scholarly journals Safety Outcomes and Near-Adult Height Gain of Growth Hormone-Treated Children with SHOX Deficiency: Data from an Observational Study and a Clinical Trial

2016 ◽  
Vol 87 (1) ◽  
pp. 42-50 ◽  
Author(s):  
Imane Benabbad ◽  
Myriam Rosilio ◽  
Christopher J. Child ◽  
Jean-Claude Carel ◽  
Judith L. Ross ◽  
...  
2017 ◽  
Vol 49 (10) ◽  
pp. 778-785 ◽  
Author(s):  
Ludmila Pedrosa ◽  
Joice de Oliveira ◽  
Paula Thomé ◽  
Cristiane Kochi ◽  
Durval Damiani ◽  
...  

AbstractAromatase inhibitors (AIs) have been used to recover height loss due to their capacity to delay growth plate closure. Long-term studies describing final heights are needed to determine the efficacy and safety profiles of these drugs for the treatment of impaired growth. This study aims to identify the therapeutic efficiency of AIs in improve growth and to describe potential adverse effects during treatment. Retrospective data analysis of 96 adolescents, among which 22 patients already attained near-final height, were followed at outpatient clinics of two referral centers. Patients were all in puberty and present idiopathic decrease in predicted adult height. Patients were treated with Anastrozole (ANZ: 1 mg/day) or Letrozole (LTZ: 2.5 mg/day) with/without recombinant human growth hormone (0.05 mg/kg/day) for 1.0 to 3.5 years (2.1±1.2 years). Height gain, body mass index, lipid, liver enzyme, gonadotropins and testosterone levels were described before and at the end of treatment. Predicted adult height (PAH) and NF height were compared with the TH. The height SDS (adjusted to bone age) significantly increased (p<0.05) in all groups [0.8±0.7 (ANZ), 0.7±0.7 (ANZ+GH), 0.3±0.5 (LTZ), and 1.2±0.8 (LTZ+GH)]; the latter group exhibited the highest increment of PAH and growth recovery to the TH (p<0.004). No significant side effects were observed. AI treatment, especially when used in association with GH was able to improve growth and the attainment of familial target height.


2019 ◽  
Vol 91 (4) ◽  
pp. 241-251 ◽  
Author(s):  
Christopher J. Child ◽  
Charmian A. Quigley ◽  
Gordon B. Cutler, Jr ◽  
Wayne V. Moore ◽  
Kupper A. Wintergerst ◽  
...  

Background/Objectives: Growth hormone (GH) treatment of idiopathic short stature (ISS) received US Food and Drug Administration approval in 2003. We assessed height gain and safety in 2,450 children with ISS treated with GH in US clinical practice. Methods: Short-term height gain, near-adult height (NAH), and safety outcomes were investigated using Genetics and Neuroendocrinology of Short Stature International Study data. Results: Compared to children with isolated idiopathic GH deficiency (IGHD), those with ISS were shorter at baseline but had similar age and GH dose. Mean ± SD height SD score (SDS) increase was similar for ISS and IGHD, with 0.6 ± 0.3 (first), 0.4 ± 0.3 (second), 0.3 ± 0.3 (third), and 0.1 ± 0.3 (fourth year) for ISS. Girls with ISS (27% of subjects) were younger and shorter than boys but had similar height gain over time. At NAH in the ISS group (n = 467), mean ± SD age, GH duration, and height SDS were 17.3 ± 2.3 years, 4.6 ± 2.7 years, and –1.2 ± 0.9, respectively. Height gain from baseline was 1.1 ± 1.0 SDS and was greater for boys than girls (1.2 ± 1.0 vs. 0.9 ± 0.9), but boys were treated longer (5.1 ± 2.8 vs. 3.6 ± 2.5 years). Adverse events were reported for 24% with ISS versus 20% with IGHD – most were common childhood conditions or previously reported in GH-treated patients. Conclusions: GH-treated children with ISS achieved substantial height gain, similar to patients with IGHD. Fewer GH-treated girls were enrolled than boys, but with similar height SDS gain over time. No ISS-specific safety issues were identified. Thus, GH treatment of ISS appears to have a safety/effectiveness profile similar to that of IGHD.


2021 ◽  
Vol 12 ◽  
Author(s):  
Saartje Straetemans ◽  
Raoul Rooman ◽  
Jean De Schepper

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.


2014 ◽  
Vol 99 (8) ◽  
pp. 2917-2924 ◽  
Author(s):  
Berit Kriström ◽  
Elena Lundberg ◽  
Björn Jonsson ◽  
Kerstin Albertsson-Wikland ◽  

Context: GH treatment significantly increased adult height (AH) in a dose-dependent manner in short non-GH-deficient children in a randomized, controlled, clinical trial; the mean gain in height SD score (heightSDS) was 1.3 (range 0–3), compared with 0.2 in the untreated group. Objective: The objective of the study was to analyze the relationship between IGF-1SDS, IGF binding protein-3 SDS (IGFBP3SDS), and their ratioSDS with a gain in the heightSDS until AH in non-GH-deficient short children. Design and Setting: This was a randomized, controlled, multicenter clinical trial. Intervention: The intervention included GH treatment: 33 or 67 μg/kg · d plus untreated controls. Subjects: One hundred fifty-one non-GH-deficient short children were included in the intent-to-treat (ITT) population and 108 in the per-protocol (PP) population; 112 children in the ITT and 68 children in the PP populations had idiopathic short stature (ISS). Main Outcome Measures: Increments from baseline to on-treatment study mean IGF-1SDS (ΔIGF-1SDS), IGFBP3SDS, and IGF-1 to IGFBP3 ratioSDS were assessed in relationship to the gain in heightSDS. Results: Sixty-two percent of the variance in the gain in heightSDS in children on GH treatment could be explained by four variables: ΔIGF-1SDS (explaining 28%), bone age delay, birth length (the taller the better), and GH dose (the higher the better). The lower IGF-1SDS was at baseline, the higher was its increment during treatment. For both the AllPP- and the ISSPP-treated groups, the attained IGF-1SDS study level did not correlate with height gain. Conclusion: In short non-GH-deficient children, the GH dose-related increment in IGF-1SDS from baseline to mean study level was the most important explanatory variable for long-term growth response from the peripubertal period until AH, when IGF-1SDS, IGFBP3SDS, and their ratioSDS were compared concurrently.


2019 ◽  
Vol 91 (6) ◽  
pp. 373-379 ◽  
Author(s):  
Jung Min Ahn ◽  
Jung Hwan Suh ◽  
Ah Reum Kwon ◽  
Hyun Wook Chae ◽  
Ho-Seong Kim

Aims: This study aimed to evaluate final adult height (AH) after recombinant human growth hormone (GH) treatment of girls with Turner syndrome (TS) and to elucidate the predicting factors for their growth response. Methods: We enrolled 73 patients with TS who underwent GH treatment and reached AH and 14 patients who did not undergo treatment. To assess the effectiveness of GH therapy, we evaluated final AH, height gain over the predicted AH, and height gain over the projected AH. In addition, to analyze the factors affecting final AH, we studied correlations between final AH (or height SDS, height gain) and treatment variables. Results: GH therapy was started at a mean age of 8.87 ± 3.73 years, and the treatment duration was 6.47 ± 3.02 years. The patients in the treated group reached a final AH of 152.03 ± 4.66 cm (final AH SDS for the general population: –1.93 ± 1.03) with a gain over projected AH at the start of treatment of 12.21 ± 4.33 cm. The untreated control subjects had a final AH of 143.57 ± 4.06 cm with a gain over projected AH at the first visit of 3.89 ± 3.80 cm. Final AH and AH SDS were positively correlated to height SDS at the start of treatment. Thirty-five patients out of the 73 GH-treated patients (47.9%) attained to a normal range of height for Korean girls. The patients having attained to a normal height range after GH treatment had shown a higher height SDS at the start of GH treatment, a higher mid-parental height SDS, and a younger age at initiation of estrogen. Conclusions: Our findings demonstrate that GH treatment at an early age is effective in improving the final height SDS and height SDS gain in TS patients. Therefore, GH administration at an early age is important for final height gain.


2000 ◽  
Vol 59 (2) ◽  
pp. 317-324 ◽  
Author(s):  
T. J. Cole

Since the 19th century there have been clearly documented secular trends to increasing adult height in most European countries, with current rates of 10–30 mm / decade. Over the same period menarcheal age has also fallen steeply, but has now stabilized at approximately 13 years and may be rising again. Height trends tend to be greater in childhood than in adulthood due to the associated advance in maturation, but no trends are apparent before the age of 2 years. In particular, birth-weight trends are small and different in shape from height trends. The adult height trend matches that at age 2 years, so that the increment in adult height has already been achieved by age 2 years. To try to identify factors relating to the secular trend, increased height gain in late infancy is hypothesized to be equivalent to a reduction in stunting, and stunting is thought to be caused by impaired growth in the long bones of the leg in later infancy. Leg growth may be regulated by the expression of growth-hormone receptors on the growth plates, which it is hypothesized are susceptible to the interaction between concurrent nutrition and the nominal growth rate set during pregnancy. The timing of menarche is also likely to be determined by some growth factor operating near the time of birth, which also affects later weight, but not height.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Dae Hyun Kim ◽  
Ju-hee Choi

Abstract Recombinant growth hormone therapy (rhGH) is known to improve the final adult height in various conditions. The effectiveness of treatment depends on the status of patients, but it is generally known that the younger age the treatment starts, the better effects obtained. The authors experienced that final adult height was dramatically improved with rhGH at the very end stage of deceleration period of growth, so we would like to share our unusual experience. A boy of 13 years and 11 months visited our clinic with cessation of growth. He was 163cm (54%) tall and 62.6kg (78%), and showed Tanner stage IV-V development. There have been no unusual findings in past history and family history. His Mid Parental Height was calculated as 170.5cm (Father: 172cm, Mother: 156cm). After experiencing an acute growth acceleration around 20cm over the past two years, growth rate was abruptly decreased, with 1cm growth in the last nine months. Bone age was 17 years by TW3 method, and pelvic AP x-ray showed Risser stage 4, which is compatible to 17 years in boy. As a result of the above findings, additional height gain was expected to less than 1-2cm and medical intervention for more height gain was expected to impossible. However, the patient and his parents strongly requested rhGH treatment. So, we decided to try rhGH treatment for only three months and then discuss whether or not to extend the treatment after checking up the result. Follow up was conducted every three months, and the height of the patient continued to grow and the closure of the remaining growth plates was confirmed to be delayed. During the one-and-a-half year treatment, no side effects appeared in patient, reaching 173 centimeters, the equivalent of the Korean male standard height. In this case, we experience that the use of Growth hormone can improve the final adult height significantly, even in the end stage of growth, without any other intervention. So, we may consider attempting limitedly to treat growth hormones for height gain, if caregivers or patient strongly request the medical intervention in end stage of the puberty or growth.


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