Endocrine Abstracts

A 71-year-old man with carcinoma of prostate and bony metastasis, presented with acute bradyarrhythmia, severe hypocalcaemia and acute renal failure 72 h after intravenous infusion of zoledronate. Before therapy, serum calcium was 2.14 mmol/l (normal, 2.10–2.55 mmol/l), serum phosphate 1.4 mmol/l (normal, 0.8–1.5 mmol/l), serum creatinine 95 umol/l and eGFR 74 ml/min. 25OH vitamin D was not measured. Three days later he presented with a syncopal episode. Initial bloo...

We describe two cases of sarcoidosis associated hypercalcaemia, renal failure and anaemia mimicking lymphoma. The diagnosis was made by lymph node biopsy. Within weeks of starting oral steroids, symptoms resolved and biochemical abnormalities almost normalized.Case 1: A 66-year-old lady, presented with generalized weakness, lymphadenopathy and splenomegaly. Hb 96 g/l, MCV 91, urea 16.6 mmol/l, creatinine 227 umol/l, eGFR 15 ml/min, serum calcium 3.4 mmol...

Adrenal lymphangiomatous cysts are rare, often found incidentally, but can also present in association with abdominal/loin pain or hypertension.1 They have occasionally been reported in association with hormone over secretion of either aldosterone, cortisol or catecholamines. We present a case of a 40-year-old serving soldier who was suddenly awoken with severe left sided abdominal and flank pain. Over the course of several months, he was forced to take time off wor...

Background: Multiple sclerosis (MS) is associated with low ambient ultraviolet B (UVB) light in childhood and in utero (relative risk of developing MS is 1.2 for those born in spring). Besides, the MS-linked HLA-DRB1 allele interacts strongly with vitamin D in vitro, and vitamin D levels are lower in MS patients. Fatigue and musculoskeletal aches/pains are prominent symptoms in both MS and vitamin D deficiency. Moreover, having any chronic disease may predispose to stay...

Dysregulation of sodium-iodide symporter (NIS) function is common in differentiated thyroid cancer, resulting in sub-optimal radioiodide therapy and poorer clinical outcome. Recent developments in identifying proteins that regulate the function of the sodium iodide symporter have highlighted two proteins involved in internalisation of NIS from the plasma membrane: AP-2 and moesin. Clathrin-mediated endocytosis (CME) of NIS is facilitated through the adaptor protein 2 (AP2) com...

Whilst the majority of familial medullary thyroid cancer (MTC) is caused by germline mutations of the RET proto-oncogene, there are families and individuals with predisposition to MTC in whom no RET mutation has been identified (non-RET MTC). Recently, we identified novel mutations in a single gene termed MTC2 in non-RET MTC individuals by whole exome sequencing. The precise role of these MTC2 germline mutations in MTC tumorigenesis is however unclear. Here, we examined the fu...

PBF is a ubiquitous glycoprotein which is over-expressed particularly in endocrine and endocrine-related cancers. Previously classified as a proto-oncogene, 11 substitution-missense mutations of PBF have now been reported in tumours from patients with ovarian, prostate and colorectal cancers via the COSMIC database, suggesting PBF may in fact be an oncogene. We have therefore examined the biological implications of all 11 mutations. Substitution mutations, which occurred acros...

Aims: Low circulating testosterone levels are associated with increased cardiovascular risk and there is evidence that androgens inhibit arterial lesion formation. This investigation addressed the hypothesis that androgens directly inhibit neointimal lesion formation by stimulation of vascular androgen receptor.Methods and results: Mice were generated with selective deletion of androgen receptor from vascular (endothelial or smooth muscle) cells. Castrat...

p53 is rarely mutated in thyroid papillary carcinomas, despite the thyroid being highly sensitive to ionising radiation. The pituitary tumor transforming gene binding factor (PBF) is a proto-oncogene overexpressed in thyroid cancer. Oncogenic levels of PBF result in cell transformation in vitro and tumourigenesis in vivo. By serendipity we have found that PBF interacts directly with the tumour suppressor protein p53. In light of these data we have investigated th...

Metastasis is a multistep process responsible for the majority of endocrine cancer deaths. Central to the ability of cells to move is the recruitment of actin fibres at the periphery of the cell by key proteins, especially the cortical actin binding protein cortactin. A full understanding of cortactin function is required in order to address metastatic cell activity within endocrine cancer. We used IP-MS to discover protein binding partners, and now identify the proto-oncogene...