Years Of Growth Hormone Treatment Research Articles

Near adult height and BMI changes in growth hormone treated short children with Noonan syndrome: the Belgian experience.

Introduction A variable near adult height (NAH) outcome after growth hormone (GH) therapy in Noonan syndrome (NS) patients with short stature has been reported. The main objective of this study was to evaluate NAH and body mass index (BMI) evolution in a large Belgian cohort of NS patients treated for short stature. The secondary objectives were to investigate whether sex, genotype, the presence of a thoracic deformity and/or a heart anomaly might affect NAH and to validate the recently developed NAH prediction model by Ranke et al. Methods Clinical and auxological data of GH treated short NS patients born before 2001 were extracted from the national Belgrow registry. NAH was available in 54 (35 male) genotyped NS using a gene panel of 9 genes, showing pathogenic variants in PTPN11 in 32 and in SOS1 in 5 patients, while in 17 patients gene panel analysis was inconclusive (no mutation group). Results After a median (P10; P90) duration of 5.4 (2.2-10.3) years of GH therapy with a median dose of 0.05 mg/kg/day NS patients reached a median NAH of -1.7 (-3.4; -0.8) SDS. Median total height gain was 1.1 (0.1; 2.3) SDS. Sex, genotype and the presence of a thoracic or cardiac malformation did not correlate with NAH or total height gain. Linear regression modelling revealed that height SDS at start (beta=0.90, p<0.001), mid-parental height SDS (beta =0.27; p=0.005), birth weight SDS (beta=0.15; p=0.051), age at start (beta=0.07; p=0032) were independently associated with NAH SDS. Median BMI SDS increased significantly (p<0.001) from -1.0 (-2.5; 0.0) at start to -0.2 (-1.5; 0.9) at NAH. The observed NAH in a subgroup of 44 patients with more than 3 years of GH treatment was not statistically different from the predicted NAH by the Noonan NAH prediction model of Ranke. Conclusion Long-term GH therapy at a dose of 0.05 mg/kg/day in short NS patients is effective in improving adult height and BMI, irrespective of the genotype and presence or absence of cardiac and or thoracic anomalies.

Exploring the Genetic Causes for Postnatal Growth Failure in Children Born Non-Small for Gestational Age.

The most common causes of short stature (SS) in children are familial short stature (FSS) and idiopathic short stature (ISS). Recently, growth plate dysfunction has been recognized as the genetic cause of FSS or ISS. The aim of this study was to investigate monogenic growth failure in patients with ISS and FSS. Targeted exome sequencing was performed in patients categorized as ISS or FSS and the subsequent response to growth hormone (GH) therapy was analyzed. We found 17 genetic causes involving 12 genes (NPR2, IHH, BBS1, COL1A1, COL2A1, TRPS1, MASP1, SPRED1, PTPTN11, ADNP, NADSYN1, and CERT1) and 2 copy number variants. A genetic cause was found in 45.5% and 35.7% of patients with FSS and ISS, respectively. The genetic yield in patients with syndromic and non-syndromic SS was 90% and 23.1%, respectively. In the 11 genetically confirmed patients, a gain in height from -2.6 to -1.3 standard deviations after 2 years of GH treatment was found. The overall diagnostic yield in this study was 41.7%. We identified several genetic causes involving paracrine signaling, the extracellular matrix, and basic intracellular processes. Identification of the causative gene may provide prognostic evidence for the use of GH therapy in non-SGA children.

Growth hormone use in pediatric inflammatory bowel disease.

Impaired linear growth is a known complication of pediatric inflammatory bowel disease (IBD), but theuse of growth hormone (GH) in this population is not well-described. The primary aim of this study is to determine whether growth hormone use in pediatric IBD leads to improved height outcomes. This was a retrospective chart review of patients with IBD aged 0-21 years followed at a single center between 2018 and 2021 treated with at least 1 year of GH. Records collected included demographics, IBD phenotype, IBD disease activity scores, medications, weight z-score, height z-score, bone age, and details of GH therapy including testing for GH deficiency. The primary outcome measure was change in height z-score after 1 year of GH treatment. Forty-six patients were identified and 18 were excluded. Of the 28 patients included (7 female; 25.0 %), 26 (92.9 %) had a diagnosis of Crohn's disease (CD) and 2 (7.1 %) had ulcerative colitis (UC). The mean (SD) age at GH initiation was 9.6 (3.4) years. Among all participants, there was a significant mean difference in height z-score from baseline to 1 year on therapy (-2.25 vs.-1.50, respectively; difference, 0.75; 95 % CI, 0.56 to 0.94; p<0.001). Among the 19 subjects thatcompleted GH therapy there was a significant mean difference between baseline and final height z-scores (-2.41vs.-0.77, respectively; difference, 1.64; 95 % CI, 1.30 to 1.98; p<0.001). GH use was associated with improved height outcomes. The pediatric IBD patients in this cohort had significant improvements in height z-scores both after one year on therapy and at completion of GH therapy.

Cognitive function during 3 years of growth hormone in previously GH-treated young adults with PWS.

Most patients with Prader-Willi syndrome (PWS) have a mild to moderate cognitive impairment. Growth hormone (GH) treatment has positive short- and long-term effects on cognition in children with PWS. Few studies, however, have investigated the effects of GH on cognitive functioning in adults with PWS. To investigate the effects of 3 years GH treatment on cognitive functioning and behavior in young adults with PWS who were treated with GH during childhood. Open-label, prospective study. Dutch PWS Reference Center. Patients were treated with 0.33 mg GH/m²/day (∼0.012 mg/kg/day; 33% of childhood dose). Cognitive functioning was measured by Wechsler Adult Intelligence (WAIS) tests. Behavior was studied by Developmental Behavior Checklist - Parents/caregivers (DBC-P). 46 young adults with PWS with a median age of 19 (IQR 17-21) years were investigated. Estimated mean (95% CI) total, verbal and performance IQ remained stable during 3 years of GH-treatment. Total IQ being 66 (63-69) at start and 67 (64-71) after 3 years (p=0.30); Verbal IQ being 65 (62-68) and 66 (62-70), resp. (p=0.31) and performance IQ being 67 (63-70) and 67 (63-72) resp. (p=0.42). Estimated mean Total DBC score did not significantly change during 3 years of GH-treatment, being 36.3 at start and 36.5 after 3 years (p=0.94) (P50). Three years of GH-treatment in young adults with PWS with 33% of the pediatric dose, maintains total, verbal and performance IQ. The emotional and behavioral disturbances remained stable and were similar compared to peers with other intellectual disabilities.

Schaaf-Yang Syndrome: Clinical Phenotype and Effects of 4 years of Growth Hormone Treatment

Introduction: Schaaf-Yang syndrome (SYS) is a rare neurodevelopmental disorder caused by truncating mutations of the MAGEL2 gene, located in the Prader-Willi syndrome (PWS) region. PWS and SYS have phenotypic overlap. Patients with SYS are often treated with growth hormone (GH), but evidence for the effectiveness of the treatment in patients with SYS is limited. Methods: This study describes 7 children with SYS. We studied their phenotype, genotype, and the effect of GH treatment on height and body mass index (BMI) during 4 years and on body composition during 1 year. Results: All patients had a normal birth weight. Most patients had hypotonia and feeding difficulties after birth (86%). Full-scale IQ ranged from <50 to 92. All patients above the age of 2 years had psycho-behavioral problems. There were no apparent correlations between the phenotype and the location of the defect in the MAGEL2 gene. Mean (95% CI) height SDS increased significantly from −1.74 (−3.55; 0.07) at start to −0.05 (−1.87; 1.77) after 4 years of GH treatment. Mean (95% CI) BMI SDS decreased significantly from 2.01 (1.02; 3.00) to 1.22 (0.18; 2.26) after 6 months and remained the same during the rest of the follow-up. Fat mass percentage SDS decreased and lean body mass did not change during 1 year of treatment in 3 patients. Conclusion: Patients presented with a phenotype of hypotonia, respiratory insufficiency, and feeding difficulties after birth, endocrine disorders, intellectual disability, and behavioral problems. Treatment with GH significantly improved height SDS and BMI over the course of 4 years.

The Effects of 5 Years of Growth Hormone Treatment on Growth and Body Composition in Patients with Temple Syndrome

Introduction: Temple syndrome (TS14) is a rare imprinting disorder caused by maternal uniparental disomy of chromosome 14, paternal deletion of 14q32.2, or an isolated methylation defect. Most patients with TS14 develop precocious puberty. Some patients with TS14 are treated with growth hormone (GH). However, evidence for the effectiveness of GH treatment in patients with TS14 is limited. Methods: This study describes the effect of GH treatment in 13 children and provides a subgroup analysis of 5 prepubertal children with TS14. We studied height, weight, body composition by dual-energy X-ray absorptiometry, resting energy expenditure (REE), and laboratory parameters during 5 years of GH treatment. Results: In the entire group, mean (95% CI) height SDS increased significantly during 5 years of GH treatment from −1.78 (−2.52; −1.04) to 0.11 (−0.66; 0.87). Fat mass percentage SDS decreased significantly during the first year of GH, and lean body mass (LBM) SDS and LBM index increased significantly during 5 years of treatment. IGF-1 and IGF-BP3 levels rose rapidly during GH treatment, and the IGF-1/IGF-BP3 molar ratio remained relatively low. Thyroid hormone levels, fasting serum glucose, and insulin levels remained normal. In the prepubertal group, median (interquartile range [IQR]) height SDS, LBM SDS, and LBM index also increased. REE was normal at start and did not change during 1 year of treatment. Five patients reached adult height and their median (IQR) height SDS was 0.67 (−1.83; −0.01). Conclusion: GH treatment in patients with TS14 normalizes height SDS and improves body composition. There were no adverse effects or safety concerns during GH treatment.

Pituitary function and the response to GH therapy in patients with Langerhans cell histiocytosis: analysis of the KIMS database.

ObjectiveTo analyze the effectiveness and safety of growth hormone (GH) replacement treatment in adult patients with Langerhans cell histiocytosis (LCH) and GH deficiency (GHD) enrolled in KIMS (Pfizer International Metabolic Database).Patients and methodsPatients with LCH and GHD were studied at baseline and some of them after 1 year of GH treatment. The effectiveness of GH is presented as change after 1 year of treatment (mean, 95% CI). The LCH population was compared to two other groups of patients enrolled in KIMS, granulomatous and lymphocytic hypophysitis.ResultsAt baseline, 81 adults with LCH (27 with childhood onset, 56% females), mean age at GHD onset of 29 (15) years were studied. Diabetes insipidus was diagnosed in 86% of patients. Analysis of 1 year of GH treatment was possible in 37 patients. One-year cross-sectional values for the GH dose were 0.39 (s.d.± 0.21) mg and −0.5 (−1.2 to 0.2) for insulin-like growth factor-1 s.d. Total cholesterol decreased 0.9 (−1.5 to −0.3 (mmol/L); P < 0.05); AGHDA-QoL-score (n = 20) was improved by 2.8 points (−5.6 to 0.0; P < 0.05), while mean BMI increased 0.6 ± 3 kg/m2 (95% CI: −0.2 to 1.4). All these effects did not differ from the two other groups after adjusting for age, gender, and baseline values. In 20 of 77 patients included in the safety analysis, 36 serious adverse events were reported during 435 patient-years (82.8/1000); no new safety signals were reported.ConclusionAfter 1 year of GH treatment in patients with LCH, metabolic variables and quality of life improved, with no new safety signals.

The association between idiopathic scoliosis and growth hormone treatment in short children.

PurposeIdiopathic scoliosis is the most common form of scoliosis, and the risk of onset and progression has been found to correlate with growth spurts. Therefore, treatment with recombinant human growth hormone (GH) treatment in short children may initiate and/or aggravate scoliosis. The aim of this study was to investigate the relationship between idiopathic scoliosis and GH treatment in short children.MethodsThe medical records of 113 subjects seen at the participating institution between January 2010 and December 2020 and who were diagnosed with GH deficiency and small for gestational age, had idiopathic short stature, and were treated with GH for at least one year were reviewed. Scoliosis was defined as a Cobb angle greater than 10 degrees as assessed using a spine x-ray. Clinical data and laboratory findings before and 12 months after GH treatment were compared.ResultsThere was significant increase in height, height-standard deviation score, insulin-like growth factor 1, and insulin-like growth factor binding protein 3 (P<0.001) with GH treatment. However, there were no significant differences in the average Cobb angle (6.2°±3.3° vs. 6.1°±3.5°, P=0.842) and the prevalence of scoliosis (9.7% vs. 13.3%, P=0.481) before and after one year of GH treatment. A comparative analysis of both initial Cobb angle and change in Cobb angle during GH treatment showed no relationship with other factors.ConclusionsAlthough GH treatment in short children increased height and growth velocity, it was not associated with development or aggravation of idiopathic scoliosis.

Long-term effectiveness of growth hormone therapy in children born small for gestational age: An analysis of LG growth study data.

PurposeGrowth hormone (GH) treatment has been used to improve growth in short children who were born small for gestational age (SGA). The aim of this study was to investigate the long-term efficacy of GH treatment in these children.MethodsData from a multicenter observational clinical trial (ClinicalTrials.gov NCT01604395, LG growth study) were analyzed for growth outcome and prediction model in response to GH treatment. One hundred fifty-two children born SGA were included.ResultsThe mean age of patients born SGA was 7.13 ± 2.59 years. Height standard deviation score (SDS) in patients born SGA increased from -2.55 ± 0.49 before starting treatment to -1.13 ± 0.76 after 3 years of GH treatment. Of the 152 patients with SGA, 48 who remained prepubertal during treatment used model development. The equation describing the predicted height velocity during 1st year of GH treatment is as follows: the predictive height velocity (cm) = 10.95 + [1.12 x Height SDS at initial treatment (score)] + [0.03 x GH dose (ug/kg/day)] + [0.30 x TH SDS at initial treatment (score)] + [0.05 x age (year)] + [0.15 x Weight SDS at initial treatment (score)] ± 1.51 cm.ConclusionsGH treatment improved growth outcome in short children born SGA. We also developed a prediction model that is potentially useful in determining the optimal growth outcome for each child born SGA.Trial registrationClinicalTrials.gov Identifier: NCT01604395.

Noonan syndrome patients with short stature at a single paediatric endocrinology centre

Introduction: Noonan syndrome (NS) is caused by mutations in RAS/MAPK signalling pathway genes. Growth hormone (GH) treatment is an established yet not fully standardized treatment. Aim: The aim of this article is to assess the first 2 years of GH treatment in NS patients at a single centre. Patients and Methods: A total of 20 (16 males) NS clinically diagnosed regularly followed patients participated (2011–2020). Of these, 9 (45%) had cardiac defects, and 8 (40%) had short stature. Growth hormone deficiency (GHD) was confirmed in 5 patients who started GH treatment, and 2 were treated as short, small for gestational age children. Patients underwent anthropometry, clinical, laboratory and imaging investigations. Results: The mean age at NS diagnosis was 7.8 ± 3.4 years (1.3 ÷ 10.5), and at GH start 9.1 ± 1.5 years. At GH start, SDS height was -3.42±0.58 (-4.1 ÷ -2.6), SDS weight -3.07 ± 0.58 (-3.73 ÷ -2.27), and SDS IGF1 -1.12 ± 0.98 (-2.44 ÷ 0.25). The mean BA at diagnosis was delayed by 2.6 ± 0.9 years. The GH starting dose was 0.035 ± 0.005 mg/kg/d, and changed little thereafter. The growth velocity for the 1 st year of treatment was 8.9 ± 1.4 cm, and for the 2 nd year 6.9±1.1 cm. The first year ΔSDS height was 0.72 (p = 0.002), ΔSDS weight was 0.83 (p = 0.025), the 2 nd year increments being insignificant. The 1 st and 2 nd year ΔSDS IGF1 were 1.70 (p = 0.007) and 0.25 (n.s.), resp. Bone age remained significantly delayed. No treatment side effects were observed. Conclusion: Our study showed that GH-treated NS patients follow the general growth patterns. In order to improve outcomes, the treatment should be further standardized.

Response to growth hormone according to provocation test results in idiopathic short stature and idiopathic growth hormone deficiency.

Purpose To investigate growth response in children with either idiopathic short stature (ISS) or growth hormone (GH) deficiency (GHD).Methods The data of prepubertal GHD or ISS children treated using recombinant human GH were obtained from the LG Growth Study database. GHD children were further divided into partial and complete GHD groups. Growth response and factors predicting growth response after 1 and 2 years of GH treatment were investigated.Results This study included 692 children (98 with ISS, 443 partial GHD, and 151 complete GHD). After 1 year, changes in height standard deviation score (ΔHt-SDS) were 0.78, 0.83, and 0.96 in ISS, partial GHD, and complete GHD, respectively. Height velocity (HV) was 8.72, 9.04, and 9.52 cm/yr in ISS, partial GHD, and complete GHD, respectively. ΔHt-SDS and HV did not differ among the 3 groups. Higher initial body mass index standard deviation score (BMI-SDS) and midparental height standard deviation score (MPH-SDS) were predictors for better growth response after 1 year in ISS and the partial GHD group, respectively. In the complete GHD group, higher Ht-SDS and BMI-SDS predicted better growth response after 1 year. After 2 years of GH treatment, higher BMI-SDS and MPH-SDS predicted a better growth outcome in the partial GHD group, and higher MPH-SDS was a predictor of good growth response in complete GHD.Conclusions Clinical characteristics and growth response did not differ among groups. Predictors of growth response differed among the 3 groups, and even in the same group, a higher GH dose would be required when poor response is predicted.

Twenty-five years of growth hormone treatment in non-dialyzed children with chronic kidney disease in Poland – efficacy, safety, metabolic effects, and factors influencing response

Twenty-five years of growth hormone treatment in non-dialyzed children with chronic kidney disease in Poland – efficacy, safety, metabolic effects, and factors influencing response

Evaluation of the growth response to growth hormone therapy in short children with normal growth hormone secretion

Introduction The availability of biosynthetic growth hormone (GH) ensures that children who are deficient can have replacement therapy, but it has also created the opportunity to treat children who are short but do not have a deficiency. The target height of children with short stature who have normal GH secretion, idiopathic short stature (ISS), without treatment, fails to reach their midparental potential. GH therapy for these children has resulted in variable height outcomes. While some children reached or exceeded genetic target height, others did not have a favorable response.Aim The aim of this study was to report the outcome of the children with ISS who had initial height standard deviation score (HtSDS) (Z score) less than −2, with normal stimulated GH levels (>10 μg/l), after treatment with biosynthetic GH for at least 1 year.Patients and methods This retrospective study included 20 children with ISS, with initial HTSDS less than −2, normal stimulated GH levels (>10 μg/l), who were treated with rhGH (0.04 mg/kg/day) for at least 1 year. None had any other systemic or endocrine disorder. All had normal complete blood count, liver, and renal functions.Results Twenty children (15 males and five females) with ISS, aged between 4.3 and 13.8 years (mean=9.88±2.62 years), who had mean peak GH=15.58±6.95 μg, were studied. All received GH treatment (average GH dose was 0.04 mg/kg/day) for a mean duration=2.49±1.61 years. The mean midparental HtSDS (MPHSDS) was −1.23±0.57. Their bone age did not differ significantly compared with their chronological age (the mean difference=−0.13±0.67 years). The mean HSDS before treatment was −2.34±0.41 and after 1 year of GH treatment was −1.83±0.48. This gave a gain of an average of 0.5 SD. At the last visit (after a mean of 2.5 years), the HtSDS −1.57±0.55 SD with a gain of 0.77±0.14 SD versus before treatment. The difference between children HtSDS compared with their MPHSDS was −1.08 SD before treatment that was changed to −0.3 SD at the last visit. The increment in HSDS was positively correlated with the duration of rhGH therapy (r=0.82, P=0.01) and negatively correlated with age at the start of treatment (r=−0.54, P=0.01).Conclusion Growth hormone therapy that benefits short children with normal growth hormone secretion achieves near-normal HSDS and approaches MPHSDS.

The Long-Term Effects of Growth Hormone Replacement on Bone Mineral Density and Trabecular Bone Score: Results of the 10-Year Prospective Follow-up.

There are only few studies concerning about long-term effect of growth hormone (GH) replacement therapy on bone mineral density and bone microstructure. To assess effect of GH replacement therapy on bone mineral density (BMD) and trabecular bone score (TBS) in adult GH deficient (AGHD) subjects over period of 10 years. From 2005 to 2018, a prospective study of AGHD patients was conducted in national referral center for treatment of GHD. All patients received subcutaneous recombinant human GH in an IGF 1-normalizing regimen once a day. Lumbar spine (L-spine) and total hip (TH) BMD using Hologic densitometers were measured at baseline and every two years during treatment with rhGH. TBS was derived from L1-L4 DXA using iNsight® software (Medimaps, France) at each time point. Periods of measurement were baseline, year 2; 4; 6; 8 and 10. In total, 63 patients (38 males, 25 females, mean age 25.1±16 years) were included in the study. After 10 years of GH treatment, IGF-1 significantly increased (~35 %), with greatest increase at year 2. During 10-year follow-up, L-spine BMD increased approximately of 7 % (NS). TH BMD increase of 11 % during follow-up (p=0.0003). The greatest increment of BMD was achieved at year 6 on both sites, L-spine (+6 %) and TH BMD (+13 %) (p<0.05). There was no significant change of TBS during whole follow-up. In this study, sustaining positive effect of GH replacement therapy on bone density in subjects with adult GH deficiency over 10 years of follow-up was observed. The study did not show effect on TBS, as indirect measure of trabecular bone microarchitecture.

Growth hormone retesting during puberty: a cohort study

Objectives To report the frequency and characteristics of growth hormone (GH) deficiency (GHD) in adolescents who had normalized GH secretion at mid-puberty and to identify possible factors predictive for GH sufficiency at puberty. Design Clinical analysis of children affected by GHD at five time points: diagnosis; first year of therapy; intermediate stage of puberty; retesting and end of growth phase. Methods The study population was 80 children with idiopathic GHD and treated with GH for at least 2 years. Treatment was discontinued at the intermediate stage of puberty. Retesting with an arginine test was performed 12 weeks later. If GH peak at retesting was ≥8 μg/L, the therapy was definitively discontinued, otherwise it was restarted and continued until achievement of near-final height. Results GH therapy was discontinued in 44 children (55%), and restarted in 36 (45%). No evidence of differences in definitive height and in the delta height between the genetic target and the definitive height was found between the two groups. The only predictive factor for GHD at mid-puberty was the insulin growth factor-1 (IGF-1) level at 1 year of GH treatment. Conclusions GH secretion should be retested at mid-puberty. Retesting at puberty may reduce potential side effects and minimize costs, without impairing growth potential and final height.

Clinical Characteristics and Growth Hormone Treatment in Patients with Prader-Willi Syndrome

Objective:To investigate clinical characteristics and response to growth hormone (GH) treatment in patients with Prader-Willi syndrome (PWS) in Turkey.Methods:The data of 52 PWS patients from ten centers was retrospectively analyzed. A nation-wide, web-based data system was used for data collection. Demographic, clinical, genetic, and laboratory data and follow-up information of the patients were evaluated.Results:The median age of patients at presentation was 1.5 years, and 50% were females. Genetic analysis showed microdeletion in 69.2%, uniparental disomy in 11.5%, imprinting defect in 1.9% and methylation abnormality in 17.3%. Hypotonia (55.7%), feeding difficulties (36.5%) and obesity (30.7%) were the most common complaints. Cryptorchidism and micropenis were present in 69.2% and 15.3% of males, respectively. At presentation, 25% had short stature, 44.2% were obese, 9.6% were overweight and 17.3% were underweight. Median age of obese patients was significantly higher than underweight patients. Central hypothyroidism and adrenal insufficiency were present in 30.7% and 4.7%, respectively. Hypogonadism was present in 75% at normal age of puberty. GH treatment was started in 40% at a mean age of 4.7±2.7 years. After two years of GH treatment, a significant increase in height SDS was observed. However, body mass index (BMI) standard deviation (SDS) remained unchanged.Conclusion:The most frequent complaints were hypotonia and feeding difficulty at first presentation. Obesity was the initial finding in 44.2%. GH treatment was started in less than half of the patients. While GH treatment significantly increased height SDS, BMI SDS remained unchanged, possibly due to the relatively older age at GH start.

Twenty Years of GH Treatment in Adults with Prader-Willi Syndrome.

Prader-Willi syndrome (PWS) is a rare neurodevelopmental genetic disorder. In adults, the syndrome is characterised by muscular hypotonia, a different body composition with more body fat than muscle mass, hyperphagia, behavioural problems, and cognitive dysfunction. Endocrine deficiencies are common, including growth hormone (GH) deficiency. Here, we present data from a cross-sectional study in adults with PWS with a focus on the long-term safety of GH treatment. A total of 22 patients (14 men) were treated with GH for a median of 20 years. Data on body composition, hormones, and metabolic parameters were retrieved from the patients’ medical records. The median age was 27 years. The median GH dose was 0.5 mg/day. Insulin-like growth factor 1 (IGF-I) and blood lipids were normal, while fasting glucose and HbA1c were slightly elevated in three men with diabetes. Fat mass was less than fat free mass in all, though this was less pronounced in women. GH treatment did not negatively affect the metabolic profile, and none developed cardiovascular diseases or cancer. All adults on long-term GH treatment had a normal body composition and our results indicate that treatment was safe. However, PWS is a complex, multisystemic disease and continuous, individual considerations are required during GH treatment, especially in patients with risk factors for adverse effects.

Adult Height in 299 Patients with Turner Syndrome with or without Growth Hormone Therapy: Results and Literature Review

Context: Treatment with growth hormone (GH) is considered effective in improving adult height (AH) in Turner syndrome (TS). However, there are few studies comparing AH between treated patients and a concurrent untreated group. Objective: To assess the efficacy of GH treatment in improving AH in TS and to review previous published studies with treated and untreated groups. Participants and Methods: We retrospectively analyzed clinical data and AH of a large cohort of GH-treated (n = 168) and untreated (n = 131) patients with TS. Data are shown as median and interquartile range (IQR). We assessed pretreatment variables related with AH and compared our results with 16 studies that also included an untreated group. Results: The GH-treated group was 6.2 cm taller than the untreated group (AH = 149 cm [IQR 144.5–152.5 cm] vs. 142.8 cm [IQR 139–148 cm], p < 0.001) after 4.9 years of GH treatment with a dose of 0.35 mg/kg/week. AH SDS corrected for target height (TH) was 7.2 cm higher in GH-treated patients. AH SDS ≥−2 was more frequent in GH-treated patients (43%) than in untreated patients (16%, p < 0.001). AH SDS was also more frequently within the TH range in the GH-treated group (52%) than in the untreated group (15%, p < 0.001). Height SDS at start of GH therapy and TH SDS were positively correlated with AH (p < 0.001; R² = 0.375). Considering the current result together with previous similar publications, a mean AH gain of 5.7 cm was observed in GH-treated (n = 696) versus untreated (n = 633) patients. Conclusions: Our study strengthens the evidence for efficacy of GH therapy in patients with TS from different populations.

Is a Two-Year Growth Response to Growth Hormone Treatment a Better Predictor of Poor Adult Height Outcome Than a First-Year Growth Response in Prepubertal Children With Growth Hormone Deficiency?

ObjectiveThe first year response to growth hormone (GH) treatment is related to the total height gain in GH treated children, but an individual poor first year response is a weak predictor of a poor total GH effect in GH deficient (GHD) children. We investigated whether an underwhelming growth response after 2 years might be a better predictor of poor adult height (AH) outcome after GH treatment in GHD children.Design and methodsHeight data of GHD children treated with GH for at least 4 consecutive years of which at least two prepubertal and who attained (near) (n)AH were retrieved from the Belgian Register for GH treated children (n = 110, 63% boys). In ROC analyses, the change in height (ΔHt) SDS after the first and second GH treatment years were tested as predictors of poor AH outcome defined as: (1) nAH SDS <−2.0, or (2) nAH SDS minus mid-parental height SDS <−1.3, or (3) total ΔHt SDS <1.0. The cut-offs for ΔHt SDS and its sensitivity at a 95% specificity level to detect poor AH outcome were determined.ResultsEleven percent of the cohort had a total ΔHt SDS <1.0. ROC curve testing of first and second years ΔHt SDS as a predictor for total ΔHt SDS <1.0 had an AUC >70%. First-year ΔHt SDS <0.41 correctly identified 42% of the patients with poor AH outcome at a 95% specificity level, resulting in respectively 5/12 (4.6%) correctly identified poor final responders and 5/98 (4.5%) misclassified good final responders (ratio 1.0). ΔHt SDS after 2 prepubertal years had a cut-off level of 0.65 and a sensitivity of 50% at a 95% specificity level, resulting in respectively 6/12 (5.5%) correctly identified poor final responders and 5/98 (4.5%) misclassified good final responders (ratio 1.2).ConclusionIn GHD children the growth response after 2 prepubertal years of GH treatment did not meaningfully improve the prediction of poor AH outcome after GH treatment compared to first-year growth response parameters. Therefore, the decision to re-evaluate the diagnosis or adapt the GH dose in case of poor response after 1 year should not be postponed for another year.

Effects of Growth Hormone Treatment on Sleep-Related Parameters in Adults With Prader-Willi Syndrome.

ContextPrader-Willi syndrome (PWS) is a rare, genetic, multisymptom, neurodevelopmental disease due to lack of the expression of the paternal genes in the q11 to q13 region of chromosome 15. The main characteristics of PWS are muscular hypotonia, hyperphagia, obesity, behavioral problems, cognitive disabilities, and endocrine deficiencies, including growth hormone (GH) deficiency. Sleep apnea and abnormal sleep patterns are common in PWS. GH treatment might theoretically have a negative impact on respiration.ObjectiveHere we present the effect of GH treatment on polysomnographic measurements.MethodsThirty-seven adults, 15 men and 22 women, with confirmed PWS were randomly assigned to 1 year of GH treatment (n = 19) or placebo (n = 18) followed by 2 years of GH treatment to all. Polysomnographic measurements were performed every 6 months. A mixed-effect regression model was used for comparison over time in the subgroup that received GH for 3 years.ResultsAt baseline median age was 29.5 years, body mass index 27.1, insulin-like growth factor 115 µg/L, apnea-hypopnea index (AHI) 1.4 (range, 0.0-13.9), and sleep efficiency (SE) 89.0% (range, 41.0%-99.0%). No differences in sleep or respiratory parameters were seen between GH- and placebo-treated patients. SE continuously improved throughout the study, also after adjustment for BMI, and the length of the longest apnea increased. AHI inconsistently increased within normal range.ConclusionSE improved during GH treatment and no clinical, significantly negative impact on respiration was seen. The etiology of breathing disorders is multifactorial and awareness of them should always be present in adults with PWS with or without GH treatment.