scholarly journals Same Phenotype in Children with Growth Hormone Deficiency and Resistance

2018 ◽  
Vol 2018 ◽  
pp. 1-4
Author(s):  
Irene Ioimo ◽  
Carmen Guarracino ◽  
Cristina Meazza ◽  
Horacio M. Domené ◽  
Mauro Bozzola
Keyword(s):  
Short Stature ◽  
Pcr Amplification ◽  
Hormone Deficiency ◽  
Saddle Nose ◽  
Laron Syndrome ◽  
First Case ◽  
Igf I ◽  
Undetectable Serum ◽  
Type Ia ◽  
Severe Short Stature

By definition, about 2.5% of children show a short stature due to several causes. Two clinical conditions are characterized by serum IGF-I low levels, idiopathic GH deficiency (IGHD), and GH insensitivity (GHI), and the phenotypic appearance of these patients may be very similar. We studied two children with short stature and similar phenotypes. The first case showed frontal bossing, doll face, acromicria, and truncal obesity, with a GH peak <0.05 ng/ml after stimuli and undetectable serum IGF-I levels. After PCR amplification of the whole GH1 gene, type IA idiopathic GHD was diagnosed. The second case had cranium hypoplasia, a large head, protruding forehead, saddle nose, underdeveloped mandible, and a micropenis. Basal GH levels were high (28.4 ng/ml) while serum IGF-I levels were low and unchangeable during the IGF-I generation test. Laron syndrome was confirmed after the molecular analysis of the GH receptor (GHR) gene. IGHD type IA and Laron syndrome is characterized by opposite circulating levels of GH, while both have reduced levels of IGF-I, with an overlapping clinical phenotype, lacking the effects of IGF-I on cartilage. These classical cases show the importance of differential diagnosis in children with severe short stature.

Insulin-like growth factor ternary complex components as biomarkers for the diagnosis of short stature

2021 ◽  
Vol 185 (5) ◽  
pp. 629-635
Author(s):  
Aristeidis Giannakopoulos ◽  
Alexandra Efthymiadou ◽  
Dionisios Chrysis
Keyword(s):  
Growth Factor ◽  
Short Stature ◽  
Ternary Complex ◽  
Final Height ◽  
Hormone Deficiency ◽  
Receiver Operating Curve ◽  
Insulin Like Growth Factor ◽  
Igf I ◽  
Stimulation Tests ◽  
Igfbp 3

Objective The diagnosis of growth hormone deficiency (GHD) in children is not always straightforward because insulin-like growth factor 1 (IGF-I) or GH stimulation tests may not be able to discriminate GHD from constitutional delay of growth and puberty (CDGP) or other causes of short stature. Design Boys and girls (n = 429, 0.7–16 years) who attended our department for short stature participated in this study. They were followed up for an average period of 9 years. At the end of follow-up after reaching the final height, a definitive diagnosis was assigned, and all the components of ternary complex (IGF-I, IGF-binding protein-3 (IGFBP-3), acid-labile subunit (ALS), and IGF-I/IGFBP-3 ratio) were evaluated as biomarkers for the respective diagnosis. Results All the components of the ternary complex were tightly correlated with each other and were positively related to age. IGF-I, IGFBP-3, ALS, and IGF-I/IGFBP-3 ratio differed significantly between GHD and normal groups. IGF-I and ALS levels were lower in GHD compared to children with familial short stature, while IGF-I and IGF-I/IGFBP-3 ratio was significantly lower in GHD compared to children with CDGP. IGF-I and IGF-I/IGFBP-3 receiver operating curve cutoff points were unable to discriminate between GHD and normal groups or between GHD and CDGP groups. Conclusion Despite the tight correlation among all the components of the ternary complex, each one shows a statistically significant diagnosis-dependent alteration. There is a superiority of IGF-I, ALS, and IGF-I/IGFBP-3 ratio in the distinction between GHD and CDGP or between GHD and normal groups but without usable discriminating power, making auxology as the primary criterion for establishing the diagnosis.

Growth hormone and insulin-like growth factor regulate insulin-like growth factor-binding protein-1 in Laron type dwarfism, growth hormone deficiency and constitutional short stature

1992 ◽  
Vol 127 (4) ◽  
pp. 351-358 ◽  
Author(s):  
Zvi Laron ◽  
Anne-Maria Suikkari ◽  
Beatrice Klinger ◽  
Aviva Silbergeld ◽  
Athalia Pertzelan ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Factor ◽  
Growth Hormone Deficiency ◽  
Short Stature ◽  
Hormone Deficiency ◽  
Pituitary Hormone ◽  
Healthy Children ◽  
Insulin Like Growth Factor ◽  
Factor Binding ◽  
Igf I

Insulin-like growth factors (IGFs) mediate the effects of growth hormone (GH), and the insulin-like growth factor-binding proteins (IGFBPs) modulate the actions of IGFs in tissues. We studied the circulating levels of IGFBP-1 in 6 children and 9 adults with Laron type dwarfism (LTD), in 11 children and 21 adults with growth hormone deficiency (GHD), and in 8 children with constitutional short stature. Compared with the situation in healthy children, the basal serum IGFBP-1 concentration was 5.4-fold higher in LTD children, 4.1-fold higher in GHD children, and 3.8-fold higher in children with short stature (p<0.02 vs controls in all groups). In adult patients with multiple pituitary hormone deficiency (MPHD), the IGFBP-1 concentration was 2-fold elevated, but it was normal in adult LTD patients. Intravenous (N= 10) or subcutaneous (N=9) administration ofIGF-I (75 μg·kg−1 and 150 μg·kg−1, respectively) in LTD children resulted in a rapid 50–60% fall in serum insulin (p<0.02), a decline in blood glucose and a concomitant 40–60% rise of IGFBP-1 levels (p<0.05). Treatment for seven days with IGF-I (150 μg·kg−1·d−1) resulted in a decrease by 34% and 44% of serum IGFBP-1 level in two out of three children with LTD. After prolonged GH therapy, the IGFBP-1 level fell in GHD children by 29% (p<0.05), in GHD adults by 52% (p<0.02) and in children with constitutional short stature by 17% (p<0.02). IGFBP-1 and insulin concentrations were inversely related in patients with GHD (r= −0.66, p<0.001) or with LTD (r= −0.57, p<0.05). Our data suggest that: (a) increased IGFBP-1 concentration in LTD, GHD and constitutional short children may, at least in part, be accounted for by an IGF-I deficiency; (b) both the rise in IGF-I and a fall in insulin contributed to the rise in IGFBP-1 after acute IGF-I administration; (c) prolonged IGF-I or GH treatment causes a persistent decline in IGFBP-1 concentration. In conclusion, IGF-I and GH may regulate IGFBP-1 secretion either directly or via insulin.

scholarly journals Etiology of severe short stature below −3 SDS in a screened Finnish population

2020 ◽  
Vol 183 (5) ◽  
pp. 481-488
Author(s):  
Juho Kärkinen ◽  
Päivi J Miettinen ◽  
Taneli Raivio ◽  
Matti Hero
Keyword(s):  
Short Stature ◽  
University Hospital ◽  
Hormone Deficiency ◽  
Growth Monitoring ◽  
Growth Data ◽  
Target Height ◽  
Hospital District ◽  
Sitting Height ◽  
Catch Up ◽  
Severe Short Stature

Objective: To describe the etiology of severe short stature in the Helsinki University Hospital district covering a population of 1.2 million that is subject to frequent growth monitoring and screening rules during childhood. Design: Retrospective cohort study. Methods: We identified all subjects born 1990 or later with a height SD score <−3, after the age of 3 years, from the Helsinki University Hospital district growth database. A total of 785 subjects (376 females and 409 males) fulfilled our inclusion criteria; we reviewed their medical records and growth data and report their underlying diagnoses. Results: A pathological cause for short stature was diagnosed in 76% of the girls and 71% of the boys (P = NS). Syndromes were the most numerous pathological cause (n = 160; 20%), followed by organ disorders (n = 127; 16%), growth hormone deficiency (GHD, n = 94; 12%), SGA without catch-up growth (n = 73; 9%), and skeletal dysplasias (n = 57; 7%). Idiopathic short stature (ISS) was diagnosed in 210 (27%) subjects. The probability of growth-related pathology, particularly of a syndrome or skeletal dysplasia, increased with the shorter height SD score and the greater deviation from the target height. Sitting height to height SDS was increased in subjects with ISS, GHD, and SGA (all P < 0.01). Conclusions: Height <−3 SDS after 3 years of age usually results from a pathological cause and should be thoroughly investigated in specialized health care. The chance of finding a specific etiology increased with the severity of short stature, and the mismatch with target height.

Growth Hormone Deficiency in 2 Siblings Associated with Combined GH1 Gene Polymorphisms

2012 ◽  
Vol 120 (05) ◽  
pp. 308-310 ◽  
Author(s):  
M. Yamamoto ◽  
G. Iguchi ◽  
H. Fukuoka ◽  
K. Miyako ◽  
Y. Takahashi
Keyword(s):  
Short Stature ◽  
Gene Polymorphisms ◽  
Gh Deficiency ◽  
Pedigree Analysis ◽  
Hormone Deficiency ◽  
Sequencing Analysis ◽  
Gh Secretion ◽  
Igf I ◽  
History Of

AbstractThis study was performed to clarify the pathophysiology of familial short stature with moderate GH deficiency.The siblings showed moderate GH deficiency with short stature. Pedigree analysis revealed an accumulation of the history of short stature in father’s relatives, although there was no consanguinity.We performed sequencing analysis of GH1 and GHSR gene in the siblings.We detected SNPs in the GH1 gene in the combination of the  − 278G,  − 57T, +1169T, and +2103C in one allele from the father and the  − 278T,  − 57G, +1169 A, and +2103T in the other allele from the mother in the siblings. In the previous report, the −278G and  − 57T allele are associated with low serum IGF-I levels in patients with isolated GH deficiency and the haplotype of the  − 278T,  − 57G, +1169 A, and +2103T allele exhibited an impaired GH secretion in vitro.It is suggested that these haplotypes were responsible at least in part for the GH deficiency and short stature in these siblings.

scholarly journals Coexistence of Growth Hormone Deficiency and Pituitary Microadenoma in a Child with Unique Mosaic Turner Syndrome: A Case Report and Literature Review

Diagnostics ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 783
Author(s):  
Eu Gene Park ◽  
Eun-Jung Kim ◽  
Eun-Jee Kim ◽  
Hyun-Young Kim ◽  
Sun-Hee Kim ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Pituitary Adenoma ◽  
Literature Review ◽  
Short Stature ◽  
Turner Syndrome ◽  
Gh Deficiency ◽  
Genetic Disorder ◽  
Hormone Deficiency ◽  
Pituitary Microadenoma ◽  
First Case

Turner syndrome (TS) is a genetic disorder with phenotypic heterogeneity caused by the monosomy or structural abnormalities of the X chromosome, and it has a prevalence of about 1/2500 females live birth. The variable clinical features of TS include short stature, gonadal failure, and skeletal dysplasia. The association with growth hormone (GH) deficiency or other hypopituitarism in TS is extremely rare, with only a few case reports published in the literature. Here, we report the first case of a patient with mosaic TS with complete GH deficiency and pituitary microadenoma, and we include the literature review. During the work-up of the patient for severe short stature, three GH provocation tests revealed peak GH levels of less than 5 ng/mL, which was compatible with complete GH deficiency. Sella magnetic resonance imaging showed an 8 mm non-enhancing pituitary adenoma with mild superior displacement of the optic chiasm. Karyotyping revealed the presence of ring chromosome X and monosomy X (46,X,r(X)/45,X/46,X,psu dic r(X;X)), which indicated a mosaic TS. It is important to consider not only chromosome analyses in females with short stature, but also the possibility of the coexistence of complete GH deficiency accompanying pituitary lesions in TS. In conclusion, the present study reports the first case of GH deficiency and pituitary adenoma in a patient with rare mosaic TS, which extends the genotype–phenotype spectrum for TS.

scholarly journals Laron syndrome in three female siblings with the development of subclinical hypothyroidism and dyslipidemia in one case: first report of a Syrian family

2021 ◽  
Vol 2021 (9) ◽  
Author(s):  
Ahmad Chreitah ◽  
Kheria Hijazia ◽  
Leen Jamel Doya
Keyword(s):  
Short Stature ◽  
Subclinical Hypothyroidism ◽  
Autosomal Recessive ◽  
Index Case ◽  
Autosomal Recessive Disorder ◽  
Facial Features ◽  
Laron Syndrome ◽  
High Clinical Suspicion ◽  
Facial Phenotype ◽  
Severe Short Stature

ABSTRACT Laron syndrome (LS) is a rare autosomal recessive disorder characterized by dwarfism and typical facial phenotype. This report is the first to present three cases of Laron syndrome affecting three female siblings from Syria. The index case presented at age of 8.5 years with severe short stature: low level of Insulin-like growth factor 1 (IGF-1), elevated levels of fasting and post-stimulation growth hormone (GH), consistent with the diagnosis of Laron syndrome. At the age of 9.5 years, she developed non-autoimmune subclinical hypothyroidism treated with Levothyroxine, then she developed dyslipidemia at the age of 11.3 years. Later, we identified two female siblings of the patient with Laron syndrome. Laron syndrome is a rare genetic disease, reporting of new cases of this rare syndrome must encourage pediatricians to develop high clinical suspicion if faced with patients with very short stature and typical facial features.

scholarly journals Branding of subjects affected with genetic syndromes of severe short stature in developing countries

2020 ◽  
Vol 13 (2) ◽  
pp. e231737 ◽  
Author(s):  
Jaime Guevara-Aguirre ◽  
Carolina Guevara ◽  
Alexandra Guevara ◽  
Antonio AWD Gavilanes
Keyword(s):  
Developing Countries ◽  
Mental Retardation ◽  
Medical Care ◽  
Short Stature ◽  
South American ◽  
Genetic Syndromes ◽  
Laron Syndrome ◽  
South American Country ◽  
Genetic Syndrome ◽  
Severe Short Stature

In Ecuador, a developing South American country, subjects affected with genetic syndromes of severe short stature are commonly referred to as dwarfs or midgets. Furthermore, and because in earlier studies some patients had evidenced mental retardation, such abnormality is assumed to exist in all affected subjects. Herein, we present two discrete instances in which this type of branding occurs. The first is that of individuals with Laron syndrome who are still called ‘dwarfs’ and considered as having a degree of mental retardation despite evidence showing otherwise. A similar problem, that of a girl affected with a genetic syndrome of short stature, which might include mental retardation, is also discussed. Considering that stigmatising is a form of discrimination, it concerns us all. Hence, the use of derogatory terms such as midget, dwarf or cretin, that might unintentionally occur even when delivering the best and most devoted medical care, must be eliminated.

scholarly journals Type IA isolated growth hormone deficiency (IGHD) consistent with compound heterozygous deletions of 6.7 and 7.6 Kb at the GH1 gene locus

2012 ◽  
Vol 56 (8) ◽  
pp. 558-563 ◽  
Author(s):  
Ana Keselman ◽  
Paula A. Scaglia ◽  
María Soledad Rodríguez Prieto ◽  
María Gabriela Ballerini ◽  
María Eugenia Rodríguez ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Pcr Amplification ◽  
Hormone Deficiency ◽  
Compound Heterozygous ◽  
Molecular Defect ◽  
Laboratory Findings ◽  
Gene Deletions ◽  
Isolated Growth Hormone Deficiency ◽  
Type Ia

Isolated growth hormone deficiency (IGHD) may result from deletions/mutations in either GH1 or GHRHR genes. The objective of this study was to characterize the molecular defect in a girl presenting IGHD. The patient was born at 41 weeks of gestation from non-consanguineous parents. Clinical and biochemical evaluation included anthropometric measurements, evaluation of pituitary function, IGF-I and IGFBP-3 levels. Molecular characterization was performed by PCR amplification of GH1 gene and SmaI digestion of two homologous fragments flanking the gene, using genomic DNA from the patient and her parents as templates. At 1.8 years of age the patient presented severe growth retardation (height 61.2 cm, -7.4 SDS), truncal obesity, frontal bossing, doll face, and acromicria. MRI showed pituitary hypoplasia. Laboratory findings confirmed IGHD. GH1 gene could not be amplified in samples from the patient while her parents yielded one fragment of the expected size. SmaI digestion was consistent with the patient being compound heterozygous for 6.7 and 7.6 Kb deletions, while her parents appear to be heterozygous carriers for either the 6.7 or the 7.6 Kb deletions. We have characterized type IA IGHD caused by two different GH1 gene deletions, suggesting that this condition should be considered in severe IGHD, even in non-consanguineous families. Arq Bras Endocrinol Metab. 2012;56(8):558-63

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