| 1. |
- Borghammar, Camilla, et al.
(författare)
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Prevalence of refractoriness when testing growth hormone levels in children
- 2023
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Ingår i: Growth Hormone and IGF Research. - 1096-6374. ; 71
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Late night spontaneous growth hormone (GH) pulses may influence the pituitary GH response to provocation tests. We evaluated GH response during arginine-insulin-tolerance test (AITT) after a GH peak during a short spontaneous nocturnal profile (SSNP) in children with short stature or low growth velocity. Design: Using SSNP and subsequent AITT, we examined 257 children 4–18 years old (138 (53.7%) males) recruited from three hospitals. Medical records were reviewed retrospectively. Refractory children were defined as a GH peak ≥7 μg/L during SSNP but no GH peak ≥7 μg/L during AITT. Results: In total, 201/257 children had a GH peak ≥7 μg/L at SSNP and/or AITT. Of these, 21.9% were refractory. The proportion of males (p = 0.033) and body mass index (BMI) standard deviation score (SDS) (p = 0.037) were higher in the refractory group than in children with a GH peak ≥7 μg/L during AITT. The median period between last GH peak ≥7 μg/L during SSNP and GHmax at AITT was 210 (30–390) minutes. The GHmax at AITT occurred 30 min earlier for children without a peak ≥7 μg/L during the SSNP (p = 0.004). The number of refractoriness differed somewhat between the hospitals (p = 0.025). Conclusions: Many children with short stature were refractory at testing; among them we found few clinical characteristics. Refractoriness might be influenced by some differences in procedure, but needs to be considered when evaluating GH response in children.
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| 2. |
- Götherström, Galina, 1962, et al.
(författare)
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Effects of 18 months of GH replacement on cardiovascular risk factors and quality of life in GH deficient adults; a randomized controlled trial using a fixed very low and a standard dose of GH
- 2022
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Ingår i: Growth Hormone & Igf Research. - : Elsevier BV. - 1096-6374. ; 67
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Little is known of the effects of a fixed very low dose of growth hormone (GH) replacement on car-diovascular risk factors, bone mass, muscle strength and quality of life (QoL) in hypopituitary patients.Design/patients/methods: This was an open-label randomized study performed at a single center. Consecutive hypopituitary patients with adult onset GH deficiency (GHD) and BMI >= 27 kg/m2 were randomized to receive a very low fixed dose of GH (LG, n = 9) or a standard dose of GH (SG, n = 9). Body composition, glucose and lipid metabolism, bone mineral content (BMC) and density (BMD), muscle strength, and QoL were measured at baseline and after 6, 12 and 18 months. Results: The fixed GH dose in LG was 0.1 mg/day. In SG, the mean baseline GH dose of 0.13 mg/day was gradually increased to 0.31 mg/day at study end. Lean body mass (LBM) as measured using DEXA as well as total body water (TBW) and extracellular water (ECW) were increased only in SG (P < 0.01, P < 0.05, and P < 0.01 vs. LG, respectively). There were no between-groups differences in BMD, BMC, insulin sensitivity, lipids, or muscle strength. Finally, although not significant compared with SG, a sustained improvement in QoL was seen in LG according to the QoL-AGHDA questionnaire. Conclusion: In this pilot study, a fixed very low GH dose improved QoL in GHD adults without any induction of fluid retention. Other effects were comparable to those produced by the standard GH dose. Replacement with a very low GH dose could therefore be a treatment option in hypopituitary patients, especially in patients who do not tolerate higher GH dosage.Trial registrationThis study is registered at ClinicalTrials.gov, EU-nr 2009-016783-37.
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| 3. |
- Hellström, Ann, 1959, et al.
(författare)
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The IGF system and longitudinal growth in preterm infants in relation to gestational age, birth weight and gender
- 2020
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Ingår i: Growth Hormone & Igf Research. - : Elsevier BV. - 1096-6374. ; 51, s. 46-57
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Growth factors in the blood of very preterm infants may reflect growth and contribute to the understanding of early development. We investigated postnatal levels of insulin-like growth factors (IGFs) in infants born very preterm and related them to early growth development. Design: Blood samples were analyzed weekly for IGF-I, IGF-II, IGF binding protein (BP)-1, IGFBP-3, and acid-label subunit (ALS). Methods: 73 children born very preterm (gestational age (GA) < 32 weeks) were divided according to their gender-specific birth weight standard deviation score (SDS) into either appropriate for GA (AGA) or small for GA (SGA). Fifty-two (71%) and forty-three (59%) infants completed follow-up with anthropometry at approximately 3 years and at 5 years of age respectively. Thirty-six subjects (49%) had blood sampling for IGF-I and IGFBP-3 measurements up to 3 years of age. Results: IGF-I, IGFBP-3, and ALS levels increased in all groups from week 31 to week 36, with generally lower levels in the SGAs, with a concomitant lower growth velocity. Postnatal ALS was strongly associated with IGF-I and IGFBP-3 in boys, girls and AGA infants. IGF-II was higher in earlier born preterms (GA < 27 weeks) at postmenstrual ages 27.5-29.9 weeks compared with SGAs and late GA (GA >= 27 weeks) preterms (p <.0001). IGF-II, in contrast to IGF-I, did not differ between SGAs and AGAs at weeks 31-36. Mean IGFBP-1 was highest in the SGAs compared to AGAs at mean week 28,5 and 31 (p=.001) and IGFBP-1 levels were elevated in relation to IGF-I in the SGAs at that period. At follow-up, the increase in IGF-I between week 31 and 33.5 was a significant positive determinant of height SDS at 3 and 5 years of age in forward multiple regression analysis, independent of target height. Conclusion: This is the first study to investigate postnatal ALS levels in preterm infants. In very preterm infants, IGF-II is less affected by size at birth during early postnatal weeks compared with IGF-I. Early elevated IGFBP-1 might protect the SGA infants from an intense metabolic rate. Our results indicate that anabolic and metabolic processes during weeks 31-36 predicts later height.
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| 4. |
- Karason, Kristjan, 1962, et al.
(författare)
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Effect of growth hormone treatment on circulating levels of NT-proBNP in patients with ischemic heart failure.
- 2020
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Ingår i: Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society. - : Elsevier BV. - 1532-2238. ; 55
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Tidskriftsartikel (refereegranskat)abstract
- Growth hormone (GH) therapy in heart failure (HF) is controversial. We investigated the cardiovascular effects of GH in patients with chronic HF due to ischemic heart disease.In a double-blind, placebo-controlled trial, we randomly assigned 37 patients (mean age 66years; 95% male) with ischemic HF (ejection fraction [EF]<40%) to a 9-month treatment with either recombinant human GH (1.4mg every other day) or placebo, with subsequent 3-month treatment-free follow-up. The primary outcome was change in left ventricular (LV) end-systolic volume measured by cardiac magnetic resonance (CMR). Secondary outcomes comprised changes in cardiac structure and EF. Prespecified tertiary outcomes included changes in New York Heat Association (NYHA) functional class and quality of life (QoL), as well as levels of insulin-like growth factor-1 (IGF-1) and N-terminal pro-brain natriuretic peptide (NT-proBNP).No changes in cardiac structure or systolic function were identified in either treatment group; nor did GH treatment affect QoL or functional class. In the GH group, circulating levels of IGF-1 doubled from baseline (+105%; p<0.001) and NT-proBNP levels halved (-48%; p<0.001) during the treatment period, with subsequently a partial return of both towards baseline levels. No changes in IGF-1 or NT-proBNP were observed in the placebo group at any time during the study.In patients with chronic ischemic HF, nine months of GH treatment was associated with significant increases in levels of IGF-1 and reductions in levels of NT-proBNP, but did not affect cardiac structure, systolic function or functional capacity.
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| 5. |
- Klevebro, S., et al.
(författare)
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Elevated levels of IL-6 and IGFBP-1 predict low serum IGF-1 levels during continuous infusion of rhIGF-1/rhIGFBP-3 in extremely preterm infants
- 2020
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Ingår i: Growth Hormone and IGF Research. - : Elsevier BV. - 1096-6374. ; 50, s. 1-8
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Steady state insulin-like growth factor-1 (IGF-1) levels vary significantly during continuous intravenous infusion of recombinant human insulin-like growth factor-1/recombinant human insulin-like growth factor binding protein-3 (rhIGF-1/rhIGFBP-3) in the first weeks of life in extremely preterm infants. We evaluated interleukin-6 (IL-6) and insulin-like growth factor binding protein-1 (IGFBP-1) levels as predictors of low IGF-1 levels. Methods: Nineteen extremely preterm infants were enrolled in a trial, 9 received rhIGF-1/rhIGFBP-3 and 10 received standard neonatal care. Blood samples were analyzed daily for IGF-1, IL-6 and IGFBP-1 during intervention with rhIGF-1/rhIGFBP-3. Results: Thirty seven percent of IGF-1 values during active treatment were <20 μg/L. Among treated infants, higher levels of IL-6, one and two days before sampled IGF-1, were associated with IGF-1 < 20 μg/L, gestational age adjusted OR 1.30 (95% CI 1.03–1.63), p = .026, and 1.57 (95% CI 1.26–1.97), p < .001 respectively. Higher levels of IGFBP-1 one day before sampled IGF-1 was also associated with IGF-1 < 20 μg/L, gestational age adjusted OR 1.74 (95% CI 1.19–2.53), p = .004. Conclusion: In preterm infants receiving continuous infusion of rhIGF-1/rhIGFBP-3, higher levels of IL-6 and IGFBP-1 preceded lower levels of circulating IGF-1. These findings demonstrate a need to further evaluate if inflammation and/or infection suppress serum IGF-1 levels. The trial is registered at ClinicalTrials.gov (NCT01096784). © 2019
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| 6. |
- Ly, Helena-Jamin, et al.
(författare)
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Comparison of two prediction models in a clinical setting to predict growth in prepubertal children on recombinant growth hormone
- 2023
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Ingår i: Growth Hormone & Igf Research. - : Elsevier BV. - 1096-6374. ; 68
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Prediction models that calculate the growth response in children on recombinant growth hormone (GH) have shown to be helpful tools in deciding who should start treatment, as identifying GH deficiency can be a challenge. The aim of the study is to compare two prediction models; the KIGS (Pfizer International Growth Study) prediction models which are more accessible and the Gothenburg model which has previously been clinically validated. Design: All prepubertal patients who commenced GH treatment at Queen Silvia Children's Hospital in Gothenburg during a 13-year-period were candidates for the study. Children were excluded if suspected syndrome, malignant disease, chronic disease, or poor adherence to treatment were found. The KIGS model and the Gothenburg model were used to make predictions. Data was obtained from medical charts for the period from birth to the end of the first year of treatment. The predicted height outcome was compared against observed.Results: The study included 123 prepubertal children (76 males). The average age at treatment start and standard deviation (SD) was 5.7 (1.8) years. Correlation analyses were performed between predicted growth by both the Gothenburg and KIGS models versus the first year observed growth response showing strong correlations of r = 0.990 and r = 0.991 respectively with studentized residuals of 0.10 (0.81) for the Gothenburg model and 0.03 (0.96) for the KIGS model.Conclusion: We found that both the Gothenburg model and the KIGS model are equivalent when applying to our clinical cohort. Both models are very precise, hence it is encouraged to use either based on accessibility for the clinic.
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| 7. |
- Nylander, Erik, 1986-, et al.
(författare)
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Growth hormone increases dendritic spine density in primary hippocampal cell cultures
- 2020
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Ingår i: Growth Hormone & IGF Research. - : Elsevier BV. - 1096-6374 .- 1532-2238. ; 50, s. 42-47
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Growth hormone (GH) is widely known for its peripheral effects during growth and development. However, numerous reports also suggest that GH exert pro-cognitive, restorative, and protective properties in the brain. In in vitro studies, the detection of dendritic spines, small protrusions extending from axons, can act as a marker for cognition-related function as spine formation is considered to be associated with learning and memory. Here we show that an acute 24-hour treatment of GH can increase dendritic spine density in primary hippocampal cell cultures.Design: Primary hippocampal cells were harvested from embryonic Wistar rats and cultured for 14 days. Cells were treated with supra-physiological doses of GH (10-1000 nM) and subjected to a high-throughput screening protocol. Images were acquired and analyzed using automated image analysis and the number of spines, spines per neurite length, neurite length, and mean area of spines, was reported.Results: GH treatment increased dendritic spine density using the highest dose while the general health of the cells was unaffected.Conclusion: The results from the present study further confirms a potential role of GH in the treatment of cognitive dysfunction.
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| 8. |
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| 9. |
- Onerup, Aron, 1983, et al.
(författare)
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Effects of a home-based exercise program on the insulin-like growth factor axis in patients operated for colorectal cancer in Sweden: Results from the randomised controlled trial PHYSSURG-C
- 2020
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Ingår i: Growth Hormone and IGF Research. - : Elsevier BV. - 1096-6374 .- 1532-2238. ; 51, s. 27-33
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: We report results from a subgroup within the ongoing PHYSSURG-C trial with the aim to examine effects of exercise on IGF-1 and IGFBP-3 in patients undergoing colorectal cancer surgery. Design: Randomised controlled trial. Setting: A Swedish university hospital. Participants: Between 2015 and 2016, 217 patients were enrolled (I = 106, C = 111), with 122 patients that had given blood samples at baseline and at least at one follow-up (I = 51, C = 71). Patients 20 year or older with colorectal cancer were eligible. Exclusion criteria were emergency surgery, local surgery, language problems or inability to perform intervention. Interventions: Patients were computer-randomised to either a daily home-based aerobic exercise intervention (I), or to usual care (C). The intervention lasted two weeks before surgery and four weeks after discharge from hospital and consisted of medium-intensity aerobic exercise and inspiratory muscle training. Circulating concentrations of IGF-1 and IGFBP-3 were determined by blinded personnel at baseline, time of surgery and 4–6 weeks postoperatively. Primary and secondary outcome measures: The outcome of this subpopulation report was change in IGF-1/IGFBP-3 ratio, IGF-1 and IGFBP-3 concentrations from baseline to surgery, and 4–6 weeks postoperatively. Results: The IGF-1/IGFBP-3 ratio increased from baseline to surgery by 11% in I and 8% in C with no difference between groups (I vs. C: 1.04, 95%CI: 0.97–1.11; p = 1.000). Postoperative change was 5% in I and 3% in C with no difference between groups (I vs. C:1.03, 95%CI: 0.96–1.10; p = 1.000). Results concerning IGF-1 and IGFBP-3 also showed statistically significant dynamics over time with no difference between groups. No adverse events were reported. Conclusions: The home-based exercise program in our trial did not have any effect on IGF-1, or IGFBP-3. Trial registration: The study was registered at ClinicalTrials.gov with identifier NCT02299596. This work was funded externally.
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