Use of Growth Hormone in the Treatment of Short Stature: Boon or Abuse?

1991 ◽  
Vol 12 (12) ◽  
pp. 355-363
Author(s):  
Paul Saenger
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Recombinant Dna ◽  
Gh Deficiency ◽  
Hormone Deficiency ◽  
Vigorous Exercise ◽  
Gh Secretion ◽  
The Many ◽  
Definition Of ◽  
First Time

Growth hormone (GH) was isolated approximately 30 years ago. Since then, we have witnessed major advances in understanding the regulation and pattern of GH secretion and its many metabolic actions.1 With the advent of recombinant DNA-generated growth hormone (rhGH) in 1985, the opportunities to treat children who have organic or idiopathic GH deficiencies are now, for the first time, unlimited. DEFINITION OF GROWTH HORMONE DEFICIENCY Although a role for GH in the treatment of certain children deficient in GH is established, the definition of GH deficiency remains controversial. The controversy surrounding the diagnosis of GH deficiency was highlighted recently when it was shown that, among the many commercial assay kits available, the same serum sample yielded GH concentrations that differed by as much as 100% for the same sample. Using different GH assay kits, a child who has short stature could be determined to be deficient in GH in the view of one endocrinologist but to have sufficient GH (ie, to be normal) by another endocrinologist.2,3 Despite these obvious limitations, GH testing has an important role in the clinical evaluation of the child who is short. When a child fails a simple screening test (ie, serum GH level of <10 ng/mL following vigorous exercise, such as running for 20 minutes), more definitive GH testing is the next step.

Isolated Growth Hormone Deficiency in Children and Adolescents

2001 ◽  
Vol 14 (s2) ◽  
Author(s):  
J. Argente ◽  
S.A.S. Abusrewil ◽  
G. Bona ◽  
F. Chiarelli ◽  
C.J.H. Kelnar ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Transcription Factor ◽  
Children And Adolescents ◽  
Growth Hormone Deficiency ◽  
Hormonal Regulation ◽  
Human Growth ◽  
Hormone Deficiency ◽  
Imaging Method ◽  
Gh Secretion ◽  
Definition Of

AbstractAlthough it is difficult to reach international agreement on the definition of growth hormone deficiency (GHD) in children and adolescents, great efforts to do so have been made during the last two decades. A somewhat limited definition of GHD is: a combination of auxological, clinical, biochemical and metabolic abnormalities caused by lack or insufficiency of GH secretion that results in a decrease in the production of GH-dependent hormones and growth factors. Its aetiology is very complex. Therefore, specific studies must be performed during different periods of childhood (neonatal, prepubertal and pubertal periods). Auxological parameters, particularly growth velocity (GV), are still considered the best clinical measures for analysing human growth. The spectacular advances in our understanding of molecular biology during the past twenty years have allowed, and will continue to allow, a more and more precise diagnosis of the molecular anomalies of human growth. This will, in turn, allow changes caused by genetic lesions to be more efficiently distinguished from those due to nutritional, organic, tumoural, psychological or traumatic causes. Our knowledge of the molecular bases of undergrowth due to a deficiency in GH has developed as a result of the localisation and characterisation of human genes which code for proteins implicated in the hormonal regulation of growth. These genes include pituitary GH (GH1), pituitary transcription factor 1 (Pit-1), the prophet of Pit-1 (PROP-1), the pituitary; transcription factor LHX3, the transcription factor HESX1 and the GH-releasing hormone receptor (GHRHr). In addition, magnetic resonance imaging is the best available imaging method for the evaluation of size and structure of the pituitary and the parasellar region.

Growth hormone (GH) responses to the combined administration of GH-releasing hormone plus GH-releasing peptide 6 in adults with GH deficiency

1995 ◽  
Vol 132 (6) ◽  
pp. 712-715 ◽  
Author(s):  
A Leal-Cerro ◽  
E Garcia ◽  
R Astorga ◽  
FF Casanueva ◽  
C Dieguez
Keyword(s):  
Growth Hormone ◽  
Gh Deficiency ◽  
Hormone Deficiency ◽  
Santiago De Compostela ◽  
Releasing Hormone ◽  
Gh Secretion ◽  
Factor I ◽  
Gh Replacement ◽  
Combined Administration ◽  
Plasma Gh

Leal-Cerro A, Garcia E, Astorga R, Casanueva FF, Dieguez C. Growth hormone (GH) responses to the combined administration of GH-releasing hormone plus GH-releasing peptide 6 in adults with GH deficiency. Eur J Endocrinol 1995;132:712–5. ISSN 0804–4643 In recent years the health problems of adults with growth hormone deficiency (GHD) and the benefits of GH replacement therapy have received considerable attention. However, the reliability of conventional GH tests in the assessment of pituitary GH reserve in this group of patients is still controversial. In this study, we assessed GH secretion after the combined administration of GH-releasing hormone (GHRH) (1 μg/kg iv) and GH-releasing peptide 6 (GHRP-6, 1 μg/kg iv) in adult patients diagnosed with GHD by conventional GH testing, and correlate this response with insulin-like growth factor I levels. Twenty-one subjects (13 male, 8 female) with long-standing diagnosis of GHD aged 21–54 years were studied. In 13 subjects GH responses to GHRH plus GHRP-6 were markedly reduced (peak GH response <10 mU/I), whereas in the remaining eight the response was greater (range 11–100 mU/l), In conclusion, our data show that combined administration of GHRH plus GHRP-6 elicited a significant increase in plasma GH levels in about 40% of patients diagnosed with GHD by conventional GH testing. C Dieguez, PO Box 563, 15700 Santiago de Compostela, Spain

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 Inclusion and Withdrawal Criteria for Growth Hormone (GH) Therapy in Children with Idiopathic GH Deficiency—Towards Following the Evidence but Still with Unresolved Problems

2022 ◽  
Author(s):  
Joanna Smyczyńska
Keyword(s):  
Growth Hormone ◽  
Gh Deficiency ◽  
Final Height ◽  
Threshold Value ◽  
Reference Ranges ◽  
Gh Therapy ◽  
Gh Secretion ◽  
Accelerate Growth ◽  
Stimulation Tests ◽  
Definition Of

According to current guidelines, growth hormone (GH) therapy is strongly recommended in children and adolescents with GH deficiency (GHD) in order to accelerate growth rate and attain normal adult height. The diagnosis of GHD requires demonstration of decreased GH secretion in stimulation tests, below the established threshold value. Currently, GHD in children is classified as secondary insulin-like growth factor-1 (IGF-1) deficiency. Most of children diagnosed with isolated GHD presents with normal GH secretion at the attainment of near-final height or even in mid-puberty. The most important clinical problems, related to the diagnosis of isolated GHD in children and to optimal duration of rhGH therapy include: arbitrary definition of subnormal GH peak in stimulation tests, disregarding factors influencing GH secretion, insufficient diagnostic accuracy and poor reproducibility of GH stimulation tests, discrepancies between spontaneous and stimulated GH secretion, clinical entity of neurosecretory dysfunction, discrepancies between IGF-1 concentrations and results of GH stimulation tests, significance of IGF-1 deficiency for the diagnosis of GHD, a need for validation IGF-1 reference ranges. Many of these issues have remained unresolved for 25 years or even longer. It seems that finding solutions to them should optimize diagnostics and therapy of children with short stature.

scholarly journals Diagnosis of growth hormone deficiency in adults by testing with GHRP-6 alone or in combination with GHRH: comparison with the insulin tolerance test

2002 ◽  
pp. 667-672 ◽  
Author(s):  
S Petersenn ◽  
R Jung ◽  
FU Beil
Keyword(s):  
Growth Hormone ◽  
Gh Deficiency ◽  
Group Versus ◽  
Tolerance Test ◽  
Insulin Tolerance Test ◽  
Hormone Deficiency ◽  
Peak Response ◽  
Gh Secretion ◽  
Insulin Tolerance ◽  
Ghrh Test

OBJECTIVE: The diagnosis of GH deficiency in adults should be made using provocative testing of GH secretion. The insulin tolerance test (ITT) is recommended as the gold standard investigation. Because of the risk of serious complications, patients with epilepsy or known ischemic heart disease should not undergo this test. GHRP-6 is a synthetic hexapeptide that releases GH by binding to specific hypothalamic and pituitary receptors. We assessed the diagnostic capability of GH stimulation by GHRP-6 alone or in combination with GHRH in comparison to the results of an ITT. DESIGN: Twenty patients underwent an ITT for suspected pituitary or adrenal disease. Either GHRP-6 (1 microg/kg) alone, or GHRP-6 in combination with GHRH (1 microg/kg) were administered on different days. Blood samples were obtained during a subsequent 90-min period for measurement of GH. RESULTS: Ten patients had a GH peak response of less than 3 microg/l during ITT and were considered growth hormone deficient (GHD). The GH mean peak (+/-S.E.M., range) in this group was 0.7 microg/l (+/-0.3, 0.1-2.9) compared with 14.5 microg/l (+/-3.5, 3.8-40.8) in the group of patients with a GH peak response of more than 3 microg/l (growth hormone sufficient (GS)). For the GHRP-6 test, the GH mean peak was 1.3 microg/l (+/-0.6, 0.1-6.7) in the GHD group versus 25.7 microg/l (+/-5.5, 7.7-54.2) in the GS group. After GHRP-6+GHRH, the GH mean peaks were 4.0 microg/l (+/-1.3, 0.2-11.9) versus 54.7 microg/l (+/-11.1, 13.9-136.0) respectively. During administration of GHRP-6, the only side effects observed were flush symptoms. CONCLUSIONS: Peak GH levels below 7 microg/l for the GHRP-6 test and below 13 microg/l for the combined GHRP-6+GHRH test identified all patients with GH deficiency correctly as defined by ITT. The results suggest that testing with GHRP-6 or GHRP-6+GHRH is as sensitive and specific as an ITT for the diagnosis of adult GH deficiency.

scholarly journals IGF-1 and IGFBP 3 in Growth Hormone Deficiency Role of Insulin Like Growth Factor-1 (IGF-1) and IGF Binding Protein 3 in the Diagnosis of Growth Hormone Deficiency: Changing Paradigm

2012 ◽  
Vol 32 (2) ◽  
pp. 154-162 ◽  
Author(s):  
SK Kota ◽  
S Jammula ◽  
K Gayatri ◽  
SK Kota ◽  
PR Tripathy ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Hormone Deficiency ◽  
Gh Deficiency ◽  
False Positive Rate ◽  
Hormone Deficiency ◽  
Provocative Test ◽  
Definitive Evidence ◽  
Gh Secretion ◽  
Igf I ◽  
Igfbp 3

GH stimulation tests are widely used in the diagnosis of GH deficiency (GHD), although they are associated with a high false positive rate. Serum IGF-I levels are monitored during GH replacement treatment in subjects with GH deficiency (GHD) to guide GH dose adjustment and to minimize occurrence of GHrelated side-effects. The need for reliance on provocative testing is based on evidence that the evaluation of spontaneous growth hormone (GH) secretion over 24 hours and the measurement of IGF-I and IGFBP-3 levels do not distinguish between normal and GHD subjects. Regarding IGF-I, it has been demonstrated that very low levels in patients highly suspected for GHD (i.e., patients with childhood-onset, severe GHD, or with multiple hypopituitarism acquired in adulthood) may be considered definitive evidence for severe GHD obviating the need for provocative tests. However, normal IGF-I levels do not rule out severe GHD and therefore adults suspected for GHD and with normal IGF-I levels must undergo a provocative test of GH secretion. We hereby review the various literatures at disposal justifying the use of IGF-1 and IGBP3 for diagnosis of growth hormone deficiency.Data Source: We searched PUBMED and MEDLINE database for relevant articles including key words. References of each article were further reviewed for final synthesis of the manuscript.J Nepal Paediatr Soc 2012;32(2):154-162 doi: http://dx.doi.org/10.3126/jnps.v32i2.5342

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.

Genetic defects causing functional and structural isolated growth hormone deficiency

2011 ◽  
Vol 2 (2) ◽  
Author(s):  
Vibor Petkovic ◽  
Primus Mullis
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Somatic Growth ◽  
Human Growth ◽  
Postnatal Growth ◽  
Metabolic Effects ◽  
Hormone Deficiency ◽  
Height Velocity ◽  
Gh Secretion ◽  
Normal Standards

AbstractNormal somatic growth requires the integrated function of many of the hormonal, metabolic, and other growth factors involved in the hypothalamo-pituitary-somatotrope axis. Human growth hormone (hGH) causes a variety of physiological and metabolic effects in humans and its pivotal role in postnatal growth is undisputed. Disturbances that occur during this process often cause subnormal GH secretion and/or subnormal GH sensitivity/responsiveness resulting in short stature. Despite the complexity of this linear growth process, the growth pattern of children, if evaluated in the context of normal standards, is rather predictable. Children presenting with short stature (i.e out of normal standards) are treated with daily injections of recombinant human GH (rhGH), which leads in almost all cases to an increase of height velocity. Although it is becoming more and more evident that many genes are involved in controlling the regulation of growth, the main aim of this review is to focus on the GH-1 gene, the various gene alterations and their important physiological and pathophysiological role in growth.

scholarly journals Association between triglyceride glucose index and peak growth hormone in children with short stature

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Qianqian Zhao ◽  
Yuntian Chu ◽  
Hui Pan ◽  
Mei Zhang ◽  
Bo Ban
Keyword(s):  
Growth Hormone ◽  
Short Stature ◽  
Gh Deficiency ◽  
Nonlinear Relationship ◽  
Gh Secretion ◽  
Tyg Index ◽  
Provocation Tests ◽  
Triglyceride Glucose Index ◽  
Peak Growth Hormone ◽  
The Relationship

AbstractGrowth hormone (GH) secretion is related to many factors, such as weight and puberty, and the reproducibility of GH provocation tests is very poor. This study aimed to evaluate whether the triglyceride (TyG) index was associated with peak GH in children with short stature. This study included 1095 children with short stature divided into two groups based on peak GH level in GH provocation tests [GH deficiency (GHD) group = 733 children; non-GHD group = 362 children]. We found that the TyG index was significantly higher in the GHD group than in the non-GHD group (P < 0.001). A nonlinear relationship was detected between the TyG index and peak GH, whose point was 7.8. A significant negative association between the TyG index and peak GH was observed when the TyG index was greater than 7.8 (β − 2.61, 95% CI − 3.98, − 1.24; P < 0.001), whereas, the relationship between the TyG index and peak GH was not significant when the TyG index was lower than 7.8 (β 0.25, 95% CI − 1.68, 2.17; P = 0.799). There is a nonlinear relationship between the TyG index and peak GH, and a higher TyG index is associated with decreased peak GH in children with short stature.

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