Endocrine Abstracts

Background: Although MRI remains the investigation of choice for pituitary imaging, it does not provide information about the ‘functionality’ of lesions (e.g. residual adenoma vs post-surgical scar tissue), and cannot reliably identify all microadenomas. These limitations are of particular relevance in acromegaly where clinical and biochemical evidence of disease activity mandates (further) treatment.Methods: We hypothesised that i) imaging wit...

Background: AIP mutations cause sporadic and familial pituitary adenomas, but establishing the pathogenic role of missense AIP variants with unknown significance is difficult. The AIP interaction partner AHR – a xenobiotic-activated transcription factor – regulates transcription of xenobiotic-metabolising enzymes, mediates xenobiotic toxicity, and has been implicated in tumorigenesis.Aim: To describe the effect of AIP...

Background: Heterozygous germline AIP mutations can lead to young-onset invasive GH-secreting adenomas. There are no data available to explain the proliferative and invasive nature of AIP-mutation positive somatotrophinomas.Methods: Cell viability (MTS assay), invasion (single cell fluorescence invasion assay) and migration assays (Boyden chambers) were used to further characterise the phenotype of AIP-silenced GH3 cells. Affymetrix gen...

Multiple Endocrine Neoplasia type 1 (MEN1) is an autosomal dominant disorder characterised by the combined occurrence of parathyroid, pituitary and pancreatic islet tumours, and is due to mutations of the MEN1 gene, which encodes the tumour suppressor protein menin. MicroRNAs (miRNA) are non-coding single stranded RNAs that post-transcriptionally regulate gene expression. Alterations in miRNA expression, including downregulation of two miRNAs, miR-15a and miR-16-1, have been r...

Background: Acromegaly (Acro) is associated with adverse psychopathological and personality outcomes despite being in remission for over a decade. We hypothesised that persistently poor psychological outcomes may be associated with morphometric changes experienced by Acro patients.Methodology: We compared 60 consecutive non-functioning adenoma (NFA) and Acro patients who had undergone pituitary surgery and/or radiation therapy (RT). A gender-specific vis...

Background: A founder mutated AIP allele, R304* was previously identified in several Irish familial isolated pituitary adenoma (FIPA) pedigrees from a small region within Mid Ulster, Northern Ireland, but the allele’s general population impact remains unknown.Aims: To estimate R304* prevalence in the general population and pituitary adenoma (PA) patients and to calculate the allele’s time to most recent common ancestor (tMRCA).<p c...

Introduction: Acromegaly is a neuroendocrine disorder caused by excessive secretion of growth hormone (GH). Current treatment includes surgery, radiotherapy and drugs like somatostatin or dopamine receptor agonist. In spite of combination of therapies cure rate is dismal. There is a quest for new therapeutic targets with optimal efficacy, least side effect without any cost constraints. Recently, a few reports have shown that tyrosine kinase inhibitor (Imatinib) causes growth f...

Introduction: Non-syndromic pituitary gigantism can result from AIP mutations and the recently identified Xq26.3 microduplications causing X-LAG.Patients and methods: DNA samples and clinical data were collected from 151 patients with pituitary gigantism. All samples were tested for AIP mutations; AIP mutation negative cases (AIPneg) were screened for Xq26.3 microduplications.Results: Xq26.3 micr...

: AIP mutation-positive familial isolated pituitary adenoma is commonly diagnosed in young patients who have a poor prognosis due to large, treatment-resistant tumours. Microarray analysis carried out on AIP knockdown pituitary (GH3) cells and control cells, identified CDC42 as one of the genes that was up-regulated by loss of AIP protein. This small Rho GTPase activates MAPK signalling, suggesting it may contribute to the proliferative phenotype of AIP knock...

ATL1103 is a second generation antisense 20mer intended to inhibit expression of the GH receptor (GHR) gene. Phosphorothioate and 2′-O-methoxyethyl modifications to nucleotides increase its plasma half-life and affinity for the target RNA to allow post-hybridization RNaseH degradation. We previously reported a phase 2, randomised, open-label, parallel group study of ATL1103 in 26 patients with acromegaly which demonstrated a fall in serum IGF-I of 26% with 200 mg twice w...

Introduction: Patient distress may be associated with a reduced quality of life (QoL), poor adherence to treatment and lower satisfaction with medical care. Best practice guidance recommends that distress is assessed at key points within the patient-care pathway. The aim of this study was to develop a pituitary-specific distress assessment tool.Method: Working with the Pituitary Foundation, a Wellbeing Survey was generated, comprising 36 pituitary-specif...

Introduction: Data on the mortality of patients with non-functioning pituitary macroadenoma (NFA) are limited. Aim: To assess the mortality of patients with NFA and predictive factors.Patients/methods: All patients presenting to our Department with NFA between 1963 and 2011 were studied. Status was recorded as either dead or alive, as of 31 December 2011.Results: 546 patients (333 males) were identified (median age at surgery 58.7 ...

Introduction: Familial isolated pituitary adenoma (FIPA) and young-onset sporadic pituitary adenoma patients are suggested to be screened for mutations in AIP, a gene described in 2006 and amenable to UK testing since 2008.Methods: affected subjects have been tested in Exeter and Oxford genetic laboratories. Data were collected from 120 FIPA-families and 193 sporadic cases with young-onset disease (<30y) from 49 centres in the UK. The Mann&#...

Non-functioning pituitary adenomas (NFPAs) are the commonest subtype of pituitary tumour. Surgical resection, accompanied by radiotherapy (RTX) in selected cases, is the treatment of choice for compressive tumours. Long-term health consequences of treatment for NFPAs are unclear. In this retrospective study, we assessed long-term pituitary function and mortality rates in a large NFPA cohort across two tertiary centres in the UK and Ireland.Case-note revi...

Background: SIADH is the most frequent underlying cause of hyponatraemia but is frequently ignored and suboptimally treated.Aim: To identify the treatment applied in clinical practice for hyponatraemia due to SIADH and to evaluate the effect of fluid deprivation.Method: A prospective, non-intervention observational study of a sequentially evaluated cohort of hyponatraemic patients during first 48 h after hospitalization from Januar...

Background: Accurate assessment of GH & IGF1 status in acromegaly is crucial for informing management to minimise excess morbidity/mortality. Expert panels have differed with respect to recommended testing modalities and thresholds – the most recent being the Endocrine Society 2014 guidelines. We evaluated their simplified algorithm, which minimises the need for day-case testing, against other more resource-intensive measures.Methods: A retrospe...

Background: Lack of expression of MGMT (O-6-methylguanine-DNA methyltransferase) is associated with a better tumour response to temozolomide. There are no systematic studies of MGMT expression in pituitary tumour series.Aim: We introduced MGMT immunohistochemistry for all pituitary adenoma specimens in 2011. In this study we investigated the immunohistochemical expression of MGMT in a large series of pituitary adenomas, in order to determine (1) the over...

Background: Correct identification of patients with HPA axis dysfunction following trans-sphenoidal pituitary surgery is important. Our centre measures post-operative day 5 0900 h serum cortisol (24 h after the last dose of glucocorticoid) to identify the need for glucocorticoid replacement. This is given if post-operative day 5 0900 h cortisol concentration is <300 nmol/l, until dynamic pituitary function assessment occurs.Methods: Data were reviewe...

61 patients (104 invited participants), within 10 years of active treatment for acromegaly, from five hospitals in the UK (one neurosurgical centre) were interviewed to explore the experience of living with acromegaly, access to information, support and their ability to make decisions about their care. Semi-structured interviews by an independent consultant (60–120 min each) included 34 males, 27 females; 25–85 years old; 85% patients had surgery. 56 (92%) experience...

We recently developed a visual scale to assess the extent of morphometric changes in Acromegaly (Acro) patients which is strongly predictive of adverse psychological outcomes. We sought to identify if there was any association between the self-drawing test and the visual morphometric scale and if there was any correlation with psychological outcomes.We compared 60 consecutive non-functioning adenoma (NFA) and Acro patients who had undergone pituitary sur...

Bilateral inferior petrosal sinus sampling (BIPSS) is the gold standard investigation in Cushing’s disease for identifying the pituitary as the ACTH source. This technique aims to demonstrate a gradient of central:peripheral ACTH levels of >2:1 in such patients, or >3:1 after CRH stimulation. In patients without significant pituitary MRI abnormalities this facilitates neurosurgical exploration.The test is limited by difficulties in achieving...

The pituitary gland that synthesises and secretes pituitary hormones is an indispensable endocrine organ. Its development progresses by plural factors. Among them, neuronatin (NNAT), which was discovered in the neonatal mouse brain and is involved in neural development, was later revealed to be an abundantly expressing gene in the pituitary gland, but its role is yet elusive.We analysed the expression profile of Nnat and its localisation in the ...

Background: Acromegaly treatment options include transsphenoidal surgery (TSS), medical management with somatostatin analogues (SSAs), growth hormone (GH) receptor antagonists and dopamine agonists, radiotherapy or a combination of these, depending on symptom nature and severity, tumour size, age and health status. In 2014 the Endocrine Society published guidelines for management of acromegaly.Methods: To describe current UK practice following guideline ...

Introduction: Increased cardiovascular risk in hypopituitary patients was first documented by Rosen in 1990. Subsequent studies confirmed increased prevalence of cardiovascular and cerebrovascular disease in these patients. The exact mechanism for this is unclear. There is no clear consensus on how best to quantify or predict cardiac risk in hypopituitarism. QRISK2 cardiovascular disease risk algorithm provides estimates of 10-year cardiovascular disease (CVD) risk in patients...

Introduction: Patients with craniopharyngioma are characterised by a high incidence of hypopituitarism, visual failure and hypothalamic dysfunction. Standardised mortality is markedly elevated and controversy exists about optimal treatment.Aim: We aimed to examine the temporal trends in the treatment of craniopharyngioma at our centre. Also, we sought to examine treatment needs and long-term morbidity in this patient group.Methods:...

Background: Inadequate glucocorticoid (GC) replacement may be associated with overexposure to GC, which can adversely influence metabolic and cardio-vascular state of hypopituitary growth hormone deficient adult patients (A-GHD). In this study we compared metabolic profile of ACTH insufficient and sufficient patients in A-GHD not treated with GH.Patients and methods: A cohort of 260 patients (age 48.6±12 years and BMI 28.7±6.6 kg/m2)...

Introduction: Insulin stress test (IST) has long been the gold standard for testing the hypothalamus-pituitary–adrenal (HPA) axis. There are concerns about the safety of IST as hypoglycaemia can give rise to various symptoms including seizure and coma although this is rarely seen in clinical practice. Hyperinsulinaemic hypoglycaemic clamp is a common research procedure used to induce hypoglycaemia in a step-wise fashion to study the effect of hypoglycaemia.<p class="a...

Introduction: Patients with acromegaly are frequently left with long-term adverse sequelae. Cross-sectional evaluation of health-related quality of life (HR-QoL) using both generic and specific questionnaires (AcroQoL) has confirmed HR-QoL to be severely impaired in acromegaly. However, long-term HR-QoL outcomes following disease control have been less well-described.Methods: The disease specific questionnaire AcroQoL and three validated generic question...

Background: The prevalence of incidental pituitary adenoma is estimated between 10 and 20% in autopsy and radiological data. Such pituitary incidentalomas are increasingly detected, as access to sensitive imaging modalities improves. We present a review of the recent pituitary incidentaloma referrals at a tertiary centre during 2 years from January 2013.Methods: All patients with pituitary incidentalomas on brain imaging between 2013 and 2015 were review...

Background: Healthcare organisations worldwide are making use of patient-reported outcome measures (PROMs) to assess the impact of care received on patient’s health-related quality of life.Aim: A cross-sectional pilot study designed to evaluate the suitability and validity of a proposed pituitary PROM questionnaire pack for patients having pituitary surgery.Methods: The PROM pack comprised five questionnaires focused on sympto...

Objective: To describe the experience of pituitary apoplexy from a single-centre modern series.Methods: We retrospectively reviewed the case notes of patients presenting to Salford Royal NHS Foundation Trust between February 2005 and April 2014 with pituitary apoplexy.Results: A total of 32 cases (20 males) presenting with classical apoplexy were identified, with a mean age at presentation of 54 years (range 22–88 years). 11 p...

Highly regulated pulsatile secretion of the GnRH is essential for reproduction. GnRH pulses act via 7TM receptors to control synthesis and secretion of FSH and LH. GnRH receptors activate a signal-transduction network that includes two parallel pathways mediated by ERK and nuclear factor of activated T cells (NFAT). ERK and NFAT in concert with other effectors mediate transcriptional regulation of FSHβ and LHβ genes following stimulation by pulsatil...

Background: Prolactinomas are the major subtype (20–30%) of pituitary adenomas. Microprolactinomas (<1 cm) are commoner in females, whereas macroprolactinomas (>1 cm) occur mainly in men. Giant prolactinomas are rare (2–3% of prolactinomas) – features include size of ≥4 cm, with significant extrasellar extension and prolactin levels of >1000 μg/l.Case report: We report the case of a 35-year-old man with type 2 diabet...

Loperamide is a poorly absorbed opioid μ-receptor agonist that is the most commonly used anti-diarrhoeal medication in the UK. Prescription cost analysis from the Department of Health and Social Care Information Centre reported that 1.79 million prescriptions of the drug were issued in 2014 and it is also freely available ‘over the counter’. It is widely believed to be very safe, with constipation as the main side-effect.A 45-year-old man ...

Background: Most cases of hypopituitarism are due to pituitary tumours or their treatment. Surgery is the treatment of choice in cases of pituitary adenomas which account for 90% of sellar and parsellar lesions. We present an unusual case of a non-adenomatous pituitary mass presenting with panhypopituitarism.Case: A 56-year-old male with background of sickle cell trait and hypertension presented with syncope, lethargy and nausea. He had an 18-month histo...

Introduction: Non-functioning pituitary macroadenoma (NFMA) can cause considerable morbidity due to pituitary dysfunction and pressure effects. We present recent experience in managing cases diagnosed with NFMA at a single tertiary centre between January 2009 and October 2013.Results: Of the 63 patients with NFMA, 28 (44%) were females. Age ranged from 22 to 91 (mean 63). Visual disturbance symptoms (35/63; 57%) were the commonest presentation. Headache ...

Background and aims: In 2010 pituitary service improvements were instigated, e.g., creation of local pituitary MDTs/joint pituitary clinics with surgeons. In the absence of national guidelines on post-surgical follow up of pituitary patients there was an evolution of local best practice standards. An audit was conducted in March 2015.Methods: Twenty-six patients underwent pituitary surgery at local tertiary centre in 2013/14 with endocrine care based at ...

Introduction: Langerhans cell histiocytosis (LCH) is a rare multisystem disease. Pituitary manifestations include failure of the anterior and/or posterior pituitary, with diabetes insipidus and gonadotrophine deficiency being most prevalent. We present a case of a female who had pituitary failure yet conceived naturally following chemotherapy.Case description: A 24-year-old female presented with polydipsia, polyuria, and lethargy. A water deprivation tes...

Endocrinopathies are becoming increasingly recognised with the use of new anticancer drugs. Ipilimumab therapy has recently been associated with hypophysitis. The presentation of hypopituitarism can be non-specific and diagnosis in an oncology setting may be challenging. We describe a 77-year-old man who presented to oncology with a short history of lethargy, nausea, anorexia, and weight loss. He had completed four cycles of ipilimumab as treatment for melanoma 7–9 months...

Acromegaly control/remission is defined by stringent criteria: normal age-/sex-adjusted IGF1 and random GH (GHr) <1 ng/ml or a GH nadir (GHn) during oral glucose tolerance test (OGTT) of <0.4 ng/ml. However discordances between GH and IGF1 have been recorded in about 30% of patients. We retrospectively analyzed the evolution in patients with acromegaly and discordant GH–IGF1 levels while being treated with somatostatin analogs (SSA) and/or cabergoline (CAB).<p...

Craniopharyngiomas are rare solid or mixed solid-cystic tumours. Although benign histologically, these tumours frequently shorten life and should be considered low-grade malignancies.We present the case of a 12-year-old boy diagnosed in 2008, at age 5, with a suprasellar tumour of 22/21/20 mm with mixed solid and cystic areas. The tumour was operated twice by left transfrontal approach in 2008 and right transfrontal approach in 2009. The pathology exam r...

A 57-year-old woman presented with a 4-week history of lethargy, weight loss, polyuria, and polydipsia. Her only past medical history of note was hypertension for which she was taking lisinopril. On admission her initial investigations showed: glucose 22.6 mmol/l, capillary blood ketones Hi and a metabolic acidosis (H+57.5 nmol/l and HCO3− 13.7 mmol/l). She was commenced on the DKA protocol and her acidosis resolved without complication. She was maintained on ...

A 73-year-old female, fit and well otherwise, was not any regular medications, was diagnosed with choroidal melanoma in 2010, and enucleated, subsequently had DTIC for multiple metastasis in 2014. She also received ipilimumab for 3 months as second line treatment for metastases. Presented to neurosurgeons with cold intolerance and dizzy spells, random cortisol was <30, started on dexamethasone 1 mg twice daily. Also had a low TSH of 0.71 with low free T4. Short ...

A 31-year-old woman presented with oligomenorrhoea and a raised prolactin. Pituitary scan revealed a 1.8 cm pituitary mass with compression of the optic chiasm. TSH was normal at 3.66 mIU/l with a raised FT4 of 25.8 pmol/l. The rest of pituitary function was normal. Visual fields demonstrated a bitemporal upper quadrantanopia. A diagnosis of TSH-secreting pituitary adenoma was suspected because of the high normal TSH in the presence of a high FT4. She und...

A 35-year-old lady was admitted at 24 weeks gestation with a 3–4 weeks history of persistent severe, left sided headaches associated with vomiting but not with visual disturbance. She had a prior history of migraines. However, her current headaches were very different in character. On examination her Glasgow Coma score was 15. There was no neck stiffness or photophobia. Visual fields and fundoscopy was normal. She was haemodynamically stable. Magnetic resonance imaging (M...

Silent corticoptroph adenomas (SCA) are pituitary tumours positive on immunohistochemical staining for ACTH but without clinical evidence of hypercortisolism. They account for 1.1–6% of surgically removed pituitary adenomas. Most tumours are macroadenomas with suprasellar extension present in 87–100% of the cases. They present with mass effects and this is in contrast to Cushing’s disease, which is mostly attributed to microadenomas. Reports suggest that these t...

Meningiomas account for about 1% of sellar masses; they can mimic macroadenomas. Although majority are WHO grade 1 tumours, these are technically challenging due to high vascularity and often present with visual disturbance. Certain radiological features might help to suspect sellar/suprasellar meningiomas. We present two cases sellar meningioma.Case 1: A 48-year-old-female with presumed diagnosis of non-functioning pituitary macroadenoma (NFPA) with mil...

A 51-year-old man presented to an optometrist with a 3-week history of visual impairment following a minor headache. He was found to have reduced visual acuity 6/24 in both eyes and a dense bitemporal hemianopia and was referred urgently to Musgrove Park Emergency Department. MRI brain showed a cystic bleed from a pituitary macroadenoma, 30 mm in diameter, with compression of the optic chiasm. He had no clinical features of Cushing’s or other hormone excess or deficiency ...