Increased growth rate following transfer to daily sc administration from three weekly im injections of hGH in growth hormone deficient children

1983 ◽  
Vol 104 (2) ◽  
pp. 148-152 ◽  
Author(s):  
K. W. Kastrup ◽  
J. Sandahl Christiansen ◽  
J. Koch Andersen ◽  
H. Ørskov

Abstract. The effect of more frequent (daily) injections of human growth hormone (hGH) on growth rate was studied in 16 growth hormone deficient children (12 boys, 4 girls) during 2 years. All had previously been treated with im injection of hGH 2–3 times weekly and in the majority of the patients a waning growth response was observed. For a total weekly dose of 12 IU hGH a daily dose of 2 IU was injected sc at night before sleep. This dosage has been shown by us to imitate the average nocturnal hGH profile in plasma. Growth response on the im treatment was 5.2 ± 1.2 cm/year (sd) in boys and 5.4 ± 0.9 cm/year in girls. A significant increase was seen during the first year of sc treatment to 7.9 ± 2.7 cm in boys and 6.3 ± 2cm in girls. During the second year the growth response was still significantly increased in boys (7.2 ± 1.9 cm). Bone age was more advanced and the period of previous im treatment was longer in girls (6.7 vs 3.6 years) which may be the main cause of the waning second year response (4.7 ±1.3 cm/year). Pubertal development occurred in 9 children during treatment. However, the highest growth rates were not found in these children. Absence of antibodies against hGH and local reactions at the injection site is evidence of the safety of the treatment, which was very well accepted by the children. Daily sc injections thus represent an effective alternative to conventional im injections ensuring high acceptance in children with growth hormone deficiency.

2016 ◽  
Vol 175 (6) ◽  
pp. 633-643 ◽  
Author(s):  
Adam Stevens ◽  
Philip Murray ◽  
Jerome Wojcik ◽  
John Raelson ◽  
Ekaterina Koledova ◽  
...  

Objective Single-nucleotide polymorphisms (SNPs) associated with the response to recombinant human growth hormone (r-hGH) have previously been identified in growth hormone deficiency (GHD) and Turner syndrome (TS) children in the PREDICT long-term follow-up (LTFU) study (Nbib699855). Here, we describe the PREDICT validation (VAL) study (Nbib1419249), which aimed to confirm these genetic associations. Design and methods Children with GHD (n = 293) or TS (n = 132) were recruited retrospectively from 29 sites in nine countries. All children had completed 1 year of r-hGH therapy. 48 SNPs previously identified as associated with first year growth response to r-hGH were genotyped. Regression analysis was used to assess the association between genotype and growth response using clinical/auxological variables as covariates. Further analysis was undertaken using random forest classification. Results The children were younger, and the growth response was higher in VAL study. Direct genotype analysis did not replicate what was found in the LTFU study. However, using exploratory regression models with covariates, a consistent relationship with growth response in both VAL and LTFU was shown for four genes – SOS1 and INPPL1 in GHD and ESR1 and PTPN1 in TS. The random forest analysis demonstrated that only clinical covariates were important in the prediction of growth response in mild GHD (>4 to <10 μg/L on GH stimulation test), however, in severe GHD (≤4 μg/L) several SNPs contributed (in IGF2, GRB10, FOS, IGFBP3 and GHRHR). Conclusions The PREDICT validation study supports, in an independent cohort, the association of four of 48 genetic markers with growth response to r-hGH treatment in both pre-pubertal GHD and TS children after controlling for clinical/auxological covariates. However, the contribution of these SNPs in a prediction model of first-year response is not sufficient for routine clinical use.


2021 ◽  
Vol 10 (21) ◽  
pp. 5100
Author(s):  
Ewelina Witkowska-Sędek ◽  
Anna Małgorzata Kucharska ◽  
Małgorzata Rumińska ◽  
Monika Paluchowska ◽  
Beata Pyrżak

Background: Hypothyroidism in children leads to growth retardation. However, there is some evidence that recombinant human growth hormone (rhGH) therapy could suppress thyroid function. The most common observation in rhGH-treated patients is a decrease in thyroxine levels, which is reported as transient, but the studies in the field are inconsistent. We aimed to evaluate thyroid function in initially euthyroid children with idiopathic isolated GH deficiency during long-term rhGH therapy and to determine who is at a higher risk of thyroid function alterations during the therapy. Methods: The study group consisted of 101 children treated with rhGH for at least three years. Serum TSH and fT4 levels were determined at baseline, after the first six months and after each full year of therapy. The associations between changes in thyroid hormone levels during rhGH therapy and GH deficit, insulin-like growth factor-1 levels and growth response were investigated. Results: A significant decrease in fT4 levels (p = 0.01) was found as early as after the first six months of rhGH therapy. This effect persisted in the subsequent years of treatment without any significant changes in TSH values and tended to be rhGH dose related. Children with a greater fT4 decrease after the initiation of rhGH therapy were older, had higher bone age and responded to that therapy worse than children with lower fT4 changes. Conclusions: Our study revealed a long-term decrease in fT4 levels during rhGH therapy in initially euthyroid GHD children. The decrease in fT4 levels was associated with a lower growth response to rhGH therapy.


PEDIATRICS ◽  
1980 ◽  
Vol 66 (2) ◽  
pp. 272-276
Author(s):  
Arlan L. Rosenbloom ◽  
William J. Riley ◽  
Janet H. Silverstein ◽  
Adolfo D. Garnica ◽  
Michael L. Netzloff ◽  
...  

Initial year growth responses to single weekly injections of 2.5 units human growth hormone (hGH) in 29 patients with hypopituitarism (130 units/yr/patient) were compared to responses in a series using smaller doses in conjunction with androgen (48 to 112 units/yr); the US collaborative study experience with the standard dose (2 units 3 times/wk = 312 units/yr), and with two size-adjusted doses (0.06 units/kg 3 times/wk = 212 ± 94 SD units/yr, 0.03 units/kg 3 times/wk = 116 ± 33 units/yr); and to the British experience with much larger doses (1,040 units/yr). During the first year of hGH treatment our patients grew an average 13% faster than the androgen-supplemented and collaborative study-0.03 units/kg/dose groups. They had a similar pace to the collaborative study-312 units/yr and 0.06 units/kg/dose patients, but grew 15% more slowly than did the British patients. Growth response correlated positively with age and negatively with hGH dose per kilogram of body weight. Of 17 patients with isolated growth hormone deficiency ten developed hypothyroidism with hGH therapy, leading to a policy of routine adjunctive thyroxine replacement.


2021 ◽  
Vol 12 ◽  
Author(s):  
Saartje Straetemans ◽  
Raoul Rooman ◽  
Jean De Schepper

ObjectiveThe first year response to growth hormone (GH) treatment is related to the total height gain in GH treated children, but an individual poor first year response is a weak predictor of a poor total GH effect in GH deficient (GHD) children. We investigated whether an underwhelming growth response after 2 years might be a better predictor of poor adult height (AH) outcome after GH treatment in GHD children.Design and methodsHeight data of GHD children treated with GH for at least 4 consecutive years of which at least two prepubertal and who attained (near) (n)AH were retrieved from the Belgian Register for GH treated children (n = 110, 63% boys). In ROC analyses, the change in height (ΔHt) SDS after the first and second GH treatment years were tested as predictors of poor AH outcome defined as: (1) nAH SDS &lt;−2.0, or (2) nAH SDS minus mid-parental height SDS &lt;−1.3, or (3) total ΔHt SDS &lt;1.0. The cut-offs for ΔHt SDS and its sensitivity at a 95% specificity level to detect poor AH outcome were determined.ResultsEleven percent of the cohort had a total ΔHt SDS &lt;1.0. ROC curve testing of first and second years ΔHt SDS as a predictor for total ΔHt SDS &lt;1.0 had an AUC &gt;70%. First-year ΔHt SDS &lt;0.41 correctly identified 42% of the patients with poor AH outcome at a 95% specificity level, resulting in respectively 5/12 (4.6%) correctly identified poor final responders and 5/98 (4.5%) misclassified good final responders (ratio 1.0). ΔHt SDS after 2 prepubertal years had a cut-off level of 0.65 and a sensitivity of 50% at a 95% specificity level, resulting in respectively 6/12 (5.5%) correctly identified poor final responders and 5/98 (4.5%) misclassified good final responders (ratio 1.2).ConclusionIn GHD children the growth response after 2 prepubertal years of GH treatment did not meaningfully improve the prediction of poor AH outcome after GH treatment compared to first-year growth response parameters. Therefore, the decision to re-evaluate the diagnosis or adapt the GH dose in case of poor response after 1 year should not be postponed for another year.


2019 ◽  
Vol 17 ◽  
pp. 205873921882423
Author(s):  
Yu Wang ◽  
Meng Sun ◽  
Xin Wang ◽  
Ya-Ying Cheng

This study aims to investigate the effects of recombinant human growth hormone (rhGH) on serum nesfatin-1 and ghrelin in children with growth hormone deficiency (GHD), in order to provide a reliable basis for the effectiveness and safety of applying rhGH in treating GHD children in the clinic. A total of 30 GHD pediatric patients were selected as the observation group. According to the peak of GH, these patients were divided into two subgroups: complete absence of growth hormone (CGHD) group and partial absence of growth hormone (PGHD) group. At the same time, 20 healthy children of normal height with matching age and gender were randomly selected as a normal control group. Serum ghrelin and nesfatin-1 levels were detected in children in the control group and observation group before rhGH treatment, and at 3 and 6 months after treatment. After 3 and 6 months of treatment, the height and growth rate of children in the PGHD and CGHD groups significantly increased ( P < 0.05), but their body weights did not significantly change ( P > 0.05), compared with those before treatment. Before treatment, ghrelin was higher in the PGHD group than in the control group, while ghrelin was lower in the CGHD group than in the control group. In addition, nesfatin-1 was higher in these two subgroups, compared with that in the control group. At pretreatment, and after 3  and 6 months of treatment, ghrelin and nesfatin-1 both decreased in the PGHD group, while ghrelin increased and nesfatin-1 decreased in the CGHD group. It was confirmed that ghrelin and nesfatin-1 were closely correlated with GHD. Furthermore, rhGH has a significant effect on children with GHD, and can significantly accelerate the annual growth rate.


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