SAT-106 Growth Hormone Treatment Response in Children

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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Growth hormone therapy in achondroplasia

Acta Endocrinologica ◽

10.1530/acta.0.1280394 ◽

1993 ◽

Vol 128 (5) ◽

pp. 394-396 ◽

Cited By ~ 13

Author(s):

Yoshikazu Nishi ◽

Michi Kajiyama ◽

Shinichiro Miyagawa ◽

Mitsuhiro Fujiwara ◽

Kazuko Hamamoto

Keyword(s):

Growth Hormone ◽

Hormone Therapy ◽

Growth Hormone Therapy ◽

Height Velocity ◽

First Year ◽

Gh Therapy ◽

Gh Treatment ◽

Gh Secretion ◽

The Status ◽

Second Year

The status of growth hormone (GH) secretion together with the effect of GH therapy was studied in six children with achondroplasia. One patient had impaired GH secretion, which may, in part, be due to obesity. The pre-GH-treatment height velocity was 3.8±0.7 cm/year, but this increased to 6.0±1.0 cm/year in the first year of treatment and to 4.4±0.6 cm/year in the second year. One patient who underwent GH therapy for 4 years showed good response in height velocity. A considerable variation was observed in response to GH therapy within the treated cases.

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The Psychological Consequences of Turner Syndrome and Review of the National Cooperative Growth Study Psychological Substudy

PEDIATRICS ◽

10.1542/peds.102.s3.488 ◽

1998 ◽

Vol 102 (Supplement_3) ◽

pp. 488-491 ◽

Cited By ~ 1

Author(s):

Patricia T. Siegel ◽

Richard Clopper ◽

Brian Stabler

Keyword(s):

Growth Hormone ◽

Behavior Problems ◽

Short Stature ◽

Turner Syndrome ◽

Child Behavior ◽

Child Behavior Checklist ◽

Idiopathic Short Stature ◽

Gh Therapy ◽

Gh Treatment ◽

Control Subjects

Objective. To present longitudinal data on the psychological profile of a cohort of girls with and without Turner syndrome (TS) treated for 3 years with growth hormone (GH). Methods. Among a sample of 283 children with short stature, 37 girls with TS were recruited at 27 US medical centers. Of the original cohort, 22 girls with TS, 13 girls with isolated growth hormone deficiency (GHD), and 12 girls with idiopathic short stature were followed through 3 years of GH therapy. All were school-age, were below the 3rd percentile for height, had low growth rates, and were naive to GH therapy. Psychological tests (the Wide Range Achievement Test and the Slosson Intelligence Test) were administered to the clinical groups within 24 hours of their first GH injection and yearly thereafter. Control subjects were 25 girls with normal stature matched for age and socioeconomic status, who were tested only at baseline. One parent of each subject also completed the Child Behavior Checklist for that subject. Results. At baseline, the clinical groups had more internalizing behavioral problems, had fewer friends, and participated in fewer activities than did the control subjects. The groups did not differ in mean IQ or academic achievement, but the TS group did have more problems in mathematics achievement. Height and growth rate significantly increased in the clinical groups over the 3 years of GH therapy, but IQ and achievement scores did not. Significant linear reductions were noted in both Internalizing and Externalizing Behavior Problems after GH treatment, with the TS group having fewer behavior problems before and after GH treatment than did the GHD–idiopathic short stature group. Decreases in specific Child Behavior Checklist subscales, including attention, social problems, and withdrawal, also were seen in the clinical groups after GH therapy. Conclusions. The comprehensive treatment of girls with TS should include educational and behavioral interventions in addition to traditional medical therapies.

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Final Height in Girls with Turner Syndrome after Long-Term Growth Hormone Treatment in Three Dosages and Low Dose Estrogens

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2002-021171 ◽

2003 ◽

Vol 88 (3) ◽

pp. 1119-1125 ◽

Cited By ~ 138

Author(s):

Yvonne K. van Pareren ◽

Sabine M. P. F. de Muinck Keizer-Schrama ◽

Theo Stijnen ◽

Theo C. J. Sas ◽

Maarten Jansen ◽

...

Keyword(s):

Turner Syndrome ◽

Low Dose ◽

Final Height ◽

Height Velocity ◽

Chronological Age ◽

First Year ◽

Bone Maturation ◽

Gh Treatment ◽

Group A ◽

Group B

Although GH treatment for short stature in Turner syndrome is an accepted treatment in many countries, which GH dosage to use and which age to start puberty induction are issues of debate. This study shows final height (FH) in 60 girls with Turner syndrome treated in a randomized dose-response trial, combining GH treatment with low dose estrogens at a relatively young age. Girls were randomly assigned to group A (4 IU/m2·d; ∼0.045 mg/kg/d), group B (first year, 4 IU/m2·d; thereafter 6 IU/m2·d), or group C (first year, 4 IU/m2·d; second year, 6 IU/m2·d; thereafter, 8 IU/m2·d). After a minimum of 4 yr of GH treatment, at a mean age of 12.7 ± 0.7 yr, low dose micronized 17β-estradiol was given orally. After a mean duration of GH treatment of 8.6 ± 1.9 yr, FH was reached at a mean age of 15.8 ± 0.9 yr. FH, expressed in centimeters or sd score, was 157.6 ± 6.5 or −1.6 ± 1.0 in group A, 162.9 ± 6.1 or −0.7 ± 1.0 in group B, and 163.6 ± 6.0 or −0.6 ± 1.0 in group C. The difference in FH in centimeters, corrected for height sd score and age at start of treatment, was significant between groups A and B [regression coefficient, 4.1; 95% confidence interval (CI), 1.4, 6.9; P < 0.01], and groups A and C (coefficient, 5.0; 95% CI, 2.3, 7.7; P < 0.001), but not between groups B and C (coefficient, 0.9; 95% CI, −1.8, 3.6). Fifty of the 60 girls (83%) had reached a normal FH (FH sd score, more than −2). After starting estrogen treatment, the decrease in height velocity (HV) changed significantly to a stable HV, without affecting bone maturation (change in bone age/change in chronological age). The following variables contributed significantly to predicting FH sd score: GH dose, height sd score (ref. normal girls), chronological age at start of treatment, and HV in the first year of GH treatment. GH treatment was well tolerated. In conclusion, GH treatment leads to a normalization of FH in most girls, even when puberty is induced at a normal pubertal age. The optimal GH dosage depends on height and age at the start of treatment and first year HV.

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

Acta Endocrinologica ◽

10.1530/eje.0.1470625 ◽

2002 ◽

pp. 625-633 ◽

Cited By ~ 40

Author(s):

MB Ranke ◽

CJ Partsch ◽

A Lindberg ◽

HG Dorr ◽

M Bettendorf ◽

...

Keyword(s):

Turner Syndrome ◽

Adult Height ◽

Bone Age ◽

First Year ◽

Gh Therapy ◽

Gh Treatment ◽

Height Gain ◽

Puberty Onset

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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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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Once-Weekly Somapacitan Versus Daily Growth Hormone in Growth Hormone Deficiency: 2-Year Efficacy Results From REAL 3, a Randomized Phase 2 Trial

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.1387 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A680-A680

Author(s):

Lars S Sävendahl ◽

Tadej Battelino ◽

Michael Højby Rasmussen ◽

Reiko Horikawa ◽

Paul Saenger

Keyword(s):

Growth Hormone ◽

Standard Deviation ◽

Height Velocity ◽

First Year ◽

Phase 2 ◽

Efficacy And Safety ◽

Gh Treatment ◽

Treatment Groups ◽

Igf I ◽

Second Year

Abstract Current treatment for growth hormone (GH) deficiency (GHD) requires daily injections, which can be burdensome for the patients/caregivers. Once-weekly somapacitan is a long-acting GH derivative currently in phase 3 for use in children with GHD and phase 2 for short children born small for gestational age. A phase 2, multinational, randomized, open-label, controlled trial (NCT02616562) investigated the efficacy and safety of somapacitan in children compared with daily GH (Norditropin®). GH-treatment-naïve prepubertal children with GHD received 0.04 (n=16), 0.08 (n=15) or 0.16 mg/kg/week (n=14) subcutaneous (s.c.) somapacitan, or s.c. daily GH 0.034 mg/kg/day (0.24 mg/kg/week; n=14) for 52 weeks, followed by a 104-week safety extension. In the extension phase, all patients on somapacitan received 0.16 mg/kg/week; daily GH dose remained unaltered. The 52-week efficacy and safety results have been reported previously. We report here the efficacy results after 104 weeks of GH treatment. At week 104, mean (standard deviation [SD]) height velocity (HV) in the first year of the safety extension was: 10.6 (1.4), 10.0 (1.6) and 9.2 (1.7) cm/year for 0.04/0.16 mg/kg/week (n=13), 0.08/0.16 mg/kg/week (n=15) and 0.16/0.16 mg/kg/week (n=14) somapacitan, respectively, versus 9.0 (2.3) cm/year for daily GH (n=11). Mean (SD) change from baseline in HV standard deviation score (SDS) was 8.04 (2.52), 6.21 (2.90) and 6.40 (3.04) for somapacitan, respectively, versus 6.58 (3.15) for daily GH. Compared with week 52, mean HV and HV SDS at week 104 were increased in children in the somapacitan 0.04/0.16 mg/kg/week and 0.08/0.16 mg/kg/week treatment groups. Height SDS values improved during the second year of treatment with somapacitan and daily GH, with the greatest change from baseline in the somapacitan 0.16/0.16 mg/kg/week treatment group. The mean (SD) change in height SDS from baseline to week 104 was 1.73 (0.76), 1.87 (0.81) and 2.18 (1.18) for somapacitan, respectively, versus 1.72 (0.65) for daily GH. The observed mean (SD) change in insulin-like growth factor-I (IGF-I) SDS from baseline was similar between the somapacitan 0.08/0.16 and 0.16/0.16 mg/kg/week treatment groups (3.15 [1.17] and 3.21 [1.12], respectively), and slightly higher compared with IGF-I SDS in the 0.04/0.16 mg/kg/week group (2.99 [1.05]) and the daily GH group (3.06 [1.26]). Mean IGF-I SDS values remained below the upper limit (+2) of the normal range for all treatment groups throughout the 104-week trial duration. Somapacitan was well tolerated at all doses investigated, with no new safety or local tolerability issues identified during the 104 weeks of treatment. In conclusion, at week 104, height-based outcomes were similar between somapacitan 0.16/0.16 mg/kg/week and daily GH, with comparable mean change in IGF-I SDS. Furthermore, the key improvements observed in the first year were maintained in the second year of the study.

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Lack of Correlation Between Growth Hormone Provocative Test Results and Subsequent Growth Rates During Growth Hormone Therapy

PEDIATRICS ◽

10.1542/peds.102.s3.518 ◽

1998 ◽

Vol 102 (Supplement_3) ◽

pp. 518-520

Author(s):

Jennifer J. Bell ◽

Ken Dana

Keyword(s):

Growth Hormone ◽

Growth Rates ◽

Recombinant Human Growth Hormone ◽

Response To Treatment ◽

First Year ◽

Test Results ◽

Gh Therapy ◽

Gh Treatment ◽

Provocative Test ◽

National Cooperative

Objectives. To determine whether there is a relationship between the peak GH level in pituitary stimulation tests and the growth rate in response to treatment with recombinant human growth hormone (GH). Methods. We identified 24 843 patients in the National Cooperative Growth Study database who had not been treated previously with GH therapy and divided them into three groups according to the peak GH level in pituitary stimulation testing: 1) <10 μg/L (n = 14 132); 2) ≥10 μg/L (n = 7476); and 3) no test results reported (n = 3235). Growth rates in each group in response to GH therapy were examined. Results. The children in each of the groups responded to GH therapy with a vigorous increase in growth rates (means, 8.4 to 9.5 cm/y) in the first year, followed by a gradual decline and then stabilization at 1.0 to 1.9 cm/y greater than the pretreatment values. There were large overlaps in the growth rates among the groups, but the differences were significant. The growth rates in a smaller group of children (n = 187) who had normal GH responses and normal growth rates before GH therapy increased similarly in the first year of therapy (to 7.7 to 9.2 cm/y), but then declined rapidly to the pretreatment values or lower. Conclusion. Because the GH response to pituitary stimulation testing is inadequate for diagnosing GH deficiency, such testing also is inadequate for determining whether GH treatment should be prescribed in a child with short stature. In addition, the waning response to GH therapy in normally growing short children suggests that this treatment may not have a sustained benefit in these children.

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Machine learning-based prediction of response to growth hormone treatment in Turner syndrome: the LG Growth Study

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2019-0311 ◽

2020 ◽

Vol 33 (1) ◽

pp. 71-78

Author(s):

Mo Kyung Jung ◽

Jeesuk Yu ◽

Ji-Eun Lee ◽

Se Young Kim ◽

Hae Soon Kim ◽

...

Keyword(s):

Machine Learning ◽

Growth Hormone ◽

Prediction Model ◽

Turner Syndrome ◽

Multiple Regression ◽

Standard Deviation Score ◽

Hormone Treatment ◽

First Year ◽

Growth Study ◽

Gh Treatment

AbstractBackgroundGrowth hormone (GH) treatment has become a common practice in Turner syndrome (TS). However, there are only a few studies on the response to GH treatment in TS. The aim of this study is to predict the responsiveness to GH treatment and to suggest a prediction model of height outcome in TS.MethodsThe clinical parameters of 105 TS patients registered in the LG Growth Study (LGS) were retrospectively reviewed. The prognostic factors for the good responders were identified, and the prediction of height response was investigated by the random forest (RF) method, and also, multiple regression models were applied.ResultsIn the RF method, the most important predictive variable for the increment of height standard deviation score (SDS) during the first year of GH treatment was chronologic age (CA) at start of GH treatment. The RF method also showed that the increment of height SDS during the first year was the most important predictor in the increment of height SDS after 3 years of treatment. In a prediction model by multiple regression, younger CA was the significant predictor of height SDS gain during the first year (32.4% of the variability). After 3 years of treatment, mid-parental height (MPH) and the increment of height SDS during the first year were identified as significant predictors (76.6% of the variability).ConclusionsBoth the machine learning approach and the multiple regression model revealed that younger CA at the start of GH treatment was the most important factor related to height response in patients with TS.

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Serum leptin in short children born small for gestational age: relationship with the growth response to growth hormone treatment. The Swedish Study Group for Growth Hormone Treatment

Acta Endocrinologica ◽

10.1530/eje.0.1370387 ◽

1997 ◽

pp. 387-395 ◽

Cited By ~ 22

Author(s):

M Boguszewski ◽

J Dahlgren ◽

R Bjarnason ◽

S Rosberg ◽

LM Carlsson ◽

...

Keyword(s):

Growth Hormone ◽

Gestational Age ◽

Growth Response ◽

Reference Group ◽

Hormone Treatment ◽

Gh Therapy ◽

Gh Treatment ◽

Serum Leptin ◽

Short Children ◽

The Mean

The product of the obese (ob) gene, leptin, is an adipocyte-derived hormone that is involved in the regulation of appetite and body weight. This study was undertaken in order to describe the basal serum levels of leptin in prepubertal short children born small for gestational age (SGA) and their relationship with growth parameters, before and during growth hormone (GH) treatment. Eighty-nine prepubertal short children (66 boys, 23 girls; height standard deviation score (SDS), -5.4 to -2.0; age, 2.0 to 12.8 years) born SGA, 12 of whom (9 boys, 3 girls) had signs of Silver-Russell syndrome, were included in the study. Serum leptin concentrations were measured by radioimmunoassay. Leptin levels in the children born SGA were compared with those in a reference group of 109 prepubertal healthy children born at an appropriate size for gestational age (AGA). The mean (S.D.) change in height SDS was 0.11 (0.22) during the year before the start of GH therapy (0.1 IU/kg/day) and increased to 0.82 (0.44) during the first year (P < 0.001) and to 1.28 (0.59) during the 2-year period of GH therapy (P < 0.001). The children born SGA were significantly leaner than the reference group. An inverse correlation was found between leptin and chronological age in the SGA group (r = -0.31, P < 0.01). The mean serum level of leptin in the children born SGA who were older than 5.5 years of age was 2.8 micrograms/l which was significantly lower than the mean value of 3.7 micrograms/l found in the children born AGA of the same age range. The difference remained after adjustment of leptin levels for sex, age, body mass index (BMI) and weight-for-height SDS (WHSDSSDS). Leptin correlated with WHSDSSDS (r = 0.32, P < 0.001) and BMI (r = 0.36, P < 0.01) in the reference population, but not in the SGA group. No correlation was found between leptin and spontaneous 24-h GH secretion, insulin-like growth factor (IGF)-I or IGF-binding protein-3 levels, or with fasting insulin or cortisol levels. Leptin levels at the start of GH treatment were correlated with the growth response over both 1 year (r = 0.46, P < 0.001) and 2 years (r = 0.51, P < 0.001) of GH therapy. Using multiple regression analysis, models including leptin levels at the start of GH therapy could explain 51% of the variance in the growth response after 1 year and 44% after 2 years of GH treatment. In conclusion, serum leptin levels are reduced in short children born SGA and are inversely correlated with chronological age. Leptin concentrations correlate with the growth response to GH treatment and might be used as a marker for predicting the growth response to GH treatment.

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