A Comprehensive Cohort Analysis Comparing Growth and GH Therapy Response in IGF1R Mutation Carriers and SGA Children

2019 ◽  
Vol 105 (4) ◽  
pp. e1705-e1717 ◽  
Author(s):  
Eric Göpel ◽  
Denise Rockstroh ◽  
Heike Pfäffle ◽  
Marina Schlicke ◽  
Susanne Bechtold-Dalla Pozza ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Growth Retardation ◽  
Growth Response ◽  
Recombinant Human Growth Hormone ◽  
Cohort Analysis ◽  
Standard Deviation Score ◽  
Model Assessment ◽  
Rhgh Therapy ◽  
Mutation Carriers ◽  
Catch Up

Abstract Context IGF1 receptor mutations (IGF1RM) are rare; however, patients exhibit pronounced growth retardation without catch-up. Although several case reports exist, a comprehensive statistical analysis investigating growth profile and benefit of recombinant human growth hormone (rhGH) treatment is still missing. Objective and methods Here, we compared IGF1RM carriers (n = 23) retrospectively regarding birth parameters, growth response to rhGH therapy, near final height, and glucose/insulin homeostasis to treated children born small for gestational age (SGA) (n = 34). Additionally, health profiles of adult IGF1RM carriers were surveyed by a questionnaire. Results IGF1RM carriers were significantly smaller at rhGH initiation and had a diminished first-year response compared to SGA children (Δ height standard deviation score: 0.29 vs. 0.65), resulting in a lower growth response under therapy. Interestingly, the number of poor therapy responders was three times higher for IGF1RM carriers than for SGA patients (53 % vs. 17 %). However, most IGF1RM good responders showed catch-up growth to the levels of SGA patients. Moreover, we observed no differences in homeostasis model assessment of insulin resistance before treatment, but during treatment insulin resistance was significantly increased in IGF1RM carriers compared to SGA children. Analyses in adult mutation carriers indicated no increased occurrence of comorbidities later in life compared to SGA controls. Conclusion In summary, IGF1RM carriers showed a more pronounced growth retardation and lower response to rhGH therapy compared to non-mutation carriers, with high individual variability. Therefore, a critical reevaluation of success should be performed periodically. In adulthood, we could not observe a significant influence of IGF1RM on metabolism and health of carriers.

scholarly journals Serum adiponectin levels, insulin resistance, and lipid profile in children born small for gestational age are affected by the severity of growth retardation at birth

2007 ◽  
Vol 156 (2) ◽  
pp. 271-277 ◽  
Author(s):  
Eleni N Evagelidou ◽  
Vasileios I Giapros ◽  
Anna S Challa ◽  
Dimitrios N Kiortsis ◽  
Agathocles A Tsatsoulis ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Lipid Profile ◽  
Gestational Age ◽  
Growth Retardation ◽  
Small For Gestational Age ◽  
Density Lipoprotein ◽  
Model Assessment ◽  
Apo B ◽  
Significant Difference ◽  
Catch Up

Objective: Insulin resistance has been linked to intrauterine growth retardation (IUGR); adiponectin is a protein with insulin-sensitizing properties. This study was designed to test whether being born small for gestational age (SGA) has an effect on blood levels of adiponectin and leptin, insulin resistance parameters, and lipid profile in pre-puberty, taking into consideration the severity of IUGR. Methods: Serum levels of adiponectin, leptin, total cholesterol (t-CHOL), high density lipoprotein (HDL)-cholesterol, low density lipoprotein (LDL)-cholesterol, triglycerides, apolipoproteins A-1 (Apo A-1), Apo B and Apo E, lipoprotein(a) (Lp(a)), fasting glucose, and insulin (Ins), the homeostasis model assessment insulin resistance index (HOMA-IR) and anthropometric indices were evaluated in 70 children aged 6–8 years, born appropriate for gestational age (AGA; n = 35) and SGA (n = 35), matched for age, gender, height, and BMI. SGA children were divided into two subgroups according to the severity of IUGR: SGA<3rd percentile (n = 20), and SGA 3rd–10th percentile (n = 15). They were also subdivided in two subgroups, those with (n = 25) and those without (n = 10) catch-up growth, considering their actual height corrected for mid-parental height. Results: SGA children had higher Ins and HOMA-IR than AGA children (Ins, 42 ± 23 vs 32 ± 11 pmol/l; HOMA-IR, 1.30 ± 0.8 vs 0.92 ± 0.3; P<0.05). No significant difference in serum leptin was found between the SGA and the AGA groups but adiponectin showed a trend to be higher in SGA children (13.6 ± 5.7 vs 10.8 ± 5.9 μg/ml respectively). SGA children without catch-up growth had higher adiponectin (15.6 ± 8.5 μg/ml, P<0.05) than AGA children. Among the SGA children, the subgroup <3rd percentile had higher Lp(a) than the subgroup 3rd–10th percentile (P<0.05). An independent positive correlation between adiponectin and Lp(a) was observed in SGA children (R = 0.59, P<0.01). Conclusion: SGA children, although more insulin resistant, had similar or higher adiponectin levels than matched AGA children in pre-puberty. The severity of IUGR appears to affect their metabolic profile during childhood.

Growth screening in children aged 3–5 years: a useful tool for public health programs in community pediatrics

2019 ◽  
Vol 32 (7) ◽  
pp. 727-732 ◽  
Author(s):  
Simon Kayemba-Kay’s ◽  
Odile Maillet ◽  
Peter Hindmarsh ◽  
Anne Heron
Keyword(s):  
Public Health ◽  
Standard Deviation ◽  
Gestational Age ◽  
Final Height ◽  
Recombinant Human Growth Hormone ◽  
Standard Deviation Score ◽  
Growth Patterns ◽  
Easy Access ◽  
Screening Programs ◽  
Catch Up

Abstract Background About 90% of children grow up normally and attain a final height within their genetic target. In children with intrauterine growth restriction (IUGR), up to 10% will not catch up spontaneously. Turner syndrome is often diagnosed late, and a number of growth-stunted children go undiagnosed and untreated. Objectives Our primary aim was to evaluate the prevalence of stunted growth in preschool-aged children. Our secondary aim was to evaluate growth patterns in children belonging to four ethnic groups in Dreux district, France. Methods Body weight, height and body mass index (BMI) were collected for children aged 3–5 years during systematic community visits. Birth variables, family history of short stature, maternal smoking, ethnic origin, etc. were also recorded. Pubertal status was staged as per Tanner’s method. Parents were instructed to attend the hospital growth clinics if their child’s height was <−2.0 standard deviation score (SDS). Results Five hundred ninety-three children were screened (301 boys, 289 girls). The mean age was 4.33 ± 0.76 standard deviation (SD) years, and 48% were Caucasians, 13.7% were North Africans, 2.5% were Black Africans, 0.8% were Asians, 1.5% included others and the ethnicity was not specified in 33.5% of the cases. 91.5% of children were term-born and 8.5% were preterm. 84.2% of children were appropriate for gestational age (AGA) and 9.4% were small for gestational age (SGA). At 5 years of age, 22.2% of macrosomic North African children were overweight. Catch-up growth was complete in 98% children, 11/540 were short statured, 8/11 attended our growth clinics (seven short statured and one micropenis) and three were started on recombinant human growth hormone (rhGH). Conclusions Growth screening programs are important and useful tools for public health. There is a need for clear objectives, proper training and automated data collection tools, along with easy access to growth specialists.

scholarly journals Undernutrition and Pubertal Timing in Female Survivors of Medulloblastoma and Other Embryonal Tumors

2020 ◽  
Vol 105 (10) ◽  
pp. e3650-e3659
Author(s):  
Jia Zhu ◽  
Henry A Feldman ◽  
Christine Chordas ◽  
Ari J Wassner ◽  
Peter E Manley ◽  
...  
Keyword(s):  
Pubertal Timing ◽  
Cohort Analysis ◽  
Standard Deviation Score ◽  
Bone Age ◽  
Embryonal Tumors ◽  
Pubertal Onset ◽  
Pediatric Medulloblastoma ◽  
Catch Up ◽  
The Impact ◽  
Age Discrepancy

Abstract Context Children with brain tumors may have pubertal onset at an inappropriately young chronologic age. Hypothalamic-pituitary irradiation ≥18Gy has been found to be a risk factor; age at irradiation is associated with pubertal timing. However, the underlying mechanisms are unknown. Objective To determine the impact of body mass index (BMI) and catch-up growth on pubertal timing in females treated for medulloblastoma and other embryonal tumors. Design, Setting, and Patients Retrospective cohort analysis of 90 female patients treated for medulloblastoma and other embryonal tumors at Dana-Farber Cancer Institute/Boston Children’s Hospital from 1996 to 2016. Eighteen individuals met inclusion criteria, with a mean ± SD follow-up period of 11.9 ± 3.4 years. Main Outcome Measures Multiple linear regression models for age at pubertal onset and bone age discrepancy from chronologic age at pubertal onset assessed the joint influences of age at irradiation, hypothalamic irradiation dose, undernutrition duration, BMI standard deviation score (SDS) at pubertal onset, and catch-up BMI SDS. Results The mean ± SD age of pubertal onset was 9.2 ± 1.3 years and hypothalamic radiation dose was 31.9 ± 9.9 Gy. There was a direct relationship between age at irradiation and age at pubertal onset (β = 0.323 ± 0.144 [standard error] year per year; P = 0.04) that was significantly attenuated after adjusting for BMI SDS at pubertal onset (P = 0.5) and catch-up BMI SDS (P = 0.08), suggesting that BMI is a mediator. Conclusions Both absolute and catch-up BMI SDS at pubertal onset are significant mediators of pubertal timing and bone age discrepancy in pediatric medulloblastoma and other embryonal tumors, and thus, are targetable risk factors to optimize pubertal timing.

scholarly journals Decreased Thyroxine Levels during rhGH Therapy in Children with Growth Hormone Deficiency

2021 ◽  
Vol 10 (21) ◽  
pp. 5100
Author(s):  
Ewelina Witkowska-Sędek ◽  
Anna Małgorzata Kucharska ◽  
Małgorzata Rumińska ◽  
Monika Paluchowska ◽  
Beata Pyrżak
Keyword(s):  
Growth Hormone ◽  
Thyroid Function ◽  
Growth Response ◽  
Recombinant Human Growth Hormone ◽  
Human Growth ◽  
Bone Age ◽  
Hormone Deficiency ◽  
Lower Growth ◽  
Rhgh Therapy

Background: Hypothyroidism in children leads to growth retardation. However, there is some evidence that recombinant human growth hormone (rhGH) therapy could suppress thyroid function. The most common observation in rhGH-treated patients is a decrease in thyroxine levels, which is reported as transient, but the studies in the field are inconsistent. We aimed to evaluate thyroid function in initially euthyroid children with idiopathic isolated GH deficiency during long-term rhGH therapy and to determine who is at a higher risk of thyroid function alterations during the therapy. Methods: The study group consisted of 101 children treated with rhGH for at least three years. Serum TSH and fT4 levels were determined at baseline, after the first six months and after each full year of therapy. The associations between changes in thyroid hormone levels during rhGH therapy and GH deficit, insulin-like growth factor-1 levels and growth response were investigated. Results: A significant decrease in fT4 levels (p = 0.01) was found as early as after the first six months of rhGH therapy. This effect persisted in the subsequent years of treatment without any significant changes in TSH values and tended to be rhGH dose related. Children with a greater fT4 decrease after the initiation of rhGH therapy were older, had higher bone age and responded to that therapy worse than children with lower fT4 changes. Conclusions: Our study revealed a long-term decrease in fT4 levels during rhGH therapy in initially euthyroid GHD children. The decrease in fT4 levels was associated with a lower growth response to rhGH therapy.

scholarly journals Long-Term Growth Hormone Therapy Does Not Advance Skeletal Maturation in Children and Adolescents

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A679-A679
Author(s):  
Benjamin Udoka Nwosu ◽  
Sadichchha Parajuli ◽  
Gabrielle Jasmin ◽  
Austin F Lee
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Adult Height ◽  
Recombinant Human Growth Hormone ◽  
Bone Age ◽  
Skeletal Maturation ◽  
Z Score ◽  
Rhgh Therapy ◽  
Catch Up

Abstract Context: There is no consensus on the effect of recombinant human growth hormone (rhGH) therapy on skeletal maturation in children despite the current practice of annual monitoring of skeletal maturation with bone age in children on rhGH therapy. Aims: To investigate the effects of long-term rhGH therapy on skeletal age in children and explore the accuracy of bone age predicted adult height (BAPAH) at different ages based on 13 years of longitudinal data. Methods: A retrospective longitudinal study of 71 subjects aged 2-18 years, mean 9.9 ± 3.8y, treated with rhGH for non-syndromic short stature for a duration of 2-14y, mean, 5.5 ± 2.6y. Subjects with syndromic short stature and systemic illnesses such as renal failure were excluded. Results: Bone age minus chronological age (BA-CA) did not differ significantly between baseline and the end of rhGH therapy (-1.05 ± 1.42 vs -0.69 ± 1.63, p=0.09). Piece-wise regression however showed a quantifiable catch-up phenomenon in BA of 1.6 months per year of rhGH therapy in the first 6.5y, 95%CI 0.023 - 0.229, p=0.017, that plateaued thereafter, β=0.015, 95% CI -0.191-0.221, p=0.88. There was no relationship between BAPAH z score – height z score and the duration of rhGH therapy, p=0.68. BAPAH overestimated final adult height in younger subjects but became more precise in older subjects (p&lt;0.0001). Conclusion: Long-term rhGH therapy demonstrated an initial catch-up phenomenon in skeletal maturation in the first 6.5y that plateaued thereafter with no overall significant advancement in bone age. These findings are reassuring and do not support the practice of yearly monitoring of skeletal maturation with bone age in children on rhGH therapy, especially in younger subjects where BAPAH is imprecise.

scholarly journals Nutritional status and metabolic profile in neurologically impaired pediatric surgical patients

2017 ◽  
Vol 30 (3) ◽  
Author(s):  
Gloria Pelizzo ◽  
Valeria Calcaterra ◽  
Veronica Carlini ◽  
Mario Fusillo ◽  
Matteo Manuelli ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Composition ◽  
Energy Intake ◽  
Diastolic Pressure ◽  
Fasting Blood Glucose ◽  
Standard Deviation Score ◽  
Density Lipoprotein ◽  
Adverse Outcomes ◽  
Model Assessment ◽  
Neurologically Impaired

AbstractBackground:Malnutrition is reported in pediatric neuromotor disability and impacts the child’s health. We described the nutritional and metabolic status in neurologically impaired (NI) children undergoing surgery.Methods:Anthropometry, body composition, hormonal and nutritional evaluations were performed in 44 NI subjects (13.7±8.0 years). Energy needs were calculated by Krick’s formula. Metabolic syndrome (MS) was defined applying the following criteria (≥3 defined MS): fasting blood glucose >100 mg/dL and/or homeostasis model assessment for insulin resistance (HOMA-IR) >97.5th percentile, trygliceride level >95th percentile, high-density lipoprotein (HDL)-cholesterol level <5th percentile, systolic/diastolic pressure >95th percentile; whilebody mass index – standard deviation score (BMI-SDS) <2 and biochemical malnutrition markers (≥2) defined undernutrition.Results:Energy intake was not adequate in 73.8% of the patients; no correlation between energy intake and BMI was noted. Undernutrition was noted in 34.1% of patients and MS in 11.36% of subjects. Fifty percent of the patients presented with insulin resistance, which was not related to BMI, body composition or other MS components.Conclusions:Nutritional and metabolic monitoring of disabled children and young adults is recommended to prevent adverse outcomes associated with malnutrition.

scholarly journals The influence of puberty on vitamin D status in obese children and the possible relation between vitamin D deficiency and insulin resistance

2015 ◽  
Vol 28 (1-2) ◽  
Author(s):  
Sonsoles Gutiérrez Medina ◽  
Teresa Gavela-Pérez ◽  
María Nieves Domínguez-Garrido ◽  
Elisa Gutiérrez-Moreno ◽  
Adela Rovira ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Standard Deviation Score ◽  
Normal Weight ◽  
Model Assessment ◽  
Vitamin D Status ◽  
Cross Sectional ◽  
Prepubertal Children ◽  
Vitamin D Levels

Abstract: Puberty can affect vitamin D levels.The goal of this study was to analyze the relation between vitamin D deficiency and puberty in obese Spanish children, along with the possible interrelation between vitamin D status and degree of insulin resistance.A cross-sectional study was carried out, in which clinical and biochemical data were gathered from 120 obese and 50 normal weight children between January 2011 and January 2013.: Mean vitamin D levels were 19.5 and 31.6 ng/mL in obese pubertal and obese prepubertal children, respectively. About 75% of the obese pubertal subjects and 46% of the obese prepubertal subjects had vitamin D deficiency. Vitamin D levels were significantly lower in pubescent subjects compared with pre-pubescent subjects in summer, fall, and winter. There was no apparent relation between vitamin D levels and homeostasis model assessment index for insulin resistence (expressed in standard deviation score for sex and Tanner stage) in either puberty or pre-puberty.: Puberty may be a risk factor for the vitamin D deficiency commonly found in the obese child population. This deficiency is not associated with higher insulin resistance in obese pubertal children compared with obese prepubertal children.

scholarly journals A Retrospective Analysis of Patients with Short Stature in Eastern China between 2013 and 2019

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Qianqian Zhao ◽  
Mei Zhang ◽  
Yuntian Chu ◽  
Hailing Sun ◽  
Hui Pan ◽  
...  
Keyword(s):  
Children And Adolescents ◽  
Short Stature ◽  
Treatment Time ◽  
Recombinant Human Growth Hormone ◽  
Eastern China ◽  
Standard Deviation Score ◽  
Real Life ◽  
Rhgh Therapy ◽  
The Mean ◽  
One Year

Objective. To identify the aetiology of growth and development diseases and assess the long-term effectiveness of recombinant human growth hormone (rhGH) therapy in a real-life clinical setting and provide better guidance in clinical strategy and decision making. Methods. This retrospective study included 1145 children and adolescents with short stature admitted to the Department of Endocrinology, Affiliated Hospital of Jining Medical University, from January 2013 to December 2019, of whom 484 received rhGH treatment. The related anthropometrics and laboratory examinations were assessed in all participants. Results. A total of 1145 children and adolescents with short stature aged 10.5 ± 3.3 years, including 740 boys and 405 girls, were analysed in this study. The number of children and adolescents with short stature gradually increased per year from 2013 to 2019. The mean pretreatment height standard deviation score (SDS) and insulin-like growth factor-1 SDS were − 2.93 ± 1.05 and -1.01 (-1.83--0.16), respectively. The majority of the children (658, 57.47%) were prepubescent. In total, 484 subjects aged 10.6 ± 3.2 years received rhGH and were followed up, and among them, 292 children were treated for more than one year. As the treatment time increased, the children’s height SDS gradually increased, and most of them attained a height SDS within the normal range. The mean height SDS in children who were treated for more than one year was − 3.0 ± 1.0 at baseline and gradually increased to − 0.8 ± 0.3 by year 6. The results were consistent across subgroups of different aetiologies of short stature. Conclusions. Increasing attention has been given to the height of children during the period of 2013–2019 in eastern China. The present findings indicate that children with short stature need to be referred to a specialist centre to diagnose the cause of growth failure and that short children receiving rhGH therapy show a significant increase in height over time.

Recombinant Human Growth Hormone (rhGH) Treatment of Children Undergoing Peritoneal Dialysis

1990 ◽  
Vol 10 (3) ◽  
pp. 209-214 ◽  
Author(s):  
Richard N. Fine ◽  
Vera H. Koch ◽  
M. Ines Boechat ◽  
Barbara H. Lippe ◽  
Pauline A. Nelson ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Peritoneal Dialysis ◽  
Growth Velocity ◽  
Recombinant Human Growth Hormone ◽  
Standard Deviation Score ◽  
Hormone Deficiency ◽  
Height Velocity ◽  
Recombinant Growth Hormone ◽  
Rhgh Therapy ◽  
Rhgh Treatment

The authors studied the effect of recombinant growth hormone (rhGH) treatment on 5 growth retarded children, age 21/12 to 178/12 years, who had end-stage renal disease (ESRD) and were undergoing continuous cycling peritoneal dialysis (CCPD). Patients received 0.125 mg/kg of subcutaneous rhGH 3 times weekly. Accelerated height velocity compared to the previous year of CCPD was noted in 2 patients and improvement in the standard deviation score (SDS) as a parameter of improved growth velocity was noted in a third patient. This was associated with an increase in weight and improvement in the midarm muscle circumference (MAMC) suggesting an anabolic effect of rhGH treatment. Bone age advancement was consistent with the period of observation; no advancement greater than that expected for the increase in chronological age was observed. No significant side effects were attributable to rhGH therapy. These preliminary results indicate some growth retarded children without growth hormone deficiency with ESRD undergoing CCPD may respond to exogenous rhGH therapy with an acceleration in growth velocity: However, the failure to achieve uniform acceleration of height velocity indicates the need for controlled studies before rhGH can be recommended for all growth retarded children with ESRD undergoing peritoneal dialysis.

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