Biochemical markers of growth hormone (GH) sensitivity in children with idiopathic short stature: individual capacity of IGF-I generation after high-dose GH treatment determines the growth response to GH

We analyzed 12-hour serial sampling of growth hormone (GH) levels in two cohorts of short children: 96 children referred to a university endocrine clinic or studied on a research protocol and 825 children in the National Cooperative Growth Study of children treated with exogenous GH. The mean 12-hour GH levels correlated with growth velocity in 60 children with normal height and growth velocity in the university study, and this correlation was stronger in the boys. The testosterone levels also correlated with growth velocity and mean 12-hour GH levels in the boys. The mean 12-hour GH levels were lower in a group of 36 children with idiopathic short stature than in the control subjects, as were the peak GH levels within 1 hour after the onset of sleep and the insulin-like growth factor I levels. In the National Cooperative Growth Study cohort, pooled 12-hour GH levels were lower in the group with idiopathic GH deficiency (n = 300) than in the group with idiopathic short stature (n = 525), but the difference was not significant. The duration of GH treatment was the most significant predictor of change in the height SD score in both groups. Indices of spontaneous secretion of GH were not predictive of the response to GH treatment, nor were the results of provocative GH testing, the responses to GH treatment being similar in both groups over time. We conclude that the results of GH testing must be interpreted for each patient and that several testing modalities may be helpful in finding GH insufficiency that originates at various levels of the somatotropic axis.

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Height Gain and Safety Outcomes in Growth Hormone-Treated Children with Idiopathic Short Stature: Experience from a Prospective Observational Study

Hormone Research in Paediatrics ◽

10.1159/000500087 ◽

2019 ◽

Vol 91 (4) ◽

pp. 241-251 ◽

Cited By ~ 1

Author(s):

Christopher J. Child ◽

Charmian A. Quigley ◽

Gordon B. Cutler, Jr ◽

Wayne V. Moore ◽

Kupper A. Wintergerst ◽

...

Keyword(s):

Growth Hormone ◽

Short Stature ◽

International Study ◽

Study Data ◽

Idiopathic Short Stature ◽

Gh Treatment ◽

Safety Issues ◽

Safety Outcomes ◽

Height Gain ◽

Over Time

Background/Objectives: Growth hormone (GH) treatment of idiopathic short stature (ISS) received US Food and Drug Administration approval in 2003. We assessed height gain and safety in 2,450 children with ISS treated with GH in US clinical practice. Methods: Short-term height gain, near-adult height (NAH), and safety outcomes were investigated using Genetics and Neuroendocrinology of Short Stature International Study data. Results: Compared to children with isolated idiopathic GH deficiency (IGHD), those with ISS were shorter at baseline but had similar age and GH dose. Mean ± SD height SD score (SDS) increase was similar for ISS and IGHD, with 0.6 ± 0.3 (first), 0.4 ± 0.3 (second), 0.3 ± 0.3 (third), and 0.1 ± 0.3 (fourth year) for ISS. Girls with ISS (27% of subjects) were younger and shorter than boys but had similar height gain over time. At NAH in the ISS group (n = 467), mean ± SD age, GH duration, and height SDS were 17.3 ± 2.3 years, 4.6 ± 2.7 years, and –1.2 ± 0.9, respectively. Height gain from baseline was 1.1 ± 1.0 SDS and was greater for boys than girls (1.2 ± 1.0 vs. 0.9 ± 0.9), but boys were treated longer (5.1 ± 2.8 vs. 3.6 ± 2.5 years). Adverse events were reported for 24% with ISS versus 20% with IGHD – most were common childhood conditions or previously reported in GH-treated patients. Conclusions: GH-treated children with ISS achieved substantial height gain, similar to patients with IGHD. Fewer GH-treated girls were enrolled than boys, but with similar height SDS gain over time. No ISS-specific safety issues were identified. Thus, GH treatment of ISS appears to have a safety/effectiveness profile similar to that of IGHD.

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Standard and low-dose IGF-I generation tests and spontaneous growth hormone secretion in children with idiopathic short stature

Clinical Endocrinology ◽

10.1046/j.1365-2265.2004.01957.x ◽

2004 ◽

Vol 60 (2) ◽

pp. 163-168 ◽

Cited By ~ 31

Author(s):

J. C. Blair ◽

C. Camacho-Hübner ◽

F. Miraki Moud ◽

S. Rosberg ◽

C. Burren ◽

...

Keyword(s):

Growth Hormone ◽

Short Stature ◽

Low Dose ◽

Hormone Secretion ◽

Growth Hormone Secretion ◽

Idiopathic Short Stature ◽

Spontaneous Growth ◽

Igf I

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Effect of Zinc Supplementation on Growth Hormone Secretion, IGF-I, IGFBP-3, Somatomedin Generation, Alkaline Phosphatase, Osteocalcin and Growth in Prepubertal Children with Idiopathic Short Stature

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem.2005.18.1.69 ◽

2005 ◽

Vol 18 (1) ◽

Cited By ~ 25

Author(s):

Sebahat Imamoglu ◽

Abdullah Bereket ◽

Serap Turan ◽

Yavuz Taga ◽

Goncagül Haklar

Keyword(s):

Growth Hormone ◽

Alkaline Phosphatase ◽

Short Stature ◽

Zinc Supplementation ◽

Hormone Secretion ◽

Growth Hormone Secretion ◽

Idiopathic Short Stature ◽

Prepubertal Children ◽

Igf I ◽

Igfbp 3

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Insulin-like growth factor I (IGF-I) measurements in growth hormone (GH) therapy of idiopathic short stature (ISS)

Growth Hormone & IGF Research ◽

10.1016/j.ghir.2005.06.011 ◽

2005 ◽

Vol 15 ◽

pp. 13-20 ◽

Cited By ~ 36

Author(s):

Patricia Park ◽

Pinchas Cohen

Keyword(s):

Growth Hormone ◽

Growth Factor ◽

Short Stature ◽

Idiopathic Short Stature ◽

Insulin Like Growth Factor ◽

Gh Therapy ◽

Factor I ◽

Igf I ◽

Growth Factor I

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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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The prevalence and volumetry of pituitary cysts in children with growth hormone deficiency and idiopathic short stature

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2017-0437 ◽

2018 ◽

Vol 0 (0) ◽

Author(s):

Nicholas Krasnow ◽

Bradley Pogostin ◽

James Haigney ◽

Brittany Groh ◽

Winston Weiler ◽

...

Keyword(s):

Growth Hormone ◽

Growth Hormone Deficiency ◽

Short Stature ◽

Growth Failure ◽

Brain Magnetic Resonance Imaging ◽

Idiopathic Short Stature ◽

Hormone Deficiency ◽

Gh Treatment ◽

Cyst Volume ◽

Pituitary Cysts

AbstractBackgroundPituitary cysts have been speculated to cause endocrinopathies. We sought to describe the prevalence and volumetry of pituitary cysts in patients with growth hormone deficiency (GHD) and idiopathic short stature (ISS).MethodsSix hundred and eighteen children evaluated for growth failure at the Division of Pediatric Endocrinology at New York Medical College between the years 2002 and 2012, who underwent GH stimulation testing and had a brain magnetic resonance imaging (MRI) prior to initiating GH treatment were randomly selected to be a part of this study. High resolution MRI was used to evaluate the pituitary gland for size and the presence of a cyst. Cyst prevalence, cyst volume and percentage of the gland occupied by the cyst (POGO) were documented.ResultsFifty-six patients had a cyst, giving an overall prevalence of 9.1%. The prevalence of cysts in GHD patients compared to ISS patients was not significant (13.5% vs. 5.7%, p=0.46). Mean cyst volume was greater in GHD patients than ISS patients (62.0 mm3vs. 29.4 mm3, p=0.01). POGO for GHD patients was significantly greater (p=0.003) than for ISS patients (15.3%±12.8 vs. 7.1%±8.0). Observers were blinded to patient groups.ConclusionsGHD patients had a significantly greater volume and POGO compared to ISS patients. This raises the question of whether cysts are implicated in the pathology of growth failure.

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Bioavailability and bioactivity of three different doses of nasal growth hormone (GH) administered to GH-deficient patients: comparison with intravenous and subcutaneous administration

Acta Endocrinologica ◽

10.1530/eje.0.1350309 ◽

1996 ◽

Vol 135 (3) ◽

pp. 309-315 ◽

Cited By ~ 31

Author(s):

Torben Laursen ◽

Birgitte Grandjean ◽

Jens OL Jørgensen ◽

Jens S Christiansen

Keyword(s):

Growth Hormone ◽

Metabolic Response ◽

Serum Insulin ◽

Subcutaneous Administration ◽

Absolute Bioavailability ◽

High Dose ◽

Gh Treatment ◽

Significant Difference ◽

Igf I ◽

Different Doses

Laursen T, Grandjean B, Jørgensen JOL, Christiansen JS. Bioavailability and bioactivity of three different doses of nasal growth hormone (GH) administered to GH-deflcient patients: comparison with intravenous and subcutaneous administration. Eur J Endocrinol 1996;135:309–15. ISSN 0804–4643 The current mode of growth hormone (GH) replacement therapy is daily subcutaneous (sc) injections given in the evening. This schedule is unable to mimic the endogenous pulsatile pattern of GH secretion, which might be of importance for the induction of growth and other GH actions. The present study was conducted in order to study the pharmacokinetics of different doses of GH following intranasal (IN) administration and the biological activity of GH after IN administration as compared with sc and intravenous (iv) delivery. Sixteen GH-deficient patients were studied on five different occasions. On three occasions GH was administered intranasally in doses of 0.05, 0.10 and 0.20IU/kg, using didecanoyl-l-α-phosphatidylcholine as an enhancer. On the other two occasions the patients received an sc injection (0.10IU/kg) and an iv injection (0.015IU/kg) of GH, respectively. The nasal doses and the sc injection were given in random order in a crossover design. In a double-blinded manner the subjects received the three nasal doses as one puff in each nostril. The patients received no GH treatment between the five studies or during the last week before the start of each study. Intravenous administration produced a short-lived serum GH peak value of 128.12 ± 6.71 μg/l. Peak levels were 13.98±1.63 μg/l after sc injection and 3.26±0.38. 7.07±0.80 and 8.37± 1.31 μg/l, respectively, after the three nasal doses. The peak values of the 0.05 and the 0.20IU/kg nasal doses were significantly different (p = 0.007). The mean levels obtained by the low nasal dose were significantly lower than those obtained with the medium (p < 0.001) and the high dose (p < 0.001). while there was no significant difference between the medium and the high doses. The absolute bioavailability of GH following sc relative to iv administration was 49.5%. The bioavailabilities of the nasal doses were: 7.8% (0.05 IU), 8.9% (0.10 IU) and 3.8% (0.20 IU). Serum insulin-like growth factor I (IGF-I) levels increased significantly after sc administration only. Mean levels were significantly higher after sc administration as compared with the iv and all three nasal does (p < 0.001). Serum IGF binding protein 3 (IGFBP-3) levels remained unchanged on all five occasions. Mean serum IGFBP-1 levels were significantly lower after sc GH injection than after administration of the iv (p < 0.001) and the three nasal doses (p < 0.005). Subcutaneous GH administration resulted in significantly higher levels of serum insulin and blood glucose (p < 0.001). In conclusion, the bioavailability of nasal GH was low (3.8–8.9%). An iv bolus injection of, on average, 1 IU of GH induced no metabolic response. Only sc GH administration induced increased levels of IGF-I, insulin and glucose. These data reveal that a closer imitation of the physiological GH pulses than achieved by sc GH administration is of limited importance for the induction of a metabolic response to GH. Torben Laursen, Medical Department M (Diabetes & Endocrinology), Aarhus Kommunehospital, DK-8000 Aarhus C. Denmark

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