Endocrine Abstracts

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...

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...

A 21-year-old man presented with tonic–clonic seizures and two-week history of nocturnal headaches, sweatiness, hot flushes and abdominal pain. Blood pressure was 220/110 mmHg and pulse 120–160 bpm. A GTN infusion was commenced and the blood pressure improved to 150/90 mmHg. Examination revealed a large, hard mass in the left hypochondrium. There was no palpable lymphadenopathy and no papilloedema. A 2 cm hard, irregular mass was present on the left testis. CT showed...

Etomidate, an imidazole derived anaesthetic agent, potently inhibits adrenocortical 11-beta-hydroxylase at non-hypnotic doses in Cushing's syndrome. We report its use in controlling hypercortisolism in a patient with aggressive Cushing's disease requiring pelvic surgery for endometrial carcinoma.IJ, a 42-year old female was diagnosed with Cushing's disease in 1998 in Malaysia. 8am cortisol was 800nmol/l, midnight cortisol 659nmol/l and ACTH 103ng/l. MRI ...

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...

Patients with acromegaly treated with medical therapy intermittently discontinue therapy to allow assessment of underlying disease activity. This is particularly so in patients treated with pituitary irradiation. Typical 'washout' times include 5 weeks for bromocriptine and 2 weeks for short-acting sc octreotide; longer periods are required for cabergoline and slow-release somatostatin analogues. Pegvisomant is a novel medical therapy for acromegaly that functions as a GH rece...

Loss of function of succinate dehydrogenase (SDH), caused by mutations in each of the 4 subunits – SDHA/B/C and D – is associated with development of phaeochromocytomas and paragangliomas (PPGLs). The mutations lead to loss of enzymatic activity and subsequent accumulation of the oncometabolite succinate, a driver of tumourigenesis. It is well established but poorly understood why mutations in SDHB are associated with more aggressi...

Background: Untreated Cushing’s disease has a high mortality rate. Transsphenoidal surgery is usually first line treatment and in the hands of a skilled experienced surgeon can achieve a cure rate of up to 80%. For those with recurrent or un-resectable disease, a combination of external beam radiotherapy, stereotactic radiotherapy, repeat transsphenoidal surgery, bilateral adrenalectomy and chemotherapy may be used. We investigated the safety and efficacy of stereotactic ...

Objective: Succinate dehydrogenase B (SDHB) germline mutations are associated with predominantly extra-adrenal paraganglioma (PGLs) and high rates of metastatic disease. Bladder paragangliomas are a rare form of chromaffin cell tumours arising from the bladder wall. The aim of the study is to highlight the preponderance of bladder paragangliomas associated with SDHB gene mutations.Design: Retrospective case series.Patients: Five of...

Objective: The aim of the study was to describe the surgical management of phaeochromocytomas and paragangliomas which lie in close proximity to or involve the great vessels including the aorta and vena cava.Design: Retrospective case-series. Patients: five subjects undergoing surgical excision of either a phaeochromocytoma or paraganglioma involving the great vessels seen at St Bartholomew’s Hospital, UK (2004–2013).Meas...