Endocrine Abstracts

3-M syndrome is characterised by post-natal growth restriction. We have identified causative mutations in three genes CUL7, OBSL1 and CCDC8. CUL7, a component of an E3 ubiquitin ligase, has a binding domain for p53 and its reduction or absence has a major impact on growth and cell division. OBSL1 is postulated to have a role as a cytoskeletal adaptor, and was not recognised previously to be a growth regulator. The domain structure of CCDC8 predicts a possi...

Objective: To assess age- and growth-dependent gene expression in children and correlate this with biological pathways.Methods: We conducted a gene expression meta-analysis on datasets from normal children curated from the NCBI Gene Expression Omnibus (GEO). Four datasets were combined to form a group of 87 individuals ranging from 0.2 to 29.3 years of age (average 7.7±6.9yr). Analysis of gene expression data was performed using hierarchical cluster...

Introduction: 131I-MIBG is a well-established treatment modality for patients with neuroendocrine tumours (NETs). Our centre has now accumulated over 10 years of experience with 131I-MIBG therapy, with long term data to evaluate effects on disease progress and other long term outcomes following therapy. Bone marrow effects of radionuclide therapy may include prolonged suppression, myelodysplasia or even frank leukaemia. Incidence is thought to be low, but...

Mitotane (o,p’DDD) is the first-line treatment for metastatic adrenocortical carcinoma (ACC) and is also regularly used in the adjuvant setting after presumed complete removal of the primary tumour. Mitotane is considered an adrenolytic substance, but no information is available regarding distinct steroidogenic effects. Here we carried out steroid metabolomics by gas chromatography/mass spectrometry in 24-hour urine samples from 106 patients with ACC and with samples coll...

Backgeound and Aims: Phaeochromocytomas (PCC) and paragangliomas (PGL) are mostly benign sympathoadrenal tumours. However, there are no available markers to predict a malignant course. Since hypoxia is involved in the pathogenesis of these tumours, we aimed to qualify the relevance of the mammalian Target of Rapamycin (m-TOR) and hypoxic pathways in benign and malignant PCC/PGL.Methods: Tissue microarray (TMA) blocks were constructed with 80 PCC/PGL, inc...

The orphan nuclear receptor, SF-1, is sumoylated in adrenal and gonadal tissues, but the role of sumoylation in pituitary gonadotrophs is currently unknown. We performed expression studies for key components of sumoylation machinery in αT3-1 and LβT2 gonadotroph cell lines, using RT-PCR. Expression of the genes encoding the SUMO proteins (Sumo1, Sumo2, Sumo3) as well as the E3 ligase enzymes responsible for their covalent linkage (Pias1, Pias2/xα, Pias...

Background: Heterozygote mutations in the aryl hydrocarbon receptor-interacting protein (AIP) predispose carriers to young-onset pituitary adenomas, most often somatotroph or lactotroph adenomas. No other tumour type has been consistently detected in AIP mutation positive families, despite the fact that AIP is ubiquitously expressed. Current clinical and experimental data suggest that AIP is a tumour suppressor gene.Aims: To investigate the tumour suppre...

UK National Acromegaly Register collects data on routine clinical practice in 34 centres. We analysed all GH and IGF1 data to assess adequacy of control & responses to medical treatment (Rx) with somatostatin analogs (SMS) & dopamine agonists (DA). Methods: Under program control, GH records (basal, profile or GTT) were correlated with IGF1, tumour size, Rx, surgery (TSS) & radiotherapy (RT) in the database, then processed in Excel to derive summary data for each pa...