Endocrine Abstracts

Introduction: The adenoma- carcinoma sequence in thyroid nodules is an enigmatic phenomenon. Genomics is the only definitive modality to resolve this hypothesis. Adenomas and papillary carcinomas tend to have mutations in RAS and highly specific BRAF gene respectively. In this context, we set out study the prevalence of these somatic mutations in surgical tissue samples.Material and Methods: This prospective study was conducted on surgically managed thyr...

We have studied clinical and pre-clinical models to investigate neuroendocrine tumour (NET) development and efficacy of novel therapy for NETs. We focused on multiple endocrine neoplasia type 1 (MEN1), an autosomal dominantly inherited condition characterised by the combined occurrence of pancreatic islet and anterior pituitary NETs with parathyroid and adrenocortical tumours. MEN1 is due to MEN1 gene mutations that inactivate Menin, a tumour suppressor. Our clinical studies r...

The calcium-sensing receptor (CaSR) is a guanine-nucleotide-binding protein (G-protein)-coupled receptor that has a central role in calcium homeostasis. Loss-of-function mutations of the CaSR result in familial hypocalciuric hypercalcemia type 1 (FHH1) and gain-of-function mutations in autosomal dominant hypocalcemia (ADH). Recently, loss-of-function Gα11 mutations have been identified to cause FHH2 and we hypothesised that gain-of-function Gα11...

Dent’s disease is a renal proximal tubular Fanconi disorder characterised by generalised loss of solutes incuding insulin, glucose, PTH, amino acids and vitamin-D binding protein and is associated with rickets in 25% and phosphaturia in ~40% of patients. Dent’s disease is caused by mutations in the chloride/proton antiporter CLC-5, which, with megalin and cubilin has a role in receptor-mediated endocytosis and vesicle trafficking. To further elucidate the role of CLC...

Vitamin D deficiency with secondary hyperparathyroidism is common in South-east Asia. In contrast, primary hyperparathyroidism is relatively rare. We present a case of severe proximal myopathy with significant diagnostic delay.A 23-year-old lady presented with a 2 years history of lower back pain, radiating to both groins and upper thighs associated with recurrent falls. Her pain and weakness progressed insidiously leading to difficulty standing or walki...

The hypoparathyroidism-deafness-renal dysplasia (HDR) syndrome is an autosomal dominant disorder caused by germline mutations of the dual zinc-finger (ZnF) transcription factor, GATA3. To date, 51 GATA3 mutations have been reported, which can be divided broadly into three structural-functional classes: i) mutations that lead to a loss of DNA binding and involve ZnF2; ii) mutations, usually of ZnF1, that bind DNA but result in reduced DNA binding affinity; and iii) mut...

The calcium-sensing receptor (CaSR) is a G-protein coupled receptor that regulates extracellular calcium concentration. The CaSR is also implicated in the pathogenesis of non-calcium disorders such as vascular calcification and diabetes, which are leading causes of cardiovascular disease. Common CaSR single nucleotide polymorphisms (SNPs) have been demonstrated to be determinants of calcium metabolism. The aim of this study was to investigate whether CaSR SNPs may influence va...

Kyphosis is a common spinal disorder affecting up to 8.3% of the population, and associated with significant morbidity. Familial and twin studies have implicated a genetic involvement. However, the causative genes have not been identified. Studies investigating the underlying molecular mechanisms are hampered by genetic heterogeneity, small families and variable modes of inheritance displayed by different kindreds. To overcome these limitations, we investigated 12 week old pro...

Osteoarthritis (OA) may be associated with endocrine disorders such as hypothyroidism, obesity, primary hyperparathyroidism or acromegaly, although often its cause remains undefined. To facilitate investigations of the underlying molecular mechanisms of OA we have investigated N-ethyl-N-nitrosourea (ENU) mutant mice using a genotype-driven approach in which candidate genes are examined for mutations. One such investigated gene is growth and differentiation factor...

The tumour suppressor menin, encoded by the multiple endocrine neoplasia type 1 (MEN1) gene, has been reported to be a component of the Wnt/β-catenin signalling pathway. To investigate the effects of menin loss on this pathway, we have determined the cDNA expression profiles of pituitary tumours from 5 Men1+/− mice and in normal pituitaries from 5 Men1+/+ littermates by extracting total RNA and by hybridizing it to Affymetrix Mous...