Endocrine Abstracts

Background and objective: Adaptive process to hypoxia of altitude involves changes in the homeostatic steady state of several endocrine variables which precede and contribute- to many physiologic adaptations. Physiologic responses to altitude-stress exhibit ethnic variation. However, there has been limited characterization of ‘ethnicity effect’ on endocrine responses to high-altitude stress. This is true for enzyme-immunoassay method (EIA) of plasma hormone analysis....

Seventy six year old man presented with sudden onset headache for 3 days. He was seen by the GP and treated for migraine. But no improvement in his headache and he developed drooping of left eyelid and blurring of vision. No other neurological symptom.On examination left ptosis with normal visual fields to confrontation method. Initial differential diagnosis was isolated 3rd nerve palsy probably due to posterior communicating artery aneurysm. He was on a...

Introduction: Pituitary apoplexy is essentially bleeding into a necrotic area of the pituitary tumour, which has presumably outgrown its blood supply and caused infarction. Usually this is a haemorrhagic infarction but rarely a non-haemorrhagic infarction can cause marked pituitary swelling and presents as pituitary apoplexy. Our case represents a typical case of pituitary apoplexy with rapid evolving neurological deficit due to pituitary necrosis rather than haemorrhage.<...

Introduction: Pituitary tumors account for 15% of all intracranial neoplasms and could remain asymptomatic for a significant period. We conducted a retrospective analysis to assess pattern of referrals and management of non-functioning pituitary adenomas at our tertiary referral centre.Methods: Data was collected on referrals for NFA received at our university hospital from 2005 to 2008. Medical records, radiology reports and endocrine department data we...

A 34-year-old lady attended clinic-requesting information on recombinant prolactin to assist with breast feeding as she was 32 weeks gestation with her third pregnancy having failed to lactate after her first two pregnancies.In 2003 she developed pre-eclampsia during her first pregnancy and required delivery by Ventouse extraction. She had a significant post-partum haemorrhage of 1200 mls with haemoglobin 7g/dl but no evidence of cardiovascular compromis...

Introduction: Diabetes insipidus can complicate up to 1 in 30 000 pregnancies and has a variety of causes, some that predate the pregnancy and others that begin during gestation. In addition, women can experience diabetes insipidus de novo in pregnancy through the actions of placental vasopressinase, which causes accelerated degradation of vasopressin. This form of diabetes insipidus may be associated with increased complications of pregnancy, including pre-eclampsia. M...

A 51-year-old asymptomatic man presented in 1998 with elevated thyroid stimulating hormone (TSH) 6.34 mIU/l (0.34–5.6 mIU/l), FT4 54.1 pmol/l (7.5–21.1 pmol/l), FT3 20.1 pmol/l (3.0–5.0 pmol/l) and TSH-α subunits 3.6 mcg/l (<2.0 mcg/l). After the first visit, he was lost to follow-up.He presented 10 years later in 2008 with 1-week history of symptoms of heart failure and hyperthyroidism. Clinically he was thy...

Sixty seven year old gentleman presented to eye clinic with blurring of vision in the left eye for 2 weeks. Patient was seen by Ophthalmologist and discharged home. Presented 3 weeks later with headache and blurring of vision. On examination no perception to light in the left eye and bitemporal hemianopia.His past history includes carcinoma prostate, diagnosed a year ago and had surgery and Radiotherapy. His recent PSA was normal. Bones scan showed no ev...

A 62-year-old male was referred by his GP querying acromegaly. His past medical history included sleep apnoea, hypertension, dislipidaemia and gout. Serum IGF1 was elevated at 827 ug/l (normal range 100–300 ug/l). Prolonged oral glucose tolerance did not show suppression of GH with a nadir of 9.0 mu/l. A pituitary MRI demonstrated a 5x6mm microadenoma. There were no visual field defects. The patient was pre-treated with somatostatin analogues and proceeded to transphenoid...

TSH-secreting pituitary adenomas are rare and the optimal investigation and management is uncertain.A 42-year-old lady presented with a three-month history of three stone weight loss, palpitations, heat intolerance and tremor. Her sister was being treated for Graves’ disease. Visual fields were intact.Thyroid function tests showed free T4 concentration 29.5 pmol/l (9.0–19.0) and TSH concentration 3.672 mU/l (0....

Background: In a vast majority of cases, hypopituitarism is caused by a tumour or a vascular event of the pituitary gland. We present a case of hypopituitarism caused by an uncommon cause identified on imaging studies.Case: A 58-year-old Caucasian woman presented with a 2-day history of diplopia, headache and vomiting with a background history of tiredness and lethargy over the past 4–6 months. Past medical history included type-II diabetes, hyperte...

We report an interesting and important case of hypopituitarism secondary herpes encephalitis and available literature evidence.Case history: Twenty-one year old gentleman admitted to tertiary neurosurgical unit with excessive water intake, feeling tired, increased sleepiness, a few weeks history of confusion and ‘strange behaviour’. He was oriented in person but not in place, had high temperature.He had lumbar puncture, C...

Objective: Growth hormone (GH) deficiency in adult patients is associated with poor quality of life and increased cardiovascular morbidity and mortality. We studied the effects of GH replacement on the lipid profile in adult patients with GH deficiency treated over a 3-year period.Method: A retrospective analysis of 70 adult patients, who had completed 3 years of GH therapy. Growth hormone is initiated at a dose of 0.3 mg/day and titrated to 0.5 mg/day o...

Pituitary metastases are uncommon, with breast and lung carcinomas being the most common primary sites. Of the minority that are symptomatic, diabetes insipidus (DI) is frequently present. We report two cases, one presenting with DI and the other with hypopituitarism and DI, who deteriorated rapidly and died within 3 months.Case 1: A previously fit 53-year-old lady presented in December 2008 with a one month history of polyuria and polydipsia. Investigat...

Objective: To audit GH deficiency in the transition service at our institution.Methods: Patients between 19–25 years old were identified from the database of patients having GH replacement. Data were obtained from case notes and electronic records.Results: Twenty-four patients in the transition service were identified to be GH deficient, 13 female and 11 male. 14/24 had CNS or pituitary tumours treated in childhood, 11 having ...

Introduction: Russell’s Viper is a venomous snake found in South and South East Asia. The snake bite causes coagulopathy, neurotoxicity, renal failure, local effects and even death. But hypopituitarism is an extremely rare complication1. There are only a few case reports from India and Burma and we report the first case from Sri Lanka.Case report: A 49 year old man from a remote part of Sri Lanka was bitten by a Russell’s viper 3 yea...

Introduction: Craniopharyngiomas are usually benign intracranial tumours which can sometimes be locally aggressive. Malignant transformation is extremely rare and has a poor prognosis. We report a case of a patient who developed carcinomatous changes in a craniopharyngioma which was first excised almost 55 years ago.Case report: Mr AM was diagnosed with a craniopharyngioma at the age of 5 years. He underwent surgery in 1952 but was lost to follow up and ...

Introduction: To assess outcome for patients with acromegaly treated at Royal Preston Hospital since 1st of January 2000.Results: Out of 22 patients (12 presenting in the last 2 years) 20 had endoscopic transsphenoidal hypophysectomy and two were managed medically. Headaches, visual disturbance and characteristic morphological features were the main presenting problems. 4 were microadenomas and 18 macroadenomas\. Exact dimensions were only available in 1...

A 34-year-old lady presented with irregular periods but no galactorrhoea. A prolactin level was 1326 mU/l.Clinical examination-Normal. BMI 26 and visual fields were full to confrontation. MRI scan of pituitary was reported as large pituitary macroadenoma measuring 11× 11× 12 mm denting the optic chiasm. Results of other endocrine tests were as follows; cortisol 265 nmol/l, TSH 0.32 mU/l, FT4 8.5 pmol/l, FSH 4 U/l, LH 1.6 U/l, oestradiol 104 pmol/l, GH 8.4 mU/l, IGF1 ...

Mr GC aged 67 presented to the ophthalmologists in December 2008 with blurring vision and headaches. Visual acuity was 6/9, 6/24 and reassured. Two weeks later he returned as an emergency with severe visual loss of left eye to finger movements and temporal field defect right eye.Past history included cancer prostate, gleason score-7 (T2 N0). TURP performed in January 08 followed by hormonal therapy and external beam irradiation.Neu...

Hypopituitarism is associated with increased cardiovascular mortality. It has been suggested that hypogonadism, hypothyroidism, growth hormone deficiency (GHD), or indeed unphysiological hormone replacement regimens, might contribute to this excess cardiovascular risk. The adverse effect of hypercortisolaemia on insulin resistance, carbohydrate metabolism and hypertension is well recognised. It is also known that glucocorticoids adversely affect the coagulation-fibrinolytic sy...

Introduction: The concept of life-long medical therapy for acromegaly has recently been challenged. Hormonal remission for up to 48 months after stopping somatostatin analogues in acromegalic patients has recently been reported. Herein, we present a further case showing the longest remission yet in growth hormone levels after somatostatin analogue treatment.Case: In 1987, a 43 year old man was diagnosed with acromegaly [nadir GH on oral glucose tolerance...

The spontaneous remission of Cushing disease (CD) might be a phase of cyclic disease, but could also be explained by an ACTH-microadenoma infarction or hemorrhage, with clinical pictures ranging from asymptomatic hypercortisolism normalization to dramatic hypocortisolism. We describe the case of a 23-years-old woman, referred for amenorrhea lasting for 5 months, overweight and acne. Physical examination showed mild hirsutism, acne, round face with a hint at rubeosis, abdominal...

Annexin-1 (ANXA1) is a 37 kDa calcium- and phospholipid-binding protein expressed abundantly in S100-positive folliculostellate (FS) cells in the anterior pituitary gland. ANXA1 is localised both intracellularly and on the cell surface in high density foci appearing at points of contact between the FS cells and the neighbouring secretory cells, where it has been demonstrated to mediate the glucocorticoid-induced negative feedback on the secretion of ACTH from corticotrophs. Gl...

Context: Prolactinomas are the most common functioning pituitary adenomas & it is recognised that gender has an influence on presentation and management of this condition.Objective: To examine the effects of gender on presentation and response to treatment in a large cohort of adults with confirmed prolactinoma (MRI performed and macroprolactin excluded).Design & patients: This retrospective cohort study design used an elec...

A 27 years old girl presented with weight gain, hirsutism, fatigue, bruising and striae. On examination she was Cushingoid. On initial assessment, 3 out of 4 24 h urinary free cortisol collections were elevated. 0800 h serum cortisol was 280 nmol/l after 1mg dexamethasone given at 2300 h. After formal 48 h low and high dose dexamethasone suppression tests cortisols were 164 and 34 nmol/l respectively. Basal 0800 h ACTH was 33 ng/l. Given the clinical features and the discrepan...

Transphenoidal surgery is an effective treatment option in patients with pituitary tumours associated with compression of the optic chiasm or hormone hypersecretion. Surgery carries with it a risk of the development of new pituitary hormone deficits but also the potential for recovery of existing pituitary hormone deficits. We have examined data concerning pituitary function in 80 patients who underwent endoscopic transphenoidal pituitary surgery at Royal Preston Hospital....

Fifty year-old year old gentleman presented unwell whilst on holiday with headache and vomiting. He also reported a clear fluid trickling down his nose. On examination he was pyrexial, photophobic and had demonstrable neck stiffness. Lumbar puncture and a subsequent culture confirmed streptococcal meningitis which responded to antibiotics.His CT scan head suggested a pituitary mass and a subsequent MRI revealed an unusual massive pituitary tumor extendin...

Background: There is no published guidance on when to request a pituitary MRI in hypogonadal men. The presence of low or low normal gonadotrophins is common in men with symptomatic testosterone deficiency and metabolic syndrome and/or type 2 diabetes. Our practise is to perform pituitary MRI scans in men with isolated hypogonadotrophic hypogonadism who have LH< 4 Iu/l.Method: One hundred and eighty-one patients that had a pituitary MRI scan between J...

Obesity is a recognised complication of craniopharyngioma (CP), but its aetiology is not understood. Leptin, which signals energy reserve, and ghrelin, which regulates appetite, are implicated in the development of obesity.Our aim was to assess leptin and ghrelin levels in CP patients and to compare these to normal and BMI-matched controls.CP patients were identified from the local database. All CP patients were on hormone replacem...

Background: Serum biomarkers which correlate with pituitary tumour growth would be valuable in the treatment and follow-up of patients with pituitary adenomas, particularly non-functioning adenomas. Vascular Endothelial Growth Factor (VEGF) mRNA is upregulated in almost all tumours, whereas matrix metalloproteinases 2 and 9 (MMP 2 and 9) have been demonstrated to be important in tumour vascularisation and invasion, particularly in prolactinomas.Aim: The ...

Background: Obesity is a common sequel to tumours of the hypothalamic region and their treatment. Weight gain occurs at a rate faster than any expected age-related increase and despite treated hormone deficiencies.Methods: Retrospective review of patients with hypothalamic-pituitary tumours attending a large neuroendocrine clinic in UK.Results: Initial review in 2002 had identified 42 adults with tumours causing hypothalamic damage...

Background: Familial isolated pituitary adenomas (FIPA) is a rare inherited disorder accounting for about 2% of pituitary adenomas. Mutations in the Aryl hydrocarbon receptor Interacting Protein (AIP) gene have been described in about 15% of FIPA families and rarely in early onset sporadic pituitary adenomas. Among the AIP mutations reported so far, the R304X represents, after the Finnish founder mutation Q14X, the second most common one.Me...

Background: Rathke’s cleft cysts (RCC) are benign, cystic lesions arising from remnants of Rathke’s pouch and reported in 13–22% of normal autopsies. Their prognosis after surgical intervention is not clearly defined.Aim: To analyse the outcome of patients who presented to our Department with RCC between 1/1977-3/2009.Patients and methods: Thirty-three cases were identified [13 males/20 females, median age at diagnos...

Background: Pituitary apoplexy has been reported in around 2% of surgically treated adenomas. Around 45% of all pituitary tumours presenting with apoplexy are non-functioning ones (NFAs). Currently, no data exist on recurrence rates in patients with NFAs who have had classical apoplexy.Aim: We therefore, put together our data aiming to provide the first reliable series on recurrence rates in patients with NFA and classical pituitary apoplexy.<p class...

A 40-year-old woman, who had developed oligomenorrhoea after discontinuing the contraceptive pill at age 30, presented with a 6-month history of intermittent vomiting associated with abdominal discomfort and distension. Ultrasound, followed by laparotomy, revealed multiple bilateral ovarian luteal cysts consistent with hyperoestrogenism and ovarian-hyperfunctioning.Only 9 months post-operatively her bilateral theca ovarian cysts had recurred. Over 4 mont...

Background: Data on the relationship between the hormonal response to somatostatin analogues and morphological subtype of somatotroph adenomas are sparse. We have previously shown that nadir GH <1.75 μg/l on the octreotide suppression test (OST) has positive and negative predictive value 94 and 100%, respectively in predicting achievement of ‘safe’ GH levels following treatment with octreotide LAR (Karavitaki et al. 2005).Aim: T...

Introduction: Remission rate in microprolactinomas after treatment with dopamine agonists (DA) is variable, from about 25% in bromocriptine-treated patients to 46% in those treated with cabergoline.Patients: We retrospectively studied the remission rate in 98 patients with prolactinomas ≤1 cm evaluated in 1982–2009 in our department and treated with DA for at least 1 year.Results: Mean age of patients is 26.5±8 year...

Background: Ergot-derived dopamine agonist therapy (EDDAT) is associated with cardiac valvulopathy in Parkinson’s disease. The risk to patients with prolactinomas is uncertain. The EMEA/MRHA and BSE recently issued guidelines for surveillance echocardiography (ECHO) of patients receiving treatment with EDDAT. Our policy is to arrange opportunistic ECHO screening at first clinic visit guidelines.Objective: We investigated the uptake and findings of e...

Gigantism is an extremely rare condition and hence the relevant literature is largely a series of case reports. We present data on patients with gigantism <20 years of age identified from Pfizer’s Acrostudy registry of patients treated with pegvisomant.Eleven patients (5M) were identified: IGF1 at diagnosis was 1.6×ULN (1.15–3.3), height +5 SDS (1.1–3.8) and age 14.5 years (4–19). The three youngest (4, 7 and 14 years) had pi...

Objective: Exogenous and endogenous opioids affect the hypothalamic–pituitary–gonadal axis through binding to receptors centrally and by peripheral inhibition of testosterone synthesis, thereby altering the release of hormones. Approximately 12% of patients with persistent non-cancer pain use strong opioid analgesics in the UK, but the action on endocrine function may not be recognised. The aim of this study is to establish the incidence of gonadotrophin and other en...

The glucagon stimulation test is commonly used to assess the hypothalamic–pituitary axis when the insulin stress test (IST) is contraindicated. The mechanism behind glucagon induced secretion of GH and cortisol is unclear. To determine whether these responses are dependent on symptoms during the glucagon test, a retrospective case note study of glucagon tests performed over 3 years in patients with pituitary disease was undertaken.Methods: Fifty-six...

Background: Pituitary apoplexy is rare resulting from acute haemorrhagic infarction of a pituitary adenoma. Optimal management in the acute stage still remains a matter of debate.Methods: Retrospective analysis of casenotes of patients presenting with acute apoplexy at a single neurosurgical centre between 1984 and 2009 in the United Kingdom.Results: Fifty-five patients (35 males, mean age 52.4 (range 14–78) years, mean years ...

Background: There is lack of consensus in the management of pituitary apoplexy. Following the 11th Clinicopathological Pituitary Conference at the RCP (2009), a multidisciplinary group produced evidence-based guidelines for management of apoplexy. A patient with apoplexy and significant neuro-ophthalmic signs or reduced level of consciousness will usually undergo surgical decompression. It is unclear what defines a significant neuro-ophthalmic deficit. There is no objective to...

Introduction: Hypercortisolaemia is characterised by an increased risk of cardiovascular disease (CVD), either through a direct action on the myocardium or by affecting traditional cardiovascular risk factors. The electrocardiogram (ECG) is the initial examination to assess the structural and functional characteristics of the myocardium.Aim of the study: To investigate whether the metabolic and cardiovascular features of Cushing’s disease (CD) are a...

Background: The route of oestrogen replacement has an influence on GH sensitivity in hypopituitary women, although the practical relevance of this effect remains unclear.Objectives: To compare the effects of oral and transdermal oestrogen replacement on GH requirement in adult females with hypopituitarism receiving GH replacement.Methods: This cross-sectional, observational study included 69 GH-deficient women each receiving a stab...

Introduction: Achieving optimal levothyroxine replacement is more difficult in TSH deficiency compared to primary hypothyroidism because of the inability to be guided by TSH. A combination of clinical symptoms and free thyroxine levels (fT4) are typically used to monitor replacement. We reviewed adequacy of levothyroxine replacement in our patients with pituitary disease, and compared with fT4 levels in patients with primary thyroid disease.<p class="...

Annexin 1 (ANXA1) was first identified as a glucocorticoid (GC)-inducible protein in macrophages and is a mediator of the powerful anti-inflammatory actions of these steroid hormones. In the pituitary ANXA1 plays a critical role in mediating the early-onset negative feedback effects of GCs on the release of ACTH. ANXA1 is expressed in abundance in the anterior pituitary gland where it is localized specifically to the S100-positive folliculo-stellate (FS) cells. GCs act on FS c...

Introduction: Hyperprolactinaemia associated with antipsychotic drug use is a commonly encountered clinical problem, yet no decision-making tools exist to guide whether to scan the pituitary gland.Methods: A 10-year data series was reviewed of 246 patients who were evaluated for prolactin excess with a cannulated prolactin study. All patients had a prolactin drawn immediately following the insertion of a forearm cannula (P1) and a second sampl...

GH replacement (GHR) has resulted in a significant improvement in quality of life for many adults with GH deficiency. Many of these patients are previously irradiated survivors of malignancy, and as such are at high risk of recurrent (RN) or secondary neoplasms (SN). There is a particularly strong association between CNS irradiation and subsequent development of meningiomas, which are known to express GH receptors. There is uncertainty as to whether GHR increases the risk of d...

Mammalian pituitary gland development is well established on a molecular and morphological level. In developmental biology the use of chick and zebrafish models is common but despite chicken pituitary gland development being characterised in 1952 these models have only recently been regularly employed in pituitary studies. The third member of the natriuretic peptide family, C-type natriuretic peptide (CNP), has been investigated in rodent embryos but little is known about its ...

Copeptin is a stable AVP marker and stoichiometrically released with AVP. It closely reflects changes in water balance. Its stimulation in severe stress has recently has been suggested for the early diagnosis of myocardial infarction but clear definition of the physiological variability is necessary. Here, we studied the pulsatile and circadian variation in healthy individuals and compared copeptin to cortisol rhythms.Copeptin levels were sampled every 2...

Gene expression in living cells is dynamic and unstable, and fluctuations in transcription may be subject to stochastic regulation of processes including transcription factor and polymerase recruitment, and chromatin remodelling. One gene that has been shown to display dynamically variable transcription and marked heterogeneity between cells is prolactin (PRL). Time-lapse imaging of PRL-reporter gene expression in single rat pituitary GH3 cells revealed distinct long-term tran...

Background: Non-functioning pituitary adenomas (NFAs) are slow growing tumours with reported 5-year recurrence rates following resection up to 51%. The time point that it is safe to stop surveillance imaging is not clearly defined.Aim: To clarify the time spectrum of recurrence in patients with NFAs offered solely surgery as primary treatment and to estimate the safe time to stop surveillance pituitary imaging.Methods: Case-note an...

Hypopituitary patients are at increased vascular risk. This may be partly attributable to changes in insulin action. It has been suggested that the addition of dehydroepiandrosterone sulphate (DHEAS), which is low in patients with secondary hypoadrenalism, to routine replacement may have beneficial effects on glucose metabolism. Previously, patient populations and techniques used to assess insulin action varied and overall results have been conflicting.W...

Cabergoline (CAB) is a selective dopamine D2-receptor agonist with long-lasting action, highly effective in treating micro- and macroprolactinoma. However, the clinical response to cabergoline can be seen only after several months of treatment, allowing the tumor shrinkage and decrease of prolactin. Despite most prolactinomas are responsive to CAB, there are up to 8% of cases in which tumor responsivity is limited. In order to asses the sensitivity to Cab, we aimed to develop ...

Objective: Our objective was to examine recurrence of hyperprolactinaemia following discontinuation of dopamine agonist (DA) therapy in patients with macroprolactinoma who have had treatment for 3–15 years.Methods: We identified retrospectively adult patients (n=15) attending OCDEM (Churchill Hospital, Oxford, UK) with a confirmed diagnosis of macroprolactinoma (established during the last 25 years), who had been treated with DA therapy for a...

Pituitary development, in particular the differentiation of anterior pituitary endocrine cells, remains to be fully understood, and may have implications for adult pituitary plasticity and hyperplasia. We have used prolactin-reporter transgenic rats to characterise prolactin transcription during the appearance of newly formed lactotroph cells during fetal development.Transgenic rats with the firefly luciferase reporter gene inserted into exon 1b of a 160...

Prolactin (PRL) is a hormone mainly produced by the lactotroph cells of the anterior pituitary gland. Besides its pivotal role in reproduction, PRL has also been found to have immuno-modulatory properties. The pituitary is the main source of circulating PRL, however it is also expressed in humans at extra-pituitary sites1. In extra-pituitary tissues, PRL mRNA contains an extra exon (exon 1a), and expression is regulated by an alternative promoter upstream of the pit...

Background: SOX2 is a member of the SOX (SRY-related HMG box) family of transcription factors, and shares homology with SOX1 and SOX3 which are members of the SOXB1 subfamily. Heterozygous, de novo, loss-of-function mutations in SOX2 were initially reported in patients with bilateral anophthalmia/microphthalmia, developmental delay and male genital tract abnormalities, with variable manifestations including defects of the corpus callosum, oes...

Considerable dichotomy exists in the phenotype of adults with severe GHD of childhood (CO-GHD) and adult-onset (AO-GHD). Those with CO-GHD show immaturity. Adults with partial GHD (GH insufficiency (GHI), peak GH 3.1–7.0 μg/l) show a similar, but milder phenotype to adults with severe GHD. Whether a similar dichotomy relating to timing of onset is observed in CO-GHI and AO-GHI adults is not known.We studied 24 adults with GHI (CO-GHI n=1...

Background: Pituitary adenomas usually occur as sporadic tumours, but familial cases are increasingly identified. Patients of 15–40% with familial-isolated-pituitary-adenoma (FIPA) harbour germline mutations in the aryl-hydrocarbon receptor interacting gene (AIP). AIP is thought to act as a tumour suppressor gene, with loss of heterozygosity shown in pituitary tumour samples at the 11q13 locus, where AIP is located. Previously we have shown AIP has properties consistent w...

Pituitary adenomas are benign tumours, which do not involve mutations in tumour suppressor genes or oncogenes. We have shown that the canonical Raf/MAPK and PI(3)K/Akt pathways are over-activated in these tumours, but their downstream effectors are modified to a much lesser extent. It is probable that the oncogenic mutations responsible for the initiation of these tumours therefore lies proximal to the convergence of these pathways, at or even upstream to the growth factor rec...

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized by the occurrence of anterior pituitary, pancreatic islet and parathyroid tumours. Mice (Men1+/−) deleted for an MEN1 allele develop these tumours. The MEN1 gene encodes a 610 amino acid protein that has been reported to upregulate caspase 8 expression and promote apoptosis. To characterize the functional effects of menin loss in vivo, we asse...

MicroRNAs (miRNAs) are small non-coding RNAs of ~22 nucleotides that negatively regulate gene expression through imperfect base pairing to the 3′ untranslated regions (UTRs) of target mRNAs. We have investigated the role of the miR-15a–miR-16-1 cluster in pituitary tumourigenesis, as it functions in other cancers as a tumour suppressor via regulation of the cell-cycle regulator cyclin D1. We have used two approaches: 1) in vitro studies examinin...