The Journal of pediatric endocrinology最新文献

Growth hormone (GH) is filtered through the kidney, and may exert effects on renal function when presented via the circulation. Investigations on kidney-related aspects of GH are increasing in number. Using in vitro and in vivo approaches, the present study attempted to provide answers to a number of unresolved or debated issues. In vitro, we detected both GH and type 1 IGF receptors (R) in a porcine renal epithelial cell line. The saturation and down regulation kinetics of the GH-R indicate that it has the properties of a classical GH-R. Furthermore, the simultaneous presence of GH-R and IGF-R on a phenotypically homogeneous cell line suggests the presence of GH-induced auto-/paracrine IGF-1 bioactivity in the kidney. Experiments with isolated proximal rabbit tubules incubated with physiological concentrations of 125I-GH demonstrated a time-and dose-dependent increase in unlabelled GH-displaceable cell-associated radioactivity, lending support to the concept of GH mediating its renal effects via proximal tubular GH-R. Short term administration of GH to rats and humans elicited electrolyte and water retention that may cause edema in adults. In the present study, long term administration of GH to rats caused only a minor increase in serum phosphate levels, with no changes observed in the renal electrolyte clearance. During the first 4 days of GH treatment in rats, no change in plasma renin activity was detected and we were thus unable to confirm the hypothesis that the renin-angiotensin system is responsible for the early phase of GH-associated fluid retention. Pharmacokinetically, when GH was administered to rats with functional disconnection of the kidneys as a model of renal insufficiency, the whole body clearance of GH decreased by ca. two thirds, and was reflected by an increase in the mean residence time and AUCplasma for GH. The plasma half-life, however, was not significantly affected, suggesting that the volume of distribution (Vd) had decreased for the GH administered to the renally compromised animals. A renal contribution to the Vd was visualized as intense radioactive staining in the kidney region on whole body autoradiographs (WBA) of rats dosed with 125I-labelled hGH. The liver region was also intensely stained. Kidney-associated radioactivity was found to be related not only to glomerular filtration, but also to peritubular uptake, since the renal clearance of free GH was found to exceed the GFR.(ABSTRACT TRUNCATED AT 400 WORDS)

Growth retardation after renal transplantation (RTx) is generally attributed to prednisone (PDN) administration, although the exact mechanism is poorly understood. In a group of 19 growth-retarded patients after RTx, we studied the effect of alternate-day (group AD, n = 12) and daily (group D, n = 7) PDN treatment on the spontaneous plasma growth hormone (GH) and cortisol profiles, for 48 h in group AD and for 24 h in group D. The maximal plasma GH response to arginine provocation (ATT) and plasma levels of insulin-like growth factor-1 (IGF-1), IGF-2 and serum IGF-binding proteins (IGFBP) were also determined. For both groups the PDN doses were recalculated as daily doses for comparison. The median PDN dose in both groups was similar, 0.15 mg/kg/day, with a range of 0.10-0.25 mg/kg/day. Glomerular filtration rate (GFR) was above 20 ml/min/1.73 m2 in all patients. We hypothesized that alternate-day PDN therapy and even more so daily PDN therapy would have a deleterious effect on GH and cortisol secretion and would result in lower GH-dependent growth factors as compared to control data of healthy children. Our findings revealed that growth-retarded renal allograft patients, receiving either alternate-day or daily PDN therapy, have significantly lower mean plasma GH levels than controls, but normal diurnal rhythm of GH and cortisol secretion as well as normal immunoreactive IGF-1 and -2 levels. Mean serum IGFBP-1 levels were normal, but mean serum IGFBP-3 levels were significantly increased, while a significant negative correlation was found between the GFR and serum IGFBP-3 levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Patient compliance is of vital importance for the outcome of any medical therapy. Compliance is a problem especially in the treatment of non-life-threatening conditions, such as growth retardation in children, where motivation can be low and the rewards delayed. One way to improve compliance is through an improvement in patient convenience. As a result of these considerations as well as the positive experiences reported with insulin pen treatment, an injection pen for growth hormone administration (Nordiject) has been introduced. Results from several patient acceptance studies have shown that the injection pen and the preparation for use in the pen have been found effective and safe with good local tolerability and reduced perception of injection pain. The injection pen was found to simplify the injection procedure and was strongly preferred to conventional syringes and vials. Special attention has been paid to local discomfort and injection pain. A double-blind, randomized cross-over study has shown that 0.9% benzyl alcohol solvent causes statistically significantly less local discomfort that a 0.25% metacresol solvent when used for reconstitution of growth hormone. In another study the 30G needle was compared with 27G, and the use of the 30G needle seems also to give a reduction in injection pain. A further reduction in injection pain can be gained by improving the needle insertion technique. A randomized cross-over study compared two experimental devices, one with manual and one with automatic needle insertion. The results from this study showed a statistically significantly lower injection pain score for the automatic device compared to the manual. The above studies have shown that it is possible to improve patient convenience. Long-term studies will show whether this improvement results in improved compliance and hence a better treatment outcome.

In 1992 we described a computer-assisted method for assigning Tanner-Whitehouse RUS skeletal maturity scores to hand-wrist radiographs. An operator positions each epiphysis in turn beneath a video camera, views the image on the computer screen and corrects the position of the radiograph by matching to templates of the TW stages displayed on the screen. The process is then automatic; the computer, not the operator, rates the bone. The image is digitized and then represented by a large number of mathematical coefficients. These coefficients are then compared to those generated by each stage of the TW standards, and the closest match is sought. Since the comparison is quantitative the system produces continuous stage scores instead of the old discrete ones such as B, C, D, etc. Thus in longitudinal data a much smoother progression of skeletal maturity scores with age is achieved. The reliability of the computer-assisted skeletal age score (CASAS) is considerably greater than that of the usual manual method. Differences between duplicate readings of a bone by a single observer average about 0.25 stage, and reach 1.0 stage or more only in about 3% of instances, compared with 15-20% characteristic of manual ratings.