Human GH (hGH) is a heterogeneous protein hormone consisting of several isoforms. This heterogeneity is the consequence of multiple hGH genes, mRNA splicing, post-translational modifications, and ...peripheral metabolism, and it represents one important reason for the disparity among GH assay results from different laboratories. However, other factors are involved: a) interference from endogenous GH binding proteins; b) different specificities of anti-GH (monoclonal and polyclonal) antibodies; c) different matrix effects among the calibrators; d) the use of different calibrators. The measurement of GH levels in response to provocative testing is an essential part of the diagnosis of GH deficiency. For this purpose, an accurate, reproducible and universally valid GH measurement would be highly desirable, but, despite a huge number of efforts in clinical biochemistry, this goal remains elusive.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Serum IGF-I and IGFBP-3 assays are used to monitor rhGH treatment. Some discrepancies in results obtained by means of different assays have been reported. The aim of this study was to establish ...normal ranges for circulating IGF-I and IGFBP-3 in children and adolescents of Hispanic and Italian origin. Circulating levels of IGF-I and IGFBP-3 were measured in 169 Hispanic and Italian prepubertal children and 66 adolescents of both sexes, using a chemiluminescent assay. Serum levels of IGF-I and IGFBP-3 increased from early childhood into adolescence. After pubertal peaks of IGF-I and IGFBP-3, slight decreases were observed with increasing age. Furthermore, serum IGF-I levels were significantly higher in girls than in boys, suggesting a sexual dimorphism in serum IGF-I values in late prepuberty and early puberty. Differences in IGF-I and IGFBP-3 absolute values between our study and previous studies suggest the need to establish reference ranges for each ethnic group.
Evidence suggests that neurohormones such as GH and IGF-I are involved in the neuroreparative processes in multiple sclerosis (MS). GH and IGF-I blood levels in naïve MS patients with different ...disease courses were investigated in this study. Serum GH and IGF-I in untreated MS patients (n=64), healthy controls (HC, n=62), and patients affected by other neurological diseases (OND, n=46) were evaluated with a solid-phase-enzyme-labeled-chemiluminescent-immunometric assay. No differences were detected in GH across MS, OND, and HC (MS=0.87±1.32 ng/mL; OND=1.66±3.7; and HC=1.69±3.35; P=0.858) when considering gender, disease duration, and disease course. However, GH was lower (P=0.007) in patients with more severe disease (expanded disability scale score, EDSS≥4.0) compared with milder forms (EDSS<4). IGF-I l did not differ across the 3 groups (P=0.160), as far as concern disease course, disability, and gender were. Lower IGF-I levels were detected in subjects older than 50 years compared to younger ones for all 3 groups. Lower GH was detected in patients with more severe MS, and age was confirmed as the main factor driving IGF-I levels in all subjects. These findings, relying on the natural course of the disease, could help in shedding lights on the mechanisms involved in autoreparative failure associated with poorer prognosis in MS.
Full text
Available for:
FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
The height of subjects with constitutionally tall stature (CTS) is at least 2 sd above the mean of subjects of the same age and sex. Apart from a few discordant data on the role of GH and its direct ...mediator, IGF-I, no studies have been conducted on other components of the IGF system, which also condition the bioavailability and activity of IGF-I. We, therefore, investigated the possibility that other components of the IGF system might play a role in determining the increased growth velocity seen in CTS. To this end, we evaluated the behavior not only of IGF-I but also of IGF-II, IGF-binding protein (IGFBP)-3, and acid-labile subunit, the subunits that constitute the main IGF complex in circulation (150-kDa complex), as well as of IGFBP-1 and IGFBP-2, which are negatively regulated by GH and, like IGFBP-3, able to influence the bioavailability of the IGFs. The study was performed on 22 prepubertal subjects affected by CTS (16 males and 6 females), aged 2.8–13.3 yr (6.8 ± 0.5 yr, mean ± sem). Thirty-seven normal prepubertal subjects (16 males and 21 females) aged between 2.2 and 13.3 yr (6.7 ± 0.5 yr), who were comparable in socioeconomic and nutritional terms, served as controls. From the auxological point of view, subjects with CTS differed significantly from controls only in terms of growth velocity (HV-sd score; CTS, 1.8 ± 0.3; controls, 0.4 ± 0.2; P < 0.0001) and height (H-sd score; CTS, 3.1 ± 0.1; controls, 0.4 ± 0.2; P < 0.0001). The results demonstrated that the concentrations of IGF-I (27.3 ± 2.0 nmol/liter), IGFBP-3 (66.9 ± 3.8), and acid-labile subunit (216.8 ± 13.6) in CTS-affected subjects were not significantly different from those determined in controls (25.0 ± 2.9, 74.4 ± 4.1, and 241.0 ± 11.9, respectively). By contrast, IGF-II levels proved significantly higher in CTS subjects (IGF-II: 87.2 ± 3.4 vs. 52.4 ± 2.3, P < 0.0001). Chromatographic analysis, performed after acid treatment of pooled sera, showed only the presence of normal 7.5-kDa IGF-II in both CTS subjects and controls. In comparison with controls, CTS children showed a lower concentration of IGFBP-1 (1.6 ± 0.3 vs. 4.1 ± 0.7, P = 0.03) and a higher concentration of IGFBP-2 (14.3 ± 1.8 vs. 9.6 ± 1.1, P = 0.03). The IGFs (IGF-I and -II)/IGFBPs (−1 + −2 + −3) molar ratio was significantly higher (P < 0.0001) in CTS children than in controls. In particular, the IGF-II/IGFBP ratio (P < 0.0001) was responsible for the excess of the IGF peptide in relation to the concentrations of IGFBPs and, therefore, for the increase in the potentially bioactive free form of the IGFs. Moreover, the IGFBP-3/IGF molar ratio was significantly reduced, being less than 1 in CTS subjects (0.6 ± 0.1 vs. 1.1 ± 0.1), so that a quantity of IGF peptides lack sufficient IGFBP-3 to form the 150-kDa complex with which are normally sequestered in the vascular compartment. The data show that in CTS: 1) the most GH-dependent components of the IGF system are normal, consistent with the finding of a normal GH secretory state; 2) the less GH-dependent IGF-II is significantly increased, in agreement with the finding of a relationship between high levels of IGF-II and overgrowth in some syndromes; and 3) the IGF/IGFBP molar ratio is increased, and, therefore, a greater availability of free IGF for target tissues may be responsible for overgrowth in CTS.
In this study we investigated 9 prepubertal children with blunted GH response to classic pharmacological stimuli in contrast with normal auxological evaluation. The children were followed to evaluate ...their growth velocity for a longer period before starting replacement GH therapy. To evaluate the pituitary reserve a supraphysiologic stimulus such as GHRH plus arginine was used. Serum GH levels were measured by a time-resolved immunofluorimetric assay before and after 1 μg/kg body weight iv injection of GHRH, while serum PRL, IGF-I, and insulin were evaluated only in basal conditions using an automatic immunometric assay. Out of 9 studied subjects, 7 underwent GHRH plus arginine administration and showed a normal GH response; the parents of the remaining 2 children refused the test. Normal serum levels of PRL, IGF-I, insulin, and a normal insulin sensitivity were observed in all children. After 1 yr, the growth rate in each patient was further improved and reached almost normal values. Our results further confirm that the decision to start replacement GH therapy should be based on both auxological parameters and laboratory findings. The GHRH plus arginine test appears to be useful to identify false GH deficiency in children showing a blunted GH response to classic stimuli in contrast with normal growth rate.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Ten healthy subjects used to performing regular physical activity and eight subjects affected by idiopathic isolated GH deficiency (GHD) were enrolled; 22- and 20-kDa GH secretion and its biological ...activity were evaluated in response to pharmacological stimuli such as arginine, L-dopa or glucagon in GHD children, while the hormonal response to exercise was studied according to Bruce protocol in healthy subjects. We found a significant increase in 22- and 20-kDa GH level in healthy subjects after monitored physical exercise (MPE; basal 0.28±0.12
vs
7.37±2.08 ng/ml and basal 0.076±0.04
vs
0.18±0.05 ng/ml, respectively). Furthermore, the 22-kDa/20- kDa ratio significantly increased in children who had undergone MPE and the GH bioactivity basal mean value also increased significantly after exercise (basal 2.86±0.76
vs
7.64±1.9 ng/ml). The mean value of 22-kDa GH in GHD patients increased significantly following GH pharmacological stimulation (2.78±0.63 ng/ml) when compared with mean basal (0.20±0.11 ng/ml) value. In the GHD group the basal concentration of 20-kDa GH significantly increased following GH pharmacological stimulation (0.34±0.11
vs
0.72±0.2 ng/ml); the 22-kDa/20-kDa ratio significantly increased too. Likewise, GH bioactivity in children with GHD increased significantly after pharmacological stimulation test (basal 2.53±0.56
vs
7.33±1.26 ng/ml). Both GH isoform concentrations and their biological activity are significantly increased in healthy subjects after submaximal exercise protocol and in GHD children after pharmacological stimuli.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Pygmies, a population characterized by short stature, have high immunoglobulin (Ig) concentrations. In this study, we evaluated Ig levels in Cameroon's Babinga Pygmies from infancy to adulthood and ...the effects of a national health program on these Ig levels. We found that IgG and IgM levels were outside the normal range for Italians of the same age and were comparable to those measured in Babinga Pygmies living in the same region by Siccardi in 1975. In conclusion, the hypergammaglobulinaemia of Babinga Pygmies is already present in infants and is not affected by sanitation improvements, suggesting that it could be partly genetically-determined.
It was postulated that a high growth hormone (GH) bioactivity might explain the rapid growth rate of neonates. The aim of this study is to verify changes in serum GH biological potency ...(Bio-/Immuno-GH ratio) and their effects on serum growth factors during the first month of life in term and preterm babies.
Blood samples were collected from 10 small-for-gestational-age preterm (SGAPT), 17 appropriate for gestational age preterm (AGAPT) and 26 AGA term (T) neonates on days 4, 15 and 30 of life to evaluate serum GH values measured by IFMA (IFMA-GH) and bioassay (Bio-GH), serum insulin-like growth factor-I (IGF-I) and IGF-binding protein-3 (IGFBP-3).
High serum Bio-GH values on the first few days of life correspond to high IFMA-GH values, suggesting full biological potency of circulating GH. Furthermore, IGF-I/IGFBP-3 molar ratio values in preterm babies were higher than in full-term infants.
These data confirmed the hypothesis that the higher growth velocity in the first month of life of preterm neonates is due to an increased bioavailability of IGF-I. A progressive maturation of the hypothalamic-pituitary-IGF-I axis without any alteration in the GH biological potency seems to underpin the increase of the growth factors early in life.
The serum GH cut-off value for pharmacological tests of GH secretion (PhT GH) depends on the type of test and also on the method used for determining serum GH. Cut-off serum GH values as different as ...5-10 ng/ml, have been reported, and have been validated biochemically. We have used the growth velocity (GV)-standard deviation score (SDS) during the first year of treatment with rhGH to validate these cut-offs on a biological basis.
Fifty pre-pubertal patients with short stature (height < or =-2 SDS and GV < or =-1.2 SDS) were studied. GH deficiency (GHD) was diagnosed in 39 patients, on the basis of clinical and auxological parameters and on the serum concentration of IGF-1, and non-GHD in the other 11 patients. Two PhT GH (arginine and clonidine) were carried out in the 50 patients. Serum GH was determined by two different methods: one detecting most of serum GH isoforms, named Total GH (HGH Bio-Tech, MAIA Clone), and another one, only detecting the 22 kDa GH, named 22K GH (GH-22K IFMA, Wallac).
Basal data: all patients with GHD and with non-GHD had maximal serum GH response (MaxR) values below and above the cut-off, respectively, for the serum Total GH and 22K GH. The mean 22K GH/Total GH ratio was similar to previous publications. Post-rhGH treatment data: the two groups improved their height SDS during the first year of treatment, particularly patients with GHD. A receiver-operator curve was used to define the best threshold for post-treatment GV-SDS that separates GHD from non-GHD patients. This value was 1.91 GV-SDS. A negative correlation between first year treatment GV-SDS and pre-treatment serum GH MaxR was found for the two assays (p < 0.001). Then, the best cut-off GV-SDS, previously calculated with the receiver-operator curve (1.91 SDS) was used to interpolate the corresponding serum GH values, as determined by the two methods. For Total GH, the value was 10.8 ng/ml, and for 22K GH, it was 5.4 ng/ml.
The cut-off values calculated by biological means to separate GHD from non-GHD were remarkably similar to those calculated biochemically (10.0 and 4.8 ng/ml, respectively) for Total and 22K GH. This is a biological validation for using different cut-off values, appropriate for each assay, to diagnose GHD.
La pharmacocinétique de l'hormone de croissance recombinante (GHr) après injection sous-cutanée a été étudiée chez neuf enfants prépubères porteurs d'un déficit en GH au cours des 12 heures suivant ...la première injection du traitement substitutif de GHr. Les taux sériques de GH ont été évalués au moyen de quatre méthodes: méthode immunofonctionnelle, méthode immunofluorométrique, et deux méthodes biologiques sur cellules Nb2. Les résultats montraient un profil pharmacocinétique très proche quelle que soit la méthode de dosage utilisée avec un pic atteint 2 à 6 heures après l'injection sous-cutanée de GHr; cependant, il existait de grandes variations individuelles dans l'amplitude des pics qui s'associaient à des variations de l'augmentation de la vitesse de croissance au cours de la première année de traitement par GHr. Ces variations de la pharmacocinétique de la GHr pourraient être le résultat de différences dans la dégradation de l'hormone au site d'injection souscutanée. L'étude de la pharmacocinétique de la GHr pourrait être utile dans l'évaluation du traitement par GHr dans le déficit en GH.
Pharmacokinetics of subcutaneously administered recombinant growth hormone (rGH) were studied in nine GH deficient children at the time of the first rGH injection at the beginning of treatment. Serum GH levels were determined by four different methods: immunofunctional assay, immunofluorometric assay and two bioassays on Nb2 cells. The results showed similar profiles whatever the type of assay with a concentration peak reached 2 to 6 hours after subcutaneous injection; however, large individual variations in peak amplitude were observed. They were related to individual variations in the growth velocity during the first year of rGH treatment. These variations are possibly related to individual differences in rGH degradation at the site of injection. Study of rGH absorption profiles appears useful in the evaluation of rGH treatment in GH deficient patients.
Full text
Available for:
IJS, IMTLJ, KILJ, KISLJ, NUK, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
PDF
