scholarly journals Prevalence of IGF1 deficiency in prepubertal children with isolated short stature

2009 ◽  
Vol 161 (1) ◽  
pp. 43-50 ◽  
Author(s):  
T Edouard ◽  
S Grünenwald ◽  
I Gennero ◽  
J P Salles ◽  
M Tauber
Keyword(s):  
Short Stature ◽  
Gestational Age ◽  
Bone Age ◽  
Pediatric Endocrinology ◽  
Exclusion Criteria ◽  
Prepubertal Children ◽  
Gh Secretion ◽  
Appropriate For Gestational Age ◽  
Low Levels ◽  
Igf1 Deficiency

Background/aims‘Primary IGF1 deficiency (IGFD)’ is defined by low levels of IGF1 without a concomitant impairment in GH secretion in the absence of secondary cause. The aims of this study were to evaluate the prevalence of non-GH deficient IGFD in prepubertal children with isolated short stature (SS) and to describe this population.MethodsThis retrospective study included all children with isolated SS seen in our Pediatric Endocrinology Unit from January 2005 to December 2007. Children were included based on the following criteria: i) SS with current height SDS ≤ −2.5, ii) age≥2 years, and iii) prepubertal status. Exclusion criteria were: i) identified cause of SS and ii) current or past therapy with rhGH. IGF1-deficient children were defined as children without GH deficiency and with IGF1 levels below or equal to −2 SDS.ResultsAmong 65 children with isolated SS, 13 (20%) had low IGF1 levels, consistent with a diagnosis of primary IGFD, four of which were born small for gestational age and nine were born appropriate for gestational age. When compared with non-IGFD children, IGFD children had higher birth weight (−0.7 vs −1 SDS, P=0.02) and birth height (−1.7 vs −2 SDS, P=0.04) and more delayed bone age (2.6 vs 1.7 years, P=0.03).ConclusionThe prevalence of primary IGFD was 20% in children with isolated SS. Concerning the pathophysiology, our study emphasizes that IGFD in some children may be secondary to nutritional deficiency or to maturational delay.

scholarly journals Delayed Bone Age Might Accelerate the Response to Human Growth Hormone Treatment in Small for Gestational Age Children with Short Stature

2019 ◽  
Vol 2019 ◽  
pp. 1-6
Author(s):  
Jung-Eun Moon ◽  
Cheol Woo Ko
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Gestational Age ◽  
Small For Gestational Age ◽  
Human Growth ◽  
Bone Age ◽  
Pediatric Endocrinology ◽  
Gh Therapy ◽  
Gh Treatment ◽  
The Impact

Purpose. Growth hormone (GH) treatment is recommended to improve growth and psychosocial problems in short stature children born small for gestational age (SGA). Although GH therapy in these patients has been extensively studied, the impact of therapy according to delays in bone age (BA) is not known well. Objective. To investigate the effects of GH therapy in SGA patients with short stature according to BA delay. Methods. We retrospectively analyzed changes in height SD score (SDS) and BA/chronological age (CA) after 6 and 12 months of GH therapy in patients grouped according to BA delay. We studied 27 SGA children with short stature in the pediatric endocrinology clinic of Kyungpook National University Children’s Hospital. Results. Of the 27 patients, 9 had <2 years of BA delay, while 18 had >2 years of delay. There were no significant differences between the two groups in terms of gestational age and weight at birth, height SDS, IGF-1 SDS, and growth hormone dosage at the beginning of therapy. However, height SDS increased significantly in the group with >2 years of BA delay after 6 months of GH therapy (−2.50 ± 0.61 vs −1.87 ± 0.82; p=0.037) and 12 months (−2.27 ± 0.70 vs −1.63 ± 0.65; p=0.002). When height SDS was compared between with and without GHD, there were no significant differences. Conclusions. Delayed BA (>2 years) may impact the response to GH treatment in SGA children with short stature.

scholarly journals SAT-086 Pituitary Volume as a Diagnostic Measure for Determining the Etiology of Short Stature in Children: Receiver Operating Characteristic Curve Analysis and Cutoff Values

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Liam McGuirk ◽  
Tara P Patale ◽  
Nicholas Andrew Krasnow ◽  
Alice Alexandrov ◽  
James Haigney ◽  
...  
Keyword(s):  
Short Stature ◽  
Standard Error ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Curve Analysis ◽  
Youden Index ◽  
Pediatric Endocrinology ◽  
Roc Curve Analysis ◽  
Gh Secretion ◽  
Cutoff Values

Abstract Background: It is speculated that pituitary volume (PV) is a marker of chronic growth hormone (GH) secretion. In previous studies, we determined that children with GH deficiency (GHD) and idiopathic short stature (ISS) had significantly smaller PVs than normal controls (NCs). Cutoff values for small PVs are needed to improve the clinical utility of PV in determining children who qualify for GH therapy. Objective: To define the cutoff between pathologic and nonpathologic PV in prepubertal and pubertal children with short stature (SS). Patients and Methods: The SS group was selected from the database of a pediatric endocrinology center, which was queried for siblings (SBs) aged 6–18 yrs who underwent a GH stimulation test and MRI between 2013–2019. All 77 SBs had SS, defined as 2 SDs below mean height for age, subnormal growth velocity for at least 6 months, or predicted height at least 2 inches discrepant from midparental height. The NC group was selected from the database of a neuroradiology center; these NCs consisted of 170 randomly selected subjects aged 6–18 yrs. Patients with MRI abnormalities were excluded. PVs were calculated using the ellipsoid formula (LxWxH/2). ROC curve analysis was utilized to generate cutoff values. The diagnosis of short stature was the dependent variable and PV was the independent variable. The PV with the highest Youden index was selected as the definitive cutoff for a small PV. Results: The mean (MN) and median (MD) age of SBs was 11.6 ±2.2 and 11.9 yrs, respectively, and the MN and MD age of the NCs was 12.6 ±3.4 and 13.2 yrs, respectively. The MN and MD age of prepubertal SBs (n=29) and NCs (n=58) were 9.3 ±1.2 and 9.7, and 8.6 ±1.4 and 8.6 yrs, respectively. The MN and MD age of pubertal SBs (n=48) and NCs (n=112) were 13.0 ±1.4 and 12.7, and 14.7 ±1.9 and 14.6 yrs, respectively. The difference in MN age between SBs and NCs was significant (p&lt;0.05). For prepubertal subjects, sensitivity was 86.21% and specificity was 68.97%. The distance to corner was 0.3396, and the highest Youden index was 0.5517, corresponding to a PV of 215.02 mm3. The Area Under the Curve (AUC) was 0.8395 with a standard error of 0.0426 (p&lt;0.001). For pubertal subjects, sensitivity was 81.25% and specificity was 79.46%. The distance to corner was 0.2781, and the highest Youden index was 0.6071, corresponding to a PV of 315.0 mm3. The AUC was 0.8460 with a standard error of 0.0337 (p&lt;0.001). Conclusion: To our knowledge, we present the first study on the sensitivity and specificity of PV in determining the etiology of SS. Our data suggest that prepubertal patients with a PV&lt;215.02 mm3 and pubertal patients with a PV&lt;315.00 mm3 have small pituitary glands. Statistically calculated cutoffs are necessary to accurately diagnose pituitary hypoplasia and should be utilized to determine the etiology of SS. Future studies should include children with Tanner staging and height SDs to generate more accurate PV cutoffs.

scholarly journals Characterization and prevalence of severe primary IGF1 deficiency in a large cohort of French children with short stature

2014 ◽  
Vol 170 (6) ◽  
pp. 847-854 ◽  
Author(s):  
R Teissier ◽  
I Flechtner ◽  
A Colmenares ◽  
K Lambot-Juhan ◽  
G Baujat ◽  
...  
Keyword(s):  
Replacement Therapy ◽  
Short Stature ◽  
Time Course ◽  
Large Cohort ◽  
Test Time ◽  
Pediatric Endocrinology ◽  
Gh Replacement ◽  
Standard Criterion ◽  
Igf1 Deficiency ◽  
Generation Test

ObjectiveThe prevalence of severe primary IGF1 deficiency (IGFD) is unclear. IGFD must be identified promptly as treatment with recombinant human IGF1 (rhIGF1) is now available. Our objective was to characterize and assess the prevalence of severe primary IGFD in a large cohort of patients evaluated for short stature at a pediatric endocrinology unit in France.DesignObservational study in a prospective cohort.MethodsConsecutive patients referred to our unit between 2004 and 2009 for suspected slow statural growth were included. Patients were classified into eight etiological categories. IGFD was defined by height ≤−3 SDS, serum IGF1 levels <2.5th percentile, GH sufficiency, and absence of causes of secondary IGFD.ResultsOut of 2546 patients included, 337 (13.5%) were born small for gestational age and 424 (16.9%) had idiopathic short stature. In these two categories, we identified 30 patients who met our criterion for IGFD (30/2546, 1.2%). In these 30 patients, we assessed the response to IGF1 generation test, time course of IGF1 levels, and efficiency of GH replacement therapy. The results indicated that only four of the 30 children were definite or possible candidates for rhIGF1 replacement therapy.ConclusionThe prevalence of severe primary IGFD defined using the standard criterion for rhIGF1 treatment was 1.2%, and only 0.2% of patients were eligible for rhIGF1 therapy.

scholarly journals Comparison of Clinical, Ultrasonographic, and Biochemical Differences at the Beginning of Puberty in Healthy Girls Born Either Small for Gestational Age or Appropriate for Gestational Age: Preliminary Results

2006 ◽  
Vol 91 (9) ◽  
pp. 3377-3381 ◽  
Author(s):  
M. I. Hernández ◽  
A. Martínez ◽  
T. Capurro ◽  
V. Peña ◽  
L. Trejo ◽  
...  
Keyword(s):  
Gestational Age ◽  
Small For Gestational Age ◽  
Pubertal Development ◽  
Tanner Stage ◽  
Bone Age ◽  
Dehydroepiandrosterone Sulfate ◽  
Early Morning ◽  
Pubic Hair ◽  
Ultrasound Measurements ◽  
Appropriate For Gestational Age

Abstract Context: There are limited and controversial data concerning puberty characteristics in girls born small for gestational age (SGA). Objective: The objective of the study was to document clinical, ultrasonographic, and biochemical characteristics at the beginning of puberty in matched healthy girls born either SGA or appropriate for gestational age (AGA) recruited from the community. Patients: Inclusion criteria were breast Tanner stage II and a body mass index between the 10th and 95th percentiles. Interventions: Recruited subjects underwent a complete physical exam, bone age, and ultrasound measurements of the internal genitalia. Hormonal assessment included fasting early morning dehydroepiandrosterone sulfate, androstenedione, SHBG, inhibin-B, FSH, LH, estradiol (E2), 17-hydroxyprogesterone (17OH Prog), and testosterone. Thereafter, a GnRH agonist test (leuprolide 500 μg, sc) was performed with FSH and LH at time 3 and 24 h for E2, 17OH Prog, and testosterone. Results: Sixty-five girls (35 AGA, 30 SGA) with a mean age of 9.9 ± 1.03 (7.8–12.5) yr, similar bone age/chronological age (1.02 ± 0.8 in AGA and 1 ± 0.76 in SGA), median height of 1.35 ± 0.06 cm, and similar waist to hip ratio were included. No differences in the presence of pubic hair, axillary hair, apocrine odor, or ultrasound measurements were found. SGA girls had increased baseline E2 as well as stimulated E2 and 17OH Prog. Conclusions: In a preliminary sample of lean, healthy girls recruited from the community born either SGA or AGA, we observed slight hormonal differences at the beginning of puberty. Longitudinal follow-up of this cohort will allow us to understand whether these differences are maintained and have a clinical impact in their pubertal development.

scholarly journals Comparison of bone age in small-for-gestationalage children vs appropriate-for-getational-age children

2010 ◽  
Vol 50 (2) ◽  
pp. 73
Author(s):  
Lionardus Edward ◽  
Sjarif Hidajat Effendi ◽  
Djatnika Setiabudi
Keyword(s):  
Gestational Age ◽  
Small For Gestational Age ◽  
Linear Growth ◽  
Prevalence Ratio ◽  
Bone Age ◽  
Cross Sectional Study ◽  
Healthy Children ◽  
Cross Sectional ◽  
Appropriate For Gestational Age ◽  
Bone Age Delay

BackgroundAbout 10-15% small-for-gestational-age children are in higher risk for having linear growth retardation due to growth hormone-insulin like growth factor 1 axis defect (GH-IGF 1) which causes bone age delay.ObjectivesTo compare bone age in 24-36 month old children born small-for-gestational-age (SGA) to that in children born appropriate-for-gestational-age (AGA).MethodsA cross-sectional study was conducted in Hasan Sadikin General Hospital, Bandung, from January to April 2009.Subjects consisted of50 healthy children of 24-36 months old (25 children born at term, SGA, 25 children born at term, AGA). We compared the appropriateness and delay of bone age between the two groups. ResultsMean bone age in the SGA group was 20.8 (SD 7.7) months, and in the AGA group was 25.7 (SD 7.1) months (P=0.022). Mean bone age deficit was -10.5 (6.5) months in the SGA group and -5.5 (SD 5.7) months in the AGA group (P=0.009). The prevalence ratio was 1.77 (95% CI: 1.19–2.62). Bone age delay was found to be higher in children born SGA than that in children of the other group (23 vs 13). On the contrary, appropriate bone age was found more in children born AGA (12 vs 2) (P=0.002).Conclusion Bone age delay in 24-36 months old children born small-for-gestational-age was found to be higher than in those born appropriate-for-gestational-age.

Measurement of Spontaneous, 12-Hour Sleep-Associated GH Secretion in Prepubertal Children with Short Stature: Clinical Relevance and Practicability?

1996 ◽  
Vol 46 (1) ◽  
pp. 33-37 ◽  
Author(s):  
H. Schmidt ◽  
H.G. D&ouml;rr ◽  
O. Butenandt ◽  
A. Galli-Tsinopoulou ◽  
W. Kiess
Keyword(s):  
Short Stature ◽  
Clinical Relevance ◽  
Prepubertal Children ◽  
Gh Secretion

Final height of patients treated for isolated GH deficiency: examination of 83 patients

1997 ◽  
pp. 53-60 ◽  
Author(s):  
E Cacciari ◽  
A Cicognani ◽  
P Pirazzoli ◽  
S Zucchini ◽  
S Salardi ◽  
...  
Keyword(s):  
Short Stature ◽  
Gh Deficiency ◽  
Final Height ◽  
Bone Age ◽  
Untreated Group ◽  
Age At Diagnosis ◽  
Chronological Age ◽  
Target Height ◽  
Gh Secretion ◽  
Height Gain

The aim of the present study was to evaluate retrospectively the influence of various auxological and laboratory parameters on final height in a group of GH-deficient children after replacement therapy and to compare their final height with that of a group of short children with normal GH secretion and hence not treated. The final height was evaluated of 83 patients (51 males and 32 females) affected by idiopathic isolated GH deficiency and treated with recombinant human GH (hGH) for 2-7 years. Inclusion criteria at the start of treatment were short stature (mean height for chronological age in standard deviation score (SDS) -2.21) due to idiopathic isolated GH deficiency (GH peak < 8 micrograms/l after two pharmacological tests and/or mean GH concentration < 3.3 micrograms/l during the night) and treatment with recombinant hGH for at least 2 years at a dose of 15-20 U/m2 per week by s.c. injection for 6 or 7 days/ week. Mean chronological age at diagnosis was 12.2 +/- 1.7 years; 35 were prepubertal and 48 pubertal. The final height of 51 untreated short stature (mean height for chronological age in SDS -2.13 at diagnosis) subjects (42 males and 9 females: 29 prepubertal and 22 pubertal at diagnosis with mean chronological age 11.6 +/- 2.4 years) with normal GH secretion was also evaluated. In the treated subjects final height SDS was higher than that of the untreated group (-1.3 vs -1.7 SDS; P = 0.01). Both treated and untreated subjects showed a final height lower than target height, but 39% of the treated subjects vs only 20% of the untreated group (P = 0.035) had a final height greater than target height. In the treated subjects this percentage was higher in the patients improving their height for bone age in the first years of therapy. While treated females showed a positive correlation only between target and final height (P = 0.0001), in treated males final height correlated with the Bayley-Pinneau prediction at diagnosis, height for chronological age and bone age at diagnosis and target height. Patients who started therapy before puberty also showed these correlations with data calculated at the onset of puberty, together with a correlation with chronological age at the onset of puberty. When considering the influence of GH response at tests on final height, the percentage of subjects exceeding target height increased progressively according to the severity of the GH deficiency. There was no difference in height gain between the patients starting therapy before or during puberty. The height gain, however modest, obtained by our treated patients, the number of patients with final height greater than target height and the favourable comparison with the untreated short-stature subjects represent a promising result, which could be improved by personalizing treatment.

scholarly journals Growth Hormone (GH) Deficiency Type II: A Novel GH-1 Gene Mutation (GH-R178H) Affecting Secretion and Action

2010 ◽  
Vol 24 (1) ◽  
pp. 276-276
Author(s):  
Vibor Petkovic ◽  
Michela Godi ◽  
Amit V. Pandey ◽  
Didier Lochmatter ◽  
Charles R. Buchanan ◽  
...  
Keyword(s):  
Short Stature ◽  
Gh Deficiency ◽  
Functional Characterization ◽  
Provocation Test ◽  
Bone Age ◽  
Janus Kinase ◽  
Dominant Form ◽  
Gh Secretion ◽  
Gh Receptor ◽  
Igf I

ABSTRACT Context and Objective Main features of the autosomal dominant form of GH deficiency (IGHD II) include markedly reduced secretion of GH combined with low concentrations of IGF-I leading to short stature. Design, Setting, and Patients A female patient presented with short stature (height −6.0 sd score) and a delayed bone age of 2 yr at the chronological age of 5 yr. Later, at the age of 9 yr, GHD was confirmed by standard GH provocation test, which revealed subnormal concentrations of GH and a very low IGF-I. Genetic analysis of the GH-1 gene revealed the presence of a heterozygous R178H mutation. Interventions and Results AtT-20 cells coexpressing both wt-GH and GH-R178H showed a reduced GH secretion after forskolin stimulation compared with the cells expressing only wt-GH, supporting the diagnosis of IGHD II. Because reduced GH concentrations found in the circulation of our untreated patient could not totally explain her severe short stature, functional characterization of the GH-R178H performed by studies of GH receptor binding and activation of the Janus kinase-2/signal transducer and activator of transcription-5 pathway revealed a reduced binding affinity of GH-R178H for GH receptor and signaling compared with the wt-GH. Conclusion This is the first report of a patient suffering from short stature caused by a GH-1 gene alteration affecting not only GH secretion (IGHD II) but also GH binding and signaling, highlighting the necessity of functional analysis of any GH variant, even in the alleged situation of IGHD II.

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