Ng S.M.,University of Liverpool |
Wong S.C.,Bone and Endocrine Research Group |
Paize F.,Neonatal Unit |
Chakkarapani E.,Southmead Hospital NHS Trust |
And 3 more authors.
Journal of Pediatric Endocrinology and Metabolism | Year: 2011
Aims: All screening programmes in the UK use a primary thyroid stimulating hormone (TSH) screen for congenital hypothyroidism. Recent attention has been paid to aspects of screening, such as the relation between blood spot TSH levels and birth weight or gestational age. The aim of our study was to determine the factors affecting screening neonatal TSH levels. Methods: We conducted a retrospective analysis of blood spot screening TSH levels of all infants screened at a single regional screening laboratory. Results: There were 6498 infants screened during a 12-week period. Screening TSH level showed negative correlation with gestational age and birth weight. Multiple linear regression analysis revealed low birth weight as the only independent factor affecting screening TSH level. Conclusions: Low birth weight infants appear to be at risk of thyroidal dysfunction. Our study showed that there were clinically significant but weak correlation between higher screening TSH levels and low birth weight. The clinical importance of these findings requires larger prospective studies to further elucidate the relevance of these factors affecting TSH screening levels. © 2011 by Walter de Gruyter •Berlin •Boston.
Farquharson C.,University of Edinburgh |
Ahmed S.F.,Bone and Endocrine Research Group
Pediatric Nephrology | Year: 2013
Linear bone growth is widely recognized to be adversely affected in children with chronic kidney disease (CKD) and other chronic inflammatory disorders. The growth hormone (GH)/insulin-like growth factor-1 (IGF-1) pathway is anabolic to the skeleton and inflammatory cytokines compromise bone growth through a number of different mechanisms, which include interference with the systemic as well as the tissue-level GH/IGF-1 axis. Despite attempts to promote growth and control disease, there are an increasing number of reports of the persistence of poor growth in a substantial proportion of patients receiving rhGH and/or drugs that block cytokine action. Thus, there is an urgent need to consider better and alternative forms of therapy that are directed specifically at the mechanism of the insult which leads to abnormal bone health. Suppressor of cytokine signaling 2 (SOCS2) expression is increased in inflammatory conditions including CKD, and is a recognized inhibitor of GH signaling. Therefore, in this review, we will focus on the premise that SOCS2 signaling represents a critical pathway in growth plate chondrocytes through which pro-inflammatory cytokines alter both GH/IGF-1 signaling and cellular function. © 2012 IPNA.
Pass C.,Roslin Institute |
Pass C.,Bone and Endocrine Research Group |
MacRae V.E.,Roslin Institute |
Huesa C.,Roslin Institute |
And 2 more authors.
Journal of Bone and Mineral Research | Year: 2012
Suppressor of Cytokine Signaling-2 (SOCS2) is a negative regulator of growth hormone (GH) signaling and bone growth via inhibition of the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway. This has been classically demonstrated by the overgrowth phenotype of SOCS2 -/- mice, which has normal systemic insulin-like growth factor 1 (IGF-1) levels. The local effects of GH on bone growth are equivocal, and therefore this study aimed to understand better the SOCS2 signaling mechanisms mediating the local actions of GH on epiphyseal chondrocytes and bone growth. SOCS2, in contrast to SOCS1 and SOCS3 expression, was increased in cultured chondrocytes after GH challenge. Gain- and loss-of-function studies indicated that GH-stimulated chondrocyte STATs-1, -3, and -5 phosphorylation was increased in SOCS2 -/- chondrocytes but not in cells overexpressing SOCS2. This increased chondrocyte STAT signaling in the absence of SOCS2 is likely to explain the observed GH stimulation of longitudinal growth of cultured SOCS2 -/- embryonic metatarsals and the proliferation of chondrocytes within. Consistent with this metatarsal data, bone growth rates, growth plate widths, and chondrocyte proliferation were all increased in SOCS2 -/- 6-week-old mice as was the number of phosphorylated STAT-5-positive hypertrophic chondrocytes. The SOCS2 -/- mouse represents a valid model for studying the local effects of GH on bone growth. © 2012 American Society for Bone and Mineral Research.
Aldhafiri F.,University of Glasgow |
Al-Nasser A.,King Faisal Specialist Hospital And Research Center |
Al-Sugair A.,King Faisal Specialist Hospital And Research Center |
Khanna S.,Bone and Endocrine Research Group |
And 4 more authors.
Journal of Pediatric Hematology/Oncology | Year: 2013
We compared DXA whole body and lumbar spine bone mineral density (BMD) using manufacturers software with a body size correction which derived bone mineral content (BMC) for bone area in survivors of acute lymphoblastic leukemia in Saudi Arabia (n=51, mean age 13.5 y). With no corrections, 29 patients (57%) had lumbar spine BMD Z score <-1.0 and 21 (41%) had whole body BMD Z score <-2. After correction, only 6 (12%) had lumbar spine BMC Z score <-1.0 and 4 (8%) had whole body BMC Z score <-2. Agreement between the methods was "poor" by weighted κ analysis. Copyright © 2012 by Lippincott Williams & Wilkins.
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.