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

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.

Acromesomelic Dysplasia, Type Maroteaux: Impact of Long-Term (8 Years) High-Dose Growth Hormone Treatment on Growth Velocity and Final Height in 2 Siblings

2020 ◽  
Vol 93 (5) ◽  
pp. 335-342
Author(s):  
Ved Bhushan Arya ◽  
Meena Raj ◽  
Maha Younes ◽  
Simon Chapman ◽  
Melita Irving ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Serum Insulin ◽  
Final Height ◽  
Hormone Treatment ◽  
High Dose ◽  
Childhood And Adolescence ◽  
Loss Of Function ◽  
Gh Treatment ◽  
Height Gain

<b><i>Introduction:</i></b> Acromesomelic dysplasia, type Maroteaux (AMDM) is a rare autosomal recessive skeletal dysplasia, characterized by severe dwarfism and disproportionate limb shortening. It results from loss-of-function <i>NPR2</i> mutations affecting the C-type natriuretic peptide receptor. Resistance to growth hormone (GH) action has previously been suggested. We describe outcomes of 2 siblings with AMDM after prolonged high-dose GH treatment. <b><i>Patients/Methods:</i></b> Two siblings (Pt-A and Pt-B; consanguineous parents) presented in early childhood with severe disproportionate short stature and radiological features of AMDM. Subsequent genetic testing identified a novel homozygous <i>NPR2</i> mutation. GH provocation testing showed relatively high GH levels. Serum insulin-like growth factor 1 (IGF-1) was ∼2 SD below age/sex-specific mean. High-dose GH (0.075 mg/kg/day) was started. Pre-GH height velocities were 3.7 (Pt-A) and 4.5 (Pt-B) cm/year. GH dose was adjusted to sustain serum IGF-1 towards +3 SDS for age/sex. Annualized height velocities for first 3 years on GH were 7.0, 5.4, and 4.7 cm/year for patient A and 9.4, 8.0, and 5.9 cm/year for patient B. Height gain during puberty was 10.6 (Pt-A) and 5.9 (Pt-B) cm. Final heights after 8.5 years of GH treatment were 130.5 cm (−6.57 SDS, Pt-A) and 134 cm (−4.58 SDS, Pt-B). <b><i>Conclusions:</i></b> To the best of our knowledge, this is the first report of final height in patients with AMDM after long-term GH treatment. Our results confirm the finding of relative GH resistance in AMDM, which when overcome with high-dose GH treatment resulted in improved height SDS during childhood and adolescence and associated quality of life. The final height of our patients was significantly higher than average reported final height (120 cm) of AMDM patients.

Whole-body leucine turnover in adults on conventional treatment for hypopituitarism

1993 ◽  
Vol 129 (2) ◽  
pp. 158-164 ◽  
Author(s):  
Salem A Beshyah ◽  
Patrick S Sharp ◽  
Susan V Gelding ◽  
David Halliday ◽  
Desmond G Johnston
Keyword(s):  
Growth Hormone ◽  
Serum Insulin ◽  
Hormone Replacement ◽  
Whole Body ◽  
Leucine Incorporation ◽  
Gh Treatment ◽  
Mean Values ◽  
Growth Hormone Replacement Therapy ◽  
Igf I ◽  
Normal Controls

This study has investigated protein metabolism in adults with hypopituitarism before and after growth hormone (GH) replacement and in matched controls. Whole-body leucine turnover was measured in 16 GH-deficient adult hypopituitary patients (nine females and seven males) on standard thyroid, adrenal and sex hormone replacement and in 20 normal controls using primed continuous infusion of l-[1 – 13C]leucine. In seven of the patients, leucine turnover was restudied following 6 months' treatment with biosynthetic human GH (0.025–0.05 IU/kg body wt daily, with the final dose determined by patient tolerance). Compared with normal controls, hypopituitary patients had significantly reduced leucine flux (mean±sd: 97.8±24.9 vs 131.0±23.0 μmol·h−1·kg−1; p<0.001), reduced leucine incorporation into protein (80.4±20.9 vs 108.8±19.6 μmol·h−1·kg−1; p<0.001) and reduced leucine oxidation (17.4±4.8 vs 22.2±8.1 μmol·h−1·kg−1; p<0.05). Leucine turnover was similar in male and female patients. In the patients, leucine flux correlated positively with body weight (p = 0.51, p<0.05) and leucine incorporation in protein correlated positively with lean body mass (p = 0.55, p <0.05) and in male patients leucine flux correlated positively with serum insulin-like growth factor I (IGF-I) levels (ρ=0.71, p<0.05). No significant relationship was observed with age or duration of hypopituitarism. Growth hormone replacement therapy did not produce a uniform effect on leucine metabolism. Mean values of leucine flux, oxidation and incorporation into protein increased, although the differences were not statistically significant. The patients on higher GH doses and with a higher serum IGF-I response were those who demonstrated an increase in leucine turnover. We conclude that leucine turnover in hypopituitary adults is reduced compared with normal controls. The effect of GH treatment for 6 months at conventional doses in hypopituitary adults is not uniform and may be dose-dependent.

Effects of four years' treatment with biosynthetic human growth hormone (GH) on body composition in GH-deficient hypopituitary adults

1996 ◽  
Vol 135 (5) ◽  
pp. 559-567 ◽  
Author(s):  
Kamal AS AI-Shoumer ◽  
Brian Page ◽  
Elizabeth Thomas ◽  
Margaret Murphy ◽  
Salem A Beshyah ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Body Composition ◽  
Body Weight ◽  
Human Growth Hormone ◽  
Serum Insulin ◽  
Human Growth ◽  
Fat Free Mass ◽  
Gh Treatment ◽  
Igf I ◽  
Total Body

Al-Shoumer KAS, Page B, Thomas E, Murphy M, Beshyah SA, Johnston DG. Effects of four years' treatment with biosynthetic human growth hormone (GH) on body composition in GH-deficient hypopituitary adults. Eur J Endocrinol 1996;135:559–67. ISSN 0804–4643 Short-term trials of growth hormone (GH) substitution in hypopituitary adults have shown beneficial effects on body composition. To evaluate the long-term effects on body composition, we followed thirteen GH-deficient adults (GH < 6 mU/l following standard provocative tests) for 4 years of GH replacement. At yearly intervals, serum insulin-like growth factor I (IGF-I), body weight, body mass index (BMI), waist, waist-to-hip circumference ratio (WHR) and resting systolic (SBP) and diastolic blood pressure (DBP) were determined, and body composition was assessed using three independent methods: total body potassium (TBK), bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA). Compared to baseline, IGF-I levels increased significantly at 1 (p = 0.0001), 2 (p = 0.0004), 3 (p = 0.006) and 4 years (p = 0.002). Body weight and BMI changed minimally at 1, 2 and 3 years and increased significantly only at the fourth year (p = 0.012 and p = 0.0009, respectively) of GH therapy. Waist and WHR decreased significantly at 1, 2 and 4 years (waist: p = 0.0009, p = 0.0004, p = 0.049; WHR: p = 0.0025, p = 0.012, p = 0.047, respectively). Neither resting SBP nor DBP changed significantly. Fat-free mass (FFM) derived from TBK and BIA increased significantly at 1 (p = 0.004; p = 0.004), 2 (p = 0.003; p = 0.05), 3 (p = 0.005; p = 0.04) and 4 years (p = 0.02; p = 0.002). Using DXA, the increase in FFM was significant at 1 (p = 0.007) and 2 years (p = 0.008) but not at 3 and 4 years. Percentage body fat measured by TBK, BIA and DXA decreased significantly at 1 (p = 0.008; p = 0.003; p = 0.03), 2 (p = 0.018; p = 0.06; p = 0.049) and 4 years (p = 0.03; p = 0.002; p = 0.04). A rise in total body water, calculated from BIA, was observed at 1 year (p = 0.004) and was maintained throughout the treatment period. These data demonstrate that 4 years of GH treatment in hypopituitary adults is associated with sustained improvement in body composition. Kamal AS Al-Shoumer, Unit of Metabolic Medicine, Imperial College School of Medicine at St. Mary's Hospital, Norfolk Place, London W2 1PG, UK

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.

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.

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