Impact of Overweight on Effectiveness of Treatment with Human Growth Hormone in Growth Hormone Deficient Children: Analysis of German KIGS Data

2011 ◽  
Vol 119 (09) ◽  
pp. 544-548 ◽  
Author(s):  
T. Reinehr ◽  
S. Bechtold-Dalla Pozza ◽  
M. Bettendorf ◽  
H.-G. Doerr ◽  
B. Gohlke ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Velocity ◽  
Normal Weight ◽  
First Year ◽  
Overweight Children ◽  
Gh Treatment ◽  
Prepubertal Children ◽  
Significant Difference ◽  
Igf I ◽  
Group A

AbstractWe hypothesized that overweight children with growth hormone deficiency (GHD) demonstrate a lower response to growth hormone (GH) as a result of a misclassification since obesity is associated with lower GH peaks in stimulation tests.Anthropometric data, response, and responsiveness to GH in the first year of treatment were compared in 1.712 prepubertal children with GHD from the German KIGS database according to BMI (underweight=group A, normal weight=group B, overweight=group C) (median age: group A, B, C: 7.3, 7.28, and 8.4 years).Maximum GH levels to tests (median: group A, B, C: 5.8, 5.8, and 4.0 µg/ml) were significantly lower in group C. IGF-I SDS levels were not different between the groups. Growth velocity in the first year of GH treatment was significantly lower in the underweight cohort (median: group A, B, C: 8.2, 8.8, and 9.0 cm/yr), while the gain in height was not different between groups. The difference between observed and predicted growth velocity expressed as Studentized residuals was not significantly different between groups. Separating the 164 overweight children into obese children (BMI>97th centile; n=71) and moderate overweight children (BMI>90th to 97th centile, n=93) demonstrated no significant difference in any parameter.Overweight prepubertal children with idiopathic GHD demonstrated similar levels of responsiveness to GH treatment compared to normal weight children. Furthermore, the IGF-I levels were low in overweight children. Therefore, a misclassification of GHD in overweight prepubertal children within the KIGS database seems unlikely. The first year growth prediction models can be applied to overweight and obese GHD children.

Correlation Between the Responses to Growth Hormone (GH) Treatment During Childhood and Adulthood in a Monocentric Cohort of GH-Deficient Patients

2018 ◽  
Vol 50 (06) ◽  
pp. 462-468
Author(s):  
Sarah Thilmany ◽  
Leila Mchirgui ◽  
Chloé Brunelle ◽  
Véronique Beauloye ◽  
Dominique Maiter ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Growth Velocity ◽  
Significant Positive Correlation ◽  
Growth Parameters ◽  
Hormone Deficiency ◽  
First Year ◽  
Z Score ◽  
Gh Treatment ◽  
Positive Correlation ◽  
Igf I

AbstractOur aim was to analyze a cohort of patients with childhood-onset growth hormone deficiency (GHD) to evaluate if there is some correlation between the response to GH treatment during childhood and adulthood, respectively. This was an observational retrospective monocentric cohort study of 47 patients treated with GH during childhood and adulthood. Changes in growth parameters during childhood were compared with the increase of IGF-I z-score and other indexes of GH response (body composition, lipid profile) after 1 year of treatment in adulthood. The only significant positive correlation was observed between final growth velocity during the last year of childhood GH treatment and increase in IGF-I z-score in GH-treated adults (r=0.592, p=< 0.01). No correlation was observed between growth-promoting effects of GH as child and metabolic changes induced by GH as adult. We also observed a negative correlation between weight at the end of childhood GH treatment and the IGF-I response during first year of treatment in adults (r=− 0.335, p <0.05). No significant positive correlation could be observed between the main parameters that evaluate response to GH treatment in children and adults. However, the final growth velocity, which may be considered as one of the main criteria of end of GH treatment in children, was identified as parameter that could predict future response to GH treatment in adulthood.

Bioavailability and bioactivity of three different doses of nasal growth hormone (GH) administered to GH-deficient patients: comparison with intravenous and subcutaneous administration

1996 ◽  
Vol 135 (3) ◽  
pp. 309-315 ◽  
Author(s):  
Torben Laursen ◽  
Birgitte Grandjean ◽  
Jens OL Jørgensen ◽  
Jens S Christiansen
Keyword(s):  
Growth Hormone ◽  
Metabolic Response ◽  
Serum Insulin ◽  
Subcutaneous Administration ◽  
Absolute Bioavailability ◽  
High Dose ◽  
Gh Treatment ◽  
Significant Difference ◽  
Igf I ◽  
Different Doses

Laursen T, Grandjean B, Jørgensen JOL, Christiansen JS. Bioavailability and bioactivity of three different doses of nasal growth hormone (GH) administered to GH-deflcient patients: comparison with intravenous and subcutaneous administration. Eur J Endocrinol 1996;135:309–15. ISSN 0804–4643 The current mode of growth hormone (GH) replacement therapy is daily subcutaneous (sc) injections given in the evening. This schedule is unable to mimic the endogenous pulsatile pattern of GH secretion, which might be of importance for the induction of growth and other GH actions. The present study was conducted in order to study the pharmacokinetics of different doses of GH following intranasal (IN) administration and the biological activity of GH after IN administration as compared with sc and intravenous (iv) delivery. Sixteen GH-deficient patients were studied on five different occasions. On three occasions GH was administered intranasally in doses of 0.05, 0.10 and 0.20IU/kg, using didecanoyl-l-α-phosphatidylcholine as an enhancer. On the other two occasions the patients received an sc injection (0.10IU/kg) and an iv injection (0.015IU/kg) of GH, respectively. The nasal doses and the sc injection were given in random order in a crossover design. In a double-blinded manner the subjects received the three nasal doses as one puff in each nostril. The patients received no GH treatment between the five studies or during the last week before the start of each study. Intravenous administration produced a short-lived serum GH peak value of 128.12 ± 6.71 μg/l. Peak levels were 13.98±1.63 μg/l after sc injection and 3.26±0.38. 7.07±0.80 and 8.37± 1.31 μg/l, respectively, after the three nasal doses. The peak values of the 0.05 and the 0.20IU/kg nasal doses were significantly different (p = 0.007). The mean levels obtained by the low nasal dose were significantly lower than those obtained with the medium (p < 0.001) and the high dose (p < 0.001). while there was no significant difference between the medium and the high doses. The absolute bioavailability of GH following sc relative to iv administration was 49.5%. The bioavailabilities of the nasal doses were: 7.8% (0.05 IU), 8.9% (0.10 IU) and 3.8% (0.20 IU). Serum insulin-like growth factor I (IGF-I) levels increased significantly after sc administration only. Mean levels were significantly higher after sc administration as compared with the iv and all three nasal does (p < 0.001). Serum IGF binding protein 3 (IGFBP-3) levels remained unchanged on all five occasions. Mean serum IGFBP-1 levels were significantly lower after sc GH injection than after administration of the iv (p < 0.001) and the three nasal doses (p < 0.005). Subcutaneous GH administration resulted in significantly higher levels of serum insulin and blood glucose (p < 0.001). In conclusion, the bioavailability of nasal GH was low (3.8–8.9%). An iv bolus injection of, on average, 1 IU of GH induced no metabolic response. Only sc GH administration induced increased levels of IGF-I, insulin and glucose. These data reveal that a closer imitation of the physiological GH pulses than achieved by sc GH administration is of limited importance for the induction of a metabolic response to GH. Torben Laursen, Medical Department M (Diabetes & Endocrinology), Aarhus Kommunehospital, DK-8000 Aarhus C. Denmark

scholarly journals Once-Weekly Somapacitan Versus Daily Growth Hormone in Growth Hormone Deficiency: 2-Year Efficacy Results From REAL 3, a Randomized Phase 2 Trial

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A680-A680
Author(s):  
Lars S Sävendahl ◽  
Tadej Battelino ◽  
Michael Højby Rasmussen ◽  
Reiko Horikawa ◽  
Paul Saenger
Keyword(s):  
Growth Hormone ◽  
Standard Deviation ◽  
Height Velocity ◽  
First Year ◽  
Phase 2 ◽  
Efficacy And Safety ◽  
Gh Treatment ◽  
Treatment Groups ◽  
Igf I ◽  
Second Year

Abstract Current treatment for growth hormone (GH) deficiency (GHD) requires daily injections, which can be burdensome for the patients/caregivers. Once-weekly somapacitan is a long-acting GH derivative currently in phase 3 for use in children with GHD and phase 2 for short children born small for gestational age. A phase 2, multinational, randomized, open-label, controlled trial (NCT02616562) investigated the efficacy and safety of somapacitan in children compared with daily GH (Norditropin®). GH-treatment-naïve prepubertal children with GHD received 0.04 (n=16), 0.08 (n=15) or 0.16 mg/kg/week (n=14) subcutaneous (s.c.) somapacitan, or s.c. daily GH 0.034 mg/kg/day (0.24 mg/kg/week; n=14) for 52 weeks, followed by a 104-week safety extension. In the extension phase, all patients on somapacitan received 0.16 mg/kg/week; daily GH dose remained unaltered. The 52-week efficacy and safety results have been reported previously. We report here the efficacy results after 104 weeks of GH treatment. At week 104, mean (standard deviation [SD]) height velocity (HV) in the first year of the safety extension was: 10.6 (1.4), 10.0 (1.6) and 9.2 (1.7) cm/year for 0.04/0.16 mg/kg/week (n=13), 0.08/0.16 mg/kg/week (n=15) and 0.16/0.16 mg/kg/week (n=14) somapacitan, respectively, versus 9.0 (2.3) cm/year for daily GH (n=11). Mean (SD) change from baseline in HV standard deviation score (SDS) was 8.04 (2.52), 6.21 (2.90) and 6.40 (3.04) for somapacitan, respectively, versus 6.58 (3.15) for daily GH. Compared with week 52, mean HV and HV SDS at week 104 were increased in children in the somapacitan 0.04/0.16 mg/kg/week and 0.08/0.16 mg/kg/week treatment groups. Height SDS values improved during the second year of treatment with somapacitan and daily GH, with the greatest change from baseline in the somapacitan 0.16/0.16 mg/kg/week treatment group. The mean (SD) change in height SDS from baseline to week 104 was 1.73 (0.76), 1.87 (0.81) and 2.18 (1.18) for somapacitan, respectively, versus 1.72 (0.65) for daily GH. The observed mean (SD) change in insulin-like growth factor-I (IGF-I) SDS from baseline was similar between the somapacitan 0.08/0.16 and 0.16/0.16 mg/kg/week treatment groups (3.15 [1.17] and 3.21 [1.12], respectively), and slightly higher compared with IGF-I SDS in the 0.04/0.16 mg/kg/week group (2.99 [1.05]) and the daily GH group (3.06 [1.26]). Mean IGF-I SDS values remained below the upper limit (+2) of the normal range for all treatment groups throughout the 104-week trial duration. Somapacitan was well tolerated at all doses investigated, with no new safety or local tolerability issues identified during the 104 weeks of treatment. In conclusion, at week 104, height-based outcomes were similar between somapacitan 0.16/0.16 mg/kg/week and daily GH, with comparable mean change in IGF-I SDS. Furthermore, the key improvements observed in the first year were maintained in the second year of the study.

Results of Four Years of Intermittent Human Growth Hormone (hGH) and Fluoxymesterone Therapy in Hypopituitary Dwarfism

PEDIATRICS ◽  
1980 ◽  
Vol 65 (3) ◽  
pp. 562-566
Author(s):  
Rebecca T. Kirkland ◽  
R. B. Harrist ◽  
George W. Clayton
Keyword(s):  
Growth Hormone ◽  
Human Growth Hormone ◽  
Growth Velocity ◽  
Combined Therapy ◽  
Combined Treatment ◽  
Human Growth ◽  
First Year ◽  
Average Growth ◽  
Group A ◽  
Second Year

In order to investigate the synergistic effect on growth of human growth hormone (hGH) and an anabolic agent, fluoxymesterone, 28 children with hypopituitarism received the combined therapy in an intermittent regimen for one to four years. Fourteen of the children had received prior therapy with growth hormone alone. All of the children were prepubertal. They had a mean chronologic age (CA) of 9.53 years ± 2.33 SD and mean bone age (BA) of 6.05 years ± 2.07 SD. The change in BA/change in height age (HA) ≤1 in 15 of the 28 children (53.6%). The change in HA/change in CA was ≥1 in 17 of 28 (60.7%). The 14 children who had received hGH therapy alone, group A, had a growth velocity of 4.72 cm/yr ± 1.24 SD in the year prior to the combined treatment. This did not differ significantly from the average growth velocity of 5.58 cm ± 1.47 SD during the first year of combined therapy. The average growth velocity of the remaining 14 children, group B, during the first year of combined therapy was 6.72 cm/yr ± 1.01 SD. This differed significantly from the growth velocity of group A before combined therapy (P &lt; .001) and also during the first year of combined therapy (P &lt; .025). The overall mean growth rate in the second year, 5.33 cm, was less than that of the first year, P &lt; .025, and was not different from that achieved with hGH alone. Furthermore, the velocity in each of the following years was similar to that of the second year. The use of intermittent combined therapy in the doses employed in this study does not appear to be of benefit in prolonging catch-up growth in hypopituitary patients. This regimen provides acceleration of growth in the initial year of therapy for those children who have not received prior hGH therapy.

scholarly journals The metabolic outcomes of growth hormone treatment in children are gender specific

2018 ◽  
Vol 7 (7) ◽  
pp. 879-887 ◽  
Author(s):  
Alessandro Ciresi ◽  
Stefano Radellini ◽  
Valentina Guarnotta ◽  
Maria Grazia Mineo ◽  
Carla Giordano
Keyword(s):  
Growth Hormone ◽  
Insulin Sensitivity ◽  
Metabolic Parameters ◽  
Sensitivity Index ◽  
Prepubertal Children ◽  
Metabolic Outcomes ◽  
Significant Difference ◽  
Igf I ◽  
Males And Females ◽  
The Impact

Objective To evaluate the impact of gender on the clinical and metabolic parameters in prepubertal growth hormone deficiency (GHD) children at diagnosis and during GH treatment (GHT). Design The data of 105 prepubertal children (61 males, 44 females, mean age 6.8 ± 0.7 years) affected by idiopathic GHD were retrospectively evaluated. Methods Body height, BMI, waist circumference (WC), IGF-I, HbA1c, lipid profile, fasting and after-OGTT glucose and insulin levels, insulin sensitivity and secretion indices were evaluated at baseline and after 24 months of GHT. Results At baseline, no significant difference was found in all clinical, hormonal and metabolic parameters between males and females. After 24 months of GHT, both males and females showed a significant increase in height (both P < 0.001), BMI (both P < 0.001), WC (P < 0.001 and P = 0.004, respectively), IGF-I (both P < 0.001), fasting glucose (P < 0.001 and P = 0.001, respectively), fasting insulin (both P < 0.001) and Homa-IR (both P < 0.001), with a concomitant significant decrease in insulin sensitivity index (ISI) (both P < 0.001) and oral disposition index (DIo) (P = 0.001 and P < 0.001, respectively). At 24 months of GHT, females showed significantly higher BMI (P = 0.027), lower ISI (P < 0.001) and DIo (P < 0.001), in concomitance with a significant greater change from baseline to 24 months of BMI (P = 0.013), WC (P < 0.001), ISI (P = 0.002) and DIo (P = 0.072), although the latter does not reach statistical significance. Conclusions Twenty-four months of GHT in prepubertal children leads to different metabolic outcomes according to gender, with a greater reduction in insulin sensitivity in females, regardless of auxological and hormonal parameters. Therefore, prepubertal GHD females should probably need a more proper monitoring in clinical practice.

scholarly journals The Role of Obesity in Predicting the Clinical Outcomes of COVID-19

Obesity Facts ◽  
2021 ◽  
pp. 1-9
Author(s):  
Serdar Sahin ◽  
Havva Sezer ◽  
Ebru Cicek ◽  
Yeliz Yagız Ozogul ◽  
Murat Yildirim ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Health Care Providers ◽  
Study Groups ◽  
Normal Weight ◽  
Overweight And Obesity ◽  
Care Providers ◽  
Significant Difference ◽  
Group A ◽  
Group B ◽  
Group D

<b><i>Introduction:</i></b> The aim of this was to describe the predictors of mortality related to COVID-19 infection and to evaluate the association between overweight, obesity, and clinical outcomes of COVID-19. <b><i>Methods:</i></b> We included the patients &#x3e;18 years of age, with at least one positive SARS-CoV-2 reverse transcriptase-polymerase chain reaction. Patients were grouped according to body mass index values as normal weight &#x3c;25 kg/m<sup>2</sup> (Group A), overweight from 25 to &#x3c;30 kg/m<sup>2</sup> (Group B), Class I obesity 30 to &#x3c;35 kg/m<sup>2</sup> (Group C), and ≥35 kg/m<sup>2</sup> (Group D). Mortality, clinical outcomes, laboratory parameters, and comorbidities were compared among 4 groups. <b><i>Results:</i></b> There was no significant difference among study groups in terms of mortality. Noninvasive mechanical ventilation requirement was higher in group B and D than group A, while it was higher in Group D than Group C (Group B vs. Group A [<i>p</i> = 0.017], Group D vs. Group A [<i>p</i> = 0.001], and Group D vs. Group C [<i>p</i> = 0.016]). Lung involvement was less common in Group A, and presence of hypoxia was more common in Group D (Group B vs. Group A [<i>p</i> = 0.025], Group D vs. Group A [<i>p</i> &#x3c; 0.001], Group D vs. Group B [<i>p</i> = 0.006], and Group D vs. Group C [<i>p</i> = 0.014]). The hospitalization rate was lower in Group A than in the other groups; in addition, patients in Group D have the highest rate of hospitalization (Group B vs. Group A [<i>p</i> &#x3c; 0.001], Group C vs. Group A [<i>p</i> &#x3c; 0.001], Group D vs. Group A [<i>p</i> &#x3c; 0.001], Group D vs. Group B [<i>p</i> &#x3c; 0.001], and Group D vs. Group C [<i>p</i> = 0.010]). <b><i>Conclusion:</i></b> COVID-19 patients with overweight and obesity presented with more severe clinical findings. Health-care providers should take into account that people living with overweight and obesity are at higher risk for COVID-19 and its complications.

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.

Urinary Growth Hormone Measurements in Children with Renal Insufficiency

1993 ◽  
Vol 30 (6) ◽  
pp. 540-544
Author(s):  
G Turner ◽  
A Skinner ◽  
J S Woodhead
Keyword(s):  
Growth Hormone ◽  
Renal Insufficiency ◽  
Causative Factor ◽  
Plasma Creatinine ◽  
Tubular Dysfunction ◽  
Control Subjects ◽  
Significant Difference ◽  
Proximal Tubular ◽  
Group A ◽  
Group B

It has been reported that intrinsic renal factors could affect urinary growth hormone (UGH) measurements. We compared UGH excretion in 21 children aged 4–16 years, with various degrees of renal insufficiency, with that in 10 control subjects aged 5–13 years. We found 100- to 1000-fold elevations in UGH in children with plasma creatinine concentrations > 120 μmol/L (Group A) compared with patients with plasma creatinine concentrations < 120 μmol/L (Group B) and control subjects. UGH excretion (μU) in the three groups was as follows: group A 804–8556 (median 2649); group B 1·0–85 (median 7·5); and controls 2·6–7·3 (median 4·0). Elevated urinary β2-microglobulin levels (μg) were also observed in group A patients: 875–15 400 (median 11 637) as compared with group B, 1·0–104 (median 32) and controls, 3–18·7 (median 8·0). There was no significant difference in albumin excretion between groups A and B though six patients in group B with nephrotic syndrome (NS) excreted significantly more albumin (P < 0·05) than the other 15 patients investigated. Our data show that abnormalities of renal function have a profound effect on growth hormone excretion and we suggest proximal tubular dysfunction as the causative factor. We conclude that UGH measurements do not provide a reliable means of assessment of hypothalamo-pituitary function in patients with renal insufficiency.

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