Endocrine Abstracts

Objective: Surgical outcome in acute acromegaly has been studied nationally and internationally with conflicting and variable results. Definition of cure varies from centre to centre.Rrecent studies have shown increased mortality in acromegalic patients with GH level >5mu/l. We studied the out come of transphenoidal surgery by a single surgeon at 6 and 12 moths after surgery to compare the results with other national and international published studies.Patients and methods...

In numerous tumour types, including those of pituitary origin, gene silencing is frequently mediated through inappropriate methylation of CpG islands. In studies designed to identify novel methylated sequences we used a technique termed arbitrarily primed methylation sensitive PCR (MsAP-PCR) to identify DNA in its hypermethylated forms. The technique relies on cutting the DNA, with methylation sensitive restriction enzymes, prior to PCR amplification. In a similar way in which...

Disruption of the normal cell cycle is one of the most frequent alterations in tumour cells, contributing to uncontrolled cell proliferation during tumour development. The CDK inhibitor p27 plays a pivotal role in controlling cell proliferation during development and tumourigenesis, and has been implicated in tumorigenesis in rats. Previous studies have demonstrated changes in p27 protein expression, in human pituitary tumours,especially in corticotroph tumours, where p27 prot...

Candidate gene approaches have identified loss of heterozygosity (LOH) at putative tumour suppressor gene (TSG) loci in sporadic pituitary tumours. This study reports a high-resolution genome wide allelotyping in a large cohort of somatotrophinomas and non-functioning pituitary adenomas (NFA). Samples were first subjected to whole genome amplification by primer extension amplification (PEP) to circumvent limitation imposed by insufficient DNA for the whole genome analysis with...

We describe the case of a 48-year-old woman, who presented with a history of six months' weight gain, easy bruising and difficulty in rising from a seated position. Examination revealed typical clinical features of Cushing's syndrome. She was hypertensive at 150/100 mmHg and diabetic. She was also agitated, emotionally labile, and disinhibited, requiring sedation. Her sister has MEN-1 (hyperparathyroidism and lung carcinoid tumour).Low-dose and high-dose...

The 1997 working party recommendations for the management of patients with pituitary tumours suggest formal assessment by an endocrinologist prior to tertiary referral. We have examined the extent of endocrine assessment in such patients performed both by endocrine and non-endocrine specialists in a large district general hospital. Using ICD 9 & 10 coding records on patients discharged between 1993 and 2000, we identified 60 patients with pituitary pathology. Of these, 1...

Hereditary multiple exostosis (HME) is an autosomal dominant disorder characterised by the development of benign cartilage-capped tumours, located at the juxtaepiphyseal regions of long bones. Patients suffer from short stature and skeletal deformities and may occasionally develop chondrosarcomas or osteosarcomas.HME is a genetically heterogeneous disorder and three loci referred to as EXT1, EXT2 and EXT3 have been mapped to chromosomes 8q24.1, 11p11-12...

Prostate and breast cancers remain common causes of cancer related deaths in the UK. The majority of cases appear to be of a multifactorial aetiology that includes a genetic component. It has been suggested that low levels of circulating 1,25 dihydroxyvitamin D3 are associated with an increased risk of both breast and prostate cancer. A number of polymorphisms in the vitamin D receptor (VDR) gene have been identified resulting in differing genotypes that may alter s...

A 47 year-old woman was referred with hypercalcaemia. She was receiving lithium, haloperidol and olanzapine for a schizo-affective disorder. Five years previously she had been diagnosed with liver metastases and a biopsy confirmed a neuroendocrine tumour. She had been told that her life-expectancy was limited, and she was discharged. Her calcium was 2.7mmol/l three years ago. At presentation to her local hospital, her calcium was >6.0mmol/l. She was treated aggressively wi...

A 29 year old woman was admitted to her local hospital with haematemesis, and found to be hypercalcaemic. A peptic ulcer was confirmed and she was commenced on omeprazole. There was biochemical evidence of primary hyperparathyroidism and a single-gland parathyroidectomy was performed. During her admission, a diagnosis of gastrinoma was suspected, but an attempt at measuring fasting gut hormone concentrations off omeprazole therapy resulted in gastro-intestinal perforation. She...

BACKGROUND We examined the relationship between cigarette smoking exposure and serum IGF-I, IGF-II, IGFBP-2, and IGFBP-3 levels in a broad-based population, as both smoking and changes in the IGF/IGFBP system have been implicated as risk factors for common epithelial cancers.METHODS Blood was collected from 442 unselected individuals (M, 232: F, 210) attending the Flexi-Scope colorectal cancer screening trial. All individuals were healthy and aged 55-64...

A 74 year old female presented with symptoms of recent fatigue, nausea and weight loss. No other symptoms were present. She had previously had a hysterectomy with conservation of both ovaries 30 years previously for fibroids. The rest of her history was unremarkable. No undue clinical findings were apparent on examination. Initial bloods revealed normal haematology, biochemistry and liver profiles. Corrected calcium was elevated at 3.07 millimoles per litre(2.1-2.6). Subsequen...

Background: Acromegaly has until now been managed almost entirely in tertiary care. Introduction of nurses specialising in endocrinology has enabled us to take their care into the community.Method: 39 patients (P) mean age 57y(29-82) with active acromegaly, required Octreotide LAR treatment, and lived 5-173(median 38) miles from the endocrine unit. A shared care (SC) protocol was approved whereby the patient's first injection was given at the hospital, ...

Hyperinsulinism in Infancy (HI) is the most common cause of recurrent or persistent hypoglycaemia in early childhood, and manifests as either diffuse abnormalities of pancreatic beta-cell function (Di-HI), or focal adenomatous hyperplasia of beta-cells (Fo-HI). Di-HI is caused by defects in KATP channel genes ABCC8 (SUR1) or KCNJ11 (Kir6.2). Fo-HI arises from somatic loss of maternal heterozygosity resulting in the expression of paternally-derived mutation(s) in SUR1 or Kir6.2...

Aim: To assess the relationship between clinical symptoms, growth hormone (GH) and IGF-1 during medical treatment for acromegaly.Methods and Patients: 6 patients, mean age 52y, (range 43-68), 4 males, were treated with Lanreotide SR (LAN). A growth hormone day curve (GHDC) and IGF-1 were assessed at week 0, pre LAN. All patients received LAN 30mg, 2weekly. GHDC was repeated at week 8, aiming for mean growth hormone (MGH) <5mu\/l. LAN was increased t...

Hormone dependent breast cancer is preferentially treated with Tamoxifen (TAM), an Estrogen Receptor antagonist. Although the initial response to TAM is tumour regression the majority of patients eventually relapse. Understanding the mechanisms that contribute to this resistant phenotype may influence the success of patient response to TAM and prevention of recurrence.A role for ER coactivator and corepressor proteins has been suggested to contribute to...

The estrogen receptor is encoded by two genes (ER-alpha and ER-beta). Both function as transcription factors to modulate expression of target genes. ER-alpha has been shown to interact with co-regulators to enhance or inhibit transcription in vitro. We hypothesised that the existence of these co-regulators contribute to the differing clinical response of patients to treatment with the anti-estrogen four hydroxytamoxifen (4-HOT). The aim of this project was to localise ER-alpha...

Cabergoline (CB) is a potent, long-acting dopamine agonist licensed for the treatment of hyperprolactinaemia and, although unlicensed, is extensively used to treat acromegaly. There is a dearth of data on the use of CB in the treatment of acromegaly. We have performed a retrospective analysis of CB therapy in 34 [19 male, mean age 46 years (range 14-82)22 macroadenomas] patients with acromegaly treated since 1975. The patients were divided into two groups, those on CB as sole ...

Somatostatin (sst) acts via five G-protein-coupled receptors (sstr) that effect angiogenesis, cell proliferation and apoptosis. We have reported the expression of these receptors in normal endometrium and in this study we have extended those observations to the expression of sstr subtypes 1, 2, 3, and 5 within hyperplastic and neoplastic endometrium using immunohistochemistry. METHOD The avidin-biotin-peroxidase method was used to immunostain formalin-fixed, paraffin-embedded ...

Background: Anecdotal reports have suggested that silent ACTH tumours behave in an aggressive fashion, however, clear comparative data are lacking.Methods: 28 patients (16 men, mean age 51.3years [range 30-80years]) who underwent trans-sphenoidal surgery in Oxford between 1975 and 2001 for clinically non-functioning adenomas where the subsequent immunostaining was positive for ACTH were identified from the patient database. The mean follow-up period was...

The insidious onset of symptoms and slow progression of acromegaly often results in a delay in diagnosis for several years. We report an unusual case who presented with progressive lymphoedema of the lower limbs 25 years before the diagnosis of acromegaly became apparent.A 51 year old lady presented to the surgical outpatient clinic with a twenty four year history of bilateral leg swelling and hypertension of 21 years duration. There was no antecedent h...

PTTG has a dual role in tumorigenesis. Firstly, it regulates expression of basic fibroblast growth factor (FGF-2), and secondly, as a human securin homologue, it inhibits sister chromatid separation in mitosis. Securins must be degraded at Destruction Box (DB) motifs by an anaphase promoting complex (APC), before cell division can proceed. We have used a variety of approaches to examine the precise roles of the PTTG Destruction Box and FGF-2 stimulation in cell transformation....

Aim: Clinical acromegaly is characterized by high GH secretion in the presence of high circulating IGF-I levels. We therefore hypothesized that the physiological IGF-I-GH negative feedback loop may be reset in somatotroph adenomas, and we investigated the role of type 1 IGF receptor (IGF-R) and GH receptor (GHR) by quantifying mRNA expression in somatotroph tumours, and investigated the possible presence of mutations of the GHR gene.Methods: Pituitary t...

The proto-oncogene Gsalpha has been implicated in a significant minority of somatotrophinomas, but the search for candidate oncogenes in the remaining somatotrophinomas, and in the great majority of other types of benign pituitary adenomas, has so far been unsuccessful. Microarray-based comparative genomic hybridisation (microarray-CGH) is a novel DNA microarray technique that has been shown to identify gain or loss at the gene level, and has been proposed as a tool to screen ...

BackgroundPreoperative localisation of parathyroid adenomas may allow more limited neck exploration. Ultrasound is the least expensive imaging technique available. However, correct localisation may be difficult. We have undertaken a study to see whether asking one radiologist (SM) to perform all scans offers a diagnostic advantage.MethodAll patients undergoing surgery for primary hyperparathyroidism since Ju...

Calcitonin assays remain a key requirement for the diagnosis and monitoring of medullary thyroid carcinoma (MTC). Until recently calcitonin assays were mainly competitive radioimmunoassays (RIA) but there are now more specific immunometric assays (IMA) available. Cost and staffing pressures are emcouraging routine clinical chemistry laboratories to perform easier kit methodologies rather than refer samples to specialist centres. However, endocrine tumours are known to secrete ...

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...

Paragangliomas are rare tumours that arise from extra-adrenal chromaffin cells within the sympathetic paraganglionic axis. While neoplasms of the adrenal medulla, (phaeochromocytomas) are normally characterized by catecholamine (CA) hypersecretion, paragangliomas can be nonfunctional. We report our findings from 5 patients (4 males, 1 female) with paragangliomas. In 4 out of 5 patients the initial presentation was related to the space-occupying effect of the tumour. Episodic s...

The physiological effects of glucocorticoids (GCs) are, at least in part, mediated by an inhibition of cell proliferation. More contentious is their anti-proliferative action and possible tumour modifying effects in neoplastic tissues. Central to the action of GCs in target tissues is the expression and function of two isozymes of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) that serve to interconvert active cortisol (F) and inactive cortisone (E). 11beta-HSD type 1 (11bet...

Quantification of the catecholamine metabolites, normetadrenaline, metadrenaline and the dopamine metabolite 3-methoxytyramine is widely used as a biochemical investigation for the presence of a phaeochromocytoma. As with any biochemical measurement it is essential that the results are compared against a reference range appropriate for the individual patient.In order to assess the suitability of published reference ranges for these analytes, observed re...

Objective: To establish the efficacy of CAB as primary and exclusive therapy in the management of macroprolactinomasMethod: Retrospective case note review of all patients with macroprolactinomas treated with CAB since the drug received a UK licence in 1994. Patients: Sixteen patients (8males, 8 females) with mean age at presentation of 42.3yrs (range 22-72 years) were treated with initial CAB doses ranging from 0.5-1mg/week (median 1mg/week). Results: T...

Background: Calcitonin is a reliable marker for medullary thyroid carcinoma (MTC) and is useful in follow-up of patients with MTC. While fine needle aspiration biopsy (FNA) is very sensitive and specific for differentiated thyroid carcinoma (follicular and papillary lesions), it is less reliable for diagnosis of MTC. It has been proposed that calcitonin should be used in assessment of patients with thyroid nodules. We have calculated the costs of this strategy.<p class="a...

Phaeochromocytoma in association with hypercortisolism is thought to be rare. However we have observed 4 cases in 3 years and question the rarity of this link. In each case there was a dominant adrenal mass (3.6-7.7cm) with contralateral adrenal hyperplasia. Three of the 4 tumours showed increased 123-I-mIBG uptake. Urinary catecholamines ranged from 872-22752nmol/24h (N < 600). Hypercortisolism was present in all 4 patients; sustained in 2 and cyclical in 2. Case 1 (JCEM ...

Background: We have previously demonstrated colonic expression of the endogenous GH secretagogue, ghrelin, but not the GHS-R, and that ghrelin exerts proliferative effects on colonic epithelial cells. However, whether these are specific to ghrelin, or which genes are affected in response is uncertain.Aims: Determine the specificity of the proliferative effects of ghrelin on colonic epithelial cells, and effects on mRNA levels of the cancer associated ge...