Months Of Growth Hormone Research Articles

Growth hormone therapy in children with idiopathic short stature – the effect on appetite and appetite-regulating hormones: a pilot study

ABSTRACTAim: To investigate the effect of growth hormone (GH) therapy on appetite-regulating hormones and to examine the association between these hormones and the response to GH, body composition, and resting energy expenditure (REE).Methods: Nine pre-pubertal children with idiopathic short stature underwent a standard meal test before and 4 months following initiation of GH treatment. Ghrelin, GLP-1, leptin, and insulin levels were measured; area under the curve (AUC) was calculated. Height, weight, body composition, REE, and insulin-like growth factor levels were recorded at baseline and after 4 and 12 months.Results: Following 4 months of GH therapy, food intake increased, with increased height-standard deviation score (SDS), weight-SDS, and REE (p < .05). Significant changes in appetite-regulating hormones included a decrease in postprandial AUC ghrelin levels (p = .045) and fasting GLP-1 (p = .038), and an increase in fasting insulin (p = .043). Ghrelin levels before GH treatment were positively correlated with the changes in weight-SDS (fasting: r = .667, p = .05; AUC: r = .788, p = .012) and REE (fasting: r = .866, p = .005; AUC: r = .847, p = .008) following 4 months of GH therapy. Ghrelin AUC at 4 months was positively correlated with the changes in height-SDS (r = .741, p = .022) and fat-free-mass (r = .890, p = .001) at 12 months of GH treatment.Conclusions: The reduction in ghrelin and GLP-1 following GH treatment suggests a role for GH in appetite regulation. Fasting and meal-AUC ghrelin levels may serve as biomarkers for predicting short-term (4 months) changes in weight and longer term (12 months) changes in height following GH treatment. The mechanisms linking GH with changes in appetite-regulating hormones remain to be elucidated.Abbreviations: SDS: standard deviation score; REE: resting energy expenditure; SMT: standard meal test; AUC: area under the curve; ISS: idiopathic short stature; SGA: small for gestational age; FFM: fat-free-mass; FM: fat mass; EER: estimated energy requirements; DRI: dietary reference intakes; IQR: inter-quartile range

Low myocardial glucose uptake in Turner syndrome is unaffected by growth hormone: a randomized, placebo-controlled FDG-PET study.

An unfavourable cardiovascular and metabolic phenotype causes threefold excess mortality in Turner syndrome (TS), and perturbed cardiac substrate metabolism is increasingly recognized as a common component of cardiovascular and metabolic diseases. We therefore hypothesized that myocardial glucose uptake (MGU) is reduced in TS and that growth hormone (GH) treatment improves MGU. To this end, this controlled trial elucidates MGU in TS and the impact of 6 months of growth hormone treatment on MGU. Women with TS (n = 9) were examined at baseline, sequentially treated with either Norditropin(®) SimpleXx or placebo and re-examined after 6 months. MGU and myocardial blood flow (MBF) were measured using 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography (FDG-PET) during a hyperinsulinaemic euglycaemic clamp (at baseline and 6 months). Blood pressure measurement, blood sampling, echocardiography and dual energy X-ray absorptiometry scan were also performed. Age-matched female controls (n = 9) were examined once. Baseline MGU was reduced in TS (0.24 ± 0.08 vs. 0.36 ± 0.13 μmol/g/min in controls; P = 0.036) despite similar insulin sensitivity (whole body glucose uptake (M-value): 9.69 ± 1.86 vs. 9.86 ± 2.58 mg/(min*kg) in controls; P = 0.9). Six months of GH carried no impact on MGU (0.25 ± 0.08 vs. 0.26 ± 0.12 μmol/g/min in the placebo group; P = 0.8). Plasma glucose, low-density cholesterol and triglycerides increased, while M-value and exercise capacity decreased during 6 months of GH treatment. MGU is reduced in TS despite normal insulin sensitivity. GH treatment does not alter MGU despite decreased whole body insulin sensitivity. A perturbed cardiac glucose uptake appears to be a feature of TS.

Growth hormone therapy, muscle thickness, and motor development in Prader-Willi syndrome: an RCT.

To investigate the effect of physical training combined with growth hormone (GH) on muscle thickness and its relationship with muscle strength and motor development in infants with Prader-Willi syndrome (PWS). In a randomized controlled trial, 22 infants with PWS (12.9 ± 7.1 months) were followed over 2 years to compare a treatment group (n = 10) with a waiting-list control group (n = 12). Muscle thickness of 4 muscle groups was measured by using ultrasound. Muscle strength was evaluated by using the Infant Muscle Strength meter. Motor performance was measured with the Gross Motor Function Measurement. Analyses of variance were used to evaluate between-group effects of GH on muscle thickness at 6 months and to compare pre- and posttreatment (after 12 months of GH) values. Multilevel analyses were used to evaluate effects of GH on muscle thickness over time, and multilevel bivariate analyses were used to test relationships between muscle thickness, muscle strength, and motor performance. A significant positive effect of GH on muscle thickness (P < .05) was found. Positive relationships were found between muscle thickness and muscle strength (r = 0.61, P < .001), muscle thickness and motor performance (r = 0.81, P < .001), and muscle strength and motor performance (r = 0.76, P < .001). GH increased muscle thickness, which was related to muscle strength and motor development in infants with PWS. Catch-up growth was faster in muscles that are most frequently used in early development. Because this effect was independent of GH, it suggests a training effect.

Height, Muscle, Fat and Bone Response to Growth Hormone in Short Children with Very Low Birth Weight Born Appropriate for Gestational Age and Small for Gestational Age

Background/Aims: Growth hormone (GH) treatment is approved for short children born SGA but not for AGA. Our aim was to study the effect of GH in short VLBW SGA and AGA children. Methods: The study group comprised 44 prepubertal short children with a birth weight <1,500 g: 27 AGA (12 females) and 17 SGA (6 females). Mean values at GH start were (AGA, SGA): age 6.94, 7.14 years, height standard deviation score (SDS) -3.33, -3.33, and GH dose (mean ± SD) 54 ± 12, 51 ± 11 µg/kg/day. Arm and calf cross-sectional muscle area using peripheral quantitative computer tomography, body composition data using dual-energy X-ray absorptiometry and body impedance assessment, maximal isometric grip force and skin fold thickness, IGF-1 and IGFBP-3 were measured at the start and after 12 months of GH. Results: At GH start, both groups had similar characteristics with low height, weight, height velocity, muscle mass, bone thickness and content. The first year of GH treatment led to changes in muscle area SDS (AGA, SGA) -2.23 to -0.73 (p = 0.0010), -3.18 to -1.17 (p = 0.060) (AGA vs. SGA p = 0.61), fat area SDS -1.06 to -1.83 (p = 0.054), -0.62 to -1.75 (p = 0.12) (AGA vs. SGA p = 0.65) and height velocity SDS -0.0015 to 4.2 (p < 0.0001), -0.18 to 3.3 (p < 0.0001) (AGA vs. SGA p = 0.36). Conclusions: Growth, muscle and fat mass are similarly impaired in short prepubertal AGA and SGA VLBW children. The children born AGA show a similar or better response to GH compared to those born SGA. These results reveal the arbitrary nature of using the criterion ‘SGA' for eligibility to GH treatment in children born with a birth weight <1,500 g.

When Do Short Children Realize They Are Short? Prepubertal Short Children’s Perception of Height during 24 Months of Catch-Up Growth Hormone Treatment

Aim: To examine perceived height during the first 24 months of growth hormone (GH) treatment in short prepubertal children. Methods: Ninety-nine 3- to 11-year-old short prepubertal children with either isolated GH deficiency (n = 32) or idiopathic short stature (n = 67) participated in a 24-month randomized trial of individualized or fixed-dose GH treatment. Children’s and parents’ responses to three perceived height measures: relative height (Silhouette Apperception Test), sense of height (VAS short/tall), and judgment of appropriate height (yes/no) were compared to measured height. Results: Children and parents overestimated height at start (72%, 54%) and at 24 months (52%, 30%). Short children described themselves as tall until 8.2 years (girls) and 9 years (boys). Prior to treatment, 38% of children described their height as appropriate and at 3 months, 63%. Mother’s height, parental sense of the child’s tallness and age explained more variance in children’s sense of tallness (34%) than measured height (0%). Conclusion: Short children and parents overestimate height; a pivotal age exists for comparative height judgments. Even a small gain in height may be enough for the child to feel an appropriate age-related height has been reached and to no longer feel short.

Growth Hormone to Improve Short Bowel Syndrome Intestinal Autonomy

The ability of growth hormone (GH) to promote the weaning-off of parenteral nutrition (PN) in short bowel syndrome (SBS) is unclear. No randomized controlled study is available in children. This study was undertaken to determine if GH could enhance the weaning off of PN in PN-dependent children with SBS. A prospective randomized open-label multicenter study was performed in 14 patients (mean age, 9 ± 1.4 years) with SBS (average small bowel length, 33 cm) and long-term PN dependency (8 years) on an unrestricted diet. A standardized PN decrease with and without GH (0.14 mg/kg/d) was conducted. The patients were randomized to either a GH group (4 months of GH) or a control (CTR) group (4 months without GH, followed by 4 months with GH). Blood tests and a nutrition assessment of enteral and parenteral intakes were performed. Groups were compared with the Wilcoxon test. Treatment with GH did not improve the weaning off of PN (decrease in PN caloric intake of 32.5% ± 9.6% in the GH group vs 35.2% ± 8.7% in the CTR group, nonsignificant). In the CTR group, GH treatment induced an additional but not statistically significant decrease of 8.8% ± 12.4% in daily calories. Parenteral needs returned to near basal rates 6 months after GH discontinuation (GH: 77.6% ± 10.6% vs CTR: 73.2% ± 7.4%). Weight decreased slightly in both groups. No biological parameters varied significantly. GH did not improve the weaning off of PN in PN-dependent children with SBS.

Effects of growth hormone treatment on arginine to asymmetric dimethylarginine ratio and endothelial function in patients with growth hormone deficiency

Patients with growth hormone deficiency (GHD) are known to have reduced life expectancy due to increased cardiovascular and cerebrovascular events. An increase in asymmetric dimethylarginine (ADMA) levels previously found in GHD patients could promote premature atherosclerosis. The aim of this study was to determine whether 6-month growth hormone (GH) replacement therapy was able to decrease ADMA levels and ameliorate endothelial dysfunction. Thirty-one GHD patients were studied before and after 6 months of GH (4 μg/[kg d], daily) replacement therapy. Reduced pretreatment levels of serum insulin-like growth factor (IGF) 1 were normalized during GH treatment (88.2 ± 62.5 to 191.7 ± 80.3 ng/mL, P < .0001). After 6 months of GH replacement, plasma cyclic guanosine monophosphate levels significantly increased (2.14 ± 0.52 to 3.54 ± 1.2 ng/mL, P < .0001), serum ADMA levels were significantly decreased (0.65 ± 0.1 vs 0.59 ± 0.11 μmol/L, P < .05), and arganine (Arg) to ADMA ratio was significantly higher (155 ± 53 vs 193 ± 61, P < .01). No changes were observed for plasma nitric oxide end products (nitrite and nitrate) levels after GH treatment (21.9 ± 14.9 vs 24.1 ± 19.0 μmol/L, not significant). Basal forearm blood flow remained unchanged, whereas reactive hyperemia increased from 7.30 ± 5.31 mL/100 mL forearm per minute before GH therapy to 13.18 ± 7.30 mL/100 mL forearm per minute after 6 months of therapy ( P < .001). There was a positive correlation between IGF-1 and cyclic guanosine monophosphate ( r = 0.73, P < .0001), IGF-1 and reactive hyperemia ( r = 0.63, P < .0001), and IGF-1 and Arg/ADMA ratio ( r = 0.44, P < .01). Conversely, a negative correlation was found between IGF-1 and ADMA levels ( r = −0.41, P < .02). At the end of the study period, fat-free mass, plasma glucose, and hemoglobin A 1c levels significantly increased, even if they were still in the reference range, suggesting moderate alteration of glucose metabolism. In conclusion, in GHD patients, GH replacement contributes to decreased, to some extent, cardiovascular risk, reducing ADMA levels and improving Arg/ADMA ratio and endothelial dysfunction.

Growth Hormone (GH) Treatment Does Not Restore Endothelial Function in Children with GH Deficiency

In adults with growth hormone (GH) deficiency (GHD), GH treatment restores impaired endothelial function, a precursor of cardiovascular disease. Its effect in children with GHD is unknown. Three months of GH (0.3 mg/kg/wk) were given to nine children with GHD. Endothelial function was measured via reactive hyperemic response. Forearm blood flow (FBF, strain gauge plethysmography) was measured before and after 5 min of upper arm arterial occlusion. Blood pressure and lipid, insulin and glucose levels were measured. Pretreatment endothelial function was compared to 18 previously studied control children. Percent fall in forearm vascular resistance was greater in controls (81.2 +/- 1.9%) than in children with GHD (69.6 +/- 5.3%, p = 0.021) but was not affected by GH (60.6 +/- 7.5%). GH markedly increased HOMAIR (21 +/- 7 versus 43 +/- 8, p = 0.004). Plasma lipid levels did not significantly differ. These results indicate that endothelial function is impaired in children with GHD. GH therapy does not restore the impairment.

Glucose Metabolism and Visceral Fat in GH Deficient Adults: Two Years of GH-Replacement

The aim of this study was to evaluate the effect of 24 months of growth hormone (GH) replacement on glucose metabolism and visceral fat in 17 adults with GH deficiency: 9 men and 8 women; age 40 +/- 1.8 yr. [range 20-61] and body mass index 25 +/- 0.8 Kg/m2. Glucose metabolism was evaluated by a standard oral glucose tolerance test (OGTT), by the homeostatic model assessment (HOMA) insulin resistance index and by the insulin sensitivity index (ISI)-composite derived from the OGTT. Visceral fat was evaluated by CT scan.Twenty-four months of GH replacement induced an increase in the prevalence of abnormal glucose tolerance, with significant progressive increment in 2h-OGTT insulin levels at 3, 12 and 24 months (p = 0.005). Plasma glucose levels and ISI-composite did not alter during the study. HOMA-IR index increased only in the group of patients (n = 8) who had abnormal OGTT at 24 months (p = 0.012). Visceral fat reduced at month 12 and remained decreased until the end of the study (p = 0.009). In conclusion, the present study suggests that adults with GH deficiency after twenty-four months of GH replacement developed abnormal glucose tolerance, probably due to an increase in insulin resistance, associated with higher insulin levels, despite favorable alterations in body composition.

Is insulin-like growth factor-1 monitoring useful in assessing the response to growth hormone of growth hormone-deficient children?

Objective: To assess the relationship between insulin-like growth factor-1 (IGF-1), the growth hormone (GH) dose utilized to treat GH-deficient children and the changes noticed in height-standard deviation score (H-SDS) and height velocity (HV). Study design: We studied 24 prepubertal GH-deficient patients with a mean age of 10.5 ± 1.8 years and a mean bone age (BA) of 8.4 ± 2.1 years. H-SDS for chronologic age (CA) and BA before therapy were −2.6 ± 0.8 and −1.2 ± 0.8, whereas height velocity (HV)-SDS was −1.1 ± 1.5. Serum IGF-1 and insulin-like growth factor binding protein-3 (IGFBP-3) levels were measured before, after 6 and 12 months of GH, and correlated with the GH dose used. Based on the increment of IGF-1 used during treatment, patients were divided into 2 groups: G1 (>1 SDS) and G2 (<1 SDS). HV-SDS and interval height increases were analyzed. Results: HV-SDS, as well as H-SDS for CA and BA during the first year of treatment, were significantly greater than before therapy. IGF-1 SDS increased significantly during the first 6 months of therapy (P <.0003), but increased no further at 12 months despite the use of a higher GH dose (0.1 vs 0.14 IU/kg/day), whereas IGFBP-3 SDS increased at both 6 and 12 months. There was no correlation between the GH dose used and IGF-1 and IGFBP-3 levels. When patients were divided according to their IGF-1 increment during therapy, a significant increase in H-SDS for BA and in HV-SDS was noted only in group 2. Conclusions: The increment in IGF-1 SDS during therapy did not correlate with the interval height increase. IGF-1 measurement may be helpful in monitoring compliance and safety, but seems to be less useful in adjusting the GH dose needed to treat prepubertal GH-deficient children. (J Pediatr 2002;141:606-10)

Cardiac Effects of Low-Dose Growth Hormone Replacement Therapy in Growth Hormone-Deficient Adults

Objective: To characterise the effect of long-term low-dose growth hormone (GH) treatment on cardiac anatomy and function. Methods: 20 patients with multiple pituitary hormone deficiencies, including severe acquired GH deficiency (GHD), were randomly assigned to GH or placebo (P) for 18 months. Echocardiographic measurements were performed at baseline and after 6, 12 and 18 months. Results: At baseline, 8 of 20 patients had diastolic dysfunction (6 severe and 2 borderline), while only 1 had systolic dysfunction. None of the investigated parameters of diastolic or systolic function changed during treatment. Conclusion: In adult onset GHD, diastolic dysfunction was present in 40% of the patients. None of the investigated values were different after 18 months of GH compared to placebo.

Growth hormone corrects vascular dysfunction in patients with chronic heart failure

ObjectivesThe goal of this study was to test the hypothesis that growth hormone (GH) administration to patients with chronic heart failure (CHF) corrects their vascular dysfunction. BackgroundEndothelial dysfunction is a prominent feature of CHF. Recent evidence indicates that GH plays a role in vascular reactivity. MethodsWe studied vascular reactivity in 16 patients with CHF (New York Heart Association class II to III) before and after three months of GH (4 IU subcutaneously every other day) or placebo administration in a randomized, double-blind trial. We measured forearm blood flow (FBF) by strain-gauge plethysmography during intrabrachial, graded infusion of acetylcholine (ACh) and sodium nitroprusside (NP). We also measured the forearm balance of nitrite and cyclic guanosine monophosphate (cGMP) before and during ACh infusion. Maximal oxygen uptake (VO2max) was measured by breath-to-breath respiratory gas analysis. ResultsBefore treatment, the response of FBF to ACh was flat (p = NS). Growth hormone, but not placebo, greatly improved this response (p = 0.03) and, concomitantly, increased the forearm release of nitrite and cGMP (p < 0.05). Growth hormone also potentiated the FBF response to NP (p = 0.013). Growth hormone interacted with ACh response (p = 0.01) but not with the response to NP (p = NS). Accordingly, GH enhanced the slope of the dose-response curve to ACh (p < 0.05) but not to NP. The VO2max increased significantly after GH treatment (20 ± 2 and 26 ± 2 ml ·Kg−1· min−1before and after GH treatment, respectively, p < 0.05) but not after placebo. ConclusionsA three-month treatment with GH corrected endothelial dysfunction and improved non-endothelium-dependent vasodilation in patients with CHF. The data highlight the potential role of GH in the progression of congestive heart failure.

Improved Cardiovascular Risk Factors and Cardiac Performance after 12 Months of Growth Hormone (GH) Replacement in Young Adult Patients with GH Deficiency

Improved Cardiovascular Risk Factors and Cardiac Performance after 12 Months of Growth Hormone (GH) Replacement in Young Adult Patients with GH Deficiency

Improved cardiovascular risk factors and cardiac performance after 12 months of growth hormone (GH) replacement in young adult patients with GH deficiency.

Adult GH deficiency (GHD) is associated with increased cardiovascular morbidity and mortality due to unfavorable lipid profile, hyperfibrinogenemia, and impairment of cardiac performance. This prospective controlled cohort study evaluated the effects of 12-month GH replacement on lipid profile, fibrinogen levels, cardiac mass by echocardiography, and performance by equilibrium radionuclide angiography. To this end we studied 20 patients (11 men and 9 women, aged 19-40 yr), 10 with childhood-onset (co-) and 10 with adult-onset (ao-) disease, and 20 sex- and age-matched healthy subjects. At study entry, insulin-like growth factor I (IGF-I; P < 0.0001) and high density lipoprotein (HDL) cholesterol (P < 0.0001) levels, left ventricular mass index (LVMi; P < 0.0001), ejection fraction (LVEF) at rest (P = 0.001) and at peak exercise (P < 0.0001), peak ejection rate (P = 0.005), and exercise duration (P < 0.0001) and capacity (P = 0.002) were lower, whereas total cholesterol (P = 0.02), triglycerides (P = 0.003), and fibrinogen (P = 0.005) levels were higher in patients than in controls. After 12 months, increases in IGF-I (P < 0.0001) and HDL cholesterol levels (P = 0.04), LVMi (P < 0.0001), LVEF at peak exercise (P < 0.0001), and exercise duration (P = 0.009) and capacity (P = 0.003) and decreases in total cholesterol (P < 0.0001), low density lipoprotein cholesterol (P < 0.0001), triglycerides (P < 0.0001), and fibrinogen (P = 0.01) levels were found in all patients, without any difference between co- and ao-GHD. At the end of treatment, however, total cholesterol, triglycerides, and fibrinogen levels were still higher, and HDL cholesterol levels, IGF-I levels, and LVEF at rest and at peak exercise were lower in patients than in controls. In conclusion, GH replacement for 12 months significantly improved lipid profile, decreased fibrinogen levels, and increased LVMi and LVEF in young adults with co- or ao-GHD. However, lipid profile, fibrinogen levels, and systolic function remained abnormal compared with those in age- and sex-matched controls, suggesting that a longer period of GH replacement is necessary to normalize cardiovascular parameters and reverse the cardiovascular risk of these patients.

Growth velocity, final height and bone mineral metabolism of short children treated long term with growth hormone.

Since human recombinant growth hormone (GH) became available a large number of short GH deficient and GH-sufficient children have been treated with growth hormone. Growth hormone deficient patients have been followed to final height and several studies have shown that even when treated with GH from very early on in life they tend to end up shorter than their target height. There is, however, a clear increase in their growth velocities particularly during the first 4-5 years of GH therapy so that patients end up with a height-SD score of aproximately -0.8. Recent studies have demonstrated decreased bone mineral densities (BMD) in children with growth hormone deficiency, both by areal and volumetric analysis. Therapy with growth hormone clearly increases their BMD with an increase in bone formation markers, as will be reviewed in detail. Growth hormone therapy of non-growth hormone deficient short children has increased their growth velocity short term, particularly in girls with Turner's syndrome and in children with chronic renal insuficiency. Recent final height data by Rosenfeld et al. and by Swedish and Dutch groups have demonstrated a gain of 8-12 cm in girls with Turner's syndrome treated with GH or with a combination of GH and oxandrolone. Neely et al. and we have demonstrated that growth hormone treated prepubertal age girls and adolescents with Turner's syndrome have normal BMD and Shaw et al. has suggested that they have normal BMD despite GH or estrogen therapy. However, we found the BMD of a group of previously GH treated young women with Turner's syndrome on estrogen replacement to be decreased compared to both age and gender matched controls and to controls of the same weight and pubertal status. Growth hormone therapy increases the growth velocity and the final height of children with chronic renal insuficiency, particularly in prepubertal children treated with GH before dialysis. We have demonstrated how the BMD of these patients, which at baseline is low when compared to healthy age matched controls, but normal when compared to height and bone age matched controls, increases with growth hormone treatment significantly, moreso than in untreated uremic controls or in untreated healthy controls paired for height and bone age. Short, slowly growing, non growth hormone deficient patients (idiopathic short stature) have been treated for prolonged periods of time with GH. We and others have demonstrated a clear increase in their growth velocity short term, but improvement of their final height remains unclear and controversial. After 4-8 years of GH treatment, Hintz et al. have found a 5-6 cm increase in final height compared to the predicted adult height before beginning therapy, but most patients did not reach their target heights. Other studies, however, have found no improvement in final height and Kawai et al. even suggests that GH therapy diminishes the final height of treated children due to an earlier puberty and a shorter pubertal growth spurt. We, have found decreased BMD in children with idiopathic short stature when compared to controls of their same height and bone age with a significant increase in BMD following 12 months of GH and with an increase in bone turnover as measured by bone formation and resorption markers. Recent short term studies in patients with hypophosphatemic rickets and osteogenesis imperfecta treated with rhGH have also yielded similar results which will be specified in the review. Some 10-20% of children born with intrauterine growth retardation (IUGR) end up short and we had already demonstrated 20 years ago how 2 years of GH therapy were capable of increasing their growth velocities significantly with an improvement of their height-SD scores. Recent studies mainly from Europe have corroborated this data long term, so that IUGR children have been shown by de Zegher et al. to increase their growth velocities and their height for age after 6 years of treatment, entering into the low normal centiles of their growth curves for age. Long term studies of these children to final height will be necessary to determine the usefulness and safety of this form of therapy.

Effect of growth hormone replacement therapy on plasma lecithin:cholesterol acyltransferase and lipid transfer protein activities in growth hormone-deficient adults

The effects of growth hormone (GH) replacement on plasma lecithin:cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP), and phospholipid transfer protein (PLTP), factors involved in high density lipoprotein (HDL) metabolism, are unknown. We carried out a 6 months study in 24 GH-deficient adults who were randomized to placebo (n = 8), low dose GH (1 U daily, n = 8), and high dose GH (2 U daily, n = 8), followed by a 6 months open extension study with high dose GH (1 dropout). No significant changes in plasma lipoproteins, LCAT, CETP, and PLTP activities, cholesterol esterification (EST) and cholesteryl ester transfer (CET) were observed after placebo. After 6 months of GH (combined data, n = 24), very low + low density lipoprotein (VLDL + LDL) cholesterol (P < 0.05) and apolipoprotein B (P < 0.05) decreased, whereas HDL cholesterol and HDL cholesteryl ester increased (P < 0.05). Prolonged treatment showed comparable effects. Plasma apolipoprotein A-I and Lp[a] remained unchanged. Plasma LCAT (P < 0.01) and CETP activities (P < 0.01), as well as EST (P < 0.01) and CET decreased (P < 0.01) after 12 months of GH (n = 15), but PLTP activity did not significantly change. Changes in EST and CET after 12 months of treatment were independently related to changes in plasma LCAT (P = 0.001 and CETP activity (P = 0.01).In conclusion, GH replacement therapy improves the lipoprotein profile in GH-deficient adults. Chronic GH replacement lowers plasma LCAT and CETP activities, contributing to a decrease in cholesterol esterification and cholesteryl ester transfer. These effects may have consequences for HDL metabolism and reverse cholesterol transport.

Effect of 30 months of growth hormone (GH) replacement therapy on bone metabolism in adults with GH deficiency

Effect of 30 months of growth hormone (GH) replacement therapy on bone metabolism in adults with GH deficiency

Glucose turnover and insulin clearance after growth hormone treatment in girls with turner's syndrome

The study was performed to elucidate, by means of a euglycemic-hyperinsulinemic clamp, whether insulin sensitivity, lipid levels, posthepatic insulin delivery, and insulin clearance are impaired in girls with Turner's syndrome in the absence of previous treatment (T0) and after 6 (T6) and 12 (T12) months of growth hormone (GH) therapy (GHT). The study was performed in six girls with Turner's syndrome and eight healthy girls. We found that previously untreated girls with Turner's syndrome had a normal insulin activity on glucose metabolism. GHT progressively and significantly decreased hepatic insulin sensitivity. In fact, residual hepatic glucose release (HGR), which was 19.6 ± 4.7 mg/m2 · min at T0, doubled at T6 (39.3 ± 5.1 mg/m2 · min) and showed a threefold increase at T12 (68.7 ± 10.8 mg/m2 · min, P < .05 v T0). On the contrary, GHT did not show an appreciable influence on peripheral insulin sensitivity. Insulin clearance was higher in girls with Turner's syndrome than in control girls at T0 (30.0 ± 2.8 v 20.2 ± 1.1 mL · kg−1 · min−1). It decreased to normal values at T6 (18.2 ± 2.0 mL · kg−1 · min−1, P < .05v T0) and remained at normal levels at T12 (23.8 ± 2.9 mL · kg−1 · min−1). The posthepatic insulin delivery rate significantly increased at T6 and T12, suggesting increased insulin secretion. In conclusion, we found that insulin-stimulated glucose turnover was normal in girls with Turner's syndrome before therapy. One year of GHT was successful in stimulating the growth rate, but significantly decreased the insulin suppressibility on HGR with only slight changes in peripheral insulin sensitivity. In addition, an increase in the insulin posthepatic delivery rate and a normalization of insulin clearance were present, probably to counteract hepatic insulin resistance.

Urinary pyridinium collagen cross-links predict growth performance in children with idiopathic short stature and with growth hormone (GH) deficiency treated with GH. Skeletal metabolism during GH treatment.

GH is able to promote longitudinal growth in children with GH-deficiency (GHD) and in some children with idiopathic short stature (ISS). The objectives of this study were to evaluate the predictive value of bone and collagen markers on the growth response to GH therapy in children with ISS and with GHD, and to characterize the effects of GH treatment on bone and collagen turnover in children with ISS and with GHD. Twenty prepubertal short, slowly growing, children treated with GH, 15 IU/m2 per week, were studied; of them 13 (10 males) had ISS and 7 (5 males) had GHD. An overnight 12-h urinary collection and a fasting morning blood sample were obtained at baseline, 1, 3, 6, and 12 months of treatment. Urinary levels of collagen cross-links, pyridinoline (Pyd) and deoxypyridinoline (Dpd), and circulating levels of osteocalcin, intact PTH, calcitonin, procollagen type III aminoterminal propeptide (PIIINP), insulin-like growth factor-I, and alkaline phosphatase were determined. Urinary collection was also obtained from 127 healthy children (51 males) aged 6-13 yr. In children with ISS, the changes in Dpd over 1 month of GH therapy were related to the changes in height velocity (HV) over 1 yr of therapy (r = 0.67; P < 0.05); the changes in Pyd after 1 month of GH treatment were related to the changes in HV at 6 months of GH treatment (r = 0.57; P < 0.05). All the other markers evaluated were not related to the HV changes in children with ISS. In children with GHD, the changes in Pyd and in Dpd after 1 month of GH treatment were positively related to the changes in HV after 12 months of therapy (r = 0.82; P < 0.05, and r = 0.82; P < 0.05, respectively). The changes in Pyd after 1 month were also related to the HV changes after 6 months of GH (r = 0.77; P < 0.05). Positive relationships between the HV after 6 months of GH and the increases of PIIINP (r = 0.80; P < 0.05) and osteocalcin (r = 0.77; P < 0.05) after 3 months of GH therapy were observed. All patients showed urinary Dpd and Pyd excretions in the normal range. In patients with ISS, Pyd (P < 0.05), Dpd (P < 0.05), osteocalcin (P < 0.01), PIIINP (P < 0.01), and alkaline phosphatase (P < 0.01) increased longitudinally during the GH treatment and the increments reached a maximum after 3-6 months of therapy. Patients with GHD showed an increase of the same markers but the increases occurred earlier, after 1 month of GH therapy. The collagen cross-links, Pyd and Dpd, could be helpful early markers in predicting the responsiveness to GH therapy in children with ISS and with GHD. GH treatment stimulates bone and collagen metabolism.

Effects of 12 months of growth hormone (GH) treatment on calciotropic hormones, calcium homeostasis, and bone metabolism in adults with acquired GH deficiency: a double blind, randomized, placebo-controlled study

Effects of 12 months of growth hormone (GH) treatment on calciotropic hormones, calcium homeostasis, and bone metabolism in adults with acquired GH deficiency: a double blind, randomized, placebo-controlled study