scholarly journals Long-Term Effectiveness and Safety of Childhood Growth Hormone Treatment in Noonan Syndrome

2020 ◽  
Vol 93 (6) ◽  
pp. 380-395
Author(s):  
Tilman R. Rohrer ◽  
Jennifer Abuzzahab ◽  
Philippe Backeljauw ◽  
Anna Camilla Birkegård ◽  
Joanne Blair ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Adverse Events ◽  
Noonan Syndrome ◽  
Standard Deviation Score ◽  
Hormone Treatment ◽  
Gh Treatment ◽  
Serious Adverse Events ◽  
Height Gain ◽  
The Mean

<b><i>Introduction:</i></b> Few data exist on long-term growth hormone (GH) treatment in patients with Noonan syndrome (NS). <b><i>Objective:</i></b> To evaluate the effectiveness and safety of GH treatment in NS in clinical practice. <b><i>Methods:</i></b> Height gain, near-adult height (NAH), and safety were assessed in 2 complementary non-interventional studies: NordiNet® IOS and ANSWER. The safety analysis included 412 patients, and the effectiveness analysis included 84 GH-treated patients (male, <i>n</i> = 67) with ≥4 years’ height standard deviation score (HSDS) data. HSDS was determined using national reference (NR) and NS-specific (NSS) data. <b><i>Results:</i></b> The mean (SD) baseline age was 8.38 (3.57) years; HSDS, −2.76 (1.03); GH dose, 41.6 (11.1) µg/kg/day. The mean (SD) HSDS increase from baseline (ΔHSDS) was 0.49 (0.37) (first year), 0.79 (0.58) (second year), and 1.01 (0.60) (third year) (NR). The mean (SD) HSDS at year 3 was −1.66 (1.00) (NR; 1.06 [1.12] [NSS]). Twenty-four patients achieved NAH. The mean (SD) NAH SDS (NR) was −1.51 (0.60) (154.90 [3.21] cm) in females and −1.79 (1.09) (165.61 [7.19] cm) in males; 70.8% (17/24) had NAH SDS ≥ −2. Adverse drug reactions and GH-unrelated serious adverse events (<i>n</i> = 34) were reported in 22/412 (5.3%) patients. Four neoplasms and 3 cases of scoliosis were reported; no cardiovascular adverse events occurred. <b><i>Conclusions:</i></b> GH-treated children with NS achieved substantial height gain during the first 3 years of follow-up. Overall, 24 patients achieved NAH, with 70.8% having NAH SDS ≥ –2. There was no evidence to support a higher prevalence of neoplasm, or cardiac or other comorbidities.

Efficacy of long-term growth hormone therapy in short non-growth hormone-deficient children

2017 ◽  
Vol 30 (2) ◽  
Author(s):  
Lucia Schena ◽  
Cristina Meazza ◽  
Sara Pagani ◽  
Valeria Paganelli ◽  
Elena Bozzola ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Final Height ◽  
Standard Deviation Score ◽  
Bone Age ◽  
Gh Treatment ◽  
Short Children ◽  
Igf I ◽  
Height Gain ◽  
The Cost

AbstractBackground:In recent years, several studies have been published showing different responses to growth hormone (GH) treatment in idiopathic short stature children. The aim of the present study was to investigate whether non-growth-hormone-deficient (non-GHD) short children could benefit from long-term GH treatment as GHD patients.Methods:We enrolled 22 prepubertal children and 22 age- and sex-matched GHD patients, with comparable height, body mass index (BMI), bone age, and insulin-like growth factor 1 (IGF-I) circulating levels. The patients were treated with recombinant human GH (rhGH) and followed until they reach adult height.Results:During GH treatment, the two groups grew in parallel, reaching the same final height-standard deviation score (SDS) and the same height gain. On the contrary, we found significantly lower IGF-I serum concentrations in non-GHD patients than in GHD ones, at the end of therapy (p=0.0055).Conclusions:In our study, the response to GH treatment in short non-GHD patients proved to be similar to that in GHD ones. However, a careful selection of short non-GHD children to be treated with GH would better justify the cost of long-term GH therapy.

scholarly journals Cardiovascular safety of growth hormone treatment in Noonan syndrome: real-world evidence

2021 ◽  
Author(s):  
Alicia Romano ◽  
Juan Pablo Kaski ◽  
Jovanna Dahlgren ◽  
Nicky Kelepouris ◽  
Alberto Pietropoli ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Noonan Syndrome ◽  
Adverse Reactions ◽  
Pulmonary Valve ◽  
Hormone Treatment ◽  
Pulmonary Valve Stenosis ◽  
Gh Treatment ◽  
Serious Adverse Events ◽  
Favourable Safety Profile ◽  
Cv Disease

Objective: To assess cardiovascular (CV) safety of growth hormone (GH) treatment in patients with Noonan syndrome (NS) in clinical practice. Design: Two observational, multicentre studies (NordiNet® IOS and the ANSWER Program) evaluating long-term effectiveness and safety of GH in >38,000 paediatric patients, of which 421 had NS. Methods: Serious adverse events, serious adverse reactions (SARs), and non-serious adverse reactions (NSARs) were reported by the treating physicians. CV comorbidities at baseline and throughout the studies were also recorded. Results: The safety analysis set comprised 412 children with NS (29.1% females), with a mean (standard deviation) baseline age of 9.29 (3.88) years, treated with an average GH dose of 0.047 (0.014) mg/kg/day during childhood. CV comorbidities at baseline were reported in 48 (11.7%), most commonly pulmonary valve stenosis and atrial septal defects. Overall, 22 (5.3%) patients experienced 34 safety events. The most common were the NSARs: headache (eight events in seven patients) and arthralgia (five events in three patients). Two SARs occurred in one patient (brain neoplasm and metastases to spine). No CV safety events were recorded in patients with NS. Five CV comorbidities in five patients were reported after initiation of GH treatment: three cases of unspecified CV disease, one ruptured abdominal aortic aneurysm and one pulmonary valve stenosis. Conclusions: GH treatment had a favourable safety profile in patients with NS, including those with CV comorbidities. Prospective studies are warranted to systematically assess the safety of GH treatment in patients with Noonan syndrome and CV disease.

Acromesomelic Dysplasia, Type Maroteaux: Impact of Long-Term (8 Years) High-Dose Growth Hormone Treatment on Growth Velocity and Final Height in 2 Siblings

2020 ◽  
Vol 93 (5) ◽  
pp. 335-342
Author(s):  
Ved Bhushan Arya ◽  
Meena Raj ◽  
Maha Younes ◽  
Simon Chapman ◽  
Melita Irving ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Serum Insulin ◽  
Final Height ◽  
Hormone Treatment ◽  
High Dose ◽  
Childhood And Adolescence ◽  
Loss Of Function ◽  
Gh Treatment ◽  
Height Gain

<b><i>Introduction:</i></b> Acromesomelic dysplasia, type Maroteaux (AMDM) is a rare autosomal recessive skeletal dysplasia, characterized by severe dwarfism and disproportionate limb shortening. It results from loss-of-function <i>NPR2</i> mutations affecting the C-type natriuretic peptide receptor. Resistance to growth hormone (GH) action has previously been suggested. We describe outcomes of 2 siblings with AMDM after prolonged high-dose GH treatment. <b><i>Patients/Methods:</i></b> Two siblings (Pt-A and Pt-B; consanguineous parents) presented in early childhood with severe disproportionate short stature and radiological features of AMDM. Subsequent genetic testing identified a novel homozygous <i>NPR2</i> mutation. GH provocation testing showed relatively high GH levels. Serum insulin-like growth factor 1 (IGF-1) was ∼2 SD below age/sex-specific mean. High-dose GH (0.075 mg/kg/day) was started. Pre-GH height velocities were 3.7 (Pt-A) and 4.5 (Pt-B) cm/year. GH dose was adjusted to sustain serum IGF-1 towards +3 SDS for age/sex. Annualized height velocities for first 3 years on GH were 7.0, 5.4, and 4.7 cm/year for patient A and 9.4, 8.0, and 5.9 cm/year for patient B. Height gain during puberty was 10.6 (Pt-A) and 5.9 (Pt-B) cm. Final heights after 8.5 years of GH treatment were 130.5 cm (−6.57 SDS, Pt-A) and 134 cm (−4.58 SDS, Pt-B). <b><i>Conclusions:</i></b> To the best of our knowledge, this is the first report of final height in patients with AMDM after long-term GH treatment. Our results confirm the finding of relative GH resistance in AMDM, which when overcome with high-dose GH treatment resulted in improved height SDS during childhood and adolescence and associated quality of life. The final height of our patients was significantly higher than average reported final height (120 cm) of AMDM patients.

scholarly journals Still too little, too late? Ten years of growth hormone therapy baseline data from the NordiNet® International Outcome Study

2018 ◽  
Vol 31 (5) ◽  
pp. 521-532 ◽  
Author(s):  
Michel Polak ◽  
Daniel Konrad ◽  
Birgitte Tønnes Pedersen ◽  
Gediminas Puras ◽  
Marta Šnajderová
Keyword(s):  
Growth Hormone ◽  
Czech Republic ◽  
Standard Deviation Score ◽  
Outcome Study ◽  
Gh Treatment ◽  
The Czech Republic ◽  
Serbia And Montenegro ◽  
The Mean ◽  
Late Start ◽  
The Uk

AbstractBackground:We investigated time trends in age, gender, growth hormone (GH) dose and height standard deviation score (SDS) in children with GH deficiency (GHD), born small for gestational age (SGA) or with Turner syndrome (TS) starting GH treatment.Methods:Data were obtained from children enrolled in the NordiNet®International Outcome Study (IOS) between 2006 and 2015 in the Czech Republic, France, Germany, Serbia and Montenegro (all indications), and Switzerland and the UK (GHD only). Trends were analyzed by linear regression. Patients were divided by age into early-, medium- or late-start groups in three different time periods.Results:Approximately one-third of children starting treatment for GHD were girls, with no apparent increase in proportion over time. The mean baseline age for starting treatment decreased significantly (p<0.001) for both GHD and SGA in the Czech Republic and Germany. In the other countries studied, over 40% of children started treatment for GHD and SGA late (girls >10, boys >11 years) between 2013 and 2015. The mean baseline GH doses were largely within recommended ranges for GHD and SGA, but below the lowest recommended starting dose for TS in almost every year since 2011 except in France.Conclusions:Approximately one-third of children starting treatment for GHD were girls. Between 2013 and 2015, more than 40% of children started treatment for GHD and SGA late except in Germany and the Czech Republic. TS patients received below-recommended doses. These results highlight the need for earlier identification of short stature in children, particularly girls, and for dose optimization in TS.

Growth Hormone Treatment for Short Stature in the USA, Germany and France: 15 Years of Surveillance in the Genetics and Neuroendocrinology of Short-Stature International Study (GeNeSIS)

2018 ◽  
Vol 90 (3) ◽  
pp. 169-180 ◽  
Author(s):  
Roland Pfäffle ◽  
Christof Land ◽  
Eckhard Schönau ◽  
Paul-Martin Holterhus ◽  
Judith L. Ross ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Standard Deviation Score ◽  
Measurement Data ◽  
International Study ◽  
Hormone Treatment ◽  
Height Velocity ◽  
Growth Disorders ◽  
Gh Treatment ◽  
The Usa

Background/Aims: To describe characteristics, auxological outcomes and safety in paediatric patients with growth disorders treated with growth hormone (GH), for cohorts from the USA, Germany and France enrolled in GeNeSIS, a post-authorisation surveillance programme. Methods: Diagnosis and biochemical measurement data were based on reporting from, and GH treatment was initiated at the discretion of, treating physicians. Auxological outcomes during the first 4 years of GH treatment and at near-adult height (NAH) were analysed. Serious and treatment-emergent adverse events were described. Results: Children in the USA (n = 9,810), Germany (n = 2,682) and France (n = 1,667) received GH (dose varied between countries), most commonly for GH deficiency. Across diagnostic groups and countries, mean height velocity standard deviation score (SDS) was > 0 and height SDS increased from baseline during the first 4 years of treatment, with greatest improvements during year 1. Most children achieved NAH within the normal range (height SDS >−2). No new or unexpected safety concerns were noted. Conclusion: GH treatment improved growth indices to a similar extent for patients in all three countries despite variations in GH doses. Data from these three countries, which together contributed > 60% of patients to GeNeSIS, indicated no new safety signals and the benefit-risk profile of GH remains unchanged.

scholarly journals 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?

2021 ◽  
Vol 12 ◽  
Author(s):  
Saartje Straetemans ◽  
Raoul Rooman ◽  
Jean De Schepper
Keyword(s):  
Growth Hormone ◽  
Growth Response ◽  
Adult Height ◽  
Poor Response ◽  
Hormone Treatment ◽  
Hormone Deficiency ◽  
First Year ◽  
Gh Treatment ◽  
Height Gain ◽  
Design And Methods

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 &lt;−2.0, or (2) nAH SDS minus mid-parental height SDS &lt;−1.3, or (3) total ΔHt SDS &lt;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 &lt;1.0. ROC curve testing of first and second years ΔHt SDS as a predictor for total ΔHt SDS &lt;1.0 had an AUC &gt;70%. First-year ΔHt SDS &lt;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.

Growth hormone treatment and bone mineral density in pediatric patients with Prader–Willi syndrome

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Yuji Oto ◽  
Nobuyuki Murakami ◽  
Takeshi Inoue ◽  
Keiko Matsubara ◽  
Sohei Saima ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Growth Hormone ◽  
Bone Mineral ◽  
Pediatric Patients ◽  
Standard Deviation Score ◽  
Hormone Treatment ◽  
Prader Willi Syndrome ◽  
Mineral Density ◽  
Gh Treatment ◽  
Total Body

Abstract Objectives Previous reports indicate that growth hormone (GH) treatment for Prader–Willi syndrome (PWS) improves bone mineral density (BMD) only when initiated at a young age and not when initiated in adulthood. However, there are no data on BMD during long-term GH treatment of Japanese children and adolescents with PWS. Thus, this study aimed to investigate BMD changes among patients with PWS, who were undergoing GH treatment from childhood to adolescence. Methods Sixty-seven pediatric patients with PWS who had GH treatment initiated during childhood between January 2003 and June 2020 were evaluated. To avoid underestimation, we used total body BMD, which was evaluated using dual-X-ray absorptiometry adjusted for the BMD z-score using patient height, sex, and age. Results In both sexes, age was negatively correlated with the BMD-standard deviation score (SDS) (male: r=−0.156 [p=0.042]; female: r=−0.197 [p=0.043]), which started to decrease in childhood. Conclusions The BMD-SDS of patients with PWS decreases gradually despite GH treatment. As there are no clear recommendations about monitoring of bone health in patients with PWS, further studies are needed to improve the guidelines for screening of BMD and treatment of patients with PWS.

Improved final height with long-term growth hormone treatment in Noonan syndrome

2007 ◽  
Vol 94 (9) ◽  
pp. 1232-1237 ◽  
Author(s):  
Deborah Osio ◽  
Jovanna Dahlgren ◽  
Kerstin Albertsson Wikland ◽  
Otto Westphal
Keyword(s):  
Growth Hormone ◽  
Noonan Syndrome ◽  
Growth Hormone Treatment ◽  
Final Height ◽  
Hormone Treatment

Prevention of Growth Failure in Turner Syndrome: Long-Term Results of Early Growth Hormone Treatment in the “Toddler Turner” Cohort

2021 ◽  
pp. 1-18
Author(s):  
Charmian A. Quigley ◽  
Patricia Y. Fechner ◽  
Mitchell E. Geffner ◽  
Erica A. Eugster ◽  
Judith L. Ross ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Pubertal Development ◽  
Standard Deviation Score ◽  
Growth Failure ◽  
Long Term Results ◽  
Extension Study ◽  
Normal Range ◽  
Gh Treatment ◽  
Catch Up

<b><i>Introduction:</i></b> In the randomized “Toddler Turner” study, girls who received growth hormone (GH) starting at ages 9 months to 4 years (early-treated [ET] group) had marked catch-up growth and were 1.6 ± 0.6 SD taller than untreated (early-untreated [EUT]) control girls after 2 years. However, whether the early catch-up growth would result in greater near-adult height (NAH) was unknown. Therefore, this extension study examined the long-term effects of toddler-age GH treatment on height, pubertal development, and safety parameters. <b><i>Methods:</i></b> Toddler Turner study participants were invited to enroll in a 10-year observational extension study for annual assessments of growth, pubertal status, and safety during long-term GH treatment to NAH for both ET and EUT groups. <b><i>Results:</i></b> The ET group was taller than the EUT group at all time points from preschool to maturity and was significantly taller at the onset of puberty (<i>p</i> = 0.016), however, the difference was not significant at NAH. For the full cohort (ET + EUT combined, <i>n</i> = 50) mean (± SD) NAH was 151.2 ± 7.1 cm at age 15.0 ± 1.3 years. NAH standard deviation score (SDS) was within the normal range (&#x3e;−2.0) for 76% of ET and 60% of EUT subjects (68% overall) and correlated strongly with height SDS at GH start (<i>r</i> = 0.78; <i>p</i> &#x3c; 0.01), which in turn had a modest inverse correlation with age at GH start (i.e., height SDS declined with increasing age in untreated girls [<i>r</i> = −0.30; <i>p</i> = 0.016]). No new safety concerns arose. <b><i>Conclusion:</i></b> Although the ET group was taller throughout, height SDS at NAH was not significantly different between groups due to catch-down growth of ET girls during lapses in GH treatment after the Toddler study and similar long-term GH exposure overall. Early initiation of GH by age 6 years, followed by uninterrupted treatment during childhood, can prevent ongoing growth failure and enable attainment of height within the normal range during childhood, adolescence, and adulthood.

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