Evaluation of growth hormone response to GHRH plus arginine test in children with idiopathic short stature: role of peak time

Castagno, Matteo; Monzani, Alice; Zanetta, Sara; Genoni, Giulia; Giglione, Enza; Ricotti, Roberta; Bona, Gianni; Prodam, Flavia; Bellone, Simonetta

doi:10.1007/s40618-017-0824-6

Cited by 6 publications

(4 citation statements)

References 26 publications

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“…Both GHSR and GHSV showed a good correlation to IoR. Although an earlier study had shown that GH peak at 45 min was associated with a better response to treatment [25], our results did not support that GHSR contributed additively to the diagnostic ability of the single GHmax value. We reached the same conclusion for the GHSV index, showing that the total GH secreted does not contribute to increased predictability of growth response to rhGH treatment.…”

Section: Discussioncontrasting

confidence: 98%

Growth hormone treatment response: associated factors and stimulated growth hormone secretion indices in prepubertal children with idiopathic GH deficiency

Giannakopoulos,

Kallimani,

Efthymiadou

et al. 2024

Preprint

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Purpose The aim of this study is to correlate the growth response in prepubertal children with idiopathic growth hormone (GH) deficiency after one year of treatment with growth hormone to the initial clinical and biochemical parameters. It also aims to study the secretory dynamics of GH by analyzing the profiles of GH stimulation tests in relation to the recombinant GH (rhGH) treatment response.Methods This a retrospective study which included 84 prepubertal children (47 males and 37 females) with a definitive diagnosis of GH deficiency. The GH secretory indexes GHmax, GH secretion rate (GHSR) and GH secretion volume (GHSV) were analyzed in relation to the response to rhGH treatment as defined by the index of responsiveness (IoR). Correlation and regression models were used to identify the best clinical and biochemical predictors to rhGH treatment.Results IoR was correlated negatively with the age (r=-0.607, p < 0.01) and positively with the distance of child’s height from its MPH r = 0.466 (p < 0.01) and pretreatment growth velocity (r = 0.247, p < 0.05). GH secretory indexes correlated together, with the highest association being observed between GHmax and GHSV (r = 0.883, p < 0.01). Regarding the GH secretory indexes, GHmax was the best predictor of IoR (β coef. = -0.514, p < 0.001) followed by the GHSV (β coef. = -0.47, p < 0.001) and GHSR (β coef. = -0.367 p < 0.001).Conclusions The age and the distance of child’s height from its MPH are major predictors of rhGH treatment response in children with idiopathic GH deficiency. The calculation of the other GH secretory indexes GHSR and GHSV are not better predictors of response to rhGH than GHmax. The combination of clinical and biochemical indexes may improve the pretreatment assessment of response to rhGH treatment.

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Section: Discussioncontrasting

confidence: 98%

Growth hormone treatment response: associated factors and stimulated growth hormone secretion indices in prepubertal children with idiopathic GH deficiency

Giannakopoulos,

Kallimani,

Efthymiadou

et al. 2024

Preprint

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“…Therefore, for proper diagnosis, are considered a H-SD lower than −2SD for age and sex in addition to a subnormal growth rate, delayed bone age, no apparent medical cause for growth failure (brain injury history, systemic, endocrine, nutritional, and chromosomal abnormalities or being born small to gestational age), and normal growth hormone (GH) response to provocative testing (43). Children with ISS are of normal size at birth but grow slowly during early childhood, so height is within the range for ISS at school beginning (44, 45). In 2003, the U.S. Food and Drug Administration approves the rhGH as a treatment for ISS and several studies have reported positive results in that approach (46–48).…”

Section: Discussionmentioning

confidence: 99%

Diagnosis of Idiopathic GHD in Children Based on Response to rhGH Treatment: The Importance of GH Provocative Tests and IGF-1

et al. 2019

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Purpose: Serum IGF-1 (Insulin like growth factor 1) and Growth Hormone (GH) provocative tests are reasonable tools for screening and diagnosis of idiopathic GH Deficiency (IGHD). However, the average cut-off points applied on these tests have a lower level of evidence and produce large amounts of false results. The aim of this study is to evaluate the sensitivity, specificity, and accuracy of IGF-1 and GH stimulation tests as diagnostic tools for IGHD, using clinical response to recombinant human GH (rhGH) treatment as diagnostic standard [increase of at least 0.3 in height standard deviation (H-SD) in 1 year].Methods: We performed a prospective study with 115 children and adolescents presenting short stature (SS), without secondary SS etiologies such as organic lesions, genetic syndromes, thyroid disorders. They were separated into Group 1 [patients with familial SS or constitutional delay of growth and puberty (CDGP), not treated with rhGH], Group 2 (patients with suspicion of IGHD with clinical response to rhGH treatment), and Group 3 (patients with suspicion of IGHD without growth response to rhGH treatment). Then, they were assessed for diagnostic performance of IGF-1, Insulin Tolerance Test (ITT) and clonidine test (CT) alone and combined at different cut-off points.Results: Based on the ROC curve, the best cut-off points found for IGF-1, ITT, and CT when they were used isolated were −0.492 SDS (sensitivity: 50%; specificity: 53.8%; accuracy: 46.5%), 4.515 μg/L (sensitivity: 75.5%; specificity: 45.5%; accuracy: 52.7%), and 4.095 μg/L (sensitivity: 54.5%; specificity: 52.6%; accuracy: 56.9%), respectively. When we had combined IGF-1 with−2SD as cut-off alongside ITT or CT, we found 7 μg/L as the best cut-off point. In this situation, ITT had sensitivity, specificity and accuracy of 93.9, 81.8, and 90.1%, while CT had 93.2, 68.4, and 85.7%, respectively.Conclusion: Our data suggest that diagnosis of IGHD should be established based on a combination of clinical expertise, auxologic, radiologic, and laboratorial data, using IGF-1 at the −2SD threshold combined, with ITT or CT at the cut-off point of 7 μg/L. Additional studies, similar to ours, are imperative to establish cut-off points based on therapeutic response to rhGH in IGHD, which would be directly related to a better treatment outcome.

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“…Tis evidence resulted in the hypothesis that ARG inhibited hypothalamic somatostatin [19]. Some evidence supports the hypothesis that ARG has somatostatin-mediated action [35]. ARG afects GH release by resisting the inhibitory efect of glucose and free fatty acids [3,5].…”

Section: Discussionmentioning

confidence: 92%

“…Most studies used infusion type supplements; however, four studies assessed the effect of oral supplements [ 6 , 28 , 33 , 34 , 36 ]. Twenty-one studies assessed the response of GH to ARG alone [ 6 , 8 , 11 – 13 , 28 – 30 , 32 , 34 , 36 , 38 , 44 , 50 , 53 – 55 , 62 , 63 , 65 , 66 ], and twenty-one studies investigated the response of GH to ARG + GHRH [ 6 , 8 , 31 , 33 , 35 , 37 , 40 – 43 , 47 – 49 , 52 , 56 – 59 , 61 , 67 , 68 ]. Some studies demonstrated the responsiveness of GH to combinations of ARG with other amino acids like lysine and ornithine [ 30 , 39 ].…”

Section: Resultsmentioning

confidence: 99%

Growth Hormone Response to L-Arginine Alone and Combined with Different Doses of Growth Hormone-Releasing Hormone: A Systematic Review and Meta-Analysis

Goli

Yazdi

Heidari‐Beni

et al. 2022

International Journal of Endocrinology

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Background. Arginine (ARG) can modulate growth hormone (GH) release by suppressing its endogenous inhibitory regulator, somatostatin. ARG also induces the release of the GH-releasing hormone (GHRH). This study aims to review the effects of L-arginine supplementation alone and combined with GHRH in different doses on GH secretion. Methods. In this systematic review and meta-analysis, an electronic literature search was conducted on Medline database (PubMed), Scopus, and Web of Science databases. All eligible studies were randomized clinical trials that reported the effects of ARG supplementation alone or with GHRH on GH levels. Mean difference (MD) and 95% confidence intervals (CI) were computed as the effect size. Results. Meta-analyses showed significant effects of ARG alone on GH release (MD = 10.07, 95% CI: 7.87, 12.28). Moreover, the response of GH was greater with ARG in combination with GHRH (MD = 24.96, 95% CI: 17.51, 32.42). There was no significant difference between the patients and healthy individuals and between oral and injection use of ARG. The systematic review revealed the important role of ARG in combination with other amino acids on GH secretion in patients with GH deficiency. Conclusion. This study revealed that in GH-deficient individuals, high doses of ARG supplementation in combination with GHRH and/or other amino acids might have potential therapeutic effects on increasing GH concentrations. These findings propose that ARG supplementation can be considered as a potential stimulator in management of GH deficiency.

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Evaluation of growth hormone response to GHRH plus arginine test in children with idiopathic short stature: role of peak time

Cited by 6 publications

References 26 publications

Growth hormone treatment response: associated factors and stimulated growth hormone secretion indices in prepubertal children with idiopathic GH deficiency

Growth hormone treatment response: associated factors and stimulated growth hormone secretion indices in prepubertal children with idiopathic GH deficiency

Diagnosis of Idiopathic GHD in Children Based on Response to rhGH Treatment: The Importance of GH Provocative Tests and IGF-1

Growth Hormone Response to L-Arginine Alone and Combined with Different Doses of Growth Hormone-Releasing Hormone: A Systematic Review and Meta-Analysis

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