Endocrine Abstracts

FGFs and T3 are required for skeletal development. Activating mutations of FGF receptor-1 (FGFR-1) and FGFR-2 cause craniosynostosis, whilst FGFR-3 is a negative regulator of chondrocyte proliferation and activating mutations cause achondroplasia. Childhood hypothyroidism causes delayed ossification and growth retardation, whereas thyrotoxicosis accelerates bone development, induces premature growth plate and skull suture closure and causes short stature and craniosynostosis. ...

T3 and fibroblast growth factors (FGFs) are critical regulators of chondrocyte proliferation during bone formation and we identified recently that T3 modulates skeletal FGF receptor-1 (FGFR1) activity. FGFRs signal via several routes including mitogen-activated protein kinase (MAPK), STAT and phospholipase C gamma pathways. Mechanisms determining which pathways are activated by FGFRs are poorly understood but include alternative splicing of exons encoding variable domains with...

Background: Anaplastic thyroid-carcinomas (ATC) and a subset of papillary (PTC) and follicular (FTC) thyroid carcinomas behave aggressively showing metastatic spread and radio-resistance. Both the PI3K and HIF pathways are associated with aggressiveness and metastasis in thyroid carcinoma.Aims: To assess if the PI3K/HIF pathways contribute to radio-resistance and assess the effect of PI3K/HIF inhibition on radio-sensitivity of thyroid-carcinoma cells (85...

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...

Acromegaly causes impaired insulin sensitivity and reduced fat mass. Using acipimox to block lipolysis, the impact of free fatty acids (FFA) on insulin sensitivity in active acromegaly was investigated. 1H MRS was used to quantify triglyceride (TG) content of liver and muscle.Methods: 6 patients with active acromegaly (AA) (5M, age 59 (34–70), IGF-I (ng/ml) (median (range)) (452 (342–1002)) were studied on 2 visits; (i) baseline (BL)...

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...

The insulin tolerance test (ITT) is used to determine the integrity of the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-somatotroph (GH) axes in patients suspected of ACTH and GH deficiency. In adults a cortisol response <500nmol/L is considered pathological and a GH peak <9mU/L is consistent with severe GH deficiency. Exercise is an alternative stimulus to GH release which may be used to diagnose GH deficiency during childhood but is rarely used during adult li...

T3, GH and IGF-1 are essential for skeletal development. GH acts directly on growth plate chondrocytes and also via a local paracrine pathway involving IGF-1, but it is unclear whether T3 stimulates bone formation directly or indirectly. To address this, we determined expression of GH-receptor, IGF-1 and IGF-1 receptor (IGF-1R) by in situ hybridisation and activation of downstream STAT5 and AKT signalling by immunohistochemistry in growth plates from four T3-receptor (TR) muta...

Plasma homocysteine is now regarded as a graded risk factor for vascular disease comparable to smoking, high cholesterol and raised blood pressure. In diabetes homocysteine values have correlated with microalbuminuria and are thought to contribute to vascular damage. Folic acid is an essential co-factor for homocysteine metabolism and folic acid supplementation has been shown to reduce plasma homocysteine by about 30%.In this study patients with Type II ...

A 47 year-old woman was referred with hypercalcaemia. She was receiving lithium, haloperidol and olanzapine for a schizo-affective disorder. Five years previously she had been diagnosed with liver metastases and a biopsy confirmed a neuroendocrine tumour. She had been told that her life-expectancy was limited, and she was discharged. Her calcium was 2.7mmol/l three years ago. At presentation to her local hospital, her calcium was >6.0mmol/l. She was treated aggressively wi...