Endocrine Abstracts

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...

T3, GH and IGF-1 are essential for skeletal development, growth and bone mineralisation. The major growth-promoting actions of GH occur in epiphyseal chondrocytes via direct effects on GH-receptor expressing cells and via a local paracrine pathway involving IGF-1. There is controversy regarding whether T3-actions in bone are direct or occur via regulation of GH secretion and action. We examined this in mice with a mutation (PV) targeted to either T3-receptor (TR) beta or alpha...

Thyroid hormone (T3) is essential for skeletal development and maintenance of bone mineralisation. T3 actions are mediated by two receptors, TRalpha and TRbeta. Mutations in TRbeta cause autosomal dominant resistance to thyroid hormone (RTH) due to dominant negative activity of the mutant receptor. Short stature and abnormal skeletal development are prominent features of RTH, whereas TRalpha mutations have not been described and are postulated to result in no phenotype or to b...

Although thyroid hormone (T3) and the T3-receptor (TR) alpha gene are essential for skeletal development, T3-signalling pathways in bone have not been characterised. We identified fibroblast growth factor receptor-1 (FGFR1) as a novel T3-inducible gene in osteoblasts by subtraction hybridisation. FGFR1 mRNA was induced 2-3 fold in osteosarcoma cells and primary cultured osteoblasts treated with T3 (0.1-1000nM, 0-48h) and FGFR1 protein was stimulated 2-4 fold over the same peri...

Thyroid hormone (T3) receptor beta (TRbeta) mutations cause resistance to thyroid hormones (RTH), characterised by decreased tissue sensitivity to T3. The TRbetaPV mutation (C-insertion at codon 448 leads to a frameshift of the carboxy-terminal 14 amino acids) was derived from a patient with severe RTH and generates a receptor lacking T3-binding and transactivation activities. Heterozygous mutant mice have a mildly impaired pituitary-thyroid axis; severe RTH and limb shortenin...

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...

A 29 year old woman was admitted to her local hospital with haematemesis, and found to be hypercalcaemic. A peptic ulcer was confirmed and she was commenced on omeprazole. There was biochemical evidence of primary hyperparathyroidism and a single-gland parathyroidectomy was performed. During her admission, a diagnosis of gastrinoma was suspected, but an attempt at measuring fasting gut hormone concentrations off omeprazole therapy resulted in gastro-intestinal perforation. She...

Towards the end of pregnancy, when maternal steroidogenesis is stimulated, the fetal adrenal gland undergoes significant developmental changes. To test responsiveness to external stimuli at this stage, we fed pregnant rats with diets containing 0.03% (low), 0.3% (normal) or 3% (high) sodium to manipulate aldosterone synthesis. Dietary sodium variations had no deleterious effects on numbers or weights of foetuses at embryo day 20. Maternal adrenal weights were unaffected by die...