Review of Turkish patients with growth hormone insensitivity (Laron type)

1995 ◽  
Vol 133 (5) ◽  
pp. 539-542 ◽  
Author(s):  
Nurşen Yordam ◽  
Nurgün Kandemir ◽  
Ibrahim Erkul ◽  
Selim Kurdoğlu ◽  
Şükrü Hatun
Keyword(s):  
Growth Hormone ◽  
Standard Deviation Score ◽  
Bone Age ◽  
High Rate ◽  
Hormone Deficiency ◽  
Turkish Children ◽  
Number Of Patients ◽  
Igf I ◽  
Growth Hormone Insensitivity ◽  
Turkish Patients

Yordam N, Kandemir N, Erkul I, Kurdoğlu S, Hatun S. Review of Turkish patients with growth hormone insensitivity (Laron type). Eur J Endocrinol 1995;133:539–42. ISSN 0804–4643 Clinical spectrum and endocrine details of thirteen Turkish children (age 0.3–14.2 years; eight females and five males; ten prepubertal, three pubertal) with growth hormone insensitivity are presented. All patients display phenotypical features of severe growth hormone deficiency, The diagnosis based on height standard deviation score (SDS), basal growth hormone (GH), basal insulin-like growth factor I (IGF-I, IGF-I response in an IGF generation test and growth hormone binding protein (GHBP) measurements. The median height SDS was −7.4 (range −3.2 to −10), weight for height index was 100 (range 81–152) and bone age/height age ratio was 2 (range 1.6–3.3). Endocrine investigations showed a median basal GH concentration of 61.4 mU/l (range 23.5–120 mU/l), Basal IGF-I level was below 10 ng/ml in all patients except one. None of the patients showed a significant IGF-I response to injections of GH (0.1 U/kg body weight for 4 days). The median IGFBP-3 level was 0.23 mg/l (range 0.1–0.56 mg/l). The GHBP level was undetectable in all of 10 patients. The high number of patients in our center may be due to the high rate of consanguinity among the Turkish population and the referral facility of our center in the area. These patients may benefit from the new therapy with recombinant human IGF-I. Nurgün Kandemir, Hacettepe University, Department of Pediatrics, Division of Endocrinology, 06100 Ankara, Turkey

Efficacy of long-term growth hormone therapy in short non-growth hormone-deficient children

2017 ◽  
Vol 30 (2) ◽  
Author(s):  
Lucia Schena ◽  
Cristina Meazza ◽  
Sara Pagani ◽  
Valeria Paganelli ◽  
Elena Bozzola ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Final Height ◽  
Standard Deviation Score ◽  
Bone Age ◽  
Gh Treatment ◽  
Short Children ◽  
Igf I ◽  
Height Gain ◽  
The Cost

AbstractBackground:In recent years, several studies have been published showing different responses to growth hormone (GH) treatment in idiopathic short stature children. The aim of the present study was to investigate whether non-growth-hormone-deficient (non-GHD) short children could benefit from long-term GH treatment as GHD patients.Methods:We enrolled 22 prepubertal children and 22 age- and sex-matched GHD patients, with comparable height, body mass index (BMI), bone age, and insulin-like growth factor 1 (IGF-I) circulating levels. The patients were treated with recombinant human GH (rhGH) and followed until they reach adult height.Results:During GH treatment, the two groups grew in parallel, reaching the same final height-standard deviation score (SDS) and the same height gain. On the contrary, we found significantly lower IGF-I serum concentrations in non-GHD patients than in GHD ones, at the end of therapy (p=0.0055).Conclusions:In our study, the response to GH treatment in short non-GHD patients proved to be similar to that in GHD ones. However, a careful selection of short non-GHD children to be treated with GH would better justify the cost of long-term GH therapy.

scholarly journals Significance of Direct Confirmation of Growth Hormone Insensitivity for the Diagnosis of Primary IGF-I Deficiency

2020 ◽  
Vol 9 (1) ◽  
pp. 240
Author(s):  
Joanna Smyczyńska ◽  
Urszula Smyczyńska ◽  
Maciej Hilczer ◽  
Renata Stawerska ◽  
Andrzej Lewiński
Keyword(s):  
Growth Hormone ◽  
Final Height ◽  
Standard Deviation Score ◽  
Height Velocity ◽  
Gh Therapy ◽  
Significant Difference ◽  
Igf I ◽  
Growth Hormone Insensitivity ◽  
Stimulation Tests ◽  
Direct Confirmation

Primary insulin-like growth factor-I (IGF-I) deficiency is a synonym of growth hormone (GH) insensitivity (GHI), however the necessity of direct confirmation of GH resistance by IGF-I generation test (IGF-GT) is discussed. GHI may disturb intrauterine growth, nevertheless short children born small for gestational age (SGA) are treated with GH. We tested the hypothesis that children with appropriate birth size (AGA), height standard deviation score (SDS) <−3.0, GH peak in stimulation tests (stimGH) ≥10.0 µg/L, IGF-I <2.5 centile, and excluded GHI may benefit during GH therapy. The analysis comprised 21 AGA children compared with 6 SGA and 20 GH-deficient ones, with height SDS and IGF-I as in the studied group. All patients were treated with GH up to final height (FH). Height velocity, IGF-I, and IGF binding protein-3 (IGFBP-3) concentrations before and during first year of treatment were assessed. Effectiveness of therapy was better in GHD than in IGF-I deficiency (IGFD), with no significant difference between SGA and AGA groups. All but two AGA children responded well to GH. Pretreatment IGF-I and increase of height velocity (HV) during therapy but not the result of IGF-GT correlated with FH. As most AGA children with apparent severe IGFD benefit during GH therapy, direct confirmation of GHI seems necessary to diagnose true primary IGFD in them.

scholarly journals Familial growth hormone deficiency with mutated GHRH receptor gene: clinical and hormonal findings in homozygous and heterozygous individuals from Itabaianinha

2000 ◽  
pp. 557-563 ◽  
Author(s):  
CY Hayashida ◽  
RG Gondo ◽  
C Ferrari ◽  
SP Toledo ◽  
R Salvatori ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Autosomal Recessive ◽  
Novel Mutation ◽  
Statistical Significance ◽  
Standard Deviation Score ◽  
Hormone Deficiency ◽  
R Gene ◽  
Igf I ◽  
Igfbp 3

OBJECTIVE: To characterize clinically and hormonally the syndrome of autosomal recessive familial growth hormone deficiency (FGHD) recently identified in Itabaianinha, Sergipe, Brazil, caused by a novel mutation (mt) that inactivates the growth hormone-releasing hormone receptor (GHRH-R) gene. DESIGN: Clinical and hormonal evaluations were performed in 21 FGHD individuals (mt/mt group) aged 8 to 63 years, 13 heterozygotes for the GHRH-R mutation (wt/mt group) and 5 homozygotes for the wild type (wt) allele (wt/wt group), identified by genotyping of peripheral blood leukocyte DNA. METHODS: Clinical and hormonal characterization included physical examination and measurement of GH, IGF-I, IGF binding protein-3 (IGFBP-3), cortisol, prolactin, LH, FSH, and free thyroxine (FT4). RESULTS: Clinical features were consistent with isolated growth hormone deficiency. Height was significantly reduced in the mt/mt group compared with the wt/mt group (mean height standard deviation score (SDS) +/- s.d.: -7.35+/-1.37 vs -1.84+/-1.44 respectively, P<0. 0001), and the wt/wt group (-1.85 +/- 0.81, P=0.0007). The height of the 13 wt/mt subjects did not differ from the 5wt/wt individuals. Serum GH, IGF-I, IGF-I SDS, IGFBP-3 and IGFBP-3 SDS were all significantly lower in the mt/mt group than in the wt/mt and wt/wt groups. Two affected children treated with GH for 1 year showed a normal growth response. Serum IGF-I and IGF-I SDS were lower in wt/mt compared with wt/wt group, but did not reach statistical significance. IGF-I and IGF-I SDS correlated inversely with age in wt/mt group. CONCLUSIONS: FGHD due to an autosomal recessive GHRH-R gene mutation leads to marked dwarfism, phenotypically and hormonally indistinguishable from other forms of isolated GH deficiency. Heterozygotes for the GHRH-R mutation appear to have a partial defect in the GH/IGF axis, with no apparent height impairment.

Syndromic growth disorders

2011 ◽  
pp. 1095-1107
Author(s):  
Thomas Edouard ◽  
Maïthé Tauber
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Clinical Presentation ◽  
Pulmonary Stenosis ◽  
Standard Deviation Score ◽  
Growth Failure ◽  
Hormone Deficiency ◽  
High Resolution Analysis ◽  
Growth Hormone Insensitivity ◽  
Underlying Mechanisms

Short stature (SS) is defined as height less than the third percentile or below –2 standard deviation score (SDS) with reference to chronological age according to standard growth curves. Children are born small for gestational age (SGA) when their birth height and/or birth weight are below or equal to –2 SDS using standards such as Usher and McLean. In patients presenting with SS associated with abnormal physical features, malformations, or delayed development, a syndromic growth disorder should be considered. Whilst individually rare, there are many syndromes with short stature as a component—in the London Dysmorphology Database (Winter and Baraitser), there are 873 such syndromes, 175 of which are of prenatal onset. In these patients, malformations and/or sensorineural abnormalities should be systematically screened by complementary exams (skeletal X-rays, cardiac and abdominal ultrasound, complete eye and hearing evaluations). In some cases, these abnormalities could help in making the diagnosis (e.g. pulmonary stenosis suggestive of Noonan’s syndrome). Different chromosome disorders may present with SS. For this reason, chromosome studies, preferably high-resolution analysis, should be performed to search for chromosome abnormalities in these children. Specific gene analysis may be requested when a specific syndrome is suspected. In these syndromes, growth failure may be due to a wide variety of mechanisms, including growth hormone deficiency (GHD), growth hormone resistance (Laron syndrome, bone dysplasia) or in combination with nutritional issues with, in many, the underlying mechanisms still being unknown. A complete evaluation of growth hormone/IGF-1 axis is necessary in these children. There are many classifications of short stature, each with specific advantages and disadvantages. Indeed, syndromes with SS could be classified according to clinical presentation and in particular auxological and anthropometrical parameters (SS with normal prenatal growth, SS with intrauterine growth retardation, SS with obesity), or to pathophysiology (GHD or growth hormone insensitivity, bone disorders and idiopathic SS). Here, a classification based on clinical presentation is used. Those syndromes with SS that are most common and are often followed by paediatric endocrinologists namely Silver–Russell, Noonan’s, Turner’s and Prader–Willi syndromes will be reviewed, as well as some rarer syndromes.

Regular Monitoring of Bone Age Is Useful in Children Treated With Growth Hormone

PEDIATRICS ◽  
1999 ◽  
Vol 104 (Supplement_5) ◽  
pp. 1039-1042
Author(s):  
Francine Ratner Kaufman ◽  
Judy P. Sy
Keyword(s):  
Growth Hormone ◽  
Standard Deviation Score ◽  
Bone Age ◽  
Hormone Deficiency ◽  
First Year ◽  
X Rays ◽  
Growth Study ◽  
Cumulative Change ◽  
National Cooperative

Objective. This study was undertaken to determine whether serial bone age (BA) radiographs were obtained in patients with growth hormone deficiency and to assess whether there were differences in outcome between subjects with and without monitoring of BA radiographs. Research Design and Methods. Data were collected from the National Cooperative Growth Study database on growth hormone-deficient subjects who were treated for at least 3 years. Comparisons were made among three groups of subjects: 1) those with BAs at entry versus those without; 2) those with BA values in the first year of follow-up if an entry radiograph had not been done versus those with no first-year examination; and 3) those with a BA at entry and yearly for 3 years versus those with no radiographs during the same period. Differences in the change in height standard deviation score (SDS); change in height age, age, pubertal progression, number of visits, growth hormone dosage; and number of growth hormone injections per week were compared. Results. Of the 6191 subjects assessed, 93% had at least one BA radiograph obtained; there was a mean of 3.6 ± 2.6 total number of BA radiographs per patient during the 5.2 ± 1.9 years of follow-up. Subjects with BA values at entry were older and had slightly higher cumulative height SDS and height age change compared with those without BA values at entry. Subjects with BA assessment during the first year were older and had shorter growth hormone treatment time and slightly better cumulative change in height SDS and height age than did those without BA in the first year. Comparing those with serial BA determination for the first 3 years of treatment versus those with no BA values, those with BA were older, more pubertal, seen more often, had more growth hormone injections per week of a comparable growth hormone dosage, and had slightly larger cumulative change in height SDS and height age than those without x-rays. Conclusions. These data suggest that National Cooperative Growth Study investigators find it of benefit to obtain baseline and follow-up measurements of BA in most subjects treated with growth hormone. Subjects with BA monitoring do slightly better than do those whose skeletal maturation is not measured. BA assessment should be considered part of the follow-up of patients treated with growth hormone therapy.

Biomarkers of Acromegaly and Growth Hormone Action

2020 ◽  
Vol 27 (12) ◽  
pp. 1231-1245
Author(s):  
Filippo Maffezzoni ◽  
Teresa Porcelli ◽  
Andrea Delbarba ◽  
Letizia Pezzaioli ◽  
Carlo Cappelli ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Biological Markers ◽  
Clinical Care ◽  
Hormone Deficiency ◽  
Surrogate Outcomes ◽  
Current State ◽  
Growth Hormone Action ◽  
Igf I ◽  
Definition Of

: Biological markers (biomarkers) play a key role in drug development, regulatory approval and clinical care of patients and are linked to clinical and surrogate outcomes. : Both acromegaly and Growth Hormone Deficiency (GHD) are pathological conditions related to important comorbidities that, in addition to having stringent diagnostic criteria, require valid markers for the definition of treatment, treatment monitoring and follow-up. GH and insulin-like growth factor-I (IGF-I) are the main biomarkers of GH action in children and adults while, in acromegaly, both GH and IGF-I are established biomarkers of disease activity. : However, although GH and IGF-I are widely validated biomarkers of GHD and acromegaly, their role is not completely exhaustive or suitable for clinical classification and follow-up. Therefore, new biological markers for acromegaly and GH replacement therapy are strongly needed. : The aim of this paper is to review and summarize the current state in the field pointing out new potential biomarkers for acromegaly and GH use/abuse.

scholarly journals Can exaggerated response to a GH provocative test identify patients with partial GH insensitivity syndrome?

2002 ◽  
pp. 319-323 ◽  
Author(s):  
Y Rakover ◽  
A Silbergeld ◽  
I Lavi ◽  
R Masalha ◽  
IB Shlomo
Keyword(s):  
Short Stature ◽  
Binding Protein ◽  
Standard Deviation Score ◽  
Bone Age ◽  
The Other ◽  
Provocative Test ◽  
Igf I ◽  
Parental Height ◽  
The Difference ◽  
Igfbp 3

OBJECTIVES: In the majority of children with short stature, the etiology is unknown. Mutations of the GH receptor (GHR) have been reported in a few children with apparent idiopathic short stature (ISS). These patients had low IGF-I, IGF-binding protein-3 (IGFBP-3) and GH-binding protein (GHBP), but a normal or exaggerated GH response to provocative stimuli, suggestive of partial GH insensitivity (GHI). We attempted to identify children with partial GHI syndrome, based on their response to GH provocative stimuli and other parameters of the GH-IGF-I axis. SUBJECTS AND METHODS: One hundred and sixty-four pre-pubertal children (97 boys, 67 girls) aged 7.2 (0.5-16.75) years were studied. All had short stature with height <3rd centile. The weight, bone age (BA) and body mass index (BMI) of the subjects, as well as the parents' heights and mid parental height (MPH) were assessed. Basal blood samples were taken for IGF-I, IGFBP-3 and GHBP. All subjects underwent a GH provocative test with either clonidine, arginine or insulin. The subjects were divided into three groups: (A) patients with peak GH concentration <18 mIU/l in two different provocative tests (GH deficiency - GHD, n=33); (B) patients with peak GH between 18.2 and 39.8 mIU/l (normal response, n=78); (C) patients with peak GH >40 mIU/l (exaggerated GH response, n=53). RESULTS: No significant differences were found in age, height (standard deviation score (SDS)), parental height (SDS) and the difference between chronological age and bone age (DeltaBA) between the groups. Patients with GHD were heavier (P=0.039) and had significantly higher BMI (SDS) (P=0.001) than the other groups. MPH (SDS) was lower in the group of exaggerated responders (P=0.04) compared with the other groups. No significant differences were found between the groups for the biochemical parameters when expressed nominally or in SDS, except for IGFBP-3 (SDS), which was lower in the GHD group (P=0.005). The GHBP levels were not lower in the group of exaggerated GH response to provocative stimuli. Height (SDS) correlated negatively with basal GH values in pooled data of all the subjects (r=-0.358, P<0.0001), in normal responders (r=-0.45, P<0.0001) and in the exaggerated responders (r=-0.341, P<0.0001), but not in the GHD group. CONCLUSION: Exaggerated GH response to provocative tests alone does not appear to be useful in identifying children with GHI.

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