Endocrine Abstracts

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Childhood hypothyroidism results in severely delayed skeletal development whereas adult thyrotoxicosis is associated with a 3–4 fold increase in osteoporotic fracture. To investigate molecular mechanisms underlying these abnormalities we characterized the skeletal phenotypes of mice harboring dominant negative mutations (TRα1PV/+, TRα1R384C/+, TRβPV/PV) or deletions (TRα0/0, TRβ−/−) of the genes encoding TRα and TRβ. Endochon...

T3 is essential for normal skeletal development. Childhood hypothyroidism causes delayed bone formation, whereas T3-excess accelerates growth and epiphyseal closure. Fibroblast growth factors (FGFs) act via receptor tyrosine kinases (FGFRs) to inhibit chondrocyte proliferation, matrix production and skeletal maturation. Dimerisation of FGFRs and their functional interaction with FGFs requires heparan sulphate proteoglycans (HSPGs). We recently showed that T3 induces FGFR-1 exp...

The cortisol day curve has been advocated in the assessment of glucocorticoid replacement therapy in adrenal failure but remains controversial.Objective: To determine the validity of this test within our practice.Method: A retrospective analysis using endocrine laboratory dataset.Results: 102 inpatient cortisol day curves from 76 patients were analysed. The serum cortisol was checked at 5 time points (pre and 1 hour post morning dose, before midday dose, pre and po...

Background: GH replacement during the childhood-adult transition period is important for somatic maturation. The aim of the study was to explore the factors influencing IGF1 response to GH during transition.Methods: KIMS (Pfizer International Metabolic Study) database in UK was interrogated, and 98 patients (55 male, median age 20.7 years (15.7–25.8)) with childhood-onset GH deficiency (Co-GHD), who were started on adult dose of GH during transition...

(This poster is based on OC33)...

Background and Aims: Type 1 diabetes mellitus (T1DM) is characterised by autoimmune destruction of pancreatic beta-cells resulting in insulin deficiency. Evaluation of novel therapies for T1DM requires reliable methods to measure beta-cell function, which is unattainable using traditional non-invasive imaging techniques. A new approach is manganese-enhanced magnetic resonance imaging (MEMRI). As a calcium analogue, manganese is taken up into pancreatic beta-cells during insuli...

Mice with dominant-negative mutations of thyroid hormone receptor α1 (TRα1) are euthyroid but display growth retardation and delayed bone age as juveniles and increased bone mass during adulthood, indicating impaired skeletal thyroid hormone responsiveness. The first autosomal dominant mutations affecting TRα1 in humans were recently described in two unrelated children and one parent who were euthyroid apart from a low T4:T3 ratio. Consiste...