Endocrine Abstracts

Background: Primary hyperparathyroidism (PHPT) is commonly diagnosed after the fifth decade of life. Current guidelines suggest that young patients with apparently sporadic PHPT should be screened as potential index cases for the multiple endocrine neoplasia type 1 (MEN-1) syndrome.Aim: To determine the prevalence of mutations in the MEN1 gene in young patients presenting with apparently sporadic PHPT before the age of 40 years.Met...

The type 3 deiodinase enzyme (D3) inactivates T3 and prevents activation of T4 to protect the fetus from premature exposure to thyroid hormones. Rapidly falling levels of D3 activity and rising levels of T3 at birth initiate the onset of cell differentiation and organ maturation during the post-natal period. Congenital hypothyroidism causes delayed ossification with reduced bone mineral deposition and short stature. We hypothesize that increase...

Heterozygous mutations of GATA3, a dual zinc-finger transcription factor, cause the hypoparathyroidism, deafness and renal dysplasia (HDR) syndrome. To study the role of GATA3 in parathyroid function we have investigated Gata3+/− mice for hypoparathyroidism. Gata3+/− and Gata3+/+ mice were challenged at weaning with a diet low in calcium (0.001%) and vitamin D (0.0 IU/g). The low calcium-vitamin D diet led to a ...

The Wellcome Trust Sanger Institute Gene Targeting Programme is deleting all mouse genes and has already generated 400 knockout mice in a C57/BL6N background with a further 4000 genes targeted in ES cells. Two hundred and fifty new knockouts will undergo limited phenotyping each year. However, the programme lacks a sensitive and sufficiently detailed screen for individual physiological systems, each of which requires high throughput methodology and unique expertise. Thus, we p...

Fetal growth restriction is associated with abnormal placental cell (cytotrophoblast) proliferation. Using an explant model of human first trimester placenta, we have demonstrated that the IGFI and -II stimulate proliferation in cytotrophoblast and are probably essential for normal placental growth. IGF activates signalling through both Akt and ERK, so the regulation of these pathways in placenta is important for normal pregnancy outcome. The tissue contains high levels of mic...

Similar to thyroid hormones, the calcineurin/NFAT pathway regulates bone mass via its actions in osteoblasts and by indirect effects on osteoclast function. Calcineurin is a calcium- and calmodulin-activated phosphatase that dephosphorylates the transcription factor NFAT enabling its translocation to the nucleus. RCAN2 is an inhibitor of calcineurin that is stimulated by T3 in brain, heart and skeletal muscle although its expression in bone has not been studied. Thu...

Background: Parathyroidectomy for primary hyperparathyroidism (PHPT) is followed by a decrease in the severity of symptoms reported on the Pasieka’s parathyroid symptoms score (PPSS) questionnaires and such changes correlate with improved quality of life assessed by the SF36 questionnaire (World J Surg 2008 32 807). Some argue that these benefits are short-lived and only apparent in the first months postoperatively.Aim: To determine wh...

Previous studies have reported increased cardiovascular disease, fractures and renal stones for patients with primary hyperparathyroidism (PHPT). These studies are mainly based on patients referred to specialist centres or unselected PHPT patients. We specifically aimed to assess the risk for patients ‘mild’ PHPT, in whom treatment is usually not recommended. Using the unique patient identifier, which is used for all medical contacts in Tayside, data linkage of recor...