scholarly journals GH Resistance Is a Component of Idiopathic Short Stature: Implications for rhGH Therapy

2021 ◽  
Vol 12 ◽  
Author(s):  
Martin O. Savage ◽  
Helen L. Storr
Keyword(s):  
Short Stature ◽  
Idiopathic Short Stature ◽  
Correct Identification ◽  
Rhgh Therapy ◽  
Short Children ◽  
Selection Of ◽  
Gh Resistance

Idiopathic short stature (ISS) is a term used to describe a selection of short children for whom no precise aetiology has been identified. Molecular investigations have made notable discoveries in children with ISS, thus removing them from this category. However, many, if not the majority of children referred with short stature, are designated ISS. Our interest in defects of GH action, i.e. GH resistance, has led to a study of children with mild GH resistance, who we believe can be mis-categorised as ISS leading to potential inappropriate management. Approval of ISS by the FDA for hGH therapy has resulted in many short children receiving this treatment. The results are extremely variable. It is therefore important to correctly assess and investigate all ISS subjects in order to identify those with mild but unequivocal GH resistance, as in cases of PAPP-A2 deficiency. The correct identification of GH resistance defects will direct therapy towards rhIGF-I rather than rhGH. This example illustrates the importance of recognition of GH resistance among the very large number patients referred with short stature who are labelled as ‘ISS’.

scholarly journals Idiopathic short stature: will genetics influence the choice between GH and IGF-I therapy?

2007 ◽  
Vol 157 (suppl_1) ◽  
pp. S33-S37 ◽  
Author(s):  
Martin O Savage ◽  
Cecilia Camacho-Hübner ◽  
Alessia David ◽  
Louise A Metherell ◽  
Vivian Hwa ◽  
...  
Keyword(s):  
Short Stature ◽  
Growth Regulation ◽  
Single Gene ◽  
Idiopathic Short Stature ◽  
Dominant Negative ◽  
Growth Responses ◽  
Igf I ◽  
The Usa ◽  
Gene Defects ◽  
Gh Resistance

Background: Idiopathic short stature (ISS) includes a range of conditions. Some are caused by defects in the GH–IGF-I axis. ISS is an approved indication for GH therapy in the USA and a similar approval in Europe may be imminent. Genetic analysis for single-gene defects has made enormous contributions to understanding the physiology of growth regulation. Can this type of investigation help in predicting growth responses to GH or IGF-I therapy? Methods: The rationale for choice of GH or IGF-I therapy in ISS is reviewed. Many ISS patients have low IGF-I, but most can generate IGF-I levels in response to short-term GH administration. Some GH resistance seems to be present. Mutation analysis in several cohorts of GHIS and ISS patients is reviewed. Results: Low IGF-I levels suggest either unrecognised GH deficiency or GH resistance. In classical GHIS patients, there was a positive relationship between IGFBP-3 levels and height SDS. No relationship exists between mutations and phenotype. There is a wide variability of phenotype in patients carrying identical mutations. Heterozygous GH receptor (GHR) mutations were present in <5% of ISS patients and their role in causing growth defects is questionable. Exceptions are dominant negative mutations that have been shown to disturb growth. Conclusions: Analysis for single-gene defects does not give sensitive predictions of phenotype and cannot predict responses to GH or IGF-I therapy. Endocrine abnormalities have closer correlations with phenotype and may thus be a better guide to therapeutic responsiveness.

scholarly journals Benefit of postponing normal puberty for improving final height

2004 ◽  
Vol 151 (Suppl_1) ◽  
pp. S41-S45 ◽  
Author(s):  
JM Wit ◽  
HV Balen ◽  
GA Kamp ◽  
W Oostdijk
Keyword(s):  
Short Stature ◽  
Bone Mineralization ◽  
Final Height ◽  
Central Precocious Puberty ◽  
Idiopathic Short Stature ◽  
Gnrh Analog ◽  
Clinical Observations ◽  
Short Children ◽  
Negative Effect ◽  
Height Prediction

Experiments of nature and clinical observations have provided indications that postponing puberty may increase final height in short children. In children with central precocious puberty, a GnRH analog (GnRHa) alone is efficacious in increasing final height, but in other conditions a combination of growth hormone (GH) and GnRHa is needed. In GH-deficient children with early onset of puberty and poor height prediction, the combination of GH and GnRHa increases final height by 1.0-1.3 s.d. In children with idiopathic short stature and persistent short stature after intrauterine growth retardation, the combination also appears to be beneficial. Potential side effects include weight gain, a negative effect on bone mineralization, and psychosocial consequences. More data on long-term safety have to be collected before the combination of GH and GnRHa in children with idiopathic short stature should be considered for clinical use outside clinical trials.

IGF1, IGF1R and SHOX Mutation Analysis in Short Children Born Small for Gestational Age and Short Children with Normal Birth Size (Idiopathic Short Stature)

2012 ◽  
Vol 77 (4) ◽  
pp. 250-260 ◽  
Author(s):  
Janina Caliebe ◽  
Sander Broekman ◽  
Merel Boogaard ◽  
Cathy A.J. Bosch ◽  
Claudia A.L. Ruivenkamp ◽  
...  
Keyword(s):  
Short Stature ◽  
Mutation Analysis ◽  
Gestational Age ◽  
Small For Gestational Age ◽  
Idiopathic Short Stature ◽  
Birth Size ◽  
Normal Birth ◽  
Short Children

scholarly journals Association between Alanine Aminotransferase and Growth Hormone: A Retrospective Cohort Study of Short Children and Adolescents

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Baolan Ji ◽  
Mei Zhang ◽  
Qianqian Zhao ◽  
Yuntian Chu ◽  
Yanying Li ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Cohort Study ◽  
Children And Adolescents ◽  
Short Stature ◽  
Retrospective Cohort Study ◽  
Alanine Aminotransferase ◽  
Retrospective Cohort ◽  
Univariate Analysis ◽  
Rhgh Therapy ◽  
Short Children

Objective. This study aimed to examine the relationship between serum alanine aminotransferase (ALT) and growth hormone (GH) in children and adolescents with short stature. Methods. In this retrospective cohort study, 670 Chinese children and adolescents with short stature were included, and 253 of them received recombinant human GH (rhGH) therapy. Anthropometric and biochemical indicators were measured. GH peak levels were assessed after provocation tests with L-dopa and insulin. The subjects were divided into 3 groups according to the GH peak level. The association between the GH peak and ALT was analyzed. The change of ALT during rhGH therapy was assessed by a generalized additive mixed model. Results. Serum ALT and incidence of ALT elevation were both decreased across the GH tertiles (P = 0.002, 0.012, respectively). A univariate analysis showed that the GH peak was negatively associated with ALT (β: -0.12; 95%CI: -0.22, -0.02; P = 0.023). Furthermore, multiple linear stepwise regression analysis demonstrated that the GH peak was independently related to ALT after adjusting for other confounding variables (β: -0.12; 95%CI: -0.24, -0.00; P = 0.042). Besides, mean values of the change in ALT from baseline displayed that, during the early stages of rhGH treatment, serum ALT level indicated a temporary upward trend, but it subsequently gradually decreased (β: -0.16; 95%CI: -0.23, -0.09; P < 0.001). Conclusions. GH secretion level was strongly negatively correlated with ALT in short children and adolescents. And rhGH therapy could reduce ALT level over time.

Screening for imprinting disorders in 58 patients with clinically diagnosed idiopathic short stature

2020 ◽  
Vol 33 (10) ◽  
pp. 1335-1339
Author(s):  
Sayaka Kawashima ◽  
Hiroko Yagi ◽  
Yasuhiro Hirano ◽  
Machiko Toki ◽  
Kei Izumi ◽  
...  
Keyword(s):  
Short Stature ◽  
Clinical Diagnosis ◽  
Standard Deviation Score ◽  
Growth Failure ◽  
Normal Growth ◽  
Postnatal Growth ◽  
Idiopathic Short Stature ◽  
Imprinted Genes ◽  
Imprinting Disorders ◽  
Short Children

AbstractObjectivesImprinted genes have important roles for normal growth and development. Imprinting disorders (IDs) such as Silver-Russell syndrome and Temple syndrome are rare diseases that typically cause short children born small for gestational age (SGA). However, some patients with short stature (SS) caused by IDs were born non-SGA. To date, the contribution of IDs to idiopathic short stature (ISS) has been poorly investigated. The aim of this study was to clarify the contribution of IDs to ISS.MethodsWe conducted methylation analysis for 10 differentially methylated regions using pyrosequencing to detect known IDs in 58 patients (31 male and 27 female children, height standard deviation score −4.2 to −2.0) carrying a clinical diagnosis of ISS.ResultsWe identified no patient with IDs among these patients with ISS.ConclusionsThese results indicate that IDs are rare in patients having ISS, and that imprinted genes affect fetal growth more than postnatal growth. Because patients with IDs born non-SGA usually have clinical features characteristic of each ID, in addition to SS, the patients with ISS as a clinical diagnosis may not be associated with IDs.It is unlikely that cases clinically diagnosed with ISS are caused by IDs leading to growth failure.

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