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ABSTRACT: Zielsetzung. Anhand der Inzidenzerhebungen in Baden-Württemberg zwischen 1987 und 1998 wurde eine Schätzung der Prävalenz des Diabetes
mellitus für 0- bis 14-Jährige in Deutschland vorgenommen.
Methodik. Die Erhebung schließt alle Kinderabteilungen des Landes (n = 31) sowie eine Diabetesfachklinik ein.
Ergebnisse. Die Inzidenz des Diabetes mellitus Typ 1 im Alter von 0–14 Jahren liegt für den Zeitraum 1987–1998 im Mittel bei 12,9/100.000/Jahr
(95% CI 12,37–13,37). Die Prävalenz der Patienten dieser Altersgruppe mit Diabetes in Baden-Württemberg lag zum 31.12.1998
bei 0,082% (95% CI 0,078–0,086). Das durchschnittliche Alter bei Diagnosestellung liegt für Knaben bei 8,7, für Mädchen bei
8,6 Jahren.
Schlussfolgerungen. Aufgrund dieser Erhebungen ist eine Hochrechnung für Deutschland möglich. Demnach liegt die Gesamtzahl diabeteskranker Kinder
im Alter von 0–14 Jahren für die Bundesrepublik bei 11.000. Die Kenntnis solcher Daten ist Grundlage für die Schaffung geeigneter
Versorgungsstrukturen in der pädiatrischen Diabetologie.
Aim. Our main objective was to estimate the prevalence of diabetes mellitus among children aged 0–14 years in Germany on the basis
of the incidence surveys done between 1987 and 1998 in Baden-Wuerttemberg.
Methods. Data were collected from the pediatric divisions of hospitals in the state (n = 31) as well as from one hospital specializing
in diabetes.
Results. The mean incidence of diabetes mellitus type 1 among children aged 0–14 years was 12.9/100,000/year (95% CI 12.37–13.37)
for the period covering 1987 to 1998. The prevalence among children aged 0–14 years in Baden-Wuerttemberg was up to December
31, 1998, 0.082% (95% CI 0.078–0.086). Average age at the time of diagnosis was 8.7 years among boys and 8.6 years among girls.
Conclusions. It is possible to extrapolate the incidence of diabetes mellitus for Germany as a whole on the basis of the results from
Baden-Wuerttemberg. Calculations done accordingly show that the total number of diabetic children in the Federal Republic
is 11,000 for children aged 0–14 years. Such estimates are fundamental for the further development of medical infrastructures
in the field of pediatric diabetes.
Monatsschrift Kinderheilkunde 04/2012; 150(2):196-200. · 0.27 Impact Factor
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ABSTRACT: To investigate the impact of variants of the FTO gene (rs1421085, rs17817449, rs9939609) in obese children before and after lifestyle intervention.
Design: Longitudinal, clinical intervention study with an increase in physical activity, and nutritional recommendations based on the 'Optimized Mixed Diet for German Children and Adolescents' (Research Institute of Child Nutrition, Germany). Study population: 75 overweight children (40 male, mean BMI 30.4±5.5 kg/m², mean age 12.6±2.6 years). Measurements: Genotyping by means of a TaqMan SNP genotyping assay. Lean and fat mass were determined by means of DXA.
For the whole study population, the 6-month lifestyle intervention resulted in a significant improvement (before intervention minus time point 6 months; mean±SD) in BMI-SDS (0.10±0.17, p<0.001), HOMA (1.41±3.19, p<0.001) and relative fat-mass-SDS (0.09±0.23, p=0.005). Before and after lifestyle intervention, there was no significant difference between heterozygote (n=52) and homozygote (n=21) carriers of the FTO gene in terms of BMI, body composition, and the metabolic profile (Insulin, HOMA, lipids, liver function tests).
Variants in the FTO gene are common in obese children but have no impact on body composition and metabolism before and after lifestyle intervention.
Experimental and Clinical Endocrinology & Diabetes 12/2011; 120(3):128-31. · 1.69 Impact Factor
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T Reinehr,
S Bechtold-Dalla Pozza,
M Bettendorf,
H-G Doerr,
B Gohlke,
B P Hauffa,
S Kaspers,
C Land,
O Mehls,
K-O Schwab,
N Stahnke, M B Ranke
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ABSTRACT: We hypothesized that overweight children with growth hormone deficiency (GHD) demonstrate a lower response to growth hormone (GH) as a result of a misclassification since obesity is associated with lower GH peaks in stimulation tests.
Anthropometric data, response, and responsiveness to GH in the first year of treatment were compared in 1.712 prepubertal children with GHD from the German KIGS database according to BMI (underweight=group A, normal weight=group B, overweight=group C) (median age: group A, B, C: 7.3, 7.28, and 8.4 years).
Maximum GH levels to tests (median: group A, B, C: 5.8, 5.8, and 4.0 µg/ml) were significantly lower in group C. IGF-I SDS levels were not different between the groups. Growth velocity in the first year of GH treatment was significantly lower in the underweight cohort (median: group A, B, C: 8.2, 8.8, and 9.0 cm/yr), while the gain in height was not different between groups. The difference between observed and predicted growth velocity expressed as Studentized residuals was not significantly different between groups. Separating the 164 overweight children into obese children (BMI>97th centile; n=71) and moderate overweight children (BMI>90th to 97th centile, n=93) demonstrated no significant difference in any parameter.
Overweight prepubertal children with idiopathic GHD demonstrated similar levels of responsiveness to GH treatment compared to normal weight children. Furthermore, the IGF-I levels were low in overweight children. Therefore, a misclassification of GHD in overweight prepubertal children within the KIGS database seems unlikely. The first year growth prediction models can be applied to overweight and obese GHD children.
Experimental and Clinical Endocrinology & Diabetes 10/2011; 119(9):544-8. · 1.69 Impact Factor
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ABSTRACT: Obese children have a twofold increased risk of fracture of the forearm compared to non-obese children.
To investigate bone strength and bone structure of the forearm, and the relationship between muscle and bone in obese children.
The study-group consisted of 84 (40 female) overweight children (mean (SD)) age 11.8 (3.2) years, BMI 29.0 (5.1) kg/m(2)). Bone geometry and strength were measured at the proximal radius of the non-dominant forearm (65% measurement site) by means of pQCT (XCT 2000). Bone mineral density and lean mass of the total body was determined by means of DXA (Lunar, DPXL/PED). Results were compared to reference values by calculating age (SDS(CA)) and height-age (SDS(HA)) dependent standard deviation scores (SDS).
Cortical density, -1.11 (1.74) SDS(HA), -0.45 (1.52) SDS(CA); cortical thickness, -1.46 (1.33) SDS(HA), -1.01 (1.46) SDS(CA); cortical area, -0.42 (1.31) SDS(HA), 0.26 (1.58) SDS(CA); total bone area +2.21 (1.47) SDS(HA), 2.91 (1.80) SDS(CA), marrow area +3.12 (2.29) SDS(HA), 3.37 (2.38) SDS(CA); strength strain index +0.10 (1.10) SDS(HA), 0.95 (1.57) SDS(CA). These changes in bone structure were independent from pubertal stage. Measurements revealed correlations between muscle area and SSI (R(2)=0.67, p<0.001), and muscle mass and bone mineral content (DXA; R (2)=0.81, p<0.001).
Low cortical density, normal cortical area and increased total bone area led to a normal strength strain index adjusted both for height and for age. We assume that this normal bone strength is not appropriate for the higher kinetic energy of impact in case of a fall in overweight children.
Experimental and Clinical Endocrinology & Diabetes 06/2011; 119(6):321-6. · 1.69 Impact Factor
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ABSTRACT: Metacarpal thickness (T), width (W), length (L) and medullary diameter (M) were measured in 3,121 X-rays from 231 healthy Caucasian children aged 3 to 19 years and analysed for bone age, age, height, weight and gender-related characteristics, showing highly differentiated growth patterns with prepubertal dips. Reference data for the four metacarpal measures are presented.
The aim of the study was to create and explore a reference database for metacarpal T, W, L and M in children.
Three thousand one hundred twenty-one left-hand X-rays (1,661 from boys) from 231 healthy Caucasian subjects (119 boys) aged 3 to 19 years were analysed by BoneXpert, a programme for automatic analysis of hand X-rays and bone age (BA; in years).
In boys, growth of T, W and L shows a prepubertal decrease from BA 7 to 13 and then accelerates again. In girls, the same is seen only for T starting from BA 8 to 11, whereas W and L grow at a declining rate. M shows steady growth until BA 10.5 in girls and BA 13.5 in boys and then grows smaller in both. W is greater in boys from BA 6 onwards, while L is greater in girls from BA 9 to 13 and T from BA 11 to 14. BA is reflected best by L until start of puberty and by T and L thereafter.
T, W, L and M show highly differentiated growth patterns. These reference data provide a basis for further research into skeletal development and the management of hormone therapies in children.
Osteoporosis International 05/2011; 22(5):1525-36. · 4.58 Impact Factor
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ABSTRACT: Growth hormone (GH) is an accepted treatment for short children born small for gestational age (SGA). The aim of this analysis was to compare the growth response to GH in children with low birth weight born SGA or appropriate for gestational age (AGA).
This retrospective observational study is from one center. Of all the children with a birth weight <2,500 g treated, 50 were primarily diagnosed as having growth hormone deficiency ([A] SGA, n = 26; [B] AGA, n = 24) and 138 were originally diagnosed SGA or AGA (reclassified: [C] SGA, n = 102; [D] AGA, n = 36).
[Median; A, B, C, D]: at an age of 4.9, 5.2, 5.8, 5.8 years, a height of -2.9, -2.4, -2.8, -2.9 SDS and a GH dose of 27, 28, 41, 39 μg/kg/day, the children grew 0.9, 0.9, 0.8, 0.9 SDS in height, respectively. Insulin-like growth factor-1 (IGF-1) at GH start was, respectively, -2.1, -2.2, -0.4, -0.9 SDS and rose to (delta IGF-1) 1.8, 2.0, 1.7, 1.5 SDS during the first year on GH. All differences were not significant.
We show for the first time that short stature children with low birth weight born AGA experience the same increase in height and IGFs to GH treatment as those born SGA irrespective of actual GH secretory status.
Hormone Research in Paediatrics 01/2011; 76(2):104-12.
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ABSTRACT: To investigate the relationship between myostatin serum levels and muscle mass, fat mass and HOMA before and after a 6-month lifestyle intervention program in obese children and adolescents.
A total of 57 overweight children and adolescents (female, n=27; age range, 6.0-16.1 years) were examined between 2007 and 2009. Mean BMI (±SD) was 31.1 (5.7) kg/m(2) corresponding to a mean BMI-SDS LMS of 2.2 (0.4). Muscle and fat mass were determined by means of DXA. Serum myostatin was measured by using a competitive ELISA. RESULTS [MEAN±SD]: After the 6-month intervention program, muscle mass (+2.1±2.7 kg, p<0.0001), and percentage myostatin serum levels (+23.7±26.7%, p<0.0001) were higher than before, whereas decreases in BMI (-0.4 kg/m(2)±1.5, p<0.0001), fat mass (-1.2±3.9 kg, p<0.0001), and HOMA insulin sensitivity index (-0.78±3.28 SD, p=0.0004) were observed. In 86% (n=49, p<0.0001) of all cases, the intervention program resulted in a higher level of myostatin. After lifestyle intervention, patients with the greatest increase of myostatin had a significantly lower increase of muscle mass (p=0.048) but did not differ for fat mass. There was no significant correlation between Myostatin and HOMA insulin sensitivity index before and after lifestyle intervention.
Both muscle mass and serum myostatin increased concordantly. Patients with the greatest rise of myostatin had a significantly lower increase of muscle mass suggesting a negative feedback loop between myostatin and muscle tissue. In our study, the change of myostatin serum levels was not associated with the amount of fat mass or HOMA insulin sensitivity index.
Experimental and Clinical Endocrinology & Diabetes 11/2010; 119(4):238-42. · 1.69 Impact Factor
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ABSTRACT: Sparse data is available on the incidence of endocrine disorders among children in Germany.
A pioneer study was established to analyse, in the German states of Baden-Wuerttemberg (BW) and Bavaria (BY), the incidence and prevalence of congenital adrenal hyperplasia (AGS; CAH), precocious puberty (PP), primary congenital hypothyreosis (PCH), Graves disease (MB), and growth disorders related to the Ullrich-Turner syndrome (UTS) and growth hormone deficiency (GHD).
Participation in the study involved each paediatric hospital in BW and BY (n = 63),and all regional paediatricians belonging to the Association of Statutory Health Insurance Physicians (SHI) practising in these states (n = 1 443). Data collection was done from January 1, 2000, to December 31, 2001, and included all patients in the 0- < 18 age range.
Completeness of data was 81 % for CAH and 55 % for UTS (capture-mark-recapture method).The incidence rate (IR, per 100 000 / year)versus prevalence rate (per 100 000 at the time point December 31, 2001) was: CAH 0.64 vs.9.60; PP 2.42 vs. 10,85; PCH 1.88 vs. 14.97; MB 0.89 vs. 3.25; UTS 2.15 vs. 29.07; and GHD 3.47(IR). Among neonates, the incidence of CAH was 1 / 7 794; PCH 1 / 2 629 and UTS 1 / 2 300.
A pioneer study has been established in Germany for investigating the frequency of AGS (CAH), PP, PCH, MB, UTS, and GHD among children and adolescents. Our data shows that these disorders occur in approx. 2,700 children per year in total Germany, and about 12 000 of these children need to be treated in specialized paediatric endocrinological centres.
Klinische Pädiatrie 02/2010; 222(2):67-72. · 1.77 Impact Factor
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ABSTRACT: Proteolysis of Insulin-like Growth Factor Binding Protein (IGFBP)--3 is a well known mechanism regulating IGF-I bioavailability and IGF-independent actions of IGFBP-3 fragments. Measurement of functional IGFBP-3 can be of use in diagnostics of growth failure or renal impairment. We herein characterize the properties of a commercially available immunoassay for the measurement of functional (IGF-I binding) IGFBP-3.
Fragmentation of IGFBP-3 is analyzed by gel filtration, SDS-PAGE, and western ligand and immunoblotting and compared with subsequent measurement of total and functional IGFBP-3 by ELISA/IFA. Furthermore, assay characteristics such as reproducibility, linearity, and sensitivity are surveyed.
Functional IGFBP-3 was reproducibly measured (6.8/5.6% Inter-/Intra assay variance). A broad range of linearity (1:50-1:300) and a high sensitivity (0.18 microg/L) allowed reliable measurement of IGF-binding IGFBP-3. Analysis of IGFBP-3 fragments reveals that the assay described only detects intact IGFBP-3. Analysis of 189 serum samples from healthy blood donors showed that on average 84% and 69% of total IGFBP-3 was functional in men and women, respectively (p < 0.01).
Functional IGFBP-3 can be measured reliably by the assay system used. Thus, this assay system is suited for the investigation of the diagnostic value of functional IGFBP-3 in human body fluids.
Clinical laboratory 01/2010; 56(11-12):535-42. · 0.90 Impact Factor
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ABSTRACT: Growth hormone (GH) replacement treatment in adults with severe growth hormone deficiency is based on its known effects on body composition, physical performance, bone and lipid metabolism, and on improvements in the quality of life. These features must be taken into consideration when planning GH treatment of patients who are in the transition phase (aged between 15 and 25 years), because developmental stages may vary. GH deficiency during the transition phase is defined as GH levels under 6 microg/l in a standard stimulation test, compared to < 10 microg/l during childhood and < 3 microg/l during adulthood. We present an overview of the diagnostic strategies recommended at international consensus conferences on the verification of GH deficiency during the transition phase. In analogy to the GH treatment of adults, the dosaging (dose at start = 0.2 - 0.5 mg/day) should be based on individual requirements as well as IGF-I concentrations in blood (> 1.0 SDS or < 2.0 SDS). GH treatment during the transition phase should be monitored by an endocrinologist with expertise in dealing with adolescent and adult patients, as well as having experience in structuring treatment and documentation.
DMW - Deutsche Medizinische Wochenschrift 05/2009; 134(21):1117-20. · 0.53 Impact Factor
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G Binder,
S Weber,
M Ehrismann,
N Zaiser,
C Meisner, M B Ranke,
L Maier,
S A Wudy,
M F Hartmann,
U Heinrich,
M Bettendorf,
H-G Doerr,
R W Pfaeffle,
E Keller
Endocrinology. 03/2009; 150(2):1070.
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ABSTRACT: We investigated whether genetic or maternal/environmental risk factors for being born small for gestational age (SGA), e.g. Silver-Russell syndrome, congenital heart defects, infections of mothers or smoking during pregnancy, explain the variation in the first-year growth response to GH therapy.
Secondary analysis was made of growth response in 135 short prepubertal German children (66% males) enrolled in a SGA phase III trial. Initial mean patient age was 6.8 +/- 2.6 years; mean patient height SDS -3.8 +/- 1.2, and GH treatment dose was 0.066 mg/kg body weight per day.
Growth velocity increased by 4.5 +/- 2.0 cm/year and height SDS by 1.0 +/- 0.5 SDS. Although patient number was limited and variation was high, both growth response (cm/year) and change in height SDS did not appear to differ between subgroups which also did not differ in terms of Studentized residuals set up in the KIGS growth prediction model for SGA. Likewise, in a step-forward multivariate analysis, the variables Silver-Russell syndrome, congenital heart defects, infections of mothers and smoking were not identified as independent factors influencing growth velocity.
The retrospectively analyzed genetic and maternal/environmental risk factors for SGA do not appear to explain the observed patient variance in response to GH. Larger prospective studies are needed, however, to substantiate these preliminary findings.
Hormone Research 02/2009; 72(2):106-13. · 2.48 Impact Factor
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ABSTRACT: Measurements of human growth hormone (hGH) are a prerequisite for identifying a deficiency or excess. Our study is the first to investigate the reliability of a very sensitive assay for the quantification of GH in dried blood spots on filter paper.
Validation of a commercially-available enzyme-linked immunoassay (ELISA) for measuring hGH from filter paper samples of dried blood.
We used an assay system (ELISA, E022, Mediagnost) based on polyclonal rabbit antibodies. Its suitability is ascribable to its very high sensitivity (1.6 ng/L) and virtual absence of interfering factors, excepting for a cross-reactivity with high pegvisomant concentrations.
hGH was found to be stable in dried blood spots on filter paper (No. 903, Whatman) over eight days at 37 degrees C. Extraction of hGH from filter paper, in comparison to EDTA plasma, was 107% (SD 8.1%; n=6) over a range from 2.4 to 34.5 microg/L. Linear regression analysis (n=119) showed a correlation of R(2)=0.97 for the hGH concentration in serum and on filter paper samples.
Our findings demonstrate the reliability of measurements of hGH in dried blood spots on filter paper. The advantages of this method are the low sample volume and the easy transport, storage, and handling of samples. This method contributes to the standardisation of diagnostics pertaining to abnormal hGH secretion as it facilitates the comparison of decisive measurements.
Growth hormone & IGF research: official journal of the Growth Hormone Research Society and the International IGF Research Society 07/2008; 18(6):526-32. · 2.35 Impact Factor
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ABSTRACT: To assess the incidence and the trend in incidence of Type 1 diabetes (T1DM) in children and adolescents < 15 years of age in Baden-Württemberg (BW), Germany.
BW is Germany's third largest federal state. All 31 paediatric departments in BW and one diabetes centre participated in the study. Case registration was done according to the EURODIAB criteria. The degree of ascertainment was 97.2%.
From 1987 to 2003, the age- and sex-standardized incidence rate was 14.1/100,000 per year [95% confidence interval (CI) 13.7, 14.6, n = 4017]. The estimated annual increase in incidence was 3.8% (95% CI 1.1, 6.6). Compared with the first years of our registry, the current mean number of new cases of T1DM has doubled (1987-1989, n = 153; 2000-2003, n = 302). Generally, the highest rise in incidence occurred in the youngest age group of 0-4-year-old patients (5.8%; 95% CI 2.5, 9.3), followed by the age groups 5-9 (3.4%; 95% CI 0.8, 6.0) and 10-14 (2.7%; 95% CI 0.3, 5.1).
In Germany, the number of children and adolescents with new-onset T1DM has been rising at a faster pace than expected. A distinct shift to younger age at onset has been observed in Germany.
Diabetic Medicine 06/2008; 25(6):755-7. · 2.90 Impact Factor
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ABSTRACT: Silver-Russell syndrome (SRS) describes a malformation syndrome with severe intrauterine and postnatal growth retardation. Currently, two major (epi)mutations have been described: while approximately 10% of patients carry a maternal uniparental disomy of chromosome 7 (UPD7), 35-60% show a hypomethylation at the H19 differentially methylated regions (DMRs) in 11p15. Until recently, a Southern-blot based test was routinely used to identify epimutation carriers. Nevertheless, this test was time consuming and hampered by the huge amount of genomic DNA needed. With the methylation-specific multiplex ligation-dependent probe amplification assay (MLPA) for SRS, a PCR-based test is now available, allowing the analysis also of small amounts of DNA. Probes in this assay hybridize to the H19 DMRs but do not cover the genomic target of the Southern-blot probe. We now screened 72 patients with SRS by MLPA. Hypomethylation of the H19 DMRs was confirmed in all patients analyzed by Southern blot. In addition, we identified six individuals with hypomethylation of the H19 DMR who had previously normal blot results. This discrepancy can be explained by the observed generally lower degree of demethylation in this group, possibly not detectable by the less sensitive Southern-blot method but also with a varying degree of methylation at different DMRs in the same individual. Apart from hypomethylation in the H19 DMR, we observed a slight demethylation for one of the IGF2 probes. The total detection rate of 11p15 hypomethylation is now increased to >38%. Considering maternal UPD7 and chromosomal aberrations, (epi)genetic alterations now account for more than 50% of SRS patients. In summary, MLPA represents an easy, low cost and reliable system in the molecular diagnostics of SRS.
Clinical Genetics 02/2008; 73(1):79-84. · 3.13 Impact Factor
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ABSTRACT: Patients in the Kabi International Growth Study (KIGS) up to 1st January 1990 who had organic growth hormone deficiency (OGHD) were identified. They accounted for 21% of all patients with growth hormone deficiency (GHD). Diagnostic categories within the OGHD group included septo-optic dysplasia, postnatal trauma, craniopharyngioma, other cranial tumours, and following acute leukaemia. Features at presentation and during the first year of hGH treatment were compared with those of children with idiopathic growth hormone deficiency (IGHD). Ninety prepubertal children with OGHD were selected for comparison of observed first-year height velocity (HV) with predicted values based on those observed in 257 children with IGHD. Those with septo-optic dysplasia, postnatal trauma and craniopharyngioma responded as predicted, whereas those with other cranial tumours appeared to grow less well than predicted. Glucocorticoid treatment did not affect response, but previous cranial or craniospinal irradiation was found to be associated with an observed HV which was significantly less than predicted.
Acta Paediatrica 01/2008; 79(s370):131 - 137. · 2.07 Impact Factor
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ABSTRACT: Autosomal dominant isolated growth hormone deficiency type II (IGHD II) is mainly caused by splice site mutations of the GH-1 gene, leading to deletion of amino acids 32-71 of the human growth hormone (hGH). The severe hGH deficit in IGHD II suggests a dominant negative effect of the partially deleted del(32-71)-hGH on the production, storage or secretion of normal wild-type (wt)-hGH in somatotrophic cells of the pituitary. To shed more light on the cellular and molecular basis of IGHD II, we established and analysed diverse clones of the rat somatotrophic cell line GH(4)C(1) stably expressing either wt-hGH, del(32-71)-hGH, or both proteins concomitantly. The cellular morphology of all transfected GH(4)C(1) cell clones showed moderate differences to untransfected GH(4)C(1) cells. On the molecular level, both cDNA-constructs induced transcription but, under normal culture conditions, only wt-hGH protein was found to be synthesised and secreted in readily detectable amounts. By contrast, only after inhibition of proteasomes did high amounts of del(32-71)-hGH show up. The solubility of del(32-71)-hGH in nondenaturing buffer was poor compared to wt-hGH, hinting at molecular aggregation, and several epitopes recognised by monoclonal hGH antibodies were not present on del(32-71)-hGH, confirming the assumption that del(32-71)-hGH must be severely misfolded. Expression of both proteins in Escherichia coli mirrored the findings from the GH(4)C(1) cell clones in terms of solubility and immunological reactivity. The results of the present study indicate that, in IGHD II, somatotrophs continuously have to remove misfolded del(32-71)-hGH via the proteasomal degradation pathway, suggesting a mechanism that may result in chronic cellular stress.
Journal of Neuroendocrinology 12/2007; 19(11):882-90. · 3.14 Impact Factor
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M Tauber,
W Ester,
F Auriol,
C Molinas,
J Fauvel,
J Caliebe,
T Nugent,
L Fryklund, M B Ranke,
M O Savage,
A J L Clark,
L B Johnston,
A C S Hokken-Koelega
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ABSTRACT: The polymorphic deletion of exon 3 of the GH receptor (d3-GHR) has recently been linked to the magnitude of growth response to recombinant human GH (rhGH) therapy in short children with or without GH deficiency. We investigated this association in a large multinational cohort from the Network of European Studies of Genes in Growth (NESTEGG), comprising short children born small for gestational age (SGA).
The study included short prepubertal SGA children treated with rhGH for 1 or 2 years.
Two hundred and forty white Caucasian SGA children (138 male, 102 female) aged 6.6 +/- 2.3 years with a height at -3.0 +/- 0.7 SDS at start of rhGH treatment; 193 ethnically matched controls.
The GHR polymorphism (fl/fl, fl/d3 or d3/d3) was genotyped by polymerase chain reaction (PCR) multiplex assay. Growth velocity (G/V) in cm/year and changes in GV during the first and second year of rhGH treatment were evaluated.
The change in GV was significantly greater in SGA children carrying one or two copies of the d3-GHR allele (P = 0.038 for the first year and P = 0.041 for the second year of GH treatment), but the change in height was not significantly different. Birthweight was significantly lower in SGA children with the d3/d3 genotype than in SGA children with the fl/fl genotype (P = 0.034) and in those with the fl/d3 genotype (P = 0.016).
Our data, based on a large cohort, showed that the exon 3 GHR polymorphism is associated with responsiveness to rhGH treatment in SGA children with short stature.
Clinical Endocrinology 10/2007; 67(3):457-61. · 3.17 Impact Factor
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ABSTRACT: Neonatal cholestatic hepatitis is frequently associated with congenital combined pituitary hormone deficiency (CCPHD). Data on the course of this hepatopathy are scarce.
We retrospectively analyzed the data of all CCPHD infants with cholestasis who presented at the University Children's Hospital, Tuebingen.
All infants (n = 9; 2 females) presented with early and prolonged jaundice, failure to thrive and recurrent hypoglycemia. All males had micropenis and 3/7 cryptorchidism. Median age at diagnosis was 1.4 months. Cholestasis began at a median age of 13 days (range 5-31) and resolved at 88 days (54-174). Maximum direct bilirubin level was 6.9 mg/dl (2.4-11.6). Peaks of ALP (median 721 U/l), ALT (148 U/l) and AST (195 U/l) occurred 2-4 weeks later, while GGT levels were elevated in only two infants (167 U/l). Functional liver parameters were always normal. Liver biopsies (n = 4) showed canalicular cholestasis and mild portal eosinophilic infiltration. TEBIDA radioisotope excretion into the intestinal tract was blocked. Substitution with Lthyroxine, hydrocortisone and growth hormone seemed to accelerate the cure from cholestasis. Liver function at follow-up (median 4 yr) stayed normal.
Cholestasis in CCPHD follows the course described here, frequently with normal GGT levels.
Journal of pediatric endocrinology & metabolism: JPEM 07/2007; 20(6):695-702. · 0.88 Impact Factor
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ABSTRACT: Data on the GH-induced catch-up growth of severely GH-deficient children affected by monogenetic defects are missing.
Catch-up growth of 21 prepubertal children (6 females, 15 males) affected with IGHD type II was analyzed in a retrospective chart review. At start of therapy, mean age was 6.2 years (range, 1.6-15.0), mean height SDS was -4.7 (-7.6 to -2.2), mean IGF-I SDS was -6.2 (-10.1 to -2.2). GH was substituted using a mean dose of 30.5microg/kg*d.
Catch-up growth was characterized by a mean height gain of +0.92, +0.82, and +0.61 SDS after 1, 2, and 3 years of GH therapy, respectively. Mean height velocities were 10.7, 9.2 and 7.7cm/year during the first three years. Mean duration of complete catch-up growth was 6 years (3-9). Mean height SDS reached was -0.97 (-2.3 to +1.1), which was within the range of the estimated target height of -0.60 SDS (-1.20 to -0.15). The younger and shorter the children were at start of therapy the better they grew during the first year independent of the dose. Mean bone age was delayed at start by 2.1 years and progressed by 2.5 years during the first two years of therapy. Incomplete catch-up growth was caused by late initiation or irregular administration of GH in four cases.
Our data suggest that GH-treated children with severe IGHD show a sustained catch-up growth over 6 years (mean) and reach their target height range. This response to GH is considered to be characteristic for young children with severe growth retardation due to IGHD.
Growth Hormone & IGF Research 07/2007; 17(3):242-8. · 2.16 Impact Factor
