| 1. |
- Decker, Ralph, 1968, et al.
(författare)
-
Early increase of the bone formation marker PINP is in a higher degree related to growth response compared to bone mineralization in GH treated prepubertal children
- 2015
-
Ingår i: Horme Research in Paediatrics. - : S. Karger AG. - 1663-2818 .- 1663-2826. ; 84:Suppl 1
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Background: It has been reported that short-term increases of the bone formation markers intact amino-terminal propeptide of type I procollagen (PINP), bone-specific alkaline phosphatase (BALP) and osteocalcin display different temporal patterns. In adults, the biphasic model of GH action in bone remodelling shows that GH treatment results initially in an increased bone resorption with a concomitant bone loss, which later on is followed by increased bone formation. In children, little is known how bone remodelling takes place. Objective and hypotheses: Bone formation markers reflect different events during osteogenesis, and respond with different time courses during anabolic GH treatment. Method: The study population comprised 128 short prepubertal children (age range 3−11 years; 90 boys, 38 girls) who participated in a longitudinal, prospective, multicenter study in individual GH dosing1, TRN 98-0198-003. The investigated children had either normal or reduced levels of GH secretion. Data from the first 2 years of GH treatment were analyzed. The bone markers were measured using the IDS-iSYS automatic system (Immunodiagnostic Systems)2. The DXA derived variable bone mineral density (BMD) was measured by Lunar DPX-L or Lunar Prodigy. Results: The bone markers PINP, BALP, osteocalcin and 25-hydroxyvitamin D (25(OH)D) at start and deltaPINP at 3 months of GH treatment explained 63% of the growth response at 2 years (p<0.0001), while only 26% of the variation in BMD response after 2 years of treatment was explained (p<0.0001). Conclusion: Bone markers at start of GH treatment, and the 3 months increase of PINP were associated with both growth response and bone mineralization after 2 years of treatment, but with different magnitude of impact on these anabolic GH effects.
|
|
| 2. |
- Decker, Ralph, 1968, et al.
(författare)
-
Long-term Effects of Growth Hormone in Children
- 2014
-
Ingår i: Update on GH and IGFs, 22-23 maj 2014, Stockholm, Sverige. Nobelforum Karolinska institutet - Svenska Endokrinolog Föreningen.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)
|
|
| 3. |
- Andersson, Björn, 1977, et al.
(författare)
-
Protein profiling identified dissociations between growth hormone-mediated longitudinal growth and bone mineralization in short prepubertal children
- 2011
-
Ingår i: Journal of Proteomics. - : Elsevier BV. - 1876-7737 .- 1874-3919. ; 74:1, s. 89-100
-
Tidskriftsartikel (refereegranskat)abstract
- Growth hormone (GH) promotes longitudinal growth and bone mineralization. In this study, a proteomic approach was used to analyze the association between serum protein expression pattern and height-adjusted bone mineralization in short prepubertal children receiving GH treatment. Patterns of protein expression were compared with those associated with longitudinal bone growth. Specific protein expression patterns associated with changes in height-adjusted bone mineralization in response to GH treatment were identified. Out of the 37 peaks found in significant regression models, 27 were uniquely present in models correlated with changes in bone mineralization and 7 peaks were uniquely present in models correlated with changes in height. The peaks identified corresponded to apolipoproteins, transthyretin, serum amyloid A4 and hemoglobin beta. We conclude that a proteomic approach could be used to identify specific protein expression patterns associated with bone mineralization in response to GH treatment and that height-adjusted bone mineralization and longitudinal bone growth are regulated partly by the same and partly by different mechanisms. Protein isoforms with different post-translational modifications might be of importance in the regulation of these processes. However, further validation is needed to assess the clinical significance of the results.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
- Decker, Ralph, 1968, et al.
(författare)
-
Case report of a girl with secondary amenorrhea associated with aurantiasis cutis
- 2016
-
Ingår i: Hormone Research in Paediatrics. - : S. Karger AG. - 1663-2818 .- 1663-2826.
-
Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- Introduction: --- Aurantiasis cutis is a condition of yellowish or golden skin discoloration that can result from eating excessive amounts of foods containing carotene leading to hypercarotenemia(1), described causing secondary amenorrhea(2). Objective & hypothesis: --- Hypercarotenemia can cause secondary amenorrhea without overconsumption of excessive quantities of carotene. Results: --- Laboratory tests showed a ß-Carotene level more than the 2-fold above the upper reference level. Hyperbilirubinemia could be excluded. Hypogonadotropic hypogonadism was not present. There was no evidence for adrenal dysfunction. Liver function tests were normal. Material/ Methods: --- A 16-year-old girl presented to our endocrine outpatient clinic with a 2-year history of varying yellow discoloration of her skin and secondary amenorrhea. The findings of the general physical examination were normal, but there was a marked yellow discoloration of the palms, soles, and nasolabial folds. A dietary history revealed a low carotene diet, but also a low carbohydrate diet. BMI was 19.9 kg/m² (-0.2 SDS) without signs of anorexia. Discussion: --- In this girl we observed hypercarotenemia associated with secondary nonhypothalamic amenorrhea in absence of excess external intake of carotenes. This suggests an intrinsic reason due to a polymorphism(3) in ß-carotene 15,15'-monooxygenase (BCO)(4), an enzyme breaking down carotenes to vitamin A(5). Phenotype-genotype association studies are needed to confirm this hypothesis. Conclusion: --- Secondary non-hypothalamic amenorrhea can be associated with hypercarotenemia. References: --- 1. Tanikawa K, Seta K, Machii A, Itoh S 1961 [Aurantiasis cutis due to overeating of dried laver (nori): a case report]. Jpn J Med Sci Biol 50:414-419 2. Kemmann E, Pasquale SA, Skaf R 1983 Amenorrhea associated with carotenemia. JAMA 249:926-929 3. Leung WC, Hessel S, Meplan C, Flint J, Oberhauser V, Tourniaire F, Hesketh JE, von Lintig J, Lietz G 2009 Two common single nucleotide polymorphisms in the gene encoding beta-carotene 15,15'-monoxygenase alter beta-carotene metabolism in female volunteers. FASEB j 23:1041-1053 4. Frumar AM, Meldrum DR, Judd HL 1979 Hypercarotenemia in hypothalamic amenorrhea. Fertil Steril 32:261-264 5. Lindqvist A, Andersson S 2002 Biochemical properties of purified recombinant human beta-carotene 15,15'-monooxygenase. J Biol Chem 277:23942-23948
|
|
| 8. |
- Decker, Ralph, 1968, et al.
(författare)
-
Decreased GH dose after the catch-up growth period maintains metabolic outcome in short prepubertal children with and without classic GH deficiency
- 2012
-
Ingår i: Clinical endocrinology. - : Wiley. - 0300-0664 .- 1365-2265. ; 77:3, s. 407-15
-
Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Few studies have evaluated metabolic outcomes following growth hormone (GH) treatment in short prepubertal children during different periods of growth. Previously, we found that individualized GH dosing in the catch-up period reduced the variation in fasting insulin levels by 34% compared with those receiving a standard GH dose. We hypothesized that the GH dose required to maintain beneficial metabolic effects is lower during the prepubertal growth phase after an earlier catch-up growth period. DESIGN: Short prepubertal children with isolated GH deficiency or idiopathic short stature were randomized to individualized GH treatment (range, 17-100 mug/kg/day) or a standard dose in a preceding 2-year study. After achieving near mid-parental height(SDS) (,) children receiving an individualized dose were randomized to either a 50% reduced individualized dose (RID, n=28) or an unchanged individualized dose (UID, n=37) for 2 years. The dose remained unchanged in 33 children initially randomized to receive a standard dose (FIX, 43 mug/kg/day).We evaluated whether the variations in metabolic parameters measured during maintenance growth diminished in RID compared with UID or FIX. RESULTS: We observed less variation in fasting insulin levels (-50%), insulin sensitivity as assessed by homeostasis model assessment (-55.1%), lean soft tissue (-27.8%) and bone mineral content (-31.3%) in RID compared with UID (all p<0.05), but no differences compared with FIX. CONCLUSIONS: Continued individualized GH treatment after the catch-up growth period is safe and reduces hyperinsulinism. Individualized GH dose can be reduced once the desired height(SDS) is achieved to avoid overtreatment in terms of metabolic outcome.
|
|
| 9. |
- Decker, Ralph, 1968, et al.
(författare)
-
Different thresholds of metabolic GH effects in prepubertal children
- 2009
-
Ingår i: Hormone Research.
-
Konferensbidrag (refereegranskat)abstract
- Context: In addition to growth hormone (GH) effects to promote linear growth in children, GH also has substantial effects on insulin sensitivity, lipolysis, lipids, and body composition. A dissociation between anabolic and lipolytic GH effects has been suggested. Objective: The objective of the present study was to further investigate dissociated GH effects by calculating the GH doses to attain half of a given metabolic effect, the effective dose 50% (ED50%). Hypothesis: The hypothesis was that there are dose-dependent thresholds in different variables reflecting metabolism. Design: A randomized, prospective, multicentre trial was performed for a 2 years period, with two treatment regimens in short prepubertal GHD and ISS children a) individualized GH dose with six different dose groups ranging 17-100 g/kg/day (n=87) and b) fixed GH dose of 43 g/kg/day (n=41). Results: Contrary to changes in fat mass, leptin, lipids and skinfold measurements, there was evidence for different thresholds in metabolic variables for a given GH dose when performing ANOVA, p<0.001. was calculated as the difference between 2 years and start of GH treatment. Besides height (SDS), growth related variables like weight SDS and BMI (kg/m ); measures of body composition such as fat-free mass (FFM) (kg), FFM index (FFMI) (kg/m ), waist (cm), hip (cm); as well as biochemical markers like IGF-1 (SDS), IGFBP-3 (SDS); insulin (mU/L) showed dose-dependency with different ED50% levels. Conclusions: Differences of the ED50% on metabolic variables were seen in-between different GH dose spans. Thus we propose that there are different thresholds in GH effects on variables reflecting different metabolic aspects, suggesting muscle tissue being more sensitive than linear growth, GH induced insulin resistance, the rise in IGF-1 and the increase in hip circumference as a measure of 3-dimensional body growth.
|
|
| 10. |
- Decker, Ralph, 1968, et al.
(författare)
-
Different thresholds of tissue-specific dose-responses to growth hormone in short prepubertal children
- 2012
-
Ingår i: BMC Endocrine Disorders. - : Springer Science and Business Media LLC. - 1472-6823. ; 12:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background In addition to stimulating linear growth in children, growth hormone (GH) influences metabolism and body composition. These effects should be considered when individualizing GH treatment as dose-dependent changes in metabolic markers have been reported. Hypothesis: There are different dose-dependent thresholds for metabolic effects in response to GH treatment. Method A randomized, prospective, multicentre trial TRN 98-0198-003 was performed for a 2-year catch-up growth period, with two treatment regimens (a) individualized GH dose including six different dose groups ranging from 17--100 mug/kg/day (n=87) and (b) fixed GH dose of 43 mug/kg/day (n=41). The individualized GH dose group was used for finding dose--response effects, where the effective GH dose (ED 50%) required to achieve 50% Delta effect was calculated with piecewise linear regressions. Results Different thresholds for the GH dose were found for the metabolic effects. The GH dose to achieve half of a given effect (ED 50%, with 90% confidence interval) was calculated as 33(+/-24.4) mug/kg/day for [increment] left ventricular diastolic diameter (cm), 39(+/-24.5) mug/kg/day for [increment] alkaline phosphatase (mukat/L), 47(+/-43.5) mug/kg/day for [increment] lean soft tissue (SDS), 48(+/-35.7) mug/kg/day for [increment] insulin (mU/L), 51(+/-47.6) mug/kg/day for [increment] height (SDS), and 57(+/-52.7) mug/kg/day for [increment] insulin-like growth factor I (IGF-I) SDS. Even though lipolysis was seen in all subjects, there was no dose--response effect for Delta fat mass (SDS) or Delta leptin ng/ml in the dose range studied. None of the metabolic effects presented here were related to the dose selection procedure in the trial. Conclusions Dose-dependent thresholds were observed for different GH effects, with cardiac tissue being the most responsive and level of IGF-I the least responsive. The level of insulin was more responsive than that of IGF-I, with the threshold effect for height in the interval between.
|
|
