Statural development parallels IGFI levels in subjects of constitutionally variant stature

1987 ◽  
Vol 114 (4) ◽  
pp. 524-530 ◽  
Author(s):  
Michel Binoux ◽  
Micheline Gourmelen
Keyword(s):  
Growth Rate ◽  
Children And Adolescents ◽  
Normal Growth ◽  
Bone Age ◽  
Serum Levels ◽  
Normal Children ◽  
Gh Secretion ◽  
Stage Of Development ◽  
Igf I ◽  
The Individual

Abstract. Using a protein-binding assay which measures mainly IGF I, serum levels of insulin-like growth factor (IGF) were determined in 263 children and adolescents of constitutionally variant stature but with normal GH secretion following provocative stimuli. A positive correlation was found between height age and the logarithm of IGF levels (r = 0.67, P < 0.001). Furthermore, a correlation was found in the tall and short subjects as a group between the ratio of IGF/normal IGF for age and between the ratio of growth rate/normal growth rate for age (r = 0.53, P < 0.001). Subjects were compared at the same stage of development. At a given bone age or stage of puberty, tall subjects had significantly higher IGF levels than short subjects (P < 0.005). After the completion of growth, IGF levels in both short and tall subjects stabilized within the normal range. Nevertheless, their mean levels remained significantly different (P < 0.001). Our results suggest that in normal children and adolescents, differences in IGF I secretion may be at least partially responsible for the individual differences in growth.

scholarly journals Stimulating effect of growth hormone on cytokine release in children

2003 ◽  
pp. 397-401 ◽  
Author(s):  
M Bozzola ◽  
F De Benedetti ◽  
M De Amici ◽  
B Jouret ◽  
P Travaglino ◽  
...  
Keyword(s):  
Short Stature ◽  
Standard Deviation Score ◽  
Bone Age ◽  
Serum Levels ◽  
Tnf Alpha ◽  
Cytokine Release ◽  
Normal Children ◽  
Short Children ◽  
Igf I ◽  
Design And Methods

OBJECTIVE: The aim of the present study was to investigate the effect of exogenously administered GH on serum levels of interleukin (IL)-1beta, IL-2, IL-12, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma and their relation with IGF-I levels in normal short stature children. DESIGN AND METHODS: 23 short prepubertal non GH-deficient children (10 females and 13 males) whose mean+/-s.d. chronological age was 11.95+/-1.85 Years (from 8.80 to 14.89 Years), and mean+/-s.d. bone age was 10.48+/-2.44 Years, were evaluated during a somatomedin generation test (human GH 0.1 IU/kg per day for 4 days) to exclude a partial GH resistance as the cause of short stature; 34 sex- and age-matched healthy subjects were studied as controls. Circulating cytokine values were measured in basal conditions in all children, and 12 h following the 4th GH subcutaneous injection in the 23 short children only. RESULTS: No significant differences were found between short children and controls in basal values of serum IGF-I (192.1+/-18.3 and 198.2+/-28.2 ng/ml respectively). In short subjects there was a significant increase in serum IGF-I levels after the 4th GH injection (from 192.1+/-18.3 ng/ml, i.e. -1.16+/-0.16 standard deviation score (SDS) to 338.2+/-27.1 ng/ml, i.e. 0.14+/-0.17; P<0.00001). No significant differences were found between short children and controls in basal concentrations of serum INF-gamma (19+/-4 and 26+/-5 mIU/ml respectively), IL-1alpha (24.950+/-3.613 and 20.896+/-2.778 pg/ml respectively), IL-2 (3.945+/-1.209 and 4.794+/-0.562 pg/ml respectively), IL-12 (1.093+/-0.269 and 1.976+/-0.596 pg/ml respectively), and TNF-alpha (1.794+/-0.559 and 2.188+/-0.346 pg/ml respectively). Likewise, a significant increase was found in serum INF-gamma (before 19+/-4 and after four GH injections 185+/-57 mIU/ml respectively; P<0.008), IL-1beta (24.950+/-3.613 to 43.339+/-5.431 pg/ml respectively; P<0.0001), IL-2 (3.945+/-1.209 to 9.165+/-2.331 pg/ml respectively; P<0.003), IL-12 (1.093+/-0.269 to 3.724+/-0.637 pg/ml respectively; P<0.0007) and TNF-alpha (1.794+/-0.559 to 9.266+/-3.066 pg/ml respectively; P<0.01). CONCLUSIONS: Cytokine release can be affected by short-term GH administration in normal children indicating a direct influence of GH on the immune system.

Growth hormone, somatomedin levels and growth regulation in Turner's syndrome

1987 ◽  
Vol 116 (2) ◽  
pp. 305-313 ◽  
Author(s):  
Michael B. Ranke ◽  
Werner F. Blum ◽  
Frank Haug ◽  
Werner Rosendahl ◽  
Andrea Attanasio ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Regulation ◽  
Bone Age ◽  
Serum Levels ◽  
Turner's Syndrome ◽  
Turner’S Syndrome ◽  
Normal Range ◽  
Cross Sectional ◽  
Gh Secretion ◽  
Igf I

Abstract. In a total of 56 children and adolescents with Turner's syndrome (41 with karyotype 45,X) basal serum levels of somatomedin bioactivity, Sm-C/IGF-I (RIA), IGF II (RIA), GH response to arginine and GHRH (GRF(1-29)NH2), and spontaneous GH secretion during 5.5 h of deep sleep were determined in a cross-sectional manner. GH responses to GRF and arginine as well as IGF-II levels were found to be in the normal range. Levels of somatomedin bioactivity were higher than normal before a bone age of 10 years, in the low-normal range thereafter, and below normal in some patients. Levels of Sm-C/IGF-I were found normal before and low-normal after a bone age of ten years. There was a trend towards increasing Sm-C/IGF-I levels with age. In contrast to the normal pattern, spontaneous sleep-related GH secretion was declining with age and did not show the puberty-associated rise. These findings suggest a normally functioning growth hormone-somatomedin axis in Turner's syndrome with alterations of its functioning level occurring secondarily as a result of absent gonadal activation. In single patients abnormally low growth hormone and/or somatomedin secretion may be present.

scholarly journals Differential Diagnosis of the Short IGF-I-Deficient Child with Apparently Normal Growth Hormone Secretion

2021 ◽  
pp. 1-24
Author(s):  
Jan M. Wit ◽  
Sjoerd D. Joustra ◽  
Monique Losekoot ◽  
Hermine A. van Duyvenvoorde ◽  
Christiaan de Bruin
Keyword(s):  
Growth Hormone ◽  
Differential Diagnosis ◽  
Growth Hormone Secretion ◽  
Normal Growth ◽  
Stimulation Test ◽  
Healthy Children ◽  
Genetic Causes ◽  
Gh Secretion ◽  
Igf I

The current differential diagnosis for a short child with low insulin-like growth factor I (IGF-I) and a normal growth hormone (GH) peak in a GH stimulation test (GHST), after exclusion of acquired causes, includes the following disorders: (1) a decreased spontaneous GH secretion in contrast to a normal stimulated GH peak (“GH neurosecretory dysfunction,” GHND) and (2) genetic conditions with a normal GH sensitivity (e.g., pathogenic variants of <i>GH1</i> or <i>GHSR</i>) and (3) GH insensitivity (GHI). We present a critical appraisal of the concept of GHND and the role of 12- or 24-h GH profiles in the selection of children for GH treatment. The mean 24-h GH concentration in healthy children overlaps with that in those with GH deficiency, indicating that the previously proposed cutoff limit (3.0–3.2 μg/L) is too high. The main advantage of performing a GH profile is that it prevents about 20% of false-positive test results of the GHST, while it also detects a low spontaneous GH secretion in children who would be considered GH sufficient based on a stimulation test. However, due to a considerable burden for patients and the health budget, GH profiles are only used in few centres. Regarding genetic causes, there is good evidence of the existence of Kowarski syndrome (due to <i>GH1</i> variants) but less on the role of <i>GHSR</i> variants. Several genetic causes of (partial) GHI are known (<i>GHR</i>, <i>STAT5B</i>, <i>STAT3</i>, <i>IGF1</i>, <i>IGFALS</i> defects, and Noonan and 3M syndromes), some responding positively to GH therapy. In the final section, we speculate on hypothetical causes.

scholarly journals Cut-off limits of the peak GH response to stimulation tests for the diagnosis of GH deficiency in children and adolescents: study in patients with organic GHD

2016 ◽  
Vol 175 (1) ◽  
pp. 41-47 ◽  
Author(s):  
Chiara Guzzetti ◽  
Anastasia Ibba ◽  
Sabrina Pilia ◽  
Nadia Beltrami ◽  
Natascia Di Iorgi ◽  
...  
Keyword(s):  
Diagnostic Accuracy ◽  
Children And Adolescents ◽  
Roc Analysis ◽  
Operating Characteristic ◽  
Gh Deficiency ◽  
Tolerance Test ◽  
Gh Secretion ◽  
Insulin Tolerance ◽  
Igf I ◽  
Stimulation Tests

ObjectiveThe diagnosis of GH deficiency (GHD) in children and adolescents is established when GH concentrations fail to reach an arbitrary cut-off level after at least two provocative tests. The objective of the study was to define the optimal GH cut-offs to provocative tests in children and adolescents.DesignRetrospective study in 372 subjects who underwent evaluation of GH secretion. GH and IGF-I were measured by chemiluminescence assay in all samples. Receiver operating characteristic (ROC) analysis was used to evaluate the optimal GH cut-offs and the diagnostic accuracy of provocative tests.MethodsSeventy four patients with organic GHD (GH peak <10μg/L after two provocative tests) and 298 control subjects (GH response >10μg/L to at least one test) were included in the study. The provocative tests used were arginine, insulin tolerance test (ITT) and clonidine. Diagnostic criteria based on cut-offs identified by ROC analysis (best pair of values for sensitivity and specificity) were evaluated for each test individually and for each test combined with IGF-I SDS.ResultsThe optimal GH cut-off for arginine resulted 6.5μg/L, 5.1μg/L for ITT and 6.8μg/L for clonidine. IGF-I SDS has low accuracy in diagnosing GHD (AUC=0.85). The combination of the results of provocative tests with IGF-I concentrations increased the specificity.ConclusionsThe results of the ROC analysis showed that the cut-off limits which discriminate between normal and GHD are lower than those commonly employed. IGF-I is characterized by low diagnostic accuracy.

scholarly journals Changes in Serum Immunoreactive and Bioactive Growth Hormone Concentrations in Boys with Advancing Puberty and in Response to a 20-Hour Estradiol Infusion1

1997 ◽  
Vol 82 (7) ◽  
pp. 2166-2171
Author(s):  
Ayse Pinar Cemeroglu ◽  
Ariel L. Barkan ◽  
Gad B. Kletter ◽  
Inese Z. Beitins ◽  
Carol M. Foster
Keyword(s):  
Serum Sample ◽  
Bone Age ◽  
Saline Infusion ◽  
Pubertal Maturation ◽  
Gh Secretion ◽  
Group 4 ◽  
Igf I ◽  
Prepubertal Boys ◽  
The Mean ◽  
Serum Gh

Acceleration of linear growth during puberty is associated with increased GH secretion, although the relationship between growth and GH is complex. As GH exists as a family of isoforms, some of which may not be identified by immunoassay, there may be alterations in isoform secretion during pubertal maturation that result in increased growth. The changes in serum immunoreactive and bioactive GH concentrations across pubertal maturation were determined in 30 boys, aged 6.5–19.3 yr, with idiopathic short stature or constitutional delay of adolescence. Data were grouped as follows: 1) 6 prepubertal boys with bone age 7 yr or less; 2) 5 prepubertal boys with bone age of more than 7 yr; 3) 10 boys in early puberty; 4) 9 boys with mid- to late puberty. Blood was obtained every 20 min from 2000–0800 h. An equal aliquot of each serum sample was pooled for determination of GH by bio- and immunoassays. The mean serum immunoreactive GH concentration increased from 2.1 ± 0.3, 1.8 ± 0.3, and 2.9 ± 0.5 μg/L in groups 1, 2, and 3, respectively, to a peak of 4.6 ± 0.7 μg/L in group 4 (P &lt; 0.05 vs. groups 1–3). The mean serum GH bioactivity was 48 ± 13 μg/L in group 1 and declined to 39 ± 8 and 31 ± 3 μg/L in groups 2 and 3, increasing to a maximum of 64 ± 15 μg/L in group 4 (P &lt; 0.05 vs. group 3). The ratio of bioactive to immunoreactive GH suggests that the biopotencies of secreted isoforms do not increase during pubertal maturation. The role of E2 in increasing GH secretion was characterized in 8 additional early pubertal boys. Each boy received a saline infusion from 1000–0800 h, followed 1 week later by an infusion of E2 at 4.6 nmol/m2·h. Blood was obtained every 15 min from 2200–0800 h for GH and LH and every 60 min for E2 and testosterone. An equal aliquot of each overnight serum sample was pooled for insulin-like growth factor I (IGF-I) and GH by immuno- and bioassays. The mean serum LH concentration decreased from 5.0 ± 0.9 to 2.3 ± 0.6 IU/L (P &lt; 0.01), and the E2 concentration increased from 22 ± 4 to 81 ± 26 pmol/L (P &lt; 0.01) during saline and E2 infusions, respectively. Mean serum GH concentrations as measured by immunoassay were similar during both infusions (6.6 ± 1.4 vs. 9.7 ± 2.1 μg/L; saline vs. E2 infusion, respectively). In contrast, the mean serum GH concentration, as measured by bioassay, decreased from 48 ± 10 μg/L during saline infusion to 16± 3 μg/L during E2 infusion (P &lt; 0.05). The mean serum IGF-I concentration also decreased significantly from 116 ± 17 to 93 ± 15 μg/L (saline vs. E2 infusion, respectively; P &lt; 0.05). Thus, although mean overnight serum GH concentrations increase in late puberty, whether measured by immuno- or bioassay, an acute increase in E2 produces an acute decline in serum GH bioactivity and a lesser decline in the serum IGF-I concentration. These unexpected changes indicate that E2 may affect pubertal growth and GH secretion in a complex or biphasic manner depending on the context in which it is administered.

scholarly journals Serum Levels of Free Insulin-Like Growth Factor (IGF)-I in Normal Children

2004 ◽  
Vol 13 (1) ◽  
pp. 71-78 ◽  
Author(s):  
Atsuko Nimura ◽  
Noriyuki Katsumata ◽  
Toshiaki Tanaka
Keyword(s):  
Growth Factor ◽  
Serum Levels ◽  
Insulin Like Growth Factor ◽  
Normal Children ◽  
Free Insulin ◽  
Igf I

scholarly journals The role of IGF binding protein-3 as a parameter of activity in acromegalic patients

1999 ◽  
pp. 145-148 ◽  
Author(s):  
I Halperin ◽  
R Casamitjana ◽  
L Flores ◽  
M Fernandez-Balsells ◽  
E Vilardell
Keyword(s):  
Binding Protein ◽  
Serum Levels ◽  
Glucose Load ◽  
Gh Secretion ◽  
Igf I ◽  
Igf Binding ◽  
Igf Binding Protein ◽  
Normal Standard ◽  
Igfbp 3

OBJECTIVE: The production of insulin-like growth factor binding protein-3 (IGFBP-3), the main IGF-I binding protein, is regulated by GH, and its serum levels are increased in acromegaly. We investigated its potential value as a parameter of acromegaly activity or remission in comparison with IGF-I, taking GH suppression below 2 microg/l after glucose load as the normal standard. METHODS: Data from 40 acromegalic patients (12 males and 28 females, aged 28 to 79 years) were obtained retrospectively from stored samples. From these, 145 pairs of IGF-I/IGFBP-3 values were collected; in 67 of them, simultaneous measurement of GH after glucose loading allowed their classification as active or inactive acromegaly. Relationships between IGF-I, IGFBP-3 and GH after glucose load were assessed, as well as differences between IGF-I and IGFBP-3 levels in active and inactive acromegaly. RESULTS: Significant positive correlation between IGF-I and IGFBP-3 in 145 samples was observed (r=0.49, P<0. 0001). As for the 67 samples in which activity or remission could be defined in terms of GH after glucose load, 50 were active and 17 inactive. Both IGF-I and IGFBP-3 significantly correlated with minimum GH (r=0.53, P<0.0001 and r=0.41, P<0.001 respectively). For both parameters, significant differences of means between active and inactive cases were observed (623+/-296 vs 300+/-108 ng/ml, P<0.0001 for IGF-I, and 4.1+/-1.3 vs 3.2+/-0.9 microg/ml, P<0.006 for IGFBP-3). Yet, when comparing in individual cases their classification as active or inactive with the finding of normal or increased IGF-I and IGFBP-3, among active cases 16% appeared as normal according to IGF-I, and 50% appeared as normal in terms of IGFBP-3. Among inactive cases, 23.5% appeared as active according to IGF-I, while 17.5% appeared as active in terms of IGFBP-3. CONCLUSION: Even though IGFBP-3 reflects GH secretion, it offers no advantage over IGF-I in the assessment of acromegaly, and it may underestimate disease activity in acromegalic patients.

scholarly journals Partial Primary Deficiency of Insulin-Like Growth Factor (IGF)-I Activity Associated with IGF1 Mutation Demonstrates Its Critical Role in Growth and Brain Development

2009 ◽  
Vol 23 (11) ◽  
pp. 1936-1936
Author(s):  
Irène Netchine ◽  
Salah Azzi ◽  
Muriel Houang ◽  
Danielle Seurin ◽  
Laurence Perin ◽  
...  
Keyword(s):  
Brain Development ◽  
Critical Role ◽  
Growth Failure ◽  
Normal Growth ◽  
Serum Levels ◽  
Partial Loss ◽  
Therapeutic Implications ◽  
Molecular Defects ◽  
Igf I ◽  
Igfbp 3

ABSTRACT Context IGF-I is essential for fetal and postnatal development. Only three IGF1 defects leading to dramatic loss of binding to its type 1 receptor, IGF-1R, have been reported. Patient We describe a very lean boy who has intrauterine growth restriction and progressive postnatal growth failure associated with normal hearing, microcephaly, and mild intellectual impairment. He had markedly reduced concentrations of IGF-I, with IGFBP-3 and ALS serum levels in the upper normal range or above. IGF-I serum concentrations differed according to the immunoassay used. A higher than average GH dose was required for catch-up growth. Given the mismatch between IGF-I and IGFBP-3 levels, we sequenced his IGF1 gene. Result We identified a homozygous missense IGF1 mutation. This causes the replacement of a highly conserved amino acid (arginine 36) by a glutamine (R36Q) in the C domain of the predicted peptide. We showed that the abnormal IGF-I peptide has reduced mitogenic activity and partial loss of binding to its receptor IGF-1R. The patient’s IGF-I level was undetectable in a highly specific monoclonal assay but elevated in a polyclonal assay. Conclusion This first report of mild deficiency of IGF-I activity demonstrates that the integrity of IGF-I signaling is important for normal growth and brain development. Molecular defects leading to partial loss of IGF-I activity may not be uncommon in patients born small for gestational age. The characterization of this complex phenotype and identification of such molecular defects have therapeutic implications, particularly now that, in addition to GH, recombinant IGF-I is available for clinical use.

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