Endocrine Abstracts

A 47-year-old businessman was admitted to the cardiology ward with a 3-week history of worsening dyspnoea, orthopnoea, paroxysmal nocturnal dyspnoea and swollen ankles. Clinical examination revealed sinus tachycardia, hypertension (190/100 mmHg), bibasal crepitations and ankle oedema. CXR showed cardiomegaly and pulmonary oedema while ECG showed left ventricular hypertrophy. Renal function and blood–glucose were normal. He was commenced on diuretics. Echocardiogram noted ...

A 26-year-old Caucasian female presented with nausea, intermittent abdominal pain and amenorrhoea of 3 months duration. She was known to have Von Hippel–Lindau disease (Exon 3A/T 742 mutation) and had undergone surgery for cerebellar haemangioblastoma. She also had presumed dermoid cyst in right ovary which had been monitored by ultrasound. Ultrasound revealed an increase in size and vascularity of right ovarian cyst. MRI scan revealed it to be a 6.3 cm lobulated mass in ...

Introduction and aim: Primary hyperparathyroidism is the commonest cause of hypercalcaemia in out patient population. Primary hyperparathyroidism has become relatively common over the recent years as calcium levels are routinely evaluated since the introduction of multichannel analysers worldwide. Our aim was to audit the use and role of preoperative imaging (Ultrasound and Sestamibi scan) in localising parathyroid adenoma.Methods: We reviewed case notes...

Aim: We had noted that certain patients with metastatic mid-gut carcinoid had subcutaneous nodules in the gluteal region. This prompted us to assess this in more detail as the concern was whether these represented metastases.Method: A cross-sectional study was designed to assess CT scans of 56 patients with metastatic mid gut carcinoid attending the Neuroendocrine Tumour Clinic. These were analysed by two independent radiologists blinded as to the treatm...

Aggressive angiomyxoma (AA) is a rare mesenchymal tumor which is more common in females, occurring predominantly in the pelvi-perineal region. It tends to be locally aggressive with high recurrence after primary excision. The majority of these tumors are positive for oestrogen and progesterone receptors. Hence hormonal manipulation provides the possibility of effective treatment.Since 2005, we have been treating two female patients with AA medically (see...

An adrenal ‘incidentaloma’ is an adrenal mass, discovered serendipitously during a radiological examination performed for indications other than an evaluation for adrenal disease. We present a case of a 66-year-old lady with an unexpected finding of a 3 cm right adrenal mass and multiple liver lesions suggestive of metastatic disease following investigations for a suspicious lung lesion which turned out to be an infective process. Liver biopsies revealed hepatic nodu...

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant negative disorder characterised by the occurrence of multiple adenomas including hyperplasia and/or neoplasm of the parathyroid glands, pancreatic islets and pituitary glands. Germline mutations in the menin gene predispose to the MEN1 syndrome; however, about 10–20% of patients with MEN1 do not have a detectable menin mutation. Recently, a mouse strain with a MEN1-like phenotype has been re...

A 34-year-old welder presented acutely unwell with a 2-week history of facial puffiness, swollen legs, and weight-gain. His GP had found him to be hypertensive and hypokalaemic and had commenced oral potassium supplements. Clinical examination revealed peripheral oedema (face and legs), BP was 179/100 mmHg, with no Cushingoid features. ECG and CXR were unremarkable. Tests showed leucocytosis but normal CRP, persistent hypokalaemia (2.5 mmol/l), normal venous bicarbonate and gl...

A 69-year-old man presented in a life threatening hypoglycaemic coma which following resuscitation required continuous intravenous dextrose to maintain euglycaemia. Random blood sugar was confirmed at 0.7 mmol/l. Past medical history included a large (19×14.5 cm) recurrent malignant fibrous tumour of the pleura which was resected in 1989 but recurred in 2006. At that time the tumour was thought not to be responsive to chemotherapy and radiotherapy and debulking surgery wa...

We present an 83-year-old female who presented with excess body hair growth, worst on her face, arms and abdomen. This was associated with features of virilasation and weight loss. Her past medical history includes; hypertension, Temporal arteritis, Gout and duodenal ulcer disease. Her medications were Felodipine 2.5 mg OD, Captopril 25 mg BD, Bendroflumethiazide 2.5 mg OD, Aspirin 75 mg OD, Ezmoprazole 20 mg OD.On examination, she was found to have deep...

The multiple endocrine neoplasia (MEN) clinic at our hospital was established in 2002 with the aim of providing integrated, comprehensive and expert regional care to patients with MEN syndrome. The clinical team consists of an adult endocrinologist, a paediatric endocrinologist, a clinical geneticist and an endocrine surgeon.In 2002, 16 patients with MEN type 1 from five different kindred were seen. These patients had previously been attending a combinat...

Pituitary tumor transforming gene (PTTG) is a multifunctional oncogene implicated in the pathogenesis of pituitary and thyroid tumours. In breast cancer, PTTG expression is a prognostic marker for lymph node invasion and tumour recurrence. PTTG expression is regulated in vitro and in vivo by oestrogen treatment. PTTG binding factor (PBF) is also a transforming gene, and was isolated due to its functional interaction with PTTG. In the current study, we examined PB...

Pancreatic endocrine tumours (PETs) have a low proliferation index and this partially accounts for their lack of response to chemotherapy. The assessment of proliferation rates relies largely on the use of markers such as Ki67 in patients, and uptake of DNA nucleotide precursors such as tritiated thymidine or 5-bromo-2-deoxyuridine (BrdU) in animals. Amongst these, BrdU is recognised to be the most reliable marker of cell proliferation as it allows the substitution of an endog...

The pituitary tumor transforming gene binding factor (PBF) is a poorly characterised gene that is over-expressed in pituitary and thyroid tumours. Recently, we showed that subcutaneous expression of PBF elicits tumours in nude mice, and expression correlates with thyroid tumour recurrence in man. Given the established role of ionising radiation in thyroid tumourigenesis, we have now investigated the relationship between PBF and the tumour suppressor gene p53, a central compone...

Adrenocortical carcinoma are rare, highly vascular tumours with a generally poor prognosis. We have studied the use of the antiangiogenic drug, thalidomide (TH), in 6 patients with metastatic adrenocortical carcinoma (5 patients had adrenalectomy and one patient was inoperable#). The response to thalidomide treatment is summarized in the following Table. Assuming the residual/metastatic tumours to have a spheroidal form, the tumour volume (V) was calculated using the eq...

The ability of the thyroid to accumulate iodide provides the basis for radioiodine ablation of differentiated thyroid cancers and their metastases. Most differentiated thyroid tumours exhibit reduced iodide uptake, however, and the mechanisms accounting for this remain poorly understood. Pituitary tumor transforming gene (PTTG) is a proto-oncogene implicated in the pathogenesis of thyroid tumours. We recently reported that PTTG and its binding factor PBF, also a potent transfo...

Background: AMPK is a metabolic enzyme regulating the energy supply of the cell but it has antiproliferative effects as well via the up-regulation of the p53-p21 axis and inhibition of the mTOR-pathway. Somatostatin (SST) analogues reduce hormone secretion from somatotroph adenomas and tumour growth inhibition can also be achieved. SST affect several signalling pathways including the mTOR-pathway. mTOR is a mediator of a pro-proliferative pathway that can be inhibited by activ...

D cells comprise 3–10% of the human endocrine pancreas and secrete somatostatin, which inhibits cell proliferation and hormone secretion. Pancreatic tumours secreting somatostatin are associated with the somatostatinoma syndrome, which is characterised by hyperglycaemia, cholethiasis, a low acid output and anaemia. We have examined for the presence of somatostatin secreting cells in pancreatic tumours from a multiple endocrine neoplastic type 1 (MEN1) knockout mouse model...

VHL is an autosomal dominant familial cancer syndrome with renal, CNS and pancreato-biliary manifestations in addition to phaeochromocytoma (PC)/paraganglioma (PGL). Importantly, there is a partial genotype–phenotype correlation, with kindreds harboring deletions and mutations of the VHL gene leading to premature termination/truncation not manifesting PC/PGL. As genetic testing in PC/PGL moves from a research-focus into clinical service, knowledge and understanding...

Hypertension in pregnancy is common and is usually caused by preeclampsia. Catecholamine-producing tumours are very infrequent in pregnancy, but a high index of suspicion is needed to detect this condition with high maternal and foetal mortality.We report a case of undiagnosed pheochromocytoma, complicated by multisystem failure.A 32-year-old lady during her second pregnancy was referred to the obstetricians with hypertension at 26...

Objective: Appendiceal carcinoid is an uncommon neuroendocrine condition that can potentially give rise to a variation in management. We aimed to assess the occurrence and mode of presentation of carcinoid tumour of appendix, and any variation of its management.Methods: All appendicectomies that took place at a single institute between January 1995 and December 2005 were considered for study.Results: A total of 1941 appendicectomie...

A 12-year-old girl presented with dizziness, palpitations, headaches and sweating associated with hypertension (170/100 mmHg) and tachycardia (180 beats per minute). Repeated urinary and serum catecholamines were initially unremarkable. Routine biochemical and haematological testing was normal as were serum gut peptides. The patient was commenced on phenoxybenzamine, nifedipine and propranolol. This improved her symptoms, and corrected her tachycardia and raised blood pressure...

At least 90% of human ovarian cancers originate in the OSE. Most studies indicate that EOC is oestrogen responsive. Paradoxically, ovarian cancer generally occurs after the menopause, which raises the question if oestrogen is involved, where does it come from? We hypothesise that the high circulating concentrations of conjugated (inactive) oestrogens in post-menopausal women are substrates for formation of active oestrogen in the OSE through the hydrolytic enzyme activity of S...

Phaeochromocytomas (PHAEO)/paragangliomas (PGL) are neuro-endocrine tumours. They may present sporadically or as the primary abnormality in a number of familial syndromes. Advances in molecular genetics have led to the identification of several PHAEO/PGL predisposing genes including VHL, NF1 and RET. Mutations in the genes encoding the subunits of Succinate Dehydrogenase (SDH) have also been reported. We describe the phenotype of a cohort of patients with a Succinate Dehydroge...

Neuroendocrine tumours of the GI tract originate from enterochromaffin cells. Somatostatin analogues are the mainstay drugs for therapy in these cancers as they ameliorate symptoms and lower hormone secretion, but only in 30–70% of patients. Such tumours are also associated with angiogenesis which has been used as a prognostic indicator; adenosine, the major regulator of angiogenesis, is released by enhanced degradation of ATP, during cellular stress, damage and hypoxia.<...

Background: Prolactinomas are usually highly sensitive to dopamine agonists. We report the use of temozolomide in a 47-year-old gentleman with MEN 1 and a highly dopamine agonist-resistant, and aggressive prolactinoma.Case summary: He presented in 2001 with a 3rd nerve palsy and recurrent headaches. MRI revealed a pituitary tumour extending into the left cavernous sinus. Prolactin levels were 29 000 mU/l. (NR<360). Primary hyperparathyroidism, a lesi...

Sub-clinical Cushing’s syndrome has, in recent years, been described among diabetic populations but no consensus has emerged about the value of screening. We enrolled 201 consecutive diabetics attending clinic and 80 controls. Local ethics committee approval was obtained. Patients with at least 2 of the following 3 criteria were offered screening: HbA1c≥7%, BMI≥25 and history of hypertension or BP≥140/90. An 11 pm salivary sample was stored at room tempe...

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by the combined occurrence of tumours of the parathyroids, pancreas and pituitary. MEN1 is caused by germline inactivating mutations of the MEN1 gene which is located on chromosome 11q13 and encodes a 610 amino acid protein, menin. MEN1 tumours show loss of heterozygosity (LOH) of chromosome 11q13, and lack menin expression, consistent with a tumour suppressor role for MEN1...

The mouse knockout model for multiple endocrine neoplasia type 1 (MEN1) closely resembles the phenotype of the human disorder, with frequent development of tumours of the parathyroids, pancreas and pituitary. These tumours have loss of heterozygosity (LOH) of the Men1 locus and lack expression of the encoded protein (menin).The aim of this study was to investigate the feasibility of detecting pituitary tumours in heterozygous (Men1+/−...

Mutations in AIP have been identified in a significant proportion of families with pituitary adenomas, most commonly in familial acromegaly. However, no data are available about the pituitary expression of AIP and how lack of AIP is involved in tumorigenesis.We identified 10 kindreds with AIP mutations out of 31 families. We studied RNA and protein expression of AIP in normal as well as familial and sporadic pituitary adenomas. In the normal pituitary st...

Background: Concordant parathyroid localization studies using sestamibi and ultrasound scans allow minimally invasive parathyroidectomy to be the procedure of choice for patients with non-familial primary hyperparathyroidism (PHPT). This study investigates the financial implications of scan-directed parathyroid surgery.Methods: Analysis of hospital records for a cohort of consecutive unselected patients treated in a tertiary referral centre over a 5-year...