| 11. |
- Lundberg, Elena, et al.
(författare)
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Broad variability in pharmacokinetics of GH following rhGH injections in children
- 2018
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Ingår i: Growth Hormone & Igf Research. - : Elsevier BV. - 1096-6374 .- 1532-2238. ; 40, s. 61-68
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Daily subcutaneous self-injection of GH is used worldwide to treat short stature in childhood; longitudinal data on the impact of this regimen on GH-uptake are lacking. Design: Children with/without GH-deficiency participating in clinical trials were followed prospectively ( s 8 times). Blood was sampled pre-GH-injection (dose GH(33)/GH(67) mu g/kg) and either every 30 min thereafter for 24 h (Experimental-setting; 59 GH-curves/15 children); or every 2 h thereafter for 16 h (Clinical-setting; 429 GHcurves/117 children). Pharmacokinetics were estimated by time T-max (h) of maximal GH-concentration (C-max , mU/L) and area under the curve for 16 h (AUC, mU/L * h). Results: In the Clinical-setting, median C-max was 71 mU/L and AUC was 534 mU/L * h, with coefficients of variation for intra-individual variation of 39% and 36%, respectively, and inter-individual variation of 44% and 42%, respectively. 43% of C-max and AUC variability was explained by GH-dose and proxies for injection depth (baseline GH-level, GH(peak) width, BMISDS). In the Experimental- versus Clinical-setting, 85% and 40% of GH-curves, respectively, reached zero-levels within 24 h. A longer duration was found following a more superficial GH-injection. Spontaneous GH-peaks were identified already 6 h after the GH-injection in about half of the curves of both GHD and non-GHD patients. Conclusion: Very broad intra-individual and inter-individual variability was found. A high GH-peak will optimize growth effects; the highest C-max was found after a deep injection of GH at the higher dose and concentration. In as many as 60% of the children, GH remained detectable in serum after 24 h; a constant GH-level will promote IGF-I and metabolic effects.
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| 12. |
- Marina, Djordje, et al.
(författare)
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Truncated somatostatin receptor 5 may modulate therapy response to somatostatin analogues - Observations in two patients with acromegaly and severe headache
- 2015
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Ingår i: Growth Hormone & IGF Research. - : Elsevier BV. - 1096-6374 .- 1532-2238. ; 25:5, s. 262-267
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Tidskriftsartikel (refereegranskat)abstract
- Background: Somatotropinomas have unique "fingerprints" of somatostatin receptor (sst) expression, which are targets in treatment of acromegaly with somatostatin analogues (SSAs). However, a significant expression of sst is not always related to the biochemical response to SSAs. Headache is a common complaint in acromegaly and considered a clinical marker of disease activity. SSAs are reported to have an own analgesic effect, but the sst involved are unknown. Patients and methods: We investigated sst expression in two acromegalic patients with severe headache and no biochemical effects of octreotide, but a good response to pasireotide. We searched the literature for determinants of biochemical and analgesic effects of SSAs in somatotropinomas. Results: Case 1 had no biochemical or analgesic effects of octreotide, a semi-selective SSA, but a rapid and significant effect of pasireotide, a pan-SSA Case 2 demonstrated discordance between analgesic and biochemical effects of octreotide, in that headache disappeared, but without biochemical improvement. In contrast, pasireotide normalized insulin-like growth factor 1. Both adenomas were sparsely granulated and had strong membranous expressions of sst2a in 50-75% and sst5 in 75-100% of tumor cells. The truncated sst5 variant TMD4 (sst5TMD4) showed expression in 20-57% of tumor cells. Conclusions: A poor biochemical response to octreotide may be associated with tumor expression of a truncated sst5 variant, despite abundant sst2a expression, suggesting an influence from variant sst5 on common sst signaling pathways. Furthermore, unrelated analgesic and biochemical effects of SSAs supported a complex pathogenesis of acromegaly-associated headache. Finally, assessment of truncated sst5 in addition to full length sst could be important for a choice of postoperative SSA treatment in somatotropinomas.
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| 13. |
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| 14. |
- Pereira-Gurgel, Virginia M., et al.
(författare)
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Abnormal vascular and neural retinal morphology in congenital lifetime isolated growth hormone deficiency
- 2016
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Ingår i: Growth Hormone and IGF Research. - : Elsevier BV. - 1096-6374 .- 1532-2238. ; 30-31, s. 11-15
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Tidskriftsartikel (refereegranskat)abstract
- © 2016 Elsevier LtdObjective Experimental models demonstrate an important role of GH in retinal development. However, the interactions between GH and the neuro-vascularization of the human retina are still not clear. A model of untreated congenital isolated GH deficiency (IGHD) may clarify the actions of GH on the retina. The purpose of this work was to assess the retinal neuro-vascularization in untreated congenital IGHD (cIGHD). Design In a cross sectional study, we performed an endocrine and ophthalmological assessment of 25 adult cIGHD subjects, homozygous for a null mutation (c.57+1G>A) in the GHRH receptor gene and 28 matched controls. Intraocular pressure measurement, retinography (to assess the number of retinal vascular branching points and the optic disc and cup size), and optical coherence tomography (to assess the thickness of macula) were performed. Results cIGHD subjects presented a more significant reduction of vascular branching points in comparison to controls (91% vs. 53% [p=0.049]). The percentage of moderate reduction was higher in cIGHD than in controls (p=0.01). The percentage of individuals with increased optic disc was higher in cIGHD subjects in comparison to controls (92.9% vs. 57.1%). The same occurred for cup size (92.9% vs. 66.7%), p<0.0001 in both cases. There was no difference in macula thickness. Conclusions Most cIGHD individuals present moderate reduction of vascular branching points, increase of optic disc and cup size, but have similar thickness of the macula.
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| 15. |
- Tidblad, Anders, et al.
(författare)
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Metabolic differences between short children with GH peak levels in the lower normal range and healthy children of normal height
- 2017
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Ingår i: Growth Hormone & IGF Research. - : CHURCHILL LIVINGSTONE. - 1096-6374 .- 1532-2238. ; 34, s. 22-27
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Severe growth hormone deficiency (GHD) leads to several metabolic effects in the body ranging from abnormal body composition to biochemical disturbances. However, less is known regarding these parameters in short children with GH peak levels in the lower normal range during provocation tests. Our aim was to study the metabolic profile of this group and compare it with that of healthy children of normal height.Design: Thirty-five pre-pubertal short children (< - 2.5 SDS) aged between 7 and 10 years, with peak levels of GH between 7 and 14 mu g/L in an arginine insulin tolerance test (AITT), were compared with twelve age- and sex-matched children of normal height. The metabolic profile of the subjects was analysed by blood samples, DEXA, frequently sampled intravenous glucose tolerance test, microdialysis and stable isotope examinations of rates of glucose production and lipolysis.Results: There were no overall significant metabolic differences between the groups. However, in the subgroup analysis, the short children with GH peaks < 10 mu g/L had significantly lower fasting insulin levels which also correlated to other metabolic parameters.Conclusion: The short pre-pubertal children with GH peak levels between 7 and 14 mu g/L did not differ significantly from healthy children of normal height but subpopulations within this group show significant metabolic differences.
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| 16. |
- Van dijk, Peter R, et al.
(författare)
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After 6years of intraperitoneal insulin administration IGF-I concentrations in T1DM patients are at low-normal level.
- 2015
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Ingår i: Growth Hormone & IGF Research. - : Elsevier BV. - 1096-6374 .- 1532-2238. ; 25:6, s. 316-319
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Low concentrations of insulin-like growth factor-I (IGFI) have been reported in type 1 diabetes mellitus (T1DM), suggested to be due to low insulin concentrations in the portal vein. The aim was to describe the long-term course of IGFI concentrations among T1DM subjects treated with continuous intraperitoneal (IP) insulin infusion (CIPII).DESIGN: Nineteen patients that participated in a randomized cross-over trial comparing CIPII and subcutaneous (SC) insulin therapy in 2006 were followed until 2012. IGF-I measurements were performed at the start of the 2006 study, after the 6month SC- and CIPII treatment phase in 2006 and during CIPII therapy in 2012. Z-scores were calculated to compare the IGF-I concentrations with age-specific normative range values of a non-DM reference population.RESULTS: In 2012, IGF-I Z-scores (-0.7; 95% confidence interval -1.3, -0.2) were significantly higher than at the start of the 2006 study (-2.5; -3.3, -1.8), the end of the SC (-2.0; -2.6, -1.5) and CIPII (-1.6; -2.1, -1.0) treatment phase with a mean difference of: 1.8 (0.9, 2.7), 1.3 (0.5, 2.1) and 0.8 (0.1, 1.6), respectively.CONCLUSION: After 6years of treatment with CIPII, IGF-I concentrations among T1DM patients increased to a level that is higher than during prior SC insulin treatment and is in the lower normal range compared to a non-DM reference population. The results of this study suggest that long-term IP insulin administration influences the IGF system in T1DM.
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| 17. |
- Wegmann, Mathilde Gersel, et al.
(författare)
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The exon3-deleted growth hormone receptor gene polymorphism (d3-GHR) is associated with insulin and spontaneous growth in short SGA children (NESGAS)
- 2017
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Ingår i: Growth Hormone and IGF Research. - : Elsevier BV. - 1096-6374. ; 35, s. 45-51
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Tidskriftsartikel (refereegranskat)abstract
- Objective The effect of a common polymorphism in the Growth Hormone (GH) receptor (d3-GHR) gene on growth, metabolism and body composition was examined in short children born small for gestational age (SGA) on GH treatment. Design In 96 prepubertal, short SGA children treated with high-dose GH (67 μg/kg/day) in the NESGAS study, insulin sensitivity (IS), insulin secretion and disposition index (DI) were determined during the first year of treatment. Body composition was analysed by DXA. The d3-GHR locus was determined by simple multiplex PCR. Results At baseline, children in the d3-GHR group (d3/fl (n = 37), d3/d3 (n = 7)) had significantly lower IS (median (25–75 percentile)) (223.3% (154.4–304.8)) vs. (269.7% (185.1–356.7)) (p = 0.03) and higher concentrations of glucose (mean (SD)) (4.4 mmol/L (0.6) vs. 4.2 mmol/L (0.7)) (p = 0.03), C-peptide (232.1 pmol/L (168.8–304.1) vs. 185.1 pmol/L (137.7–253.9)) (p = 0.04) and insulin (19.2 pmol/L (11.8–32.2)) vs. (13.7 pmol/L (9.3–20.8)) (p = 0.04) compared to children homozygous for the full length allele (fl/fl-GHR (n = 52)). There were no differences in DI or insulin secretion. Postnatal, spontaneous growth was significantly greater in the d3-GHR group compared to the fl/fl-GHR group (p = 0.02). There were no significant differences in growth response, body composition or metabolism after one year of GH therapy. Conclusion Short SGA children carrying the d3-GHR polymorphism had increased spontaneous growth, lower IS and a compensatory increase in glucose, C-peptide and insulin before GH therapy compared to children homozygous for the full-length allele.
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| 18. |
- Yang, Yi, et al.
(författare)
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Serum IGF-1 is higher in patients with idiopathic normal pressure hydrocephalus than in the population
- 2015
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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. - 1096-6374 .- 1532-2238. ; 25:6, s. 269-73
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Hypopituitarism has been reported in patients with idiopathic normal pressure hydrocephalus (iNPH), which could enhance characteristic symptoms like impaired wakefulness, gait, body balance, and subcortical cognitive deterioration. PURPOSE: To compare basal serum levels of pituitary and sex hormones and serum insulin-like growth factor-1 (S-IGF-1) in patients with iNPH and an age-matched control population, and to correlate the preoperative hormone levels with symptoms and signs pre-operatively and three months after surgery. METHODS: A cross-sectional case control design was used. Patients diagnosed with iNPH, n=108 (65 men and 43 women, mean age 72.3years), were consecutively included during 2006-2011 at Sahlgrenska University Hospital, Gothenburg, Sweden. S-TSH, S-free T4, S-FSH, S-LH, S-prolactin, plasma ACTH, S-testosterone, S-oestradiol and S-IGF-1 were examined. Symptoms and signs were scored using the iNPH scale score. Population controls, n=146, were recruited from the WHO MONICA project, Gothenburg in 2008. RESULTS: Men and women with iNPH had higher S-IGF-1 than controls (p<0.001). Women with iNPH had lower S-TSH (p=0.016) than controls, but the frequency of levothyroxine substitution was similar. Among men, a higher level of S-IGF-1 was associated with milder symptoms, while higher levels of S-FSH and S-LH were associated with more severe symptoms. CONCLUSIONS: Patients with iNPH did not have lower levels of pituitary or sex hormones but presented with higher levels of S-IGF-1, compared with healthy, age-matched controls. Higher S-IGF-1 in men was related to milder mental and physical symptoms and signs.
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| 19. |
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