Variable Degree of Growth Hormone (GH) and Insulin-Like Growth Factor (IGF) Sensitivity in Children with Idiopathic Short Stature Compared with GH-Deficient Patients: Evidence from an IGF-Based Dosing Study of Short Children

Cohen, Pinchas; Germak, John; Rogol, Alan D.; Weng, Wayne; Kappelgaard, Anne-Marie; Rosenfeld, Ron G.

doi:10.1210/jc.2009-2139

Cited by 102 publications

(107 citation statements)

References 26 publications

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“…Variation in the responsiveness to GH therapy implies that individualised dosing of GH according to GH sensitivity may be required in SGA patients. Cohen et al (16,17) showed that targeting higher IGF1 levels by increasing the GH dose in GHD and ISS children resulted in increased change in height in the group of patients who had a GH dosage titrated to achieve IGF1 levels in the upper limit of the normal range compared with those who either had the fixed conventional dose or had received a dosage titrated to achieve IGF1 levels at the mean of a normal range. However, this study only included patients with low IGF1 levels (below K1 SDS), which may exclude those with potential IGF1 resistance.…”

Section: Discussionmentioning

confidence: 99%

“…By contrast, the study on IGF1 titration in GHD and ISS children calculated the difference between measured and target IGF1 SDS using a 20% change in dose for each S.D. unit difference (16,17,18).…”

Section: Discussionmentioning

confidence: 99%

“…Experience in GH-deficient (GHD) and idiopathic short-stature (ISS) children demonstrated not only an increased growth response, but also a higher average GH dose, in those with GH titrated to the upper limit of normal IGF1 (SDS) levels compared with those titrated to achieve a mean IGF1 (SDS) or the conventional dose (16,17,18). IGF1 titration of GH doses in SGA children has not been explored previously.…”

Section: Introductionmentioning

confidence: 99%

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A randomised controlled trial evaluating IGF1 titration in contrast to current GH dosing strategies in children born small for gestational age: the North European Small-for-Gestational-Age Study

Jensen

Thankamony

O’Çonnell

et al. 2014

European Journal of Endocrinology

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Background: Short children born small for gestational age (SGA) are treated with a GH dose based on body size, but treatment may lead to high levels of IGF1. The objective was to evaluate IGF1 titration of GH dose in contrast to current dosing strategies. Methods: In the North European Small-for-Gestational-Age Study (NESGAS), 92 short pre-pubertal children born SGA were randomised after 1 year of high-dose GH treatment (67 mg/kg per day) to three different regimens: high dose (67 mg/kg per day), low dose (35 mg/kg per day) or IGF1 titration. Results: The average dose during the second year of the randomised trial did not differ between the IGF1 titration group (38 mg/kg per day, S.D. 0.019) and the low-dose group (35 mg/kg per day, S.D. 0.002; PZ0.46), but there was a wide variation in the IGF1 titration group (range 10-80 mg/kg per day). The IGF1 titration group had significantly lower height gain (0.17 SDS,

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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A randomised controlled trial evaluating IGF1 titration in contrast to current GH dosing strategies in children born small for gestational age: the North European Small-for-Gestational-Age Study

Jensen

Thankamony

O’Çonnell

et al. 2014

European Journal of Endocrinology

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“…The IGF-1 target chosen affects GH dose requirements, while adjustment of the GH dose to achieve a higher IGF-1 target leads to a faster growth rate. 39,40 However, there are not yet any long-term data regarding whether using a higher serum IGF-1 target will lead to taller adult height.…”

Section: Igf Titration Involves Adjusting the Gh Dose To Keep Igf-1 Imentioning

confidence: 99%

“…52 IGF titration permits adjustment for differences in GH sensitivity between individuals and by gender and by changes in GH sensitivity with age. 20,39,40,53 With standard GH dosing, there is a significant variation in growth rate response and in adult height achieved. More consistently, optimal response might be achieved with individualising treatment.…”

Section: Igf Titration Involves Adjusting the Gh Dose To Keep Igf-1 Imentioning

confidence: 99%

Optimal Therapy of Growth Hormone Deficiency in the Child and Adolescent

Rose¹

2010

European Endocrinology

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Paediatric endocrinologists aspire to provide the best care for children, including improving outcomes in growth hormone deficiency (GHD).The challenging issues are sometimes simple ones, such as which children should be seen in the endocrine clinic for evaluation of their growth, or standards for diagnosis of GHD, or methods of delivering standard therapy for GHD.1 Historically accepted solutions require review as knowledge and technology advance. 2-4This article addresses ways to optimise treatment strategy for children diagnosed with GHD. Optimal therapy of growth disorders depends on accurate diagnosis of the aetiology and identification of the goals of therapy. It is important to understand normal patterns of growth hormone (GH) and insulin-like growth factor (IGF) secretion in order to appreciate differences between normal physiology and hormone patterns induced by therapy. Finally, monitoring for efficacy and safety, identification of interfering factors and making appropriate dose adjustment are all part of optimising GH therapy in childhood GHD. Accurate DiagnosisMany factors besides GH participate in the regulation of normal growth (nutrition, thyroid hormone, genetics, prenatal health, family growth patterns and psychosocial adjustment [see Figure 1]). GH has been administered to children with severe GHD since 1958. Of course, there is no difficulty in making the diagnosis of GHD when the condition is severe. However, with the increasing availability of synthetic recombinant GH, GH therapy has been used in more conditions (see Figure 2). 5 There continues to be controversy about methods for accurate diagnosis of milder degrees of GHD, as well as controversy about which children should be treated with GH.Standardisation of GH assays and cutoff values for normal GH secretion may permit more uniform diagnosis, enabling therapy decisions to be based on reliable data from assays. Goals of TherapyThe purpose of GH treatment must be considered. GH therapy clearly speeds up linear growth in the GHD child and adolescent. However, GHD leads to metabolic effects in addition to slowed linear growth. In untreated GHD, body composition is altered with increased fat mass, decreased lean body mass and decreased accrual of bone mineral. 8-10In addition, individuals with GHD may have decreased exercise tolerance and a sense of fatigue, along with a raised risk for AbstractOptimal therapy of growth disorders depends on accurate diagnosis and clear goals for therapy. Understanding normal patterns of growth hormone (GH) and insulin-like growth factor (IGF) secretion are necessary to appreciate the different hormone pattern induced by therapy.Finally, monitoring efficacy and safety, identifying interfering factors and adjusting doses are all part of optimising GH therapy in childhood GH deficiency (GHD). Prevention of development of GHD would avoid the need for therapy. Options for optimising GH therapy in childhood GHD include initiating treatment as young as possible, facilitating adherence to a therapy plan and adjusti...

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Insulin-Like Growth Factor 1 in the Cardiovascular System

Aguirre

González-Guerra

Espinosa

et al. 2018

Reviews of Physiology, Biochemistry and Pharmacology

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Non-communicable diseases, such as cardiovascular diseases, are the leading cause of mortality worldwide. For this reason, a tremendous effort is being made worldwide to effectively circumvent these afflictions, where insulin-like growth factor 1 (IGF1) is being proposed both as a marker and as a central cornerstone in these diseases, making it an interesting molecule to focus on. Firstly, at the initiation of metabolic deregulation by overfeeding, IGF1 is decreased/inhibited. Secondly, such deficiency seems to be intimately related to the onset of MetS and establishment of vascular derangements leading to atherosclerosis and finally playing a definitive part in cerebrovascular and myocardial accidents, where IGF1 deficiency seems to render these organs vulnerable to oxidative and apoptotic/necrotic damage. Several human cohort correlations together with basic/translational experimental data seem to confirm deep IGF1 implication, albeit with controversy, which might, in part, be given by experimental design leading to blurred result interpretation.

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Variable Degree of Growth Hormone (GH) and Insulin-Like Growth Factor (IGF) Sensitivity in Children with Idiopathic Short Stature Compared with GH-Deficient Patients: Evidence from an IGF-Based Dosing Study of Short Children

Cited by 102 publications

References 26 publications

A randomised controlled trial evaluating IGF1 titration in contrast to current GH dosing strategies in children born small for gestational age: the North European Small-for-Gestational-Age Study

A randomised controlled trial evaluating IGF1 titration in contrast to current GH dosing strategies in children born small for gestational age: the North European Small-for-Gestational-Age Study

Optimal Therapy of Growth Hormone Deficiency in the Child and Adolescent

Insulin-Like Growth Factor 1 in the Cardiovascular System

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