Gewebeplastizit?t, Hormone und Geschlecht

Ohne ZusammenfassungMit 30 Abbildungen.Aus dem Kaiser Wilhelm-Institut für Biologie, Berlin-Dahlem, Abt. ProfessorHartmann.     

The role of insulin like growth factor (IGF) — 1 and IGF — binding protein-3 in diagnosis of Growth Hormone Deficiency in short stature children

Objective  The purpose of this study was to evaluate the role of IGF-1 and IGFBP-3 in diagnosis of short stature children and adolescents in whom Growth Hormone Deficiency (GHD) was found. Methods  In this cross sectional study the referred short stature children and adolescents to Namazi Hospital in Shiraz- Iran, in 2003–2005 were studied. The inclusion criteria were proved short stature based on the physical examination, weight, height, standard deviation score (SDS) of height < −2, with considering stage of puberty and predicted height in children without any genetic or chronic disorders. The exclusion criteria were any positive physical or laboratory data suggesting hypothyroidism, rickets or liver disorders. For all patients a provocative growth hormone test was performed with propranolol and L-dopa and serum IGF-1 and IGFBP-3 were measured. GHD defined as peak(cutoff) serum GH level under 10 ìg/L and low IGF-1 and IGFBP-3 considered as cutoff serum level under −2 standard deviation. Results  Eighty one short stature patients (39 boys and 42 girls) with mean age of 10.6 ± 3.5 years completed the study. Seventeen patients with GHD were found and in 18 patients IGF-1 level were low. Only in 6 patients both GH and IGF-1 were low and 2 of them had low IGFBP-3. There were no correlations between the levels of GH,IGF-1 and IGFBP-3 in children with short stature due to GHD. The sensitivity and specifity of IGF-1 and IGFBP-3 in assessment of GHD were 35% and 81% for IGF-1 and 12% and 94% for IGFBP-3, respectively. Conclusion  No correlations were found between GH level and serum levels of IGF-1 and IGFBP-3 in short patients and the sensitivity of those tests in assessment of GHD were poor.     

Growth of children with β-thalassemia major

Hypertransfusion and regular chelation therapy have allowed improved survival in patients with thalassemia major (TM). Despite medical advances, growth failure and hypogonadism remain significant clinical problems in these patients in adolescence. Disproportionate truncal shortening which is common especially among adolescents with thalassemia, is due to platyspondyly resulting from a combination of factors like hemosiderosis, desferrioxamine toxicity or deficiency of trace elements. Although growth hormone (GH) deficiency and GH neurosecretory dysfunction have been described in TM patients, most short TM patients have normal GH reserve. The low serum IGF-1 and IGFBP-3 concentrations in TM patients despite having normal GH reserve and serum GH binding protein levels suggest that a state of secondary GH insensitivity exists. The pubertal growth spurt may be impaired in TM patients going through spontaneous or induced puberty and may have a negative effect on final adult height. GH therapy in dosages ranging from 0.5–1.0 IU/kg/wk has resulted in a significant improvement in growth velocity in short TM children without any adverse effects on skeletal maturation, blood pressure, glucose tolerance and serum lipids. There is limited evidence that GH treatment can result in an improved final adult height in short TM children. Careful and regular clinical and biochemical monitoring should be preformed on these patients while they are treated with GH.     

Immunolocalization of Transforming Growth Factor α and Epidermal Growth Factor Receptor in Lungs of Patients with Cystic Fibrosis

Transforming growth factor α (TGF-α) is expressed in respiratory epithelial cells and alveolar macrophages during development and following lung injury. In the present study, the presence and sites of synthesis of TGF-α and its receptor, the epidermal growth factor receptor (EGF-R), were assessed in lung tissue from patients with severe lung disease caused by cystic fibrosis (CF). Lung sections from 24 individuals with CF, obtained at the time of lung transplantation, were compared to lung sections from five lung donors without CF. Cellular sites of TGF-α, EGF-R, and cellular sites of proliferation were assessed by immunohistochemistry. All CF lung sections contained multiple cell types with detectable TGF-α. Compared to control sections, intensity of TGF-α immunostaining in macrophages, airway epithelial cells, and peribronchial submucosal cells was increased. EGF-R was detected in respiratory epithelial and peribronchial stromal cells but not in alveolar macrophages. The intensity of EGF-R staining in CF lung tissue did not differ from that of controls. An increased number of cells expressing Ki-67 nuclear antigen was detected in peribronchial submucosal cells but not bronchiolar epithelial cells in the CF lungs. The increased expression of TGF-α in CF lung tissue supports the concept that TGF-α plays a role in paracrine/autocrine regulation of lung remodeling associated with injury and repair in the lungs of individuals with cystic fibrosis.     

Growth hormone in short children: beyond medicine?

The indications for growth hormone (GH) treatment in non-GH-deficient short children are in debate, with some arguing that this treatment does not belong solely in the medical domain. We describe three different approaches to the issue, and argue that neither a disease-oriented nor client-oriented approach is sufficient. Both lead to withdrawal of medical interventions or to an undesirable application. Conclusion: An approach focusing on suffering as an indication for treatment of short stature is the most appropriate. The challenge is to develop proper tools by which to evaluate suffering and the efficacy of GH treatment in these children in order to relieve or prevent suffering.     

Growth charts for children with Ellis–van Creveld syndrome

Ellis–van Creveld (EvC) syndrome is a congenital malformation syndrome with marked growth retardation. In this study, specific growth charts for EvC patients were derived to allow better follow-up of growth and earlier detection of growth patterns unusual for EvC. With the use of 235 observations of 101 EvC patients (49 males, 52 females), growth charts for males and females from 0 to 20 years of age were derived. Longitudinal and cross-sectional data were collected from an earlier review of growth data in EvC, a database of EvC patients, and from recent literature. To model the growth charts, the GAMLSS package for the R statistical program was used. Height of EvC patients was compared to healthy children using Dutch growth charts. Data are presented both on a scale for age and on a scale for the square root of age. Compared to healthy Dutch children, mean height standard deviation score values for male and female EvC patients were −3.1 and −3.0, respectively. The present growth charts should be useful in the follow-up of EvC patients. Most importantly, early detection of growth hormone deficiency, known to occur in EvC, will be facilitated.     

Pune low birth weight study — Growth from birth to adulthood

Objective

To assess the growth, adiposity and blood pressure of non-handicapped low birthweight children at 18 years.

Design

Prospective cohort study.

Setting

Infants born between 1987-1989 with birthweight less than 2000g, discharged from a neonatal special care unit of a referral hospital and followed up till the age of 18 years.

Methods

The height, weight, and head circumference were measured. Measurements for adiposity, blood pressure, parental height and weight were recorded.

Results

The cohort of 161 low birth weight (LBW) infants was divided into three groups according to their gestation — preterm SGA (n=61), full term SGA (n=30) and preterm AGA (n=70). 71 full term AGA infants served as controls. Preterm SGA males had height of 164.5 cms (162–166.9, 95% CI) which was significantly less (mean deficit = 5.7 cms) than that of controls (P=0.02). However, PTSGA children were short inspite of normal midparental height. Preterm SGA and AGA children had smaller head circumference. There was no evidence of adiposity and no child had hypertension. Mid-parental height was an important determinant of height in LBW children. Both parentss’ weight and BMI were important determinants of weight and BMI, respectively in all LBW children.

Conclusion

Preterm SGA males were short, but there was no difference in the weight of the LBW group and controls. Preterms had smaller head circumference. There was no evidence of adiposity or hypertension.

     

Growth hormone treatment and pseudotumor cerebri: coincidence or close relationship?

Pseudotumor cerebri (PTC) is an uncommon disorder in the pediatric population. It is not a benign condition. It can cause permanent vision loss. The most recently recognized risk factor for this disorder is recombinant human growth hormone (GH) therapy. Data from Genentech's National Cooperative Growth Study (NCGS), a postmarketing surveillance program, are analyzed to examine the relationship between GH therapy and PTC. Several areas are addressed, including plausibility, probability, clinical and laboratory presentations, management, clinical outcome, present state of knowledge, and future recommendations.     

Growth monitoring of low birthweight infants: What references to use?

Growth charts are the mainstay of monitoring growth in babies who were born small or preterm. A variety of different charts are available, each with specific limitations. Most birthweight centile charts underestimate growth restriction in preterm babies and there are few good charts for monitoring longitudinal growth in preterm babies; it is important to be aware of the limitations of using cross-sectional data for monitoring longitudinal growth. Customised centile charts of fetal growth are used increasingly for antenatal monitoring for small-for-gestational age fetuses despite a lack of robust evidence. It is also unclear whether customised centile charts should be used for assessing birthweight, particularly in babies born at term. Faltering post-natal growth in preterm babies is very common but need not be universal with close attention to nutrition. Monitoring of growth trajectories through infancy following either fetal growth restriction or post-natal faltering growth is important to ensure proportional growth, particularly during periods of accelerated growth. This review will discuss these issues in the context of current practice in Australia and New Zealand.     

Aflatoxin B1 Level in Relation to Child’s Feeding and Growth

Objective  

To study the influence of sociological factors, breast feeding and weaning on aflatoxin exposure in children as well as to determine the effect of aflatoxin exposure on child’s growth.     

Growth hormone deficiency: a possible complication of glucose transporter 1 deficiency?

Glucose transporter 1 deficiency syndrome (GLUT1DS) is an autosomal dominant disorder of brain energy metabolism caused by impaired GLUT1-mediated glucose transport across the blood-brain barrier. Although the clinical spectrum of this disorder is expanding rapidly, the growth patterns and endocrine status of these patients are not well known. We report the case of a boy aged 12 years and 7 months who has GLUT1DS complicated by growth failure. His failure to grow had progressed since birth, and his body height was 125 cm (-3.6 SDS). Growth hormone stimulation tests showed severe growth hormone deficiency (GHD), and we initiated GH replacement therapy. After 2 years of treatment, the boy's growth rate recovered from 1.7 cm/year before treatment, to 7.5 cm/year and 4.3 cm/year after treatment with no adverse effects. We speculate that GHD is a possible complication of GLUT1DS and discuss the underlying causative mechanism. CONCLUSION: GHD may be a possible complication of GLUT1DS.     

Growth charts for Wolf-Hirschhorn syndrome (0–4 years of age)

Wolf-Hirschhorn syndrome is characterized by severe growth and mental retardation, microcephaly, seizures and ‘Greek helmet’ facies, caused by partial deletion of the short arm of chromosome 4. Growth charts are given from 0–4 years of age, based on the study of 101 individuals. Use of these specific growth charts is recommended, because standard growth charts are inapplicable for patients with WHS.     

Serum concentrations of Anti-Müllerian Hormone (AMH) in 95 patients with Klinefelter syndrome with or without cryptorchidism

Aim: Anti‐Müllerian hormone (AMH) is produced by foetal Sertoli cells at the time of sexual differentiation and is responsible for the regression of the Müllerian ducts in the male foetus. AMH is a testis‐specific marker of diagnostic value in infants with ambiguous genitalia or with bilateral cryptorchidism. However, little is known about AMH in boys and adult men with normal or abnormal gonadal function. We therefore aimed at determining circulating AMH concentrations in patients with 47,XXY Klinefelter syndrome (KS) with or without cryptorchidism. Methods: AMH was determined in 95 47,XXY patients aged 0.2–64.5 years, of which 12 patients had a history of cryptorchidism. Results: AMH was within the normal range in boys with Klinefelter syndrome until puberty. The pubertal decline was delayed, especially in patients with a history of cryptorchidism. AMH was below ?2 SD in 85% of adult KS. Conclusion: AMH secretion in patients with 47,XXY KS was within normal limits during mini‐puberty and until puberty. Thereafter, AMH declined to subnormal levels in all patients. We hypothesize that this decline was a result of the hyalinization of seminiferous tubules in relation to puberty, rather than caused by disrupted regulatory mechanisms at the level of the pituitary–gonadal axis.     

Growth hormone and 17β-oestradiol treatment of Turner girls — 2-year results

Girls with Turner syndrome are mainly characterized by growth retardation and gonadal insufficiency. In order to evaluate the effect of growth hormone (GH) and/or low dose 17-oestradiol (E2) on growth and pubertal development, 39 Turner girls with a chronological age (CA) of 7.6–18.1 years were divided into three groups depending on pretreatment bone age (BA). They were treated with either GH 0.1 IE/kg per day (n=13, BA 7.1–10.2), peroral E2 0.01 mg/kg per day (n=8, BA 8.5–12.7) or both (n=18, BA 10.5–15.3). In the 2nd year the E2 group also received GH, while the E2 dose was reduced 30%. In the 1st year height velocity (HV) expressed as standard deviation scores (SDS) increased in all groups (mean): from –0.4 to 3.3 (P<0.01) in the GH group, –0.5 to 2.7 (P<0.01) in the E2 group, and –0.8 to 4.6 (P<0.001) in the GH +E2 group. A possible synergistic effect from combination therapy was seen, as HV increase was higher in group 3 than groups 1 and 2 (P<0.05). In the 2nd year HV was unchanged in groups 1 and 2, while a clear decrease was seen in the GH+E2 group (P<0.001). In the 1st year BA progression in the E2 group was rapid (1.9 BA/CA year) and higher than in the other groups (P<0.05). In the 2nd year progression slowed down-particularly in the E2 group (0.7 BA/CA year,P=0.07). Predicted final height (PFH) increased gradually over the 2 years in the GH group up to 4.1 cm (P<0.01), while in the GH+E2 group PFH increased 2.6 cm (P=0.001) after 1 year, but progressed no further during the 2nd year. In the E2 group PFH decreased –3.1 cm (P=0.055) during the 1st year, while in the 2nd year PFH returned to pretreatment levels. Insulin-like growth factor (IGF-I) increased during the 1st year in the GH and the GH+E2 groups (P<0.01 andP<0.05), while it was unchanged in the E2 group (P>0.4). Except for some of the youngest and oldest girls, breast development was appropriate. No major side-effects were noted. In one girl growth of naevi was noted, but they disappeared spontaneously within 3 months. We conclude that GH and peroral E2 both stimulate HV and appear to have a synergistic effect. The effect of peroral E2 is not mediated by increasing IGF-I. When BA is below 11 years, E2 leads to an accelerated BA maturation, which potentially decreases final height. An initial dose lower than 10 g E2/kg per day and a minimum BA of 11 years are recommended to initiate treatment. Participating in the study: I. L. Pedersen, Paediatric Department, Herning Centralsygehus; M. Rix, Paediatric Department, Aalborg Sygehus Nord; U. Friedrich, Cytogen. Laboratory, Psych. Hospital; K. Lillquist, Paediatric Department, Hjorring Centralsygehus; B. Djernes, C. Pedersen, Paediatric Department, Esbjerg Centralsygehus; N. Clausen, Paediatric Department, Aarhus Kommunehospital; B. Kragh-Olsen, Paediatric Department, Aarhus Kommunehospital; K. Brostrom, Paediatric Department, Hillerod Centralsygehus, I. Pelck, Haderslev; C. Gaardsted, Frederikshavn; I. Ahnfeldt-Mollerup, Bryrup; A. V. Torsson, Paediatric Department, St. Josephs Hospital, Reykjavik, Iceland; L. Kirk, Paediatric Department 5004, Rigshospitalet, Copenhagen; N. C. Christensen, Paediatric Department, Sonderborg, Sygehus; B. B. Jacobsen, Paediatric Department, Odense Sygehus, S. Krabbe, Paediatric Department, Hvidovre Hospital