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Port Glasgow, United Kingdom

Wong S.C.,Bone and Endocrine Research Group | Smyth A.,Bone and Endocrine Research Group | McNeill E.,Bone and Endocrine Research Group | Galloway P.J.,Hepatology and Nutrition | And 4 more authors.
Clinical Endocrinology | Year: 2010

Context There is scarce knowledge about the growth hormone (GH) insulin-like growth factor-1 (IGF1) axis in children & adolescents with inflammatory bowel disease (IBD) and growth retardation. Objective To describe the pattern of GH and IGF1 secretion in children & adolescents with IBD. Design A retrospective review of 28 patients (23 M) of IBD (25 Crohn's Disease and three Ulcerative Colitis) and growth retardation who had investigation of the GHIGF-1 axis. Height velocity (HV) and serum IGF1 were converted to standard deviation score (SDS); to account for delayed puberty in girls over 11 years and boys over 12 years, HV and serum IGF1 SDS were adjusted for bone age. Results Median (range) age and Ht SDS at the time of endocrine evaluation was 14·3 years (7·7,17·0) and -2·0(-3·6,- 0·9), respectively. Median HVSDS over the prior 12 months was -2·2(-7·7,2·8). Median peak serum GH on insulin tolerance test (ITT) was 5·8 mcgl (1·3, 24·0), and median serum IGF1 SDS was -0·9(-3·1, 0·1). Five of 28 (18%) had a peak serum GH of >12 mcgl. Overall, four had biochemical evidence of functional GH deficiency (peak GH < 3 mcgl and IGF1 SDS < 0) and 11 children had biochemical evidence suggesting GH resistance (peak GH > 6 mcgl and IGF1 SDS < 0). However, only one child had a peak serum GH > 6 mcgl and a very low IGF1 SDS of <-2·0. There was a negative association between peak serum GH and Ht SDS (r = -0·49, P = 0·008), but there was no association with HV and there was no association between IGF1 SDS and Ht or HV SDS. IGF1 SDS showed a negative association with erythrocyte sedimentation rate (r = -0·41, P = 0·04). Conclusion Growth retardation in children and adolescents with IBD is commonly associated with a range of biochemical abnormalities ranging from functional GH deficiency to GH resistance. In these children, poor relationship between systemic markers of growth and height velocity point to an important role of growth factors at the target organ level in modulating growth in children with IBD. The value of assessing the GHIGF-1 axis and whether it predicts subsequent response to growth-promoting therapy requires further exploration. © 2010 Blackwell Publishing Ltd. Source

Webb E.A.,Developmental Endocrinology Research Group | O'Reilly M.A.,University College London | Clayden J.D.,University College London | Seunarine K.K.,University College London | And 5 more authors.
Brain | Year: 2012

The growth hormone-insulin-like growth factor-1 axis plays a role in normal brain growth but little is known of the effect of growth hormone deficiency on brain structure. Children with isolated growth hormone deficiency (peak growth hormone <6.7g/l) and idiopathic short stature (peak growth hormone >10g/l) underwent cognitive assessment, diffusion tensor imaging and volumetric magnetic resonance imaging prior to commencing growth hormone treatment. Total brain, corpus callosal, hippocampal, thalamic and basal ganglia volumes were determined using Freesurfer. Fractional anisotropy (a marker of white matter structural integrity) images were aligned and tract-based spatial statistics performed. Fifteen children (mean 8.8 years of age) with isolated growth hormone deficiency [peak growth hormone <6.7g/l (mean 3.5g/l)] and 14 controls (mean 8.4 years of age) with idiopathic short stature [peak growth hormone >10g/l (mean 15g/l) and normal growth rate] were recruited. Compared with controls, children with isolated growth hormone deficiency had lower Full-Scale IQ (P<0.01), Verbal Comprehension Index (P<0.01), Processing Speed Index (P<0.05) and Movement-Assessment Battery for Children (P<0.008) scores. Verbal Comprehension Index scores correlated significantly with insulin-like growth factor-1 (P<0.03) and insulin-like growth factor binding protein-3 (P<0.02) standard deviation scores in isolated growth hormone deficiency. The splenium of the corpus callosum, left globus pallidum, thalamus and hippocampus (P<0.01) were significantly smaller; and corticospinal tract (bilaterally; P<0.045, P<0.05) and corpus callosum (P<0.05) fractional anisotropy were significantly lower in the isolated growth hormone deficiency group. Basal ganglia volumes and bilateral corticospinal tract fractional anisotropy correlated significantly with Movement-Assessment Battery for Children scores, and corpus callosum fractional anisotropy with Full-Scale IQ and Processing Speed Index. In patients with isolated growth hormone deficiency, white matter abnormalities in the corpus callosum and corticospinal tract, and reduced thalamic and globus pallidum volumes relate to deficits in cognitive function and motor performance. Follow-up studies that investigate the course of the structural and cognitive deficits on growth hormone treatment are now required to confirm that growth hormone deficiency impacts significantly on brain structure, cognitive function and motor performance. © 2011 The Author. Source

Wong S.C.,Developmental Endocrinology Research Group | Dalzell A.M.,Royal Liverpool Childrens Hospital | Mcgrogan P.,Royal Hospital for Sick Children | Didi M.,Royal Liverpool Childrens Hospital | And 2 more authors.
Journal of biological regulators and homeostatic agents | Year: 2015

It is unclear whether recombinant human growth hormone (rhGH) in inflammatory bowel disease (IBD) alters cytokine profile. The objective of this study is to evaluate changes in cytokines and systemic markers of the insulin growth factor axis following 6 months of rhGH treatment in children with IBD. In a six-month randomised control trial in children with IBD treated with rhGH at 0.067 mg/kg/day and controls (11 in each group), we measured pro-, anti-inflammatory cytokines and systemic markers of the IGF axis (total IGF-1, free IGF-1, total IGFBP-3, ALS, IGFBP-2) at baseline (T+0), and six months (T+6). Results expressed as median (range). In the rhGH group, TNFα was 3.1pg/ml (2.9, 100.6) and 3.6pg/ml (3.1, 5.3) at T+0 and T+6, respectively (p=0.85), whereas in the controls this was 3.3pg/ ml (2.7, 4.0) and 3.1pg/m l (2.7, 4.7), respectively (p=0.79). In the rhGH group, IL1β was 18.0pg/ml (5.0,716.7) and 18.0pg/ml (1.7, 52.2) at T+0 and T+6 respectively(p=0.90), whereas in the controls this was 19.8pg/ml (4.1, 27.1) and 19.1pg/ml (2.4,77.3), respectively (p=0.65). None of the twenty-eight other cytokines analysed was different at T+6 in either group. Despite increase in total IGF1 in the rhGH group (p=0.03), free IGF1, IGFBP3, ALS and IGFBP2 did not change in either group at T+6. Percentage change in IGFBP3, was significantly associated with percentage change in IL2 (r=0.77, p=0.009) and IL4 (r=0.58, p=0.01). Percentage change in ALS was significantly associated with percentage change in IL2 (r=0.90, p less than 0.0001) and IL4 (r=0.63, p=0.04). Although changes in markers of the GH/IGF-1 axis do show an association with cytokines (IL-2, IL-4) in pediatric IBD, six months of rhGH treatment was not associated with any significant changes in levels of a range of pro and anti-inflammatory cytokine. Careful evaluation of disease process is required in future trials of rhGH in paediatric IBD. Source

Ahmed S.F.,Developmental Endocrinology Research Group | Rodie M.,Developmental Endocrinology Research Group | Jiang J.,University of Glasgow | Sinnott R.O.,University of Glasgow
Sexual Development | Year: 2010

Disorders of sex development (DSD) are a rare group of conditions which require further research. Effective research into understanding the aetiology, as well as long-term outcome of these rare conditions, requires multicentre collaboration often across national boundaries. The EU-funded EuroDSD programme (www.eurodsd.eu) is one such collaboration involving clinical centres and clinical and genetic experts across Europe. At the heart of the EuroDSD collaboration is a European DSD registry and a targeted virtual research environment (VRE) that supports the sharing of DSD data. Security, ethics and information governance are cornerstones of this infrastructure. This paper describes the infrastructure that has been developed, the inherent challenges in security, availability and dependability that must be overcome for the enterprise to succeed and provides a sample of the data that are stored in the registry along with a summary analysis of the current data sets. Copyright © 2010 S. Karger AG, Basel. Source

Chen S.C.,Developmental Endocrinology Research Group | Mason A.,Developmental Endocrinology Research Group | Donaldson M.D.C.,Developmental Endocrinology Research Group | Ahmed S.F.,Developmental Endocrinology Research Group | Shaikh M.G.,Developmental Endocrinology Research Group
Hormone Research in Paediatrics | Year: 2015

Background: Congenital nasal pyriform aperture stenosis (CNPAS) is an increasingly recognised cause of upper airway obstruction associated with midline abnormalities. Studies have described pituitary dysfunction in 40% of patients. We aimed to develop guidelines for: (a) the early identification of pituitary insufficiency to minimise surgical risk and (b) to stratify patients for follow-up. Methods: Retrospective case note review of patients with CNPAS between 2000 and 2014 in a tertiary paediatric unit. Results: 20 patients (12 female:8 male) were analysed; 16 were diagnosed during the neonatal period while 4 were diagnosed later. There was no consistent approach in the evaluation of the pituitary axis at diagnosis. Pituitary dysfunction was identified in 3 (15%) patients, 2 of whom were found during evaluation of short stature in mid-late childhood. Hypoglycaemia and conjugated hyperbilirubinaemia, but not the degree of stenosis, were highly predictive of pituitary dysfunction (p < 0.05). Available height standard deviation score (SDS) data at 1 year of 70% of our patients identified both of the late-diagnosed growth hormone-deficient patients, with SDS of-2.6 and-3.6, respectively. Conclusion: All CNPAS patients should have MRI of the brain and baseline endocrine investigations at diagnosis. Growth monitoring for at least 1 year is recommended as low, or falling, height SDS at 1 year is a good predictor of pituitary dysfunction. © 2015 S. Karger AG, Basel. Source

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