterol by 7.5 % ( P = 0.016 ) and 14.7 % ( P = 0.002 ) ( P = 0.04 vs. placebo ) . Mean lean body mass increased by 2.2 kg ( P = 0.004 ) , fat mass decreased by 1.7 kg ( P = 0.21 ) , and percent body fat decreased by 2.5 % ( P = 0.018 ) , although between-group changes were not significant . CONCLUSIONS Human GH did not improve exercise performance or echocardiographic parameters or decrease fat mass but significantly decreased total and low-density lipoprotein cholesterol , increased IGF-I , and increased lean body mass . These results indicate that responses to human GH are variable and should be assessed at baseline and during treatment CONTEXT The effects of GH replacement in elderly GH-deficient ( GHD ) adults are not well known . OBJECTIVE / DESIGN / PATIENTS In this prospect i ve , single-center , open-label study , baseline characteristics and the effects of 2-yr GH replacement were determined in 24 GHD adults above 65 yr of age and in 24 younger GHD patients ( mean age , 37 yr ; range , 27 - 46 yr ) . All patients had adult onset disease , and both groups were comparable in terms of the number of pituitary hormonal deficiencies , gender , body mass index , and waist/hip ratio . Duration of hypopituitarism was , however , longer in the elderly patients . RESULTS The mean maintenance dose of GH was 0.31 ( sem , 0.03 ) mg/d in the elderly GHD patients and 0.44 ( 0.04 ) mg/d in the younger patients . The less marked response in IGF-I sd score , total body fat , and extracellular water in the elderly patients lost significance when the dose of GH was accounted for in the statistical analyses . Despite the lower dose in the elderly GHD group , these patients had a more marked reduction in waist/hip ratio and serum low-density lipoprotein-cholesterol level , and these differences remained also after correction for duration of hypopituitarism . There was no difference at baseline or in responsiveness in lean mass , bone mineral density , and glucose homeostasis . CONCLUSIONS This study identifies elderly GHD adults as a GH-sensitive group in whom a low dose of GH can improve body composition and serum lipid profile without any significant impairment of glucose metabolism .  GH replacement should therefore be considered in elderly GHD adults CONTEXT GH secretion and response to GH replacement are gender-related . OBJECTIVE The objective of this study was to investigate the effects of GH deficiency ( GHD ) and replacement on the cardiovascular system according to gender . DESIGN The design was open and prospect i ve . SETTING The study was conducted at a university hospital . SUBJECTS Subjects included 36 severe adult-onset GHD patients ( 18 men , 20 women , aged < 45 yr ) ; 36 gender- , age- , and body mass index-matched healthy subjects served as controls . INTERVENTIONS Subjects received GH replacement at a median dose of 6.5 microg/kg.d in men and 7.7 microg/kg.d in women for 2 yr . MAIN OUTCOME MEASURES Homeostasis model assessment index , total to HDL cholesterol ratio , fibrinogen and C-reactive protein levels , left ventricular mass index , blood pressure , heart rate , diastolic filling , and systolic function at rest and at peak exercise and intima-media thickness ( IMT ) at common carotid arteries were measured . RESULTS Basal prevalence and /or degree of insulin resistance , lipid alterations , compromised cardiac function , and IMT were similar in women and men . Diastolic dysfunction was more prevalent in men ( 61 vs. 25 % , P = 0.036 ) . After GH replacement , IGF-I levels normalized in all patients . Lipid profile , fibrinogen , and C-reactive protein levels normalized in all cases . The total to HDL ratio ( P = 0.04 ) was higher in women than men . The homeostasis model assessment index persisted higher in GHD patients than controls and decreased only in GHD men ( P = 0.017 ) . Left ventricular mass index normalized during treatment in both women and men , abnormal diastolic function persisted in three women ( P = 0.031 ) , and abnormal systolic performance persisted in six women and one man ( P = 0.13 ) . IMT decreased similarly in women and men , persisting higher than in controls . Exercise performance normalized in all . CONCLUSIONS Two-year GH replacement has similar beneficial effects on cardiac and exercise performance and atherosclerosis in women and men with severe GHD Objective : Adult GH deficiency ( GHD ) syndrome is characterized by increased risk of atherosclerosis and hence of cardio- and cerebrovascular mortality . Oxidative stress appears to play an important role in early atherogenesis . Oxidized LDL represents an important predictor of cardiovascular risk and is mainly responsible for oxidative damage of the endothelium . Its concentrations are increased in GHD , but the association between this abnormality and oxidative stress is still unclear , due to the discordant results yielded by the few available studies . Design and methods : In 13 GHD patients , plasma lipid peroxide concentrations were measured before and after a 4-month treatment with recombinant human GH ( rhGH ) and compared with those of 13 age- and sex-matched controls . In the same subjects , the so-called “ lag-time ” , an index of anti-oxidant activity and thus of plasma oxidative balance , was also measured using a fluorescence kinetics method . Results : Before treatment , peroxide levels were significantly higher in patients than in controls ( 374.0±31.52 vs 268.0±8.51 U.C. , p<0.01 ) , whereas the lag-time was significantly lower ( 113.0±10.70 vs 168.0±7.80 min , p<0.01 ) . RhGH administration to patients result ed both in a significant decrease in lipid peroxide levels ( from 374.0±31.52 to 336.0±33.17 U.C. , p<0.01 ) and a significant prolongation of lag-time ( from 113.0±10.70 to 144.0±15.00 min , p<0.01 ) . After treatment , both parameters were no longer significantly different in patients and controls . Lagtime and peroxide levels at baseline did not show any correlation with IGF-I concentrations in GHD patients . After replacement therapy , however , lag-time was positively ( r2= 0.62 , p<0.01 ) , and peroxide levels negatively ( r2=0.41 , p<0.05 ) , correlated with IGF-I levels . Conclusions : These data support the view that adult GHD syndrome is characterized by an unbalance between pro- and anti-oxidant factors with marked preponderance of the former . This abnormality , likely contributing to the increased atherogenic risk of GHD patients , is corrected by short-term GH administration at a dose able to increase , although not to fully normalize , IGF-I levels OBJECTIVE Patients with growth hormone deficiency ( GHD ) have increased cardiovascular risk and may show elevated triglyceride and reduced high density lipoprotein ( HDL ) cholesterol concentrations , two lipid abnormalities usually accompanied by increased small dense LDL in the ' atherogenic lipoprotein phenotype ' ( ALP ) . In the present study , we directly investigated ( 1 ) whether hypopituitary patients with GHD have increased small dense LDL ; ( 2 ) whether growth hormone replacement therapy ( GHRT ) beneficially impact on such particles ; ( 3 ) the prevalence of ALP in GHD and GHRT patients . DESIGN AND METHODS In 14 hypopituitary patients with GHD ( 44 + /- 13 years , body mass index ( BMI ) 27 + /- 3 ) before and after 4 months of GHRT , and in 11 healthy age- and BMI -matched controls we measured plasma lipids and LDL size and subclasses by gradient gel electrophoresis . RESULTS Compared with controls , GHD showed increased triglycerides ( P = 0.0024 ) , similar total and LDL cholesterol levels and a tendency towards reduced HDL cholesterol concentrations ( P = 0.0894 ) . GHRT reduced total and LDL cholesterol levels ( P = 0.0303 and 0.0120 respectively ) , but no effect was found on triglycerides and HDL cholesterol levels . LDL size was unchanged in GHD versus controls ( 269 + /- 9 vs 274 + /- 6 A , P = ns ) , but LDL subclass analysis revealed a shift towards more dense particles ( P = 0.0046 ) . GHRT had no significant impact on LDL size and subclasses . The prevalence of ALP was 14 % in GHD and 7 % in GHRT . CONCLUSIONS In GHD patients , individual features of ALP ( including increased small dense LDL ) may be common , but complete ALP is relatively uncommon . Short-term replacement therapy seems to be ineffective on such lipid alterations , but the effect of a longer GHRT remains to be assessed BACKGROUND Adult GHD syndrome is associated with clustering of adverse cardiovascular ( CV ) risk factors such as abnormal body composition , dyslipidemia , insulin resistance and abnormal haemostatic factors . There is a wealth of evidence linking CV events with elevated levels of inflammatory markers ( hs-CRP and IL-6 ) in the general population ; however data on their abnormalities in GHD and specially the effects of GH replacement ( GHR ) on these inflammatory markers are limited . OBJECTIVE To study the effects of GHR on inflammatory markers , glucose homeostasis and body composition in a cohort of adults with recently diagnosed severe GHD due to hypothalamic pituitary disease . DESIGN Fifteen hypopituitary adults ( 11 males , mean age 48.5 years ) with recently diagnosed , severe GHD were recruited . Patients received GHR ( in addition to other pituitary hormone replacements ) titrated to clinical response and to normalize age and gender adjusted IGF-1 levels . Weight , waist hip ratio ( WHR ) , body composition , fasting plasma glucose and insulin , insulin resistance index ( HOMA-IR ) , fasting serum lipid levels , hs-CRP , IL-6 and TNF-alpha were measured at baseline and following a minimum 6 months of stable maintenance GHR . RESULTS GHR result ed in a physiological increase in IGF-1 SDS [ median -0.6 to + 0.39 , P<0.0001 ] , improved quality of life ( mean pre-treatment AGHDA score 16 vs. post-treatment score 7 , P<0.0001 ) and reduction in WHR ( 0.94 vs. 0.92 , P=0.01 ) . There were no significant changes in body weight and composition . Levels of hs-CRP ( log transformed , mean ( SD ) ) were significantly reduced following GHR ( pre 1.21 ( 0.9 ) vs. post 0.27 ( 0.9 ) , P<0.0001 ) but TNF-alpha and IL-6 levels remained unchanged . Fasting glucose ( mmol/L ) [ 4.6 ( 0.1 ) vs. 5.1 ( 0.1 ) , P=0.003 ] , fasting insulin ( muU/mL ) [ 9.4 ( 8.1 ) vs. 12.1 ( 9.2 ) , P=0.03 ] and HOMA-IR [ 1.2 ( 1.0 ) vs. 1.5 ( 1.1 ) P=0.02 ] ( all pre-GHR vs. post-GHR and mean ( SD ) ) significantly increased following GHR indicating increased insulin resistance . Significant improvements were noted in fasting LDL-cholesterol ( LDL-C ) and HDL-cholesterol ( HDL-C ) levels following GHR [ 3.4 ( 0.9 ) vs. 2.9 ( 0.7 ) , P=0.03 and 1.2 ( 0.2 ) vs. 1.3 ( 0.2 ) , P=0.02 , respectively ] ( all pre-GHR vs. post-GHR and mean ( SD ) ) . Levels of total cholesterol and triglycerides did not change following GHR . CONCLUSIONS Physiological GHR for at least 6 months in hypopituitary adults with recently diagnosed severe GHD result ed in favourable changes in hs-CRP , WHR , fasting LDL-C and HDL-C levels all of which are recognised CV risk markers . However , there remains a high prevalence of obesity in this population and given the worsening of insulin sensitivity in the short term with GHR , monitoring and aggressive treatment of established CV risk factors is essential to reduce premature atherosclerotic CVD in this patient population Objective Few studies have determined the effects of more than 5–10 years of GH replacement  in adults on  body composition and cardiovascular risk factors . Design / patients In this prospect i ve , single-center , open-label study , the effects of 15 years of GH replacement on body composition and cardiovascular risk factors were determined in 156 hypopituitary adults ( 93 men ) with adult-onset GH deficiency ( GHD ) . Mean age was 50.5 ( range 22–74 ) years at study start .  Body composition was measured using dual-energy X-ray absorptiometry . Results The mean initial GH dose of 0.55 ( s.e.m . 0.03 ) mg/day was gradually lowered to 0.40 ( 0.01 ) mg/day after 15 years . The mean serum IGF1 SDS increased from −1.53 ( 0.10 ) at baseline to 0.74 ( 0.13 ) at study end ( P<0.001 vs baseline ) . Lean soft tissue ( LST ) increased to 3 % above the baseline level at study end ( P<0.001 ) . After a 9 % decrease during the first year of treatment ( P<0.001 vs baseline ) , body fat ( BF ) started to increase and had returned to the baseline level after 15 years . Serum levels of total cholesterol and LDL-cholesterol decreased and serum HDL-cholesterol level increased . Fasting plasma glucose increased from 4.4 ( 0.1 ) at baseline to 4.8 ( 0.1 ) mmol/l at study end ( P<0.001 ) . However , blood HbA1c decreased from 5.0 ( 0.1 ) to 4.6 ( 0.1 ) % ( P<0.001 ) . Conclusions Fifteen-year GH replacement in GHD adults induced a transient decrease in BF and sustained improvements of LST and serum lipid profile . Fasting plasma glucose increased whereas blood HbA1c was reduced It is now a consensus to resume GH treatment in adolescents with severe GH deficiency ( GHD ) at retesting to prevent the occurrence of adult GHD syndrome . However , we do not have any data on the follow-up of adolescents with nonsevere GHD at completion of treatment . This report presents preliminary data from a 1-yr prospect i ve study that includes the first 91 patients retested .  Anthropometric data , IGF-I and IGF binding protein-3 levels , glycemia and insulinemia , lipid profile , and body composition using dual x-ray absorptiometry and abdominal computed tomography scan were recorded at completion of GH treatment and 1 yr later . Body composition was significantly different at both evaluations , with increased total body fat and decreased lean body mass in the partial GHD group vs. the normal group . Moreover , these alterations worsened after 1 yr without GH in the partial GHD group , whereas there were no modifications in the normal group . We did not find any metabolic alterations such as elevated triglyceride , total cholesterol , or insulin levels .  Adolescents with reconfirmed partial GHD exhibit alterations in body composition after 1 yr without GH , whereas those retested normal do not . These changes are similar to those described in severe GHD , although less marked , and justify a precise follow-up The aim of this study was to assess the effects of replacement with recombinant human growth hormone ( rhGH ) in patients with GH deficiency ( GHD ) after treatment of acromegaly . Intervention study . Sixteen patients ( 8 men , age 56 years ) , treated for acromegaly by surgery and radiotherapy , with an insufficient GH response to insulin-induced hypoglycaemia , were treated with 1 year of rhGH replacement . Study parameters were assessed at baseline and after 1 year of rhGH replacement . Study parameters were cardiac function , body composition , bone mineral density ( BMD ) , fasting lipids , glucose , bone turnover markers , and Quality of Life ( QoL ) . During rhGH replacement  IGF-I concentrations increased from −0.4 ± 0.7 to 1.0 ± 1.5 SD ( P = 0.001 ) , with a mean daily dose of 0.2 ± 0.1 mg in men and 0.3 ± 0.2 mg in women . Nonetheless , rhGH replacement  did not alter cardiac function , lipid and glucose concentrations , body composition or QoL. Bone turnover markers ( PINP and β crosslaps ) levels increased ( P = 0.005 and P = 0.021 , respectively ) , paralleled by a small , but significant decrease in BMD of the hip . The beneficial effects of rhGH replacement in patients with GHD during cure from acromegaly are limited in this study Context Hyporituitarism in adults is known to be associated with deleterious effects on body composition , lipid profile and quality of life ( QoL ) . This was attributed to GH deficiency . The potential role of glucocorticoid overreplacement had never been investigated . Objective To investigate whether reduction in glucocorticoid replacement dose to more physiological one could ameliorate the “ AO-GHD”-attributed symptomatology in patients with hypopituitarism . Design Eleven patients with panhypopituitarism taking 20–30 mg/day of hydrocortisone , but on no GH replacement  were switched to 10–15 mg of hydrocortisone daily . Both basally and 6–12 months later , their body mass index , body composition by dual-energy X-ray absorptiometry , lipid profile , and the score of quality of life , QOL-AGHDA were measured . Results Within 6–12 months of lower hydrocortisone dose , subjects lost an average of 7.1 kg of total body fat and 4.1 kg of abdominal fat . No changes were seen in lean body mass , bone mineral content and HOMA-IR . Plasma total cholesterol and triglyceride concentrations decreased significantly ( < 0.05 ) and the QoL improved ( P = 0.018 ) . Conclusions Our pilot study suggests that decreasing the glucocorticoid replacement dose to ~15 mg/day is beneficial in terms of patients ’ body composition , lipid profile and quality of life GH deficiency is associated with increased cardiovascular morbidity , which may be determined by alterations in vascular risk factors . We report the effect of partially treated hypopituitarism and subsequent GH replacement ( mean dose , 0.2 IU/kg.week ) on putative cardiovascular risk factors in 22 nondiabetic hypopituitary subjects in a 6-month , double blind , controlled study ( active/placebo ratio , 11:11 ) . All patients were subsequently treated with GH for a further 6 months .  Total fat , percent body fat , and central fat were measured by dual energy x-ray absorptiometry .  The hypopituitary patients had increased percent fat ( P = 0.03 ) and central fat ( P < 0.01 ) compared with body mass index-matched controls . Before GH treatment , fasting ( total ) and specific insulin positively correlated with body mass index ( P = 0.02 and P < 0.001 , respectively ) , waist/hip ratio ( P = 0.05 and P = 0.01 ) , and central fat ( P = 0.03 and P = 0.003 ) . Specific insulin and insulin sensitivity ( IS ) , calculated by homeostatic model of assessment , were related to total fat ( P < 0.001 and P = 0.02 ) . GH treatment for 6 months led to a reduction in total fat ( P < 0.02 ) , percent fat ( P = 0.002 ) , central fat ( P = 0.012 ) , waist/hip ratio ( P < 0.05 ) , total cholesterol ( P = 0.03 ) , and apolipoprotein-B ( P = 00001 ) , as well as a decrease in the IS from 36.9 % ( range , 12 - 100 % ) to 25 % ( range , 2.5 - 55 % ; P = 0.0002 ) . This was paralleled by a rise in fasting ( total ) and specific insulin ( P = 0.016 and P = 0.002 ) . The degree of correlation among indices of IS , body composition , and fat distribution increased after GH treatment . Fasting plasma glucose rose significantly , but was within the reference range . During 12 months of GH therapy , a significant increase in serum lipoprotein-(a ) was observed ( P < 0.05 ) . Although GH has beneficial effects on central adiposity and lipid fractions , it is also associated with a decrease in IS ; these effects may vary between individuals OBJECTIVE Increased cardiovascular mortality/morbidity observed in patients with hypopituitarism is ascribed to growth hormone deficiency ( GHD ) because of its unfavorable cardiovascular risk profile . Abnormalities in the coagulation system may also contribute to increased cardiovascular morbidity/mortality . To get a better insight into the role of hemostasis in GHD we assessed several hemostatic markers at baseline and after 6 months of GH replacement therapy ( GHRT ) . DESIGN - PATIENTS : Nineteen patients with adult onset GHD were enrolled ( twelve patients into the treatment and seven patients into the placebo group )  into the study . Platelet count , collagen/epinephrine closure time , collagen/ADP closure time , fibrinogen , prothrombin time ( PT ) , activated partial thromboplastin time ( aPTT ) , antithrombin III ( AT III ) , protein C activity , protein S activity , lupus anticoagulant , antiphospholipid antibody immunoglobulin M , and antiphospholipid antibody immunoglobulin G were measured at baseline and 6 months after treatment . RESULTS The investigated parameters in the groups were similar at baseline except for low protein S ( PS ) activity . Protein S deficiency was observed in three of the patients in the GH treatment group at baseline , however the PS activity values normalized following GHRT .  AT III and protein C activities decreased when compared to baseline values in the treatment group but not in the placebo group . CONCLUSIONS We observed protein S deficiency more frequent than seen in the general population and normalization of protein S activity and decreases , in other natural anticoagulants following GHRT . Further studies are required to underst and the impact of these changes in cardiovascular morbidity and mortality in this patient population BACKGROUND Adult maintenance hemodialysis ( MHD ) patients experience high mortality and morbidity and poor quality of life ( QoL ) . Markers of protein-energy wasting are associated with these poor outcomes . The OPPORTUNITY ™ Trial examined whether recombinant human growth hormone ( hGH ) reduces mortality in hypoalbuminemic MHD patients . Secondary end points were effects on number of hospitalizations , cardiovascular events , lean body mass ( LBM ) , serum proteins , exercise capacity , QoL and adverse events . METHODS We performed a r and omized , double-blind , placebo-controlled , multicenter multinational trial stratified for diabetic status . Clinical ly , stable adult MHD patients with serum albumin < 4.0 g/dL were r and omized to subcutaneous injections of hGH , 20 μg/kg/day , or placebo . Planned treatment duration was 24 months for 2500 patients . The trial was terminated early due to slow recruitment . RESULTS Seven hundred and twelve patients were r and omized until trial termination ; 695 patients received at least one dose of trial medication . Mean treatment duration was 20 weeks ( no completers ) . There were no differences between groups in all-cause mortality , cardiovascular morbidity or mortality , serum albumin , LBM , physical exercise capacity or QoL.  The hGH group , compared to placebo , displayed a reduction in body weight , total body fat , serum high-sensitivity C-reactive protein and possibly homocysteine and an increase in serum high-density lipoprotein-cholesterol and transferrin levels . CONCLUSIONS Although the OPPORTUNITY ™ Trial was terminated early , treatment with hGH , compared to placebo , improved certain cardiovascular risk factors but did not reduce mortality , cardiovascular events or improve nutritional factors or QoL. The power for showing differences was substantially reduced due to the marked decrease in treatment duration and sample size OBJECTIVE  GH deficiency ( GHD ) in adults is associated with adverse effects on metabolism and increased cardiovascular risk . Pregnancy-associated plasma protein-A ( PAPP-A ) is a protease that promotes IGF-I availability in vascular tissues . PAPP-A levels appear to correlate with carotid intima-media thickness and have been proposed as an early predictor of cardiac events . The aim of our study was to evaluate PAPP-A levels in GHD adults at baseline and after GH replacement and correlate them with changes in body composition , lipid profile , glucose homeostasis , inflammatory markers and in leptin and adiponectin . PATIENTS AND METHODS Fourteen GHD adults were evaluated at baseline and after 1 year of GH therapy .  All patients were compared at baseline with 28 age- , sex- and body mass index ( BMI ) -matched control subjects . RESULTS At baseline , GHD adults showed higher PAPP-A levels ( P=0.03 ) and higher leptin ( P=0.04 ) , fibrinogen ( P=0.002 ) and highly sensitive C-reactive protein ( P=0.01 ) values than controls . Therapy with GH  reduced PAPP-A ( P=0.03 ) and fibrinogen levels ( P=0.002 ) while increased BMI ( P=0.01 ) and reduced waist-hip ratio ( WHR ; P=0.05 ) were observed . Insulin and homeostasis model assessment of insulin resistance index increased after treatment ( P<0.004/P=0.007 ) , without changes in leptin or adiponectin levels . PAPP-A values correlated positively with BMI and WHR and negatively with adiponectin before and after treatment , with no correlation with glucose homeostasis parameters , lipid profile or leptin . CONCLUSIONS Our study suggests that PAPP-A expression is increased in GHD adults , and that 1 year of GH replacement therapy is able to reduce PAPP-A levels in this population . However , further studies are required to determine whether this decrease correlates with an improvement in atherosclerosis OBJECTIVE We have studied the effects on body composition and metabolism of a fixed low dose of growth hormone ( GH ) , 0.6 IU ( 0.2 mg)/day , administered for 12 months to GH-deficient ( GHD ) adults . DESIGN AND METHODS Prospect i ve open-label study , using 18 GHD patients ( 11 women , 7 men ; aged 21 - 58 years ) . All investigations were performed at baseline and after 12 months . Body composition was determined by dual energy X-ray absorptiometry . RESULTS Total body fat decreased ( -1.74+/-2.87 % ) and lean body mass ( LBM ) increased ( 1.27+/-2.08 kg ) after therapy ( P < 0.05 ) . Changes in truncal fat did not reach statistical significance , but a decrease varying from 0.72 to 2.78 kg ( 1 to 8.7 % ) was observed in 13 ( 72 % ) patients . Bone mineral density ( BMD ) increased at lumbar spine , total femur and femoral neck ( P < 0.05 ) . Levels of total and low-density lipoprotein (LDL)-cholesterol were lower after therapy ( P < 0.05 ) , and their changes were directly associated with values at baseline . Insulin levels increased and the insulin resistance index worsened at 12 months ( P < 0.05 ) . Median IGF-I s.d . score was -4.30 ( range , -11.03 to -0.11 ) at baseline and -1.73 ( range , -9.80 to 2.26 ) at 12 months . Normal age-adjusted IGF-I levels were obtained with therapy in 5 of 11 patients who had low IGF-I levels at baseline . Changes in IGF-I levels were not correlated with any biological end point , except changes in LBM ( r = 0.53 , P = 0.02 ) . Side effects were mild and disappeared spontaneously . CONCLUSIONS One-year of a fixed low-dose GH regimen in GHD adults result ed in a significant reduction in body fat , total cholesterol and LDL-cholesterol , and a significant increase in LBM and BMD at lumbar spine and femur , regardless of normalization of IGF-I levels . This regimen led to an elevation of insulin levels and a worsening of the insulin resistance index
Emerging cardiovascular risk factors/markers such as proinflammatory cytokines , C-reactive protein , and adipokines are also increased in GHD patients .
Increased cardiovascular morbidity and mortality have also been reported in GHD .
GH treatment has been shown to improve both traditional and emerging cardiovascular risk factors and markers .
The GHD population may be considered at high cardiovascular risk , and GH substitution may be expected to bring an added value to patients with hypopituitarism in terms of cardiovascular protection .
CONTEXT GH deficiency ( GHD ) of the adult is a clinical condition characterized by the presence of several traditional and emerging cardiovascular risk factors that can significantly increase cardiovascular morbidity and mortality .
It is still an open issue whether GH replacement is able not only to improve cardiovascular risk factors but also to decrease cardiovascular morbidity and mortality .
EVIDENCE SYNTHESIS In untreated GHD , cardiovascular risk is increased due to abnormal lipid profile ( increased total and low-density lipoprotein cholesterol , increased triglycerides , and reduced high-density lipoprotein cholesterol ) and impaired glucose metabolism .