Duration Of Growth Hormone Treatment Research Articles

The Impact of Growth Hormone Co-Treatment Duration on Outcomes in IVF/ICSI Cycles Among Poor Ovarian Responders.

The efficiency of in vitro fertilization is improved by growth hormone (GH) during ovarian stimulation. Additionally, patients with diabetes experience impaired insulin resistance and compromised glucose tolerance, which further exacerbate their condition. Due to these side effects, in this study, the duration of GH treatment was compared in IVF/ICSI cycles among poor ovarian responders. In this study, POSEIDON criteria were used to choose patients. Subcutaneous administration of gonadotropin-releasing hormone (GnRH) antagonist was done beginning on the sixth day of the cycle and continuing through the day of human chorionic gonadotropin (hCG) injection. In one group, GH was administered 4 units/day from the 2nd day of the cycle until hCG injection, and in another group, the first dose was administered on the 6th day of the cycle. Following the administration of hCG, which lasted from 24 to 36 hr, oocytes were retrieved with the support of B-mode sonography. In our analysis, no significant differences were observed between the two groups in terms of the number of retrieved oocytes, metaphase II oocytes, and quality of grade A and B embryos. The results show that the treatment or conditions did not have a significant impact on the outcomes among the studied groups. Our findings indicate that a shorter duration of GH administration can yield similar outcomes compared to a longer duration in IVF/ICSI cycles involving poor ovarian responders. This result holds the potential for a more cost-effective and patient-friendly approach in managing assisted reproductive technology procedures. It may lead to reduced side effects and improved adherence to medication regimens in patients.

Early GH Treatment Is Effective and Well Tolerated in Children With Turner Syndrome: NordiNet® IOS and Answer Program.

Despite having normal growth hormone (GH) secretion, individuals with Turner syndrome (TS) have short stature. Treatment with recombinant human GH is recommended for TS girls with short stature. This work aimed to evaluate the effectiveness and safety of Norditropin (somatropin, Novo Nordisk) with up to 10 years of follow-up in children with TS. Secondary analysis was conducted of Norditropin data from 2 non-interventional studies: NordiNet® IOS (NCT00960128) and the ANSWER program (NCT01009905). A total of 2377 girls with TS were included in the safety analysis set (SAS), with 1513 in the treatment-naive effectiveness analysis set (EAS). At the start of treatment, 1273 (84%) participants were prepubertal (EAS); mean (SD) age was 8.8 (3.9) years. Mean (SD) dose received at the start of GH treatment was 0.045 (0.011) mg/kg/day (EAS). Mean (SD) baseline insulin-like growth factor-1 (IGF-I) SD score (SDS) was -0.86 (1.52), and mean (SD) duration of GH treatment (SAS) was 3.8 (2.8) years.Height SDS (HSDS) increased throughout follow-up, with near-adult HSDS reached by 264 (17%) participants (mean [SD] -1.99 [0.94]; change from baseline +0.90 [0.85]). During the study, 695 (46%) participants (EAS) entered puberty at a mean (SD) age of 12.7 (1.9) years (whether puberty was spontaneous or induced was unknown). Within the SAS, mean IGF-I SDS (SD) at year 10 was 0.91 (1.69); change from baseline +1.48 (1.70). Serious adverse reactions were reported in 10 participants (epiphysiolysis [n = 3]). GH-treated participants with TS responded well, without new safety concerns. Our real-world data are in agreement with previous studies.

Abstract 7: Use of growth hormone therapy in short patients born small for gestational age: Data from real-life French clinical practice

Background: A national French registry was created to address the absence of data on final height and safety following long-term exposure to supraphysiological doses of growth hormone (GH) in children born small for gestational age (SGA).Methods: This observational, non-interventional study (NCT01578135) included GH-naïve and non-naïve SGA children treated with GH at 126 sites in France. The inclusion period was 2005–2010 with follow-up until 2018 or until final adult (FA) height (height velocity <2 cm/year). The primary endpoints were proportion of patients with normal (>–2) height standard deviation score (HSDS) at last visit, and with normal FA HSDS. Secondary endpoints included change from baseline in HSDS and safety. Multivariate logistic regression analysis with stepwise elimination was used to identify factors associated with achieving normal HSDS.Results: Of the 1408 registered patients, every fifth child was randomly selected (n = 291) for inclusion in this long-term follow-up study. For the full population and subpopulation, mean (SD) baseline age was 8.79 (3.53) and 8.08 (3.32) years; HSDS was –2.55 (0.95) and –3.07 (0.86); 48.4% and 46.0% were female, respectively. Normal HSDS was reached in 193/291 children (66.3%). Among the 24.7% of patients who achieved FA height at last visit, 66.7% had FA HSDS >–2. Mean change from start of treatment to last visit in HSDS was +1.35 (0.97). Factors associated with reaching normal HSDS were baseline HSDS (taller better; odds ratio [95% confidence interval]: 5.65 [3.22;9.92], P < 0.0001); age at treatment start (younger better; 0.88 [0.79;0.98], P=0.0166); treatment duration excluding discontinuation periods (longer better; 1.20 [1.04;1.38], P=0.0166); and absence of a chronic disease (0.43 [0.21;0.87], P=0.0188). The majority (70.0%) of adverse events (AEs) were non-serious; 39.0% of all AEs and 7.0% of serious AEs were considered possibly/probably related to GH treatment. The most common AEs (% of patients) were increased insulin-like growth factor-I (IGF-I; 17.2%), headache (9.3%) and arthralgia (4.5%). Sixteen patients (5.5%) discontinued treatment prematurely, most commonly because of increased IGF-I (n = 4). One malignant tumour (nephroblastoma) with a fatal outcome was reported and considered unrelated to GH treatment.Conclusions: GH therapy was effective in most short children born SGA. No new safety concerns were observed. The likelihood of achieving normal HSDS with GH therapy increased with greater baseline HSDS, longer duration of GH treatment, absence of a chronic disease and younger baseline age, reinforcing the importance of early identification and treatment of short patients born SGA.

Evidence for Accelerated Biological Aging in Young Adults with Prader-Willi Syndrome.

ObjectiveAdults with Prader–Willi syndrome (PWS) are at increased risk of developing age-associated diseases early in life and, like in premature aging syndromes, aging might be accelerated. We investigated leukocyte telomere length (LTL), a marker of biological age, in young adults with PWS and compared LTL to healthy young adults of similar age. As all young adults with PWS were treated with growth hormone (GH), we also compared LTL in PWS subjects to GH-treated young adults born short for gestational age (SGA).DesignCross-sectional study in age-matched young adults; 47 with PWS, 135 healthy, and 75 born SGA.MeasurementsLTL measured by quantitative polymerase chain reaction, expressed as telomere/single copy gene ratio.ResultsMedian (interquartile range) LTL was 2.6 (2.4–2.8) at a median (interquartile range) age of 19.2 (17.7–21.3) years in PWS, 3.1 (2.9–3.5) in healthy young adults and 3.1 (2.8–3.4) in the SGA group. Median LTL in PWS was significantly lower compared to both control groups (P < .01). In PWS, a lower LTL tended to be associated with a lower total IQ (r = 0.35, P = .08). There was no association between LTL and duration of GH treatment, cumulative GH dose, or several risk factors for type 2 diabetes mellitus or cardiovascular disease.ConclusionsYoung adults with PWS have significantly shorter median LTL compared to age-matched healthy young adults and GH-treated young adults born SGA. The shorter telomeres might play a role in the premature aging in PWS, independent of GH. Longitudinal research is needed to determine the influence of LTL on aging in PWS.

SAT-282 Outcomes in Children Treated with Growth Hormone for Prader-Willi Syndrome: Data from the Answer® Program and Nordinet® International Outcome Study (IOS)

Background: The American Norditropin® Studies: Web-Enabled Research (ANSWER) Program and the NordiNet® International Outcome Study (NordiNet® IOS) are complementary, large-scale, non-interventional studies designed to gather long-term data on the effectiveness and safety of Norditropin® (somatropin) treatment in the usual clinical setting. Data were collected in the United States (US) and Europe from 2006 to 2016 in both children and adults. Objective: To assess the clinical outcomes of growth hormone (GH)-treated pediatric patients with Prader-Willi Syndrome (PWS) enrolled in the ANSWER® Program or NordiNet® IOS. Methods: Patient information was entered by participating physicians using a web-based data entry tool. Change from baseline in height standard deviation scores (HSDS) and body mass index standard deviation scores (BMI SDS) were analyzed based on availability of follow-up data. The explanatory variables in the repeated measures model analysis included baseline HSDS/BMI SDS, gender, age, target height, region (US/Europe), and GH dose. Results: From a total of 129 PWS GH-naïve patients, available data for HSDS and BMI SDS analysis included 129 and 98 patients respectively on a GH dose of 0.03 (±0.01) mg/kg/d. In the HSDS analysis with equal number of males and females, the mean age at the start of treatment was 4.42 (±4.51) years, and mean treatment period was 2.48 (±1.31) years. Further analysis determined that baseline age and years on treatment had a significant impact on the change in HSDS (P=0.014 and P<0.0001, respectively. In the BMI SDS analysis, 51% were males. At the start of treatment, the mean age was 5.56 (±4.79) years, with a mean duration of GH treatment of 2.45 (±1.32) years. The mean BMI was 18.04 (±4.9) for NordiNet® patients and 24.68 (±7.75) for ANSWER® patients. The baseline BMI SDS of NordiNet® patients (0.4±1.54) was lower compared with that of ANSWER® patients (1.80±1.68). Longer GH treatment time lead to a greater change in BMI SDS from baseline (P<0.0001). In addition, those patients with a higher BMI at the start of treatment had a greater decrease in BMI over time [t(624)=-8.01, P<0.0001]. Conclusions: GH is effective in the management of children with PWS. Earlier treatment resulted in a greater gain in height, and longer treatment period resulted in better outcomes for both height and BMI.

Analysis of characteristics and outcomes by growth hormone treatment duration in adult patients in the Italian cohort of the Hypopituitary Control and Complications Study (HypoCCS)

PurposeTo examine differences in effects according to growth hormone (GH) treatment duration in adult GH-deficient patients.MethodsIn the Italian cohort of the observational Hypopituitary Control and Complications Study, GH-treated adults with GH deficiency (GHD) were grouped by duration of treatment; ≤ 2 years (n = 451), > 2 to ≤ 6 years (n = 387) and > 6 years (n = 395). Between-group differences in demographics, medical history, physical characteristics, insulin-like growth factor-I standard deviation score (IGF-I SDS) and lipid profile at baseline, last study visit and changes from baseline to last study visit were assessed overall, for adult- and childhood-onset GHD and by gender using ANOVA for continuous variables and Chi-squared test for categorical variables.ResultsAt baseline, treatment duration groups did not differ significantly for age, gender, body mass index, GHD onset, IGF-I SDS, lipid profile, and quality of life. Mean initial GH dose did not differ significantly according to treatment duration group in any subgroup, except female patients, with highest mean dose seen in the longest duration group. In the longest duration group for patients overall, adult-onset patients and male patients, there were significant decreases in GH dose from baseline to last visit, and in total and low-density lipoprotein (LDL)-cholesterol concentrations. IGF-I SDS increased, to a greater extent, in the longest duration group for patients overall and female patients.ConclusionsThe results show that long-term GH treatment is associated with decreasing GH dose, increased IGF-I, decreased LDL-cholesterol and the presence of surrogate markers that help to give confidence in a diagnosis of GHD.

Treatment of Pre-pubertal Patients with Growth Hormone Deficiency: Patterns in Growth Hormone Dosage and Insulin-like Growth Factor-I Z-scores.

Objective:To describe the range of insulin-like growth factor-I (IGF-I) z-score values (IGF-Iz) and growth hormone (GH) dose adjustments in pre-pubertal patients with GH deficiency (GHD) treated with GH in a single tertiary care center.Methods:This is a retrospective review of GH-treated patients of ages ≤9 years with GHD, seen in an endocrinology clinic in 2013-2014. Patient demographics and pre-treatment anthropometrics, GH treatment duration, IGF-Iz, and GH dosage (mg/kg/week) were extracted. Multipredictor linear regression was used to evaluate the associations between IGF-Iz and GH dosage and subject gender, race, insurance type, age, and clinical characteristics. Logistic regression was used to calculate the odds ratio of direction of GH dose adjustment (decrease/no change versus increase) and IGF-Iz category based on patient clinical characteristics, accounting for provider random effect.Results:Forty-one percent (57/139) of IGF-Iz were outside the “normal” range of between -2 and +2 standard deviation; the majority of IGF-Iz beyond the “normal” range (93%) were supraphysiologic [>+2 standard deviation score (SDS)]. Of the IGF-Iz >+2, 10/53 (18%) were followed by a GH dose increase and 30/53 (57%) had no dose change. Patient clinical characteristics and demographics did not significantly increase the odds of being in the IGF-Iz >+2 SDS category or having a dose increase in multipredictor logistic regression models.Conclusion:GH dosages and IGF-Iz varied, without significant patient clinical predictors. IGF-Iz was frequently supraphysiologic, and these levels often did not prompt a reduction in GH dose, likely influenced by a variety of factors. Our study emphasizes the need for better understanding of long-term safety and efficacy of maintaining supraphysiologic levels of IGF-Iz.

Impact of discontinuation of growth hormone treatment on lipids and weight status in adolescents.

While the main role of growth hormone (GH) replacement therapy in children is to promote linear growth, GH has also an effect on lipids and body composition. There is an ongoing discussion whether discontinuation of GH treatment is associated with deterioration of lipids. We analyzed weight status [as body mass index-standard deviation score (BMI-SDS)], insulin like growth factor (IGF)-1, triglycerides, total, low-density liporptoein (LDL)- and high-density lipoprotein (HDL)-cholesterol at the end of GH treatment and in mean 6 months later in 90 adolescents (53 with GH deficiency, 16 with Turner syndrome [TS] and 21 born small-for-gestational age [SGA]). After stopping GH treatment, total cholesterol (+10±24 mg/dL vs. -4±13 mg/dL) and LDL-cholesterol (+15±20 mg/dL vs. -6±12 mg/dL) increased significantly higher in severe (defined by GH peak in stimulation test <3 ng/mL) compared to moderate GHD. In patients with TS, total cholesterol (+19±9 mg/dL), LDL-cholesterol (+9±12 mg/dL) and HDL-cholesterol (+4.3±3.5 mg/dL) increased significantly. In adolescents born SGA, triglycerides increased (+34±51 mg/dL) and HDL-cholesterol decreased significantly (-3.8±7.1 mg/dL). In multiple linear regression analyses, changes of total and LDL-cholesterol were significantly negatively related to peak GH in stimulation tests, but not to gender, age at GH start, duration of GH treatment, observation time, changes of BMI-SDS or IGF-1 after the end of GH treatment. The BMI-SDS did not change after the end of GH treatment. Discontinuation of GH treatment leads to a deterioration of lipids in TS, SGA and severe but not moderate GHD.

Efficacy and safety of growth hormone treatment in children with short stature: the Italian cohort of the GeNeSIS clinical study.

PurposeWe examined auxological changes in growth hormone (GH)-treated children in Italy using data from the Italian cohort of the multinational observational Genetics and Neuroendocrinology of Short Stature International Study (GeNeSIS) of pediatric patients requiring GH treatment.MethodsWe studied 711 children (median baseline age 9.6 years). Diagnosis associated with short stature was as determined by the investigator. Height standard deviation score (SDS) was evaluated yearly until final or near-final height (n = 78). Adverse events were assessed in all GH-treated patients.ResultsThe diagnosis resulting in GH treatment was GH deficiency (GHD) in 85.5 % of patients, followed by Turner syndrome (TS 6.6 %). Median starting GH dose was higher in patients with TS (0.30 mg/kg/week) than patients with GHD (0.23 mg/kg/week). Median (interquartile range) GH treatment duration was 2.6 (0.6–3.7) years. Mean (95 % confidence interval) final height SDS gain was 2.00 (1.27–2.73) for patients with organic GHD (n = 18) and 1.19 (0.97–1.40) for patients with idiopathic GHD (n = 41), but lower for patients with TS, 0.37 (−0.03 to 0.77, n = 13). Final height SDS was >−2 for 94 % of organic GHD, 88 % of idiopathic GHD and 62 % of TS patients. Mean age at GH start was lower for organic GHD patients, and treatment duration was longer than for other groups, resulting in greater mean final height gain. GH-related adverse events occurred mainly in patients diagnosed with idiopathic GHD.ConclusionsData from the Italian cohort of GeNeSIS showed auxological changes and safety of GH therapy consistent with results from international surveillance databases.

X-chromosome gene dosage as a determinant of impaired pre and postnatal growth and adult height in Turner syndrome.

Short stature is a key aspect of the phenotype of patients with Turner syndrome (TS). SHOX haploinsufficiency is responsible for about two-thirds of the height deficit. The aim was to investigate the effect of X-chromosome gene dosage on anthropometric parameters at birth, spontaneous height, and adult height (AH) after growth hormone (GH) treatment. We conducted a national observational multicenter study. Birth parameter SDS for gestational age, height, and AH before and after GH treatment respectively, and height deficit with respect to target height (SDS) were classified by karyotype subgroup in a cohort of 1501 patients with TS: 45,X (36%), isoXq (19%), 45,X/46,XX (15%), XrX (7%), presence of Y (6%), or other karyotypes (17%). Birth weight, length (P<0.0001), and head circumference (P<0.001), height and height deficit with respect to target height (SDS) before GH treatment, at a median age of 8.8 (5.3-11.8) years and after adjustment for age and correction for multiple testing (P<0.0001), and AH deficit with respect to target height at a median age of 19.3 (18.0-21.8) years and with additional adjustment for dose and duration of GH treatment (P=0.006), were significantly associated with karyotype subgroup. Growth retardation tended to be more severe in patients with XrX, isoXq, and, to a lesser extent, 45,X karyotypes than in patients with 45,X/46,XX karyotypes or a Y chromosome. These data suggest that haploinsufficiency for an unknown Xp gene increases the risk of fetal and postnatal growth deficit and short AH with respect to target height after GH therapy.

Growth hormone treatment of Prader–Willi syndrome has long‐term, positive effects on body composition

Growth hormone (GH) treatment is a relatively new concept in adults, and the knowledge of its long-term effects is limited. We studied ten men with Prader-Willi Syndrome (PWS) after more than 5 years of GH treatment. Study participants underwent a detailed physical examination, including blood tests. Five had received GH as childhood and five had started GH as adults. The total duration of GH treatment was 16 ± 4 years in the childhood PWS group and 15 ± 1 years in the adulthood PWS group. Their respective mean ages were 27 ± 4 years and 44 ± 4 years, mean heights were 178 ± 11 cm and 156 ± 5 cm, and mean body mass indexes were 32.4 ± 10.3 kg/m(2) and 28.9 ± 4.6 kg/m(2) . There were no differences in body composition between the groups and all lipids and insulin-like growth factor 1 were normal or close to normal. Four had well-controlled type 2 diabetes. The GH doses in the childhood and adulthood groups were 0.4 mg and 0.3 mg, respectively. Men with PWS who received GH treatment displayed positive effects on body composition independent of when the GH treatment had started. Only patients who gained weight developed diabetes. The duration of GH treatment should balance the benefits and observed side effects.

Is growth hormone treatment in children associated with weight gain?--longitudinal analysis of KIGS data.

Growth hormone (GH) increases lean body mass and reduces fat mass. However, the long-term changes in weight status during growth hormone treatment, according to age and weight status at onset of treatment, have not previously been reported in large data sets. Changes in BMI-SDS between starting GH treatment and attaining near adult height (NAH) were analysed in 2643 children with idiopathic GH deficiency (IGHD), 281 children small for gestational age (SGA), 1661 girls with Turner syndrome (TS), and 142 children with Prader-Willi syndrome (PWS) in the KIGS database. BMI-SDS increased significantly between onset of GH treatment and NAH (IGHD:+0·29, SGA:+0·69, TS:+0·48) except in PWS (-0·02). These increases were greater in children with younger age at onset of GH treatment (significant in all indications) and with lower doses of GH treatment (significant in IGHD & TS) in multiple linear regression analyses also including gender, duration of GH treatment, BMI-SDS and height-SDS at onset of treatment, and birth weight-SDS. Obese children at onset of GH treatment decreased their BMI-SDS, while underweight and normal weight children at onset of GH treatment increased their BMI-SDS independently of GH treatment indication. Long-term GH treatment was associated with changes in weight status, which were beneficial for underweight and obese children independent of the indication for GH. However, the increase in BMI-SDS in normal weight children treated with GH needs to be investigated in future prospective longitudinal studies to analyse whether this represents an increase of fat mass, lean body mass or both.

Bone Quantitative Ultrasound in Congenital and Acquired Childhood Multiple Pituitary Failure

The aim of the present study is to investigate bone status by phalangeal quantitative ultrasound (QUS) in a cohort of hypopituitaric pediatric subjects, and to relate measurement outcome to their clinical, laboratory, and therapeutical features. Forty-three hypopituitaric children were submitted to bone measurement by QUS with DBM sonic bone profiler 1200 (IGEA, Carpi, Modena, Italy). This method measures bone transmission time (BTT) and amplitude-dependent speed of sound (AD-SoS) of an ultrasound beam crossing the first four phalanges of the hand and provides respective standard deviation scores (SDS). These two parameters provide information on bone mineral density and structure. Clinical, laboratory and therapeutical features were considered to look for correlations. Overall BTT and AD-SoS SDS were significantly reduced (-0.87 ± 1.52, p = 0.001, and -0.97 ± 1.56, p = 0.001) as well as respective height- or bone age-corrected SDS. Bone condition proved significantly worse in subjects with higher number of hormonal deficiencies ( p = 0.001 for both parameters) and in those with acquired hypopituitarism ( p = 0.020 for BTT and p = 0.010 for AD-SoS) than in those with congenital forms. In participants under growth hormone (GH) treatment, regression analysis revealed that QUS measurement outcome was significantly associated with age at GH therapy start ( p = 0.001), time interval before therapy initiation ( p = 0.011), treatment duration ( p = 0.007) and administered dosage ( p = 0.036). Our data show that childhood hypopituitarism is associated with bone morbidity, detectable at QUS measurement independently of potential confounders as stature and bone age. Skeletal impairment is related to acquired hypopituitarism, number of hormonal deficiencies and duration of disease before replacement therapies, whereas GH treatment duration and doses are associated with a better skeletal condition. Phalangeal QUS measurements of BTT and AD-SoS promise as a reliable method for obtaining quantitative measurements of bone disease in individuals with hypopituitarism but more studies are needed for verification. (E-mail: mussa_alessandro@yahoo.it)

Height Gains in Response to Growth Hormone Treatment to Final Height Are Similar in Patients with SHOX Deficiency and Turner Syndrome

Background: Patients with mutations or deletions of the <under>S</under>hort Stature <under>H</under>omeob<under>ox</under>-containing(SHOX) gene have variable degrees of growth impairment, with or without mesomelic skeletal dysplasia. If untreated, short patients with SHOX deficiency remain short in adulthood. Growth hormone (GH) treatment improves short-term linear growth; however, there are no data on GH treatment effects on final height. Patients: In a retrospective study, we assessed the relative effects of GH on final height gain in patients with SHOX deficiency (n = 14; 12 females) and Turner syndrome (TS) (n = 158). Patients were included if they fulfilled the following criteria: genetically-confirmed SHOX deficiency or TS, baseline height SDS <1.5, GH treatment started at Tanner stage ≤2, duration of GH treatment >2 years, and final height attained. Results: Both groups of patients were short at baseline (height SDS [mean ± SD]: SHOX deficiency, –3.3 ± 0.9; TS, –2.9 ± 0.8). Height SDS gain from baseline to final height was significant for each patient group (SHOX deficiency, 1.1 ± 0.7; TS, 1.2 ± 0.8; p < 0.001); however, it was not significantly different between groups (p = 0.708). Conclusions: Patients with SHOX deficiency receive similar final height benefit from GH treatment to those with TS.

Analysis of Craniofacial and Extremity Growth in Patients with Growth Hormone Deficiency during Growth Hormone Therapy

Background/Aims: There are many controversies regarding side effects on craniofacial and extremity growth due to growth hormone (GH) treatment. Our aim was to estimate GH action on craniofacial development and extremity growth in GH-deficient patients. Methods: Twenty patients with GH deficiency with a chronological age ranging from 4.6 to 24.3 years (bone age from 1.5 to 13 years) were divided in 2 groups: group 1 (n = 6), naive to GH treatment, and group 2 (n = 14), ongoing GH treatment for 2–11 years. GH doses (0.1–0.15 U/kg/day) were adjusted to maintain insulin-like growth factor 1 and insulin-like growth factor binding protein 3 levels within the normal range. Anthropometric measurements, cephalometric analyses and facial photographs to verify profile and harmony were performed annually for at least 3 years. Results: Two patients with a disharmonious profile due to mandibular growth attained harmony, and none of them developed facial disharmony. Increased hand or foot size (>P97) was observed in 2 female patients and in 4 patients (1 female), respectively, both not correlated with GH treatment duration and increased levels of insulin-like growth factor 1. Conclusions: GH treatment with standard doses in GH-deficient patients can improve the facial profile in retrognathic patients and does not lead to facial disharmony although extremity growth, mainly involving the feet, can occur.

Optimal use of growth hormone therapy for maximizing adult height in children born small for gestational age

Growth retardation is a well-known complication of being born small for gestational age (SGA). Approximately 10% of children born SGA do not experience postnatal catch-up growth and are at risk for short adult height. The use of growth hormone (GH) therapy in these short children appears to increase their adult height, but modalities of GH administration remain controversial. Numerous therapeutic strategies have been developed to optimize the efficacy of GH treatment. Data concerning the influence of age at start of GH treatment, duration of GH treatment, GH dosage and method of GH administration on height gain and adult height are reported in this chapter. Longitudinal studies addressing the safety of GH treatment in SGA children are reassuring, but long-term follow-up remains necessary. Recommendations on the management of SGA children during GH treatment are given.

Relationship between GH-induced metabolic changes and changes in body composition: A dose and time course study in GH-deficient adults

Objective Although growth hormone (GH)-induced changes in fat and protein metabolism are likely to underlie changes in body composition, the relationship has not been clearly defined. The aim was to study the effects of dose and time course on substrate metabolism and relate to body compositional changes during GH treatment. Design In an open randomised-controlled study, 16 GH-deficient adults were randomised to treatment with GH 3 μg/kg/d (low dose, n = 6) or 6 μg/kg/d (higher dose, n = 10) for 12 weeks. Changes in whole body protein metabolism, estimated using the leucine turnover technique, and resting energy expenditure (REE) were assessed after short-term GH (two weeks) and longer-term GH (12 weeks). Changes in lean body mass (LBM) and fat mass (FM) over 12 weeks were assessed by DXA. Results The maximal changes in leucine oxidation (Lox) (−3.9 ± 1.1 versus +0.8 ± 1.8 μmol/min, p = 0.03) and REE (+132 ± 36 versus −28 ± 41 kcal/d, p = 0.01) were significantly greater in the higher, than the low dose group. FM fell (−1.4 ± 0.4 kg, p = 0.005) and LBM increased (+2.2 ± 0.7 kg, p = 0.01) significantly in the higher dose group only. The acute reduction in Lox at two weeks in the higher dose group was no longer significant after 12 weeks. The change in Lox after two ( r = −0.53, p = 0.035), but not 12, weeks was significantly correlated with the change in LBM. Conclusions GH-induced changes in protein metabolism were influenced by the dose and duration of GH treatment. Suppression of protein oxidation occured soon after initiation of GH in the higher dose group and predicted a later gain in LBM. Early assessment of whole body protein metabolism may allow prediction of the anabolic potential of GH.

Growth Hormone Treatment and Left Ventricular Dimensions in Turner Syndrome

To determine whether cardiac dimensions were different in girls with Turner syndrome (TS) who received growth hormone (GH) compared with those who did not receive GH. This retrospective, cross-sectional study analyzed echocardiograms in 86 females with TS divided into GH-treated (n = 67) and untreated (n = 19) groups. The subjects all participated in the National Institutes of Health protocol between 2001 and 2006. The average age was 16.2 years (range, 10 to 25 years), and average duration of GH treatment was 4.4 years (range, 1 to 14 years). The GH-treated group was taller by approximately 7 cm (P = .004), but cardiac dimensions normalized to body surface area (BSA), including septal and posterior wall thickness and left ventricular (LV) mass and internal diameters, did not differ significantly between the 2 groups. The fractional shortening index was similar in the 2 groups. Multiple regression analyses indicated that BSA, but not duration of GH treatment, predicted LV dimensions in girls with TS. GH treatment of girls with TS increases stature but does not disproportionately affect cardiac dimensions.

Veränderung des Kohlenhydratstoffwechsels und der Insulinresistenz bei Patienten mit Prader-Willi-Syndrom unter einer Wachstumshormontherapie

Life expectance and life quality have markedly changed in PWS patients within the last 10-15 years. A strict diet, improved physical activity and an additive growth hormone treatment have led to these changes. Growth hormone therapy decreases body fat and improves final height. But growth hormone also antagonizes insulin and therefore increases the diabetic potential. The purpose of our study was to investigate incidence and multiple dependencies of development of impaired carbohydrate metabolism in patients with PWS under growth hormone therapy and to determine suitable parameters for the work-up. 34 patients with genetically approved PWS have been treated with growth hormone for at least 0.5 years. The mean duration of growth hormone treatment was 2.15 years (0.5-4.51). At the start of growth hormone treatment patients were 1.33 to 16.47 years old. The clinical picture and the nutritional situation of children with PWS change age-dependent and can be divided up into three phases. The patients were duty subdivided into three age-groups at the beginning of growth hormone treatment. Group 1: 15 PWS patients, mean age 2.62 years (1.33-3.78). Group 2: 10 PWS patients, mean age 5.54 years (4.08-7.61). Group 3: 9 PWS patients, mean age 11.35 years (8.89-16.47). Data were collected within 0.3-0.38 years before start of treatment and every 6 months throughout the treatment period. Anthropometrical data, fat mass by bioelectric impedance analysis (BIA), fasting insulin, HbA1c, C-peptide, blood fats and the blood sugar profile in oral glucose tolerance tests (OGT/1.75 g glucose/kg body mass) were obtained. Growth hormone therapy was started with an average dose of 0.031 mg/kg body mass in all groups. Insulin resistance was based on Homeostasis Model Assessment-Test (HOMA). No IR or pathological OGT were detected when growth hormone therapy started before the 4th year of life. When therapy started between the 4th and 8th year, PWS patients with normal weight did not develop an IR under GH therapy. 6% developed a glucose tolerance (IGT) disorder and 4% developed an increased fasting glucose (IFG). 5 of 9 PWS patients older than 8 years at therapystart showed a transient disorder of glucose metabolism: 11% of the results obtained in these patients presented an IR with no pathological OGT, 13% showed an IR with IGT, 7% showed an IR with IFG, and 2% showed an IR with transient diabetes. For 4% the IFG persisted with no IR, for 4% the IGT persisted with no IR. These patients differed from younger ones by an increased average BMI, an increase fat body ratio and an increase fasting insulin as well as an already reached puberty. No difference was found in C-peptide, HbA1c or GH dose/kg/body mass. Transient glucose metabolism disorders with no development of manifest insulin resistance are shown by PWS patients with normal weight starting from 4th year under GH therapy. Changes in the glucose metabolism with and with no development of IR appear after start of puberty and weight increase. Changes persisted partially for 18 months. GH therapy was not interrupted for any patient, whereby physical training and dietetic measurements were increased for all patients. HOMA-index and OGT shall be used in parallel to monitor glucose metabolism as both show independently distinctive features. HbA1c and C-peptide are not suitable parameters for monitoring carbohydrate metabolism in PWS patients under GH treatment.

Psychometric properties of two measures of psychological well-being in adult growth hormone deficiency

BackgroundPsychometric properties of two measures of psychological well-being were evaluated for adults with growth hormone deficiency (GHD): the General Well-being Index, (GWBI) – British version of the Psychological General Well-being Index, and the 12-item Well-being Questionnaire (W-BQ12).MethodsReliability, structure and other aspects of validity were investigated in a cross-sectional study of 157 adults with treated or untreated GHD, and sensitivity to change in a randomised placebo-controlled study of three months' growth hormone (GH) withdrawal from 12 of 21 GH-treated adults.ResultsVery high completion rates were evidence that both questionnaires were acceptable to respondents. Factor analyses did not indicate the existence of useful GWBI subscales, but confirmed the validity of calculating a GWBI Total score. However, very high internal consistency reliability (Cronbach's alpha = 0.96, N = 152), probably indicated some item redundancy in the 22-item GWBI. On the other hand, factor analyses confirmed the validity of the three W-BQ12 subscales of Negative Well-being, Energy, and Positive Well-being, each having excellent internal reliability (alphas of 0.86, 0.86 and 0.88, respectively, N from 152 to 154). There was no sign of item redundancy in the highly acceptable Cronbach's alpha of 0.93 (N = 148) for the whole W-BQ12 scale. Whilst neither questionnaire found significant differences between GH-treated and non-GH-treated patients, there were correlations (for GH-treated patients) with duration of GH treatment for GWBI Total (r = -0.36, p = 0.001, N = 85), W-BQ12 Total (r = 0.35, p = 0.001, N = 88) and for all W-BQ12 subscales: thus the longer the duration of GH treatment (ranging from 0.5 to 10 years), the better the well-being. Both questionnaires found that men had significantly better overall well-being than women. The W-BQ12 was more sensitive to change than the GWBI in the GH-Withdrawal study. A significant between-group difference in change in W-BQ12 Energy scores was found [t(18) = 3.25, p = 0.004, 2-tailed]: patients withdrawn from GH had reduced energy at end-point. The GWBI found no significant change.ConclusionThe W-BQ12 is recommended in preference to the GWBI to measure well-being in adult GHD: it is considerably shorter, has three useful subscales, and has greater sensitivity to change.