Endocrine Abstracts

ApoB isoforms are components of the chylomicron, and of the atherogenic LDL and Lp(a) particles. Ex26 is exceptionally long at 7.57kb as most exons are <500bp. Ex26 is also the site of RNA editing, which generates the ApoB48 isoform instead of ApoB100. The first 3kb of ex26 contains 15 sequences matching the splice site consensus, which could be used in splicing, but are not. Splice sites matching the consensus but which are not used are called pseudosites. How the spliceos...

Pseudoexons resemble true exons by current bioinformatic criteria and may outnumber true exons by 10:1. They are, however, never spliced into mature mRNA. A point mutation in the GHR gene results in abnormal splicing of a pseudoexon, leading to Laron syndrome. The GHR pseudoexon lies between exons six and seven and the point mutation is adjacent to the pseudoexon 5' splice site.Our studies aimed to define the elements that normally prevent splicing of this pseudoexon.A...

Growth hormone insensitivity, also known as Laron Syndrome (LS), is caused by mutations within the GH receptor (GHR). A 1.5 year-old boy with consanguineous parents was referred with postnatal linear growth failure (length 64 cms, minus 6 SDS). Facial features were typical of LS. Investigation revealed elevated serum GH (1145 mIU per litre) and low IGF-I (4 nmol per litre). Genomic DNA was isolated from peripheral blood leucocytes and all GHR exons, including intron-exon bound...

Introduction: Growth hormone (GH) replacement is widely used in the management of patients with adult-onset (AO) GH deficiency (GHD). In most cases, AO-GHD arises as a result of pituitary/peri-pituitary tumours and/or their treatment. The aim of this study was to examine the effect of GH replacement on growth/recurrence of non-anterior pituitary parasellar tumours.Methods: Fifty consecutive patients (21 males; mean age 45.9) with severe AO-GHD (peak seru...

Selective Parathyroid Venous Sampling in Patients with Complicated Primary HyperparathyroidismCM Ogilvie, PL Brown, M Matson, R Carpenter, WM Drake, PJ Jenkins, SL Chew, JP MonsonCentre for Endocrinology and Departments of Surgery and Radiology, St Bartholomew's Hospital, QMUL, London EC1A 7BEThe role of pre-operative localisation of abnormal parathyroid glands remains controversial but is particularly releva...

Obstructive sleep apnoea (OSA)is associated with increased cardiovascular morbidity and mortality and is an independent risk factor for the development of hypertension. A recent study demonstrated elevated urinary catecholamine excretion in hypertensive males with OSA. However, we have recently observed the phenomenum whereby OSA can rarely induce catecholamine production of sufficient severity to mimic the clinical and biochemical presentation of phaeochromocytoma.<p clas...

Obstructive sleep apnoea (OSA)is associated with increased cardiovascular morbidity and mortality and is an independent risk factor for the development of hypertension. A recent study demonstrated elevated urinary catecholamine excretion in hypertensive males with OSA. However, we have recently observed the phenomenum whereby OSA can rarely induce catecholamine production of sufficient severity to mimic the clinical and biochemical presentation of phaeochromocytoma.<p clas...

Background: Patients with acromegaly have an increased risk of colorectal neoplasia. In non-acromegalic subjects, carcinomas develop from dysplastic tubular adenomas and colonoscopic removal of these reduces the subsequent incidence of carcinoma. The frequency of such screening in acromegaly is controversial and it is uncertain which patients should be considered to be at particular increased risk. Methods: We reviewed the incidence of new colonic lesions amongst our large coh...

THE SENSITIVITY OF 123I-MIBG IN THE DETECTION OF HISTOLOGICALLY CONFIRMED CATECHOLAMINE-PRODUCING TUMOURS.M Ismail, R Foley, WM Drake, AB Grossman, PJ Jenkins, SL Chew, GMBesser, R Reznek, K Britton, JP MonsonDepartments of Endocrinology, Nuclear Medicine and Radiology, StBartholomew's Hospital (QMUL), London EC1A 7BERadionuclide imaging is widely used for the loc...

Background: Mutations in the GHR result in extreme short stature (Laron's syndrome). We have studied mutations from two patients with Laron's syndrome. Patient 1 (GHRextra) has a mutation in the GHR extracellullar domain due to a 108bp inframe pseudoexon between exons 6 and 7. Patient 2 (GHRintra) has a 22bp deletion in exon 10 of the GHR leading to premature termination of the GHR upstream of the intracellular STAT5 binding site.Aim: To compare GHR str...