Adult height after GH therapy in 188 Ullrich-Turner syndrome patients: results of the German IGLU Follow-up Study 2001

OBJECTIVES: We aimed to evaluate the factors influencing true adult height (HT) after long-term (from 1987 to 2000) GH treatment in Ullrich-Turner syndrome (UTS) based on modalities conceived in the 1980s. DESIGN: Out of 347 near-adult (>16 Years) patients from 96 German centres, whose longitudinal growth was documented within KIGS (Pharmacia International Growth Database), 188 (45, X=59%; bone age >15 Years) were available for further anthropometric measurements. RESULTS: At a median GH dose of 0.88 (10th/90th percentiles: 0.47/1.06) IU/kg per week, a gain of 6.0 (-1.3/+13) cm above the projected adult height was recorded. Variables were recorded at GH start, after 1 Year GH, puberty onset, and last visit on GH therapy. At these visits, the median ages were 11.7, 12.7, 14.2, 16.6 and 18.7 Years; and median heights, 0.4, 1.1, 1.7, 1.7 and 1.3 SDS (UTS) respectively. Height gain (DeltaHT) after GH discontinuation was 1.5 cm. Total DeltaHT correlated (P<0.001) negatively with bone age and HT SDS at GH start, but positively with DeltaHT after the first Year, DeltaHT at puberty onset, and GH duration. Final HT correlated (P<0.001) positively with HT at GH start, first-Year DeltaHT, and HT at puberty onset. Body mass index increased slightly (P<0.05), with values at start and adult follow-up correlating highly (R=0.70, P<0.001). No major side effects of GH occurred. CONCLUSIONS: GH dosages conceived in the 1980s are safe but too low for most UTS patients. HT gain and height are determined by age and HT at GH start. Height gain during the first Year on GH is indicative of overall height gain. After spontaneous or induced puberty, little gain in height occurs.

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Final Adult Height after Growth Hormone Treatment in Patients with Turner Syndrome

Hormone Research in Paediatrics ◽

10.1159/000500780 ◽

2019 ◽

Vol 91 (6) ◽

pp. 373-379 ◽

Cited By ~ 1

Author(s):

Jung Min Ahn ◽

Jung Hwan Suh ◽

Ah Reum Kwon ◽

Hyun Wook Chae ◽

Ho-Seong Kim

Keyword(s):

Growth Hormone ◽

Turner Syndrome ◽

Adult Height ◽

Final Height ◽

Early Age ◽

Gh Therapy ◽

Gh Treatment ◽

Height Range ◽

Final Adult Height ◽

Height Gain

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.

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SAT-107 Improved Adult Height in Brazilian Turner Syndrome Patients Treated with Growth Hormone

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1649 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Renata Da Cunha Scalco ◽

Adriana Farrant Braz ◽

Alexsandra C Malaquias ◽

Sonir Roberto Rauber Antonini ◽

Gil Guerra-Junior ◽

...

Keyword(s):

Growth Hormone ◽

Turner Syndrome ◽

Adult Height ◽

Delayed Diagnosis ◽

Bone Age ◽

Treated Group ◽

Gh Treatment ◽

Significant Difference ◽

Referral Hospitals ◽

Height Gain

Abstract Background: Short stature is the most frequent clinical manifestation in Turner syndrome (TS), occurring in 98% of these patients. Growth hormone was shown to improve adult height in TS patients from diverse genetic backgrounds. However, there are few studies on adult height in TS patients from developing countries, where the diagnosis is frequently delayed. Objective: To compare adult height between GH-treated and untreated TS patients. Patients and methods: 120 GH-treated and 109 GH-untreated TS patients from 3 referral hospitals in Brazil were evaluated. The most common reasons for not treating TS patients with GH were late diagnosis or GH unavailability. Data on karyotype, parents’ height, puberty development and GH treatment were obtained from their medical records. Adult height was determined when growth velocity was inferior to 1cm/year during a minimum follow-up period of 12 months. Results: The frequency of 45,X karyotype was similar between the groups (48.7% vs. 41.9% in GH-treated vs. GH-untreated TS patients, respectively, P= 0.639). GH-treated TS patients started GH therapy at a chronological age (CA) of 11.2 ± 3.7 yr, bone age of 9.3 ± 3.1 yr, height SDS (British 1965 standards) -3.1 ± 1.1. GH mean dose was 48µg/kg.d and GH treatment duration was 5.4 ± 3.0 yr. Estrogen replacement was started late, at CA of 14.3 ± 2.0 yr in GH-treated and at 14.9 ± 1.9 yr in GH-untreated patients, and the rate of spontaneous puberty was similar between the groups (GH-treated 16.8% vs. GH-untreated 22,8%, P=0.304). Adult height was significantly higher after GH treatment (150.1 ± 5.8 cm vs. 143.3 ± 7.2 cm in GH-treated vs. untreated TS patients, respectively, P < 0.001), even with a small but significant difference in target height between the groups (158.2 ± 4.8 vs. 159.8± 4.5 cm in GH-treated vs. untreated TS patients, respectively, P= 0.015). More than half of the TS GH-treated patients reached normal adult height (equal or higher than 150.2 cm), whereas only 15.6% of GH-untreated patients reached it. Conclusion: Despite the delayed diagnosis of TS patients in our cohort, GH treatment was associated with a significant height gain, and the TS GH-treated group was around 7 cm taller than the GH-untreated group.

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

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2016-0297 ◽

2017 ◽

Vol 30 (2) ◽

Cited By ~ 3

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.

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Anthropometric, metabolic, and reproductive outcomes of patients with central precocious puberty treated with leuprorelin acetate 3-month depot (11.25 mg)

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2021-0142 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Carolina O. Ramos ◽

Ana P M Canton ◽

Carlos Eduardo Seraphim ◽

Aline Guimarães Faria ◽

Flavia Rezende Tinano ◽

...

Keyword(s):

Precocious Puberty ◽

Adult Height ◽

Central Precocious Puberty ◽

Bone Age ◽

Overweight And Obesity ◽

Leuprorelin Acetate ◽

The Mean ◽

Hormone Analogs

Abstract Objectives Longer-acting gonadotropin-releasing hormone analogs (GnRHa) have been widely used for central precocious puberty (CPP) treatment. However, the follow-up of patients after this treatment are still scarce. Our aim was to describe anthropometric, metabolic, and reproductive follow-up of CPP patients after treatment with leuprorelin acetate 3-month depot (11.25 mg). Methods Twenty-two female patients with idiopathic CPP were treated with leuprorelin acetate 3-month depot (11.25 mg). Their medical records were retrospectively evaluated regarding clinical, hormonal, and imaging aspects before, during, and after GnRHa treatment until adult height (AH). Results At the diagnosis of CPP, the mean chronological age (CA) was 8.2 ± 1.13 year, and mean bone age (BA) was 10.4 ± 1.4 year. Mean height SDS at the start and the end of GnRHa treatment was 1.6 ± 0.8 and 1.3 ± 0.9, respectively. The mean duration of GnRHa treatment was 2.8 ± 0.8 year. Mean predicted adult heights (PAH) at the start and the end of GnRH treatment was 153.2 ± 8.6 and 164.4 ± 7.3 cm, respectively (p<0.05). The mean AH was 163.2 ± 6.2 cm (mean SDS: 0.1 ± 1). All patients were within their target height (TH) range. There was a decrease in the percentage of overweight and obesity from the diagnosis until AH (39–19% p>0.05). At the AH, the insulin resistance and high LDL levels were identified in 3/17 patients (17.6%) and 2/21 patients (9.5%), respectively. The mean CA of menarche was 12.2 ± 0.5 years. At the AH, PCOS was diagnosed in one patient (4.8%). Conclusions Long-term anthropometric, metabolic, and reproductive follow-up of patients with CPP treated with longer-acting GnRHa revealed effectivity, safety, and favorable outcomes.

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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?

Frontiers in Endocrinology ◽

10.3389/fendo.2021.678094 ◽

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 <−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.

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IGF-1 and Growth Response to Adult Height in a Randomized GH Treatment Trial in Short Non-GH-Deficient Children

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2014-1101 ◽

2014 ◽

Vol 99 (8) ◽

pp. 2917-2924 ◽

Cited By ~ 13

Author(s):

Berit Kriström ◽

Elena Lundberg ◽

Björn Jonsson ◽

Kerstin Albertsson-Wikland ◽

Keyword(s):

Clinical Trial ◽

Growth Response ◽

Adult Height ◽

Bone Age ◽

Controlled Clinical Trial ◽

Dependent Manner ◽

Gh Treatment ◽

Randomized Controlled ◽

Short Children ◽

Height Gain

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.

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Papillary thyroid carcinoma after recombinant GH therapy for Turner syndrome

Acta Endocrinologica ◽

10.1530/eje.1.01988 ◽

2005 ◽

Vol 153 (4) ◽

pp. 499-502 ◽

Cited By ~ 12

Author(s):

P Cabanas ◽

T García-Caballero ◽

J Barreiro ◽

L Castro-Feijóo ◽

R Gallego ◽

...

Keyword(s):

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Turner Syndrome ◽

Carcinoma Cells ◽

Receptor Expression ◽

Papillary Thyroid ◽

Long Term Effects ◽

Gh Therapy ◽

Gh Treatment

Turner syndrome (TS) has been included for several years among the indications for GH treatment, generally with satisfactory outcomes. Nevertheless, the long-term effects of this treatment in non-GH deficient patients are not fully known. The incidence of thyroid carcinoma is rare in patients during childhood, it is unusual to find this neoplasia in children under sixteen years old. This article reports the cases of two Spanish patients with papillary thyroid carcinoma after GH treatment for TS. Recent studies have indicated a possible relationship between the GH–IGF axis and the pathogenesis of neoplasias, questioning the chance association of these two pathologies. In line with this, we detected GH receptor expression in the papillary carcinoma cells. Long-term prospective studies are required to clarify the possible effects of GH treatment on the risk of neoplasia.

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

Hormone Research in Paediatrics ◽

10.1159/000516869 ◽

2021 ◽

pp. 1-8

Author(s):

Naiara C.B. Dantas ◽

Adriana F. Braz ◽

Alexsandra Malaquias ◽

Sofia Lemos-Marini ◽

Ivo J.P. Arnhold ◽

...

Keyword(s):

Growth Hormone ◽

Turner Syndrome ◽

Adult Height ◽

Growth Hormone Therapy ◽

Treated Group ◽

Untreated Group ◽

Target Height ◽

Gh Therapy ◽

Gh Treatment ◽

Different Populations

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.

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Long-term GH treatment improves adult height in children with Noonan syndrome with and without mutations in protein tyrosine phosphatase, non-receptor-type 11

Acta Endocrinologica ◽

10.1530/eje-08-0413 ◽

2008 ◽

Vol 159 (3) ◽

pp. 203-208 ◽

Cited By ~ 43

Author(s):

C Noordam ◽

P G M Peer ◽

I Francois ◽

J De Schepper ◽

I van den Burgt ◽

...

Keyword(s):

Protein Tyrosine Phosphatase ◽

Noonan Syndrome ◽

Adult Height ◽

Final Height ◽

Tyrosine Phosphatase ◽

Receptor Type ◽

Gh Therapy ◽

Gh Treatment ◽

Protein Tyrosine

ContextNoonan syndrome (NS) is characterized by short stature, typical facial dysmorphology and congenital heart defects. Short-term effect of GH therapy in NS is beneficial, reports on the effect on adult height are scarce.ObjectiveTo determine the effect of long-term GH therapy in children with NS.DesignTwenty-nine children with NS were treated with GH until final height was reached.SettingHospital endocrinology departments.PatientsChildren with the clinical diagnosis of NS, with mean age at the start of therapy of 11.0 years, 22 out of 27 tested children had a mutation in the protein tyrosine phosphatase, non-receptor-type 11 gene (PTPN11 gene).InterventionsGH was administered subcutaneously at 0.05 mg/kg per day until growth velocity was 1 cm/6 months.Main outcome measureLinear growth (height) was measured at 3-month intervals in the first year and at 6-month intervals thereafter until final height.ResultsAt the start of treatment, median height SDS (H-SDS) was −2.8 (−4.1 to −1.8) and 0.0 (−1.4 to +1.2), based on national and Noonan standards respectively. GH therapy lasted for 3.0–10.3 years (median, 6.4), producing mean gains in H-SDS of +1.3 (+0.2 to +2.7) and +1.3 (−0.6 to +2.4), based on national and Noonan standards respectively. In 22 children with a mutation in PTPN11 mean gain in H-SDS for National standards was +1.3, not different from the mean gain in the five children without a mutation in PTPN11+1.3 (P=0.98).ConclusionLong-term GH treatment in NS leads to attainment of adult height within the normal range in most patients.

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SAT-106 Growth Hormone Treatment Response in Children

Journal of the Endocrine Society ◽

10.1210/jendso/bvaa046.1596 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

Author(s):

Mitchell Rath ◽

Daniele Pacaud ◽

Karin Winston ◽

Josephine Ho ◽

Jonathan M Dawrant ◽

...

Keyword(s):

Growth Hormone ◽

Turner Syndrome ◽

Tertiary Care ◽

Stimulation Test ◽

Height Velocity ◽

First Year ◽

Gh Therapy ◽

Gh Treatment ◽

Common Diagnosis ◽

The Mean

Abstract OBJECTIVES: Growth hormone (GH) therapy is an effective treatment in addressing growth failure in children with GH deficiency (GHD). It has also been increasingly used in non-GH deficient (nGHD) conditions. We sought to report the growth response of GHD and nGHD patients who received GH therapy at a tertiary care center. METHODS: Data was collected from health records of patients followed in the endocrinology clinic at Alberta Children’s Hospital, Calgary, Canada, from 2005 to 2019, and used to analyze clinical responses based on indication for GH treatment. RESULTS: A total of 167 patient records (87 males and 80 females) were used for analysis. The average age at the start of GH therapy was 7.3 years (range 0.25 to 16.98 yrs). 74 patients were in the GHD group while 93 were nGHD. Of the patients in the nGHD group, the most common diagnosis were: idiopathic short stature (ISS)(n=45), Turner syndrome (TS)(n=26), and Prader Willi Syndrome (PWS)(n=8). The mean height velocity (HV) in year 1 was highest in the GHD group at 11.68 cm/year (n= 62, sd = 5.93), followed by ISS at 9.41cm/year (n = 52, sd = 4.34). The mean first year HV of those who had received chemotherapy (n= 5, mean = 5.48, sd = 1.92) or had Turner syndrome (n= 24, mean = 7.20, sd = 2.15) was significantly lower than both the GHD and ISS groups. GH peak during a GH stimulation test at baseline was not correlated to the first year height velocity while on GH treatment. However there was a negative linear correlation between baseline IGF1 level and first year height velocity (Spearman’s rho = 0.312216, p-value= 0.01516). Age at GH initiation was negatively correlated with height velocity during GH treatment. Height velocity over time decreased sharply from year 1 to year 3, and became stable for the remaining years of GH therapy. For the entire group, HV for years 1-5 was 9.81 (sd=4.83), 7.40 (sd=2.89), 6.29 (sd=2.38), 5.92 (sd=2.56), 5.66 (sd=2.51). There is no significant correlation between GH dose and height velocity response after adjusting for diagnosis. CONCLUSION: In our population, the response to GH therapy was consistent with those reported in the literature. Response to GH therapy was not associated with GH peak on stimulation but rather to baseline IGF-1 level and age at initiation. Although peak GH to stimulation is required to obtain public funding for GH therapy, these findings demonstrate that GH stimulation test results may not indicate which patients may benefit the most from GH therapy. Follow-up until final adult height will allow us to have a better understanding of the efficacy of GH therapy in patients with both GHD and nGHD conditions.

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