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Purpose There is no compelling outcome data or clear guidance surrounding postoperative venous thromboembolism (VTE) prophylaxis using low molecular weight heparin (chemoprophylaxis) in patients undergoing pituitary surgery. Here we describe our experience of early chemoprophylaxis (post-operative day 1) following trans-sphenoidal pituitary surgery. Methods Single-centre review of a prospective surgical database and VTE records. Adults undergoing first time trans-sphenoidal pituitary surgery were included (2009–2018). VTE was defined as either deep vein thrombosis and/or pulmonary embolism within 3 months of surgery. Postoperative haematomas were those associated with a clinical deterioration together with radiological evidence. Results 651 Patients included with a median age of 55 years (range 16–86 years). Most (99%) patients underwent trans-sphenoidal surgery using a standard endoscopic single nostril or bi-nostril trans-sphenoidal technique. More than three quarters had pituitary adenomas (n = 520, 80%). Postoperative chemoprophylaxis to prevent VTE was administered in 478 patients (73%). Chemoprophylaxis was initiated at a median of 1 day post-procedure (range 1–5 days postoperatively; 92% on postoperative day 1). Tinzaparin was used in 465/478 patients (97%) and enoxaparin was used in 14/478 (3%). There were no cases of VTE, even in 78 ACTH-dependent Cushing’s disease patients. Six patients (1%) developed postoperative haematomas. Chemoprophylaxis was not associated with a significantly higher rate of postoperative haematoma formation (Fisher’s Exact, p = 0.99) or epistaxis (Fisher’s Exact, p > 0.99). Conclusions Chemoprophylaxis after trans-sphenoidal pituitary surgery on post-operative day 1 is a safe strategy to reduce the risk of VTE without significantly increasing the risk of postoperative bleeding events.

PURPOSE: To assess and compare outcome of surgical management of non-functioning pituitary adenohypophyseal tumours in patients under 65-years, and 65-years and older at tertiary neurosurgical referral centre.METHODS: Data was retrospectively analysed from pituitary database. Forty-four patients aged 65 or older (Group 1) and 93 patients under 65 (Group 2) underwent endoscopic trans-sphenoidal surgery (ETSS) between January 2017 and July 2019. The surgical, endocrinological, ophthalmological and radiological outcomes were compared.RESULTS: 6.8% of Group 1 patients had peri-operative surgical complications compared to 12.9% in Group 2 (p = 0.29). Improved visual fields and acuity were seen in 65.2% and 82.8% of Group 1 and Group 2 respectively (p = 0.124), although there were pre-existing ocular problems in 15.9% of Group 1. New hormone deficiencies were observed in 31.8% of Group 1 patients, and 24.7% of Group 2 (p = 0.555). Tumour regrowth/recurrence was seen in 2.3% of Group 1 (p = 0.553). The rate of repeat surgery was 6.8% in the Group 1 and 12.9% in Group 2 (p = 0.28). There was no significant relationship between extent of resection, complications or hormonal deficiency. The mean duration of follow-up was 10.5 ± 13.0 months for Group 1 patients and 13.0 ± 16.0 months for Group 2 patients (p = 0.526).CONCLUSIONS: ETSS for non-functioning pituitary adenohypophyseal tumours is safe and well tolerated in the patients aged 65 and older. Advanced age by itself should not be a contra-indication for ETSS. It is however highly recommended that the care of such patients to be offered at a high volume, dedicated pituitary surgical units.

Introduction: Magnetic resonance imaging (MRI) is the main modality to diagnose adenohypophyseal tumours, while biochemical assessment of pituitary hormones allows for their functional classification. In this retrospective exploratory cohort study, we investigated if quantitative differences in tumour MR signal intensity (SI) could be utilized to predict the function and histotype. Methods: Clinically acquired pretreatment MRI images were retrospectively analysed in 67 clinically non-functioning gonadotropinomas (NFG), 38 somatotropinomas, and 16 medically treated giant macroprolactinomas. Mean T1- and T2-weighted SI values were determined for each tumour and normalized against either centrum semiovale white matter or CSF to derive relative T1W and T2W SI values and the relative tumour T2/T1 SI ratio. Inter-group differences in quantitative MR parameters were compared, and the power of each parameter to discriminate tumour type and subtype was assessed using the area under the receiver operator characteristic curve (AUROC). In resected somatotropinomas, the relationship between tumour granulation status, relative MR SI values, and biochemical data was also compared. Results: Compared to somatotropinomas, NFG and macroprolactinomas displayed higher relative T2W SI (p < 0.001) and higher relative tumour T2/T1 SI ratio values (p < 0.001, ANOVA). Compared to intermediate/densely granulated tumours, sparsely granulated somatotropinomas were larger (p = 0.006, Mann-Whitney U test), had higher relative T2W SI (p ≤ 0.005), and higher relative tumour T2/T1 SI ratios (p ≤ 0.001, 2-tailed t test). Relative tumour T2W SI values and relative tumour T2/T1 ratio values demonstrated good discriminatory power in differentiating NFG from somatotropinoma (AUROC = 0.87–0.94) and predicting somatotropinoma subtypes (AUROC = 0.87–0.95). Conclusion: Quantitative SI-based MR parameters derived using clinical acquisition MRI protocols may help non-invasively discriminate the functional status of adenohypophyseal tumours and the histological subtype of somatotropinomas.

Introduction Prolonged elevated cortisol in Cushing’s Syndrome can lead to adrenal insufficiency post-adrenalectomy. Metyrapone is licensed to suppress endogenous cortisol production pre-operatively for symptom relief. The aim of this study was to investigate whether pre-treatment of patients with metyrapone led to reduced adrenal insufficiency, hence reduced steroid dependence post-op. Methods Cases were identified from UKRETS submissions between 2008–2020, with Electronic Patient Records used for data collection. Patients with adrenocortical carcinoma (ACC) and/or lost to follow-up were excluded. The remaining cases were divided into those treated with metyrapone pre-operatively and those not. Results were analysed via IBM SPSS Statistics software. Results Of 59 patients, those lost to follow up (n=6) and those with ACC (n=4) were excluded leaving 49 cases. Metyrapone patients (n=29) had a median of 3 symptoms of cortisol excess (0–9) compared to 2 symptoms (0–5) in non-metyrapone (n=20) (p=0.061). 82.8% (n=24) of metyrapone patients and 65% (n=13) of non-metyrapone patients were successfully weaned off steroids post-op, with the remaining patients still steroid dependent. Cox proportional hazards regression showed metyrapone did not impact steroid dependence (p=0.230). Metyrapone treatment increased the likelihood of adrenal recovery whereas increasing symptom burden reduced the likelihood (hazard ratio 0.271 and -0.143 respectively), however these findings were not significant (p=0.445 and p=0.117 respectively). Conclusion We found metyrapone had no significant impact on rate of adrenal failure. A larger series may more accurately determine whether metyrapone pre-operatively confers a higher likelihood of adrenal recovery and determine whether high symptom burden pre-operatively increases risk of steroid dependence post-operatively.

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Depending on severity of presentation, pituitary apoplexy can be managed with acute surgery or non-operatively. We aim to assess long-term tumour control, visual and endocrinological outcomes following pituitary apoplexy with special emphasis on patients treated non-operatively.Multicentre retrospective cohort study. All patients with symptomatic pituitary apoplexy were included. Patients were divided into 3 groups: group 1: surgery within 7 days; group 2: surgery 7 days-3 months; group 3: non-operative. Further intervention for oncological reasons during follow-up was the primary outcome. Secondary outcome measures included visual and endocrinological function at last follow-up.One hundred sixty patients were identified with mean follow-up of 48 months (n = 61 group 1; n = 34 group 2; n = 64 group 3). Factors influencing decision for surgical treatment included visual acuity loss (OR: 2.50; 95% CI: 1.02-6.10), oculomotor nerve palsy (OR: 2.80; 95% CI: 1.08-7.25) and compression of chiasm on imaging (OR: 9.50; 95% CI: 2.06-43.73). Treatment for tumour progression/recurrence was required in 17%, 37% and 24% in groups 1, 2 and 3, respectively (p = 0.07). Urgent surgery (OR: 0.16; 95% CI: 0.04-0.59) and tumour regression on follow-up (OR: 0.04; 95% CI: 0.04-0.36) were independently associated with long-term tumour control. Visual and endocrinological outcomes were comparable between groups.Urgent surgery is an independent predictor of long-term tumour control following pituitary apoplexy. However, 76% of patients who successfully complete 3 months of non-operative treatment may not require any intervention in the long term.

Primary salivary gland-like tumors of the sella are rare and often challenging to diagnose. They reportedly derive from serous and mucinous glands that remain trapped in the infundibulum during embryogenesis. We report a 68-year-old man who presented with partial left third cranial nerve palsy, visual loss in the left eye without visual field defects, headache, weight loss and reduced muscle bulk. Neuroimaging studies demonstrated a solid and cystic, avidly enhancing lesion expanding the pituitary fossa and extending to the left cavernous sinus. The patient underwent craniotomy and the tissue removed showed features of epithelial-myoepithelial carcinoma similar to the salivary gland, skin and breast counterpart. No primary tumor was found outside the sella. The lesion behaved aggressively despite radio-chemotherapy and the patient died 22 months from the onset. The tumor showed a novel TP53 in-frame deletion (Gly154del) while no variants were found in H-RAS hotspot regions (codons 12, 13 and 61). Our report expands the spectrum of salivary gland-like tumors primarily occurring in the sella and emphasizes the need for specialist review of rare, non-neuroendocrine tumors of the pituitary and sella regions.

To assess and compare outcome of surgical management of non-functioning pituitary adenohypophyseal tumours in patients under 65-years, and 65-years and older at tertiary neurosurgical referral centre.Data was retrospectively analysed from pituitary database. Forty-four patients aged 65 or older (Group 1) and 93 patients under 65 (Group 2) underwent endoscopic trans-sphenoidal surgery (ETSS) between January 2017 and July 2019. The surgical, endocrinological, ophthalmological and radiological outcomes were compared.6.8% of Group 1 patients had peri-operative surgical complications compared to 12.9% in Group 2 (p = 0.29). Improved visual fields and acuity were seen in 65.2% and 82.8% of Group 1 and Group 2 respectively (p = 0.124), although there were pre-existing ocular problems in 15.9% of Group 1. New hormone deficiencies were observed in 31.8% of Group 1 patients, and 24.7% of Group 2 (p = 0.555). Tumour regrowth/recurrence was seen in 2.3% of Group 1 (p = 0.553). The rate of repeat surgery was 6.8% in the Group 1 and 12.9% in Group 2 (p = 0.28). There was no significant relationship between extent of resection, complications or hormonal deficiency. The mean duration of follow-up was 10.5 ± 13.0 months for Group 1 patients and 13.0 ± 16.0 months for Group 2 patients (p = 0.526).ETSS for non-functioning pituitary adenohypophyseal tumours is safe and well tolerated in the patients aged 65 and older. Advanced age by itself should not be a contra-indication for ETSS. It is however highly recommended that the care of such patients to be offered at a high volume, dedicated pituitary surgical units.

Introduction: Surgical remission for acromegaly is dependent on a number of factors including tumour size, invasiveness, and surgical expertise. We studied the value of early post-operative growth hormone (GH) level as a predictor of outcome and to guide early surgical re-exploration for residual disease in patients with acromegaly. Methods: Patients with acromegaly undergoing first-time endoscopic transsphenoidal surgery between 2005 and 2015, in 2 regional neurosurgical centres, were studied. Insulin-like growth factor-1 (IGF-1), basal GH (i.e., sample before oral glucose), and GH nadir on oral glucose tolerance test (OGTT) were tested at various time points, including 2–5 days post-operatively. Definition of disease remission was according to the 2010 consensus statement (i.e., GH nadir Results: We investigated 81 consecutive patients with acromegaly, 67 (83%) of which had macroadenomas and 22 (27%) were noted to be invasive at surgery. Mean follow-up was 44 ± 25 months. Overall, surgical remission was achieved in 55 (68%) patients at final follow-up. On univariate analysis, the remission rates at the end of the study period for patients with early post-operative GH nadir on OGTT of N = 43), between 0.4 and 1 (N = 28), and >1 μg/L (N = 8) were 88, 54, and 20%, respectively. Similar results were seen with basal GH on early post-operative OGTT. On multivariate regression analysis, pre-operative IGF-1 (odds ratio of 13.1) and early post-operative basal GH (odds ratio of 5.0) and GH nadir on OGTT (odds ratio of 6.8) were significant predictors of residual disease. Based on a raised early GH nadir and post-operative MR findings, 10 patients underwent early surgical re-exploration. There was reduction in post-operative GH levels in 9 cases, of which 5 (50%) achieved long-term remission. There was an increased risk of new pituitary hormone deficiencies in patients having surgical re-exploration compared to those having a single operation (60 vs. 14%). Conclusions: An early post-operative basal GH and GH nadir on OGTT are reliable predictors of long-term disease remission. It can be used to guide patients for early surgical re-exploration for residual disease, although there is increased risk of hypopituitarism.

We document a patient with colon adenocarcinoma who presented with rapidly worsening visual impairment. Staging computer tomography and subsequent magnetic resonance scans documented a sellar, suprasellar lesion compressing the optic chiasm. The patient underwent trans-sphenoidal surgery to relieve optic chiasm compression and obtain tissue for diagnosis. Histological examination revealed a metastatic mucinous adenocarcinoma in a gonadotroph pituitary neuroendocrine tumour (PitNET, formerly pituitary adenoma). The patient underwent adjuvant radiotherapy to the sella and chemotherapy but he died nine months after pituitary surgery. This report highlights the diagnostic and management challenges of metastases to PitNET.

Background Pre-/postoperative pituitary endocrine deficiencies in patients with sellar/parasellar non-adenomatous lesions are poorly described and studies have not considered the effect of sellar invasion on endocrine outcome. The aim of this study was to relate the need for pituitary hormone replacement pre-/postoperatively, with sellar invasion, in non-adenomatous sellar/parasellar lesions. Methods Single-centre review of adults with histologically confirmed non-adenomatous sellar/parasellar lesion and follow-up ≥ 3 months or until postop radiotherapy. Pituitary dysfunction was defined by hormone replacement. The sellar encroachment score (0–6) was calculated as the sum of the thirds of radiological encroachment into the sellar region in the coronal and sagittal planes. Multivariate analysis with binary logistic regression was used to determine factors associated with pituitary hormone replacement. Results One hundred and seventeen patients were included with a median age of 49 years (range 16–84 years) and median follow-up of 13 months. Surgery was trans-sphenoidal (53%), trans-cranial (36%) or a combination (11%). The commonest histology types were meningioma (n = 33, 28%) and craniopharyngioma (n = 20, 17%). The median sellar encroachment score was 6 (range 0–6). Most (n = 86, 74%) did not require pituitary hormone replacement preoperatively. The need for pituitary hormones increased after surgery in 41 (35%) patients. In multivariate analysis, the sellar encroachment score was the only factor predictive of pre- (OR = 2.6, 95% CI = 1.2–5.5; p = 0.01) and postoperative risk of new pituitary hormone replacement (OR = 4.1, 95% CI = 1.7–10.1, p = 0.002). Conclusion A significant proportion of these patients present with need for pituitary hormone replacement that may worsen postoperatively. The degree of sellar encroachment is predictive of pituitary hormone replacement status pre-/postoperatively.

We set out to describe the modern day management of Lymphocytic hypophysitis (LH) with respect to its diagnosis, treatment and long-term endocrine and visual outcomes. We deliberately included patients with a clinical diagnosis of LH and compared them with those with a histological diagnosis following surgery.A multi-centre observational study was performed. Twenty-two patients were included and studied over a mean follow-up period of 8.6 years (range 4-26 years).Patients presented with headache (N = 15; 68 %), visual field disturbances (N = 7; 32 %) or a combination of these symptoms (N = 5; 23 %). The time lag between onset of symptoms and diagnosis was1 month, 1-6 months or6 months in approximately a third of the patients each, respectively. In two-thirds of the patients (N = 14) LH was diagnosed based on their clinical, biochemical and radiological findings. The surgical cohort (N = 8) was statistically more likely to have presented with larger lesions, with suprasellar extension and greater visual field defects. During follow-up there was improvement in headaches and visual symptoms, but the rate of hypopituitarism as reflected by the need for on-going pituitary hormone replacement persisted. At the 1, 5 and 10 year follow-up there was no significant difference between the medically and surgically managed cohorts in terms of ongoing symptomatology or need for pituitary hormone replacement.In the modern era, most patients with LH are diagnosed by non-surgical means and managed medically. There remains a significant time lag between the onset of symptoms and the eventual diagnosis of LH. Despite the considerable morbidity attached to LH, overall prognosis is good.

SummaryObjective To describe the clinical presentation, management and outcome of pituitary apoplexy from a single centre and retrospectively apply the Pituitary Apoplexy Score (PAS). Design Retrospective review of patients presenting with classical pituitary apoplexy to a single neurosurgical centre in the Greater Manchester region. Results A total of 31 cases with classical pituitary apoplexy were identified between 2005 and 2014. The mean age at presentation was 55 years, and there were 19 men. In only one patient was there prior knowledge of a pituitary adenoma. Eleven (35%) patients were managed conservatively and 20 (65%) patients managed surgically. Emergency surgery was carried out in 11 patients. At presentation, visual symptoms were present in a higher proportion of patients in the surgical group (90%) compared to the conservatively managed group (64%). At final follow-up, visual recovery was apparent in most patients in both the surgical (100%) and conservatively (86%) managed groups. The proportion of patients with hypopituitarism was high in both the surgical (86%) and conservative (73%) groups at presentation, and this failed to improve at final follow-up (90% vs 73%, respectively). The median PAS scores were higher in the surgical (PAS 2), compared to the conservatively managed group (PAS 0). Conclusion In pituitary apoplexy patients managed conservatively or surgically, there is good recovery of visual symptoms but not endocrine function. Patients should be managed on a case-by-case basis based on the severity of symptoms at presentation, progression of disease and surgical expertise available. Further prospective studies using the PAS are required to determine its usefulness in clinical practice.

We present the case of a patient with Cushing's syndrome secondary to ectopic ACTH secretion. A MR of the head showed a left-sided nasal mass extending down from the cribriform plate. The patient underwent endoscopic resection with nearly complete removal of the mass. Histological examination showed an ACTH-secreting olfactory neuroblastoma (ONB). The patient's cortisol levels returned to normal range after surgery and have remained normal for over a year. ONB is a rare cause for ectopic ACTH secretion. This case highlights the diagnostic and management difficulties in patients with ectopic ACTH secretion, and provides a brief review of ONB.

OBJECTIVE: The variation in reported prevalence of growth hormone deficiency (GHD) post subarachnoid haemorrhage (SAH) is mainly due to methodological heterogeneity. We report on the prevalence of GHD in a large cohort of patients following SAH, when dynamic and confirmatory pituitary hormone testing methods are systematically employed.DESIGN: In this cross-sectional study, pituitary function was assessed in 100 patients following SAH. Baseline pituitary hormonal profile measurement and glucagon stimulation testing (GST) was carried out in all patients. Isolated GHD was confirmed with an Arginine stimulation test and ACTH deficiency was confirmed with a short synacthen test.RESULTS: The prevalence of hypopituitarism in our cohort was 19% and the prevalence of GHD was 14%. There was no association between GHD and the clinical or radiological severity of SAH at presentation, treatment modality, age, or occurrence of vasospasm. There were statistically significant differences in terms of Glasgow Outcome Scale (GOS; p = 0.03) between patients diagnosed with GHD and those without. Significant inverse correlations between GH peak on GST with body mass index (BMI) and waist hip ratio (WHR) was also noted (p CONCLUSION: Using the current testing protocol, the prevalence of GHD detected in our cohort was 14%. It is unclear if the BMI and WHR difference observed is truly due to GHD or confounded by the endocrine tests used in this protocol. There is possibly an association between the development of GHD and worse GOS score. Routine endocrine screening of all SAH survivors with dynamic tests is time consuming and may subject many patients to unnecessary side-effects. Furthermore the degree of clinical benefit derived from growth hormone replacement in this patient group, remains unclear. Increased understanding of the most appropriate testing methodology in this patient group and more importantly which SAH survivors would derive most benefit from GHD screening is required.

Purpose In pituitary apoplexy (PA), there are preliminary reports on the appearance of sphenoid sinus mucosal thickening (SSMT). SSMT is otherwise uncommon with an incidence of up to 7% in asymptomatic individuals. The aim of this study was to evaluate the incidence and clinical significance of SSMT in patients with PA and a control group of surgically treated non-functioning pituitary adenomas (NFPAs). Methods Retrospective review of clinical and imaging variables in PA and NFPA patients. Sphenoid sinus mucosal thickness was measured on the presenting MRI scan by a blinded neuroradiologist. Pathological SSMT was defined as >1 mm adjacent to the pituitary fossa. Forward stepwise logistic regression was used to identify factors associated with SSMT. Results There were 50 NFPA and 47 PA patients. PA patients were managed conservatively (N = 11) or surgically (N = 36). The median sphenoid sinus mucosal thickness was greater in the PA than NFPA groups (2.0 vs. 0.5 mm; p

Objective Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are associated with pituitary adenoma, acromegaly and gigantism. Identical alleles in unrelated pedigrees could be inherited from a common ancestor or result from recurrent mutation events. Design and methods Observational, inferential and experimental study, including: AIP mutation testing; reconstruction of 14 AIP-region (8.3 Mbp) haplotypes; coalescent-based approximate Bayesian estimation of the time to most recent common ancestor (tMRCA) of the derived allele; forward population simulations to estimate current number of allele carriers; proposal of mutation mechanism; protein structure predictions; co-immunoprecipitation and cycloheximide chase experiments. Results Nine European-origin, unrelated c.805_825dup-positive pedigrees (four familial, five sporadic from the UK, USA and France) included 16 affected (nine gigantism/four acromegaly/two non-functioning pituitary adenoma patients and one prospectively diagnosed acromegaly patient) and nine unaffected carriers. All pedigrees shared a 2.79 Mbp haploblock around AIP with additional haploblocks privately shared between subsets of the pedigrees, indicating the existence of an evolutionarily recent common ancestor, the ‘English founder’, with an estimated median tMRCA of 47 generations (corresponding to 1175 years) with a confidence interval (9–113 generations, equivalent to 225–2825 years). The mutation occurred in a small tandem repeat region predisposed to slipped strand mispairing. The resulting seven amino-acid duplication disrupts interaction with HSP90 and leads to a marked reduction in protein stability. Conclusions The c.805_825dup allele, originating from a common ancestor, associates with a severe clinical phenotype and a high frequency of gigantism. The mutation is likely to be the result of slipped strand mispairing and affects protein–protein interactions and AIP protein stability.

Objective Mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are associated with pituitary adenoma, acromegaly and gigantism. Identical alleles in unrelated pedigrees could be inherited from a common ancestor or result from recurrent mutation events. Design and methods Observational, inferential and experimental study, including: AIP mutation testing; reconstruction of 14 AIP-region (8.3 Mbp) haplotypes; coalescent-based approximate Bayesian estimation of the time to most recent common ancestor (tMRCA) of the derived allele; forward population simulations to estimate current number of allele carriers; proposal of mutation mechanism; protein structure predictions; co-immunoprecipitation and cycloheximide chase experiments. Results Nine European-origin, unrelated c.805_825dup-positive pedigrees (four familial, five sporadic from the UK, USA and France) included 16 affected (nine gigantism/four acromegaly/two non-functioning pituitary adenoma patients and one prospectively diagnosed acromegaly patient) and nine unaffected carriers. All pedigrees shared a 2.79 Mbp haploblock around AIP with additional haploblocks privately shared between subsets of the pedigrees, indicating the existence of an evolutionarily recent common ancestor, the ‘English founder’, with an estimated median tMRCA of 47 generations (corresponding to 1175 years) with a confidence interval (9–113 generations, equivalent to 225–2825 years). The mutation occurred in a small tandem repeat region predisposed to slipped strand mispairing. The resulting seven amino-acid duplication disrupts interaction with HSP90 and leads to a marked reduction in protein stability. Conclusions The c.805_825dup allele, originating from a common ancestor, associates with a severe clinical phenotype and a high frequency of gigantism. The mutation is likely to be the result of slipped strand mispairing and affects protein–protein interactions and AIP protein stability.

Summary Introduction Surgical remission rates for acromegaly vary and are dependent on the tumour morphology, biochemical definition of disease remission and surgical expertise. A previous report from the Manchester region in 1998 reported an overall surgical remis- sion rate of 27% using accepted criteria for biochemical remission at the time. The establishment of the 2010 Consensus guidelines further tightens biochemical criteria for remission. This report aims to assess the impact of establishing a specialist pituitary sur- gery service in Manchester in 2005, with reduced surgeon numbers on the remission rates for acromegaly surgery. Methods Patients with acromegaly undergoing first time endo- scopic transsphenoidal surgery between 2005 and 2010 were stud- ied. Surgery was performed by a single surgeon. Review of a prospectively collected acromegaly surgery database was performed with documentation of pre- and postoperative biochemical tests (oral glucose tolerance test (oGTT) and IGF-1), as well as clinical, pathological and radiological data. Definition of disease remission was according to the 2010 Consensus criteria (GH nadir

ObjectivesSphenoid sinus mucosal thickening (SSMT) is described in small preliminary studies in the setting of pituitary apoplexy (PA). The aim of this study was to explore the possible association between PA and SSMT, and the microbial profile of SSMT.DesignSingle-centre case notes and tissue samples review (2007–2016).SubjectsPA group: radiological/histologically confirmed PA; control group: non-functioning pituitary adenomas (NFPAs).MethodsSSMT was measured on presenting MRI scans (pathological >1 mm). Forward stepwise logistic regression was used to identify factors associated with SSMT. Sphenoid sinus mucosal specimens were microbiologically profiled by PCR in a subset.ResultsImaging arm: 50 NFPA and 47 PA patients included. In multivariate analysis of both the PA and NFPA groups, the presence of PA was the only factor associated with SSMT (OR=0.043, 95% CI 0.012 to 0.16; pConclusionsSSMT is associated with PA, especially during the acute phase. SSMT is also associated with microbiota seen in sinusitis. Our results require further validation.

INTRODUCTION: Innate immune sensors such as TLR2 are consistently overexpressed in bone marrow CD34+ cells from low risk MDS patients (pts), and a gain of function mutation in TLR2 correlates with progression. Ex vivo inhibition of TLR2 in cultures of CD34+ cells using Tomaralimab (OPN-305), a fully humanised antagonistic IgG4 monoclonal antibody, led to an increase in differentiation of erythroid cultures. We previously reported a human trial with Tomaralimab in low risk/Int-1 MDS that failed HMA therapy (HMA-F) using 5 mg/kg Tomaralimab (n=11), with 4 pts treated at a higher dose of 10 mg/kg monthly. Here we report response data in an expanded 10 mg/kg HMA-F cohort. Tomaralimab was administered as a third line therapy to heavily pre-treated transfusion-dependent (TD) pts with >50% of pts having received ≥4 previous therapies. The data indicate that Tomaralimab is a potential therapy for low risk/Int-1 MDS. METHODS: We designed a phase I/II multi-site clinical trial of Tomaralimab for pts with low or Int-1 risk MDS after failure with prior therapy with HMA. Pts were treated every 4 weeks for up to 9 cycles, with the potential of continued use thereafter. Azacitidine (AZA) could be added back into the therapy regimen after 16 weeks of Tomaralimab monotherapy if there was no response. The primary endpoint was the induction of transfusion independence for two consecutive cycles as defined in IWG criteria (major responders). A minor response was characterised by at least a 50% reduction in the need for transfusions compared to their transfusions prior to Tomaralimab therapy. We also evaluated the toxicity, pharmacokinetic profile, receptor occupancy, cytokine profile, as well as a novel set of TLR2 related genes. RESULTS: At the time of this report, 51 pts have received Tomaralimab at 10 mg/kg in HMA-F pts. The median age was 72 years and 79% of the pts were male. Twenty two pts were fully evaluable, having completed the study at Week 36 and either achieving transfusion independence or, if not, receiving AZA add-back unless previously withdrawn due to toxicity or disease progression. Pre-study, the average transfusion was 10 units (median = 3.5 units) and the average on-study was 2 units (median = 1.5 units). Even though these pts were very heavily pre-treated with previous therapies, there were 6 pts who met the primary endpoint (27%) across multiple centres, 5 of which were on Tomaralimab monotherapy at the time of response. Furthermore, there were 5 minor responders (23%), giving an overall response rate (ORR) of 50%. Additionally, 10 pts (45%) remained stable throughout the therapy window. There were no dose limiting toxicities or development of anti-drug antibodies. Tomaralimab receptor occupancy (RO) was measured by flow cytometry in both the BM (CD34+CD38- cells) and PB (CD14+ CD45+). Measured RO levels in both indicated that there was full receptor occupancy in both compartments and that Tomaralimab penetrated the BM. Compared to non-responders, there was a non-significant increase in the expression of TLR1, IRAK4, IL-6, GATA-2, CD71, TRAF6 and S100A9 and a non-significant decrease in GATA-1, TLR2 and TLR6. These are non-significant because of low numbers in the non-responder group. Gene expression was increased in all cases relative to age matched non-MDS healthy controls. Of these genes, of particular interest is S100A9. This has been shown in the literature to be increased in the BM plasma of MDS pts. Furthermore, using the cell line THP-1XBlue we showed that S100A9 signals via TLR2 in vitro and this effect was ameliorated by incubation with Tomaralimab. CONCLUSIONS: Early data suggest that Tomaralimab therapy presents a novel and safe treatment for heavily pre-treated low risk/Int-1 MDS HMA-F pts. Tomaralimab exhibited a 50% ORR in heavily pre-treated, transfusion dependent HMA-F patents. Treatment was well tolerated and penetrated the bone marrow. RO in the blood could also be used as a surrogate for RO in the bone marrow. Surprisingly, there was no correlation between efficacy and cytokine concentration in the plasma, although cytokine changes in the bone marrow were not determined. There were however non-significant alterations in TLR2 and related genes in purified bone marrow cells from pts. Studies using these cells are underway to further elucidate the mechanism of action. In brief, Tomaralimab therapy presents a potential therapeutic option for heavily pre-treated low risk pts that have failed HMA therapy. Disclosures Jabbour: novartis: Research Funding. Konopleva:cellectis: Research Funding; abbvie: Research Funding; Immunogen: Research Funding; Stemline Therapeutics: Research Funding. Daver:Pfizer: Research Funding; Incyte: Research Funding; Novartis: Research Funding; Novartis: Consultancy; ARIAD: Research Funding; BMS: Research Funding; ImmunoGen: Consultancy; Pfizer: Consultancy; Otsuka: Consultancy; Alexion: Consultancy; Incyte: Consultancy; Sunesis: Research Funding; Daiichi-Sankyo: Research Funding; Sunesis: Consultancy; Kiromic: Research Funding; Karyopharm: Consultancy; Karyopharm: Research Funding. DiNardo:Agios: Consultancy; Bayer: Honoraria; Karyopharm: Honoraria; Abbvie: Honoraria; Medimmune: Honoraria; Celgene: Honoraria. Bose:Celgene Corporation: Honoraria, Research Funding; Incyte Corporation: Honoraria, Research Funding; Pfizer, Inc.: Research Funding; Astellas Pharmaceuticals: Research Funding; Constellation Pharmaceuticals: Research Funding; Blueprint Medicines Corporation: Research Funding; CTI BioPharma: Research Funding. Komrokji:Novartis: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding. Roboz:AbbVie: Consultancy; Otsuka: Consultancy; Bayer: Consultancy; Bayer: Consultancy; Sandoz: Consultancy; Celltrion: Consultancy; Pfizer: Consultancy; Astex Pharmaceuticals: Consultancy; Jazz Pharmaceuticals: Consultancy; Argenx: Consultancy; Cellectis: Research Funding; Celgene Corporation: Consultancy; Cellectis: Research Funding; Orsenix: Consultancy; Daiichi Sankyo: Consultancy; Janssen Pharmaceuticals: Consultancy; Roche/Genentech: Consultancy; Aphivena Therapeutics: Consultancy; Aphivena Therapeutics: Consultancy; Celgene Corporation: Consultancy; Orsenix: Consultancy; Astex Pharmaceuticals: Consultancy; Jazz Pharmaceuticals: Consultancy; Janssen Pharmaceuticals: Consultancy; Eisai: Consultancy; AbbVie: Consultancy; Pfizer: Consultancy; Eisai: Consultancy; Novartis: Consultancy; Argenx: Consultancy; Daiichi Sankyo: Consultancy; Celltrion: Consultancy; Sandoz: Consultancy; Roche/Genentech: Consultancy; Otsuka: Consultancy; Novartis: Consultancy. Miller:Opsona Therapeutics: Employment. Arbe-Barnes:Opsona Therapeutics: Employment. Reilly:Opsona Therapeutics: Employment. McGuirk:Opsona Therapeutics: Employment. Kearney:Opsona Therapeutics: Employment. Keogh:Opsona Therapeutics: Employment.

BACKGROUND: The use of the fiberoptic endoscope is a recent innovation in pituitary surgery. OBJECTIVE: To investigate the evidence of an operative learning curve after the introduction of endoscopic transsphenoidal surgery in our unit. METHODS: The first 125 patients who underwent endoscopic transnasal transsphenoidal surgery for pituitary fossa lesions between 2005 and 2007 performed by 1 surgeon were studied. Changes in a number of parameters were assessed between 2 equal 15-month time periods: period 1 (53 patients) and period 2 (72 patients). RESULTS: There were 67 patients (54%) with nonfunctioning adenomas, 22 (18%) with acromegaly, and 10 (8%) with Cushing's disease. Between study periods 1 and 2, there was a decrease in the mean duration of surgery for nonfunctioning adenomas (from 120 minutes to 91 minutes; P < .01). This learning effect was not apparent for functioning adenomas, the surgery for which also took longer to perform. The proportion of patients with an improvement in their preoperative visual field deficits increased over the study period (from 80% to 93%; P < .05). There were nonsignificant trends toward improved endocrine remission rates for patients with Cushing's disease (from 50% to 83%), but operative complications, notably the rates of hypopituitarism, did not change. Overall length of hospital stay decreased between time periods 1 and 2 (from 7 to 4 days median; P < .01). CONCLUSION: The improvements in the duration of surgery and visual outcome noted after about 50 endoscopic procedures would favor the existence of an operative learning curve for these parameters. This further highlights the benefits of subspecialization in pituitary surgery.

Background: Cushing's syndrome (CS) is a severe condition with excess mortality and significant morbidity necessitating control of hypercortisolemia. There are few data documenting use of the steroidogenesis inhibitor metyrapone for this purpose. Objective: The objective was to assess the effectiveness of metyrapone in controlling cortisol excess in a contemporary series of patients with CS. Design: This was designed as a retrospective, multicenter study. Setting: Thirteen University hospitals were studied. Patients: We studied a total of 195 patients with proven CS: 115 Cushing's disease, 37 ectopic ACTH syndrome, 43 ACTH-independent disease (adrenocortical carcinoma 10, adrenal adenoma 30, and ACTH-independent adrenal hyperplasia 3). Measurements: Measurements included biochemical parameters of activity of CS: mean serum cortisol “day-curve” (CDC) (target 150–300 nmol/L); 9 am serum cortisol; 24-hour urinary free cortisol (UFC). Results: A total of 164/195 received metyrapone monotherapy. Mean age was 49.6 ± 15.7 years; mean duration of therapy 8 months (median 3 mo, range 3 d to 11.6 y). There were significant improvements on metyrapone, first evaluation to last review: CDC (91 patients, 722.9 nmol/L [26.2 μg/dL] vs 348.6 nmol/L [12.6 μg/dL]; P < .0001); 9 am cortisol (123 patients, 882.9 nmol/L [32.0 μg/dL] vs 491.1 nmol/L [17.8 μg/dL]; P < .0001); and UFC (37 patients, 1483 nmol/24 h [537 μg/24 h] vs 452.6 nmol/24 h [164 μg/24 h]; P = .003). Overall, control at last review: 55%, 43%, 46%, and 76% of patients who had CDCs, UFCs, 9 am cortisol less than 331 nmol/L (12.0 μg/dL), and 9 am cortisol less than upper limit of normal/600 nmol/L (21.7 μg/dL). Median final dose: Cushing's disease 1375 mg; ectopic ACTH syndrome 1500 mg; benign adrenal disease 750 mg; and adrenocortical carcinoma 1250 mg. Adverse events occurred in 25% of patients, mostly mild gastrointestinal upset and dizziness, usually within 2 weeks of initiation or dose increase, all reversible. Conclusions: Metyrapone is effective therapy for short- and long-term control of hypercortisolemia in CS. Cushing's syndrome (CS) is a severe condition with excess mortality and significant morbidity necessitating effective biochemical control (1). Where a cause amenable to surgical intervention is identified, surgery at a center with appropriate expertise is the optimum management. Nevertheless, many patients need urgent control of severe or persisting hypercortisolemia. Options for medical treatment include steroidogenesis enzyme inhibitors suitable for all causes of CS (ketoconazole, metyrapone, mitotane), agents to suppress ACTH in Cushing's disease (CD), such as dopamine agonists and pasireotide, and the glucocorticoid receptor antagonist, mifepristone (2, 3). The modern use of ketoconazole has recently been reported in a multicenter French Study (4), although its availability in the United States has been restricted after an Food and Drug Administration safety warning for hepatotoxicity in 2013 (5, 6), but it is widely available in Europe in 2015 (7).The cortisol-lowering effect of metyrapone was described as early as 1958 by Liddle et al (8), with later reports confirming metyrapone as a potent inhibitor of the steroidogenesis enzyme 11β-hydroxylase (8, 9). Since then, it has been used as a diagnostic test of adrenal reserve and to treat the hypercortisolism of CS. Despite its widespread use, data on metyrapone are scarce, with the largest study to date (including 91 patients) being published over 25 years ago (10). Here, we have assessed the effectiveness of metyrapone therapy in a contemporary series of patients with CS, by performing a retrospective study of patients treated in the United Kingdom.

In this study, we concurrently examined the effects of 8 and 40 weeks of growth hormone replacement (GHR) on lipids, lipoprotein composition, low-density lipoprotein (LDL) size, very-low-density lipoprotein (VLDL) apolipoprotein (apo)B kinetics and LDL apoB kinetics. Eight weeks of GHR did not alter lipid profiles. Forty weeks of GHR increased high-density lipoprotein-cholesterol (HDL-C) concentration (P =.01), nonsignificantly reduced LDL-C (P =.06), and reduced the HDL/LDL-C ratio (P =.04). Forty weeks of GHR increased HDL free cholesterol (P =.03), total cholesterol (P =.01), and cholesterol ester (P

Extra-ventricular neurocytoma (EVN) is rare, mainly described within the cerebral hemispheres or spinal cord. We report a case of sellar neurocytoma presenting with chiasmal compression.A 50-year-old woman presented with decreasing vision and a bitemporal field deficit. CT and MRI demonstrated an enhancing invasive sellar lesion extending into the sphenoid sinus and left cavernous sinus, with speckled calcification and compression of the optic chiasm. Pituitary function was normal apart from a mildly elevated prolactin level consistent with stalk effect.Endoscopic trans-sphenoidal resection of the lesion was performed revealing a firm, vascular tumour. Some residual tumour was left within the left cavernous sinus. Histology revealed a neurocytic tumour with nests, islands and strands of neuropil. Diffuse synaptophysin, chromogranin, neurofilament protein and CD56 positivity was seen. A histological diagnosis of EVN, WHO grade II was made and adjuvant radiotherapy was given for the residual tumour.This is only the second case of neurocytoma of the sella reported. It should be considered in the differential diagnoses of sellar lesions that appear radiologically atypical for pituitary adenomas.

The dyslipidemia associated with hypopituitarism may contribute to increased vascular mortality. The atherogenic potential of lipoproteins is determined not only by concentration but also by their composition. We therefore studied very low-density lipoprotein composition and apolipoprotein B kinetics in 16 hypopituitary subjects and 16 controls. Hypopituitarism was associated with reduced high-density lipoprotein cholesterol (0.98[0.82-1.18] vs. 1.35[1.15-1.41] mmol/liter, P < 0.001) and increased triglyceride concentrations (1.64[1.09-2.77] vs. 1.12[0.66-1.67] mmol/liter, P = 0.01). Total (P = 0.76) and low-density lipoprotein cholesterol (P = 0.56) concentrations were similar. Very low-density lipoprotein- triglyceride was significantly increased (1.48[1.02-2.55] vs. 0.9[0.31-2.30] mmol/liter, P = 0.004), but very low-density lipoprotein cholesterol levels were similar (P = 0.93). The molar ratios of very low-density lipoprotein-triglyceride:apolipoprotein B (6193[4283-9566] vs. 3599[3188-6854], P = 0.005) and very low-density lipoprotein-triglyceride:cholesterol (2.8[1.98-3.78] vs. 1.6[1.44-2.80], P < 0.003) were significantly increased; very low-density lipoprotein-cholesterol:apolipoprotein B molar ratios (P = 0.93) were similar. Very low-density lipoprotein apolipoprotein B fractional synthetic rate (a measure of apolipoprotein B catabolism, P = 0.42) and pool size (P = 0.63) were similar. The very low-density lipoprotein apolipoprotein B absolute synthetic rate (a measure of apolipoprotein B synthesis) tended to be higher in hypopituitarism (17.7[2.91-19.50] vs. 26.6[19.64-28.05] mg/kg per day, P = 0.24) but failed to reach statistical significance. The absolute synthetic rate, and hence very low-density lipoprotein production, correlated with very low-density lipoprotein triglyceride:apolipoprotein B ratio (P = 0.02, Rs = 0.63), suggesting that triglyceride enrichment of very low-density lipoprotein is important in the mechanism underlying very low-density lipoprotein overproduction in hypopituitarism. Because triglyceride-enriched lipoproteins are proatherogenic, this may contribute to the vascular mortality observed in hypopituitarism. The reasons for these observations are unknown; GH deficiency or routine endocrine replacement may be important.

INTRODUCTION: Alterations of innate immune signaling, including overexpression of TLR2, are common in MDS. Signaling mediated by this receptor results in activation of NF-kB and the histone demethylase JMJD3 (KDM6B) leading to expression of multiple cytokines that can result in inhibition of hematopoiesis. Significant TLR2 overexpression in MDS bone marrow CD34+ cells, especially after HMA therapy, has been reported (Wei, Leukemia 2013). OPN-305 is a fully humanized antagonistic IgG4 kappa monoclonal antibody to TLR2 which significantly increases the formation of erythroid colonies (CFU-E) in BM CD34+ cells isolated from pts with lower-risk MDS in vitro. This data suggested the potential therapeutic value of OPN-305 in patients (pts) with MDS. METHODS: We designed a phase I/II trial of OPN-305 for pts with Low or Int-1 risk MDS by IPSS after failure to prior therapy with a HMA. Pts with isolated del(5q) should have received therapy with lenalidomide. Pts with prior history of AML or alloSCT were excluded from the study. Because, OPN-305 had not been previously used in pts with hematological malignancies, the study had an initial phase of N=10 pts using OPN-305 at a dose of 5 mg/kg every 4 weeks for a maximum of 9 cycles. Therapy could be repeated as long as there was no excess toxicity or progression. If after 16 weeks of therapy, there was no response, azacitidine on a 3 day schedule, could be added to OPN-305. Responses were evaluated following the revised 2006 IWG criteria. This initial cohort allowed evaluation of toxicity, pharmacokinetic analysis, receptor occupancy, and sequential analysis of cytokine profile. Depending on results, dose escalation to 10 mg/kg monthly could be instituted in a second cohort of N=5 pts. RESULTS: At the time of this report, 15 pts have been enrolled, 11 at the initial 5 mg dose and 4 at 10 mg/kg. All pts were evaluable for toxicity and 12 (80%) were evaluable for response. Patient characteristics are shown in Table 1. Median age was 73 years (range 48-87). Three (20%) pts were classified as Low risk and 12 (80%) as Intermediate-1 risk by IPSS. Seven pts had normal karyotype, 2 del(5q), 2 trisomy 8, 1 del(20q), 1 monosomy Y and 2 other single or double abnormalities. Median number of prior therapies was 2 (range 1-4) with a median duration of prior therapies of 28 months (range 4-62) (Figure 1). A total of 13 (87%) pts were transfusion dependent of red cells prior to enrollment. Median follow up is 8 months (1-16). Median number of cycles administered is 5 (2-17) with 5 (33%) pts having received addition of azacitidine after 16 weeks of therapy. A total of 5 (42%) pts developed AEs related to OPN-305. All AEs were grade 1 with gastrointestinal disorders being the most frequent (33%). At this point, no significant drug related toxicity has been documented with no excess infectious complications. Overall response rate in the form of hematological improvement was 50% (6/12) with 2 (17%) pts achieving transfusion independence. A total of 5 (33%) pts remain on study with 3 pts continuing on therapy off study. Three (20%) pts were taken off study due to progression to AML and 4 (27%) due to no response. Half-lives of OPN-305 in serum were >200 h at 5 mg/kg and >300 h at 10 mg/kg (Figure 2A). There was a greater-than-dose proportional increase in mean OPN-305 exposure (AUC) between 5 and 10 mg/kg. PK profiles after repeated dosing at 5 mg/kg in N=2 subjects and pre-dose (trough) levels in other subjects indicated some variability in the potential for accumulation. TLR-2 receptor occupancy in blood PBMCs and bone marrow aspirates was essentially complete in virtually all samples taken after OPN-305 administration (Figure 2B). There is no evidence of treatment related anti-drug antibodies. Compared with baseline, no statistically significant dynamic changes of IL-23, IL-18, IFN-r, IL-10, IL-1β, IL-6, IL-12 (p40), IL-12 (p70) and IL-8 levels where observed after treatment, among responders or non-responders or based on OPN-305 dosing. CONCLUSIONS: Treatment with OPN-305 in pts with previously treated lower-risk MDS was well tolerated with no significant toxicities and 50% ORR. Correlative studies suggest adequate receptor occupancy with no correlation between responses and cytokine levels. Because no effect on cytokine profile, we plan to continue to escalate the dose of OPN-305 and investigate its activity profile in front line therapy. Table 1. Table 1. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures DiNardo: Daiichi Sankyo: Research Funding; Agios: Research Funding; Abbvie: Research Funding; Novartis: Research Funding; Celgene: Research Funding. Konopleva:Reata Pharmaceuticals: Equity Ownership; Abbvie: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Stemline: Consultancy, Research Funding; Eli Lilly: Research Funding; Cellectis: Research Funding; Calithera: Research Funding.

Central nervous system spread from prostate cancer is typically associated with raised prostate specific antigen (PSA) levels. The authors describe a unique case of a "collision tumor" of a prostatic metastasis to the pituitary, juxtaposed to a suprasellar meningioma, with normal PSA levels. This case also emphasizes the need to consider prostatic metastasis in the differential diagnosis of a pituitary mass in patients with a known prostatic cancer, despite the normal PSA levels.

Lymphocytic hypophysitis (LH) is a rare inflammatory disorder of the pituitary gland that typically affects women in the peripartum period. We describe two male patients (ages 43 years and 36 years), who presented with headaches, visual disturbance and hypopituitarism. MRI revealed a heterogeneous pituitary lesion that extended into the suprasellar region and with a thickened pituitary stalk. In both patients a histopathological diagnosis of LH was made after endoscopic transsphenoidal surgery. LH in males, although rare, should be considered as a differential diagnosis in those with hypopituitarism and a heterogeneous pituitary fossa mass, extending into pituitary stalk.

Surgical remission rates for acromegaly vary and are dependent on the tumour morphology, biochemical definition of disease remission and surgical expertise. A previous report from the Manchester region in 1998 reported an overall surgical remission rate of 27% using accepted criteria for biochemical remission at the time. The establishment of the 2010 Consensus guidelines further tightens biochemical criteria for remission. This report aims to assess the impact of establishing a specialist pituitary surgery service in Manchester in 2005, with reduced surgeon numbers on the remission rates for acromegaly surgery.Patients with acromegaly undergoing first time endoscopic transsphenoidal surgery between 2005 and 2010 were studied. Surgery was performed by a single surgeon. Review of a prospectively collected acromegaly surgery database was performed with documentation of pre- and postoperative biochemical tests [oral glucose tolerance test (oGTT) and IGF-1], as well as clinical, pathological and radiological data. Definition of disease remission was according to the 2010 Consensus criteria (GH nadir0·4 μg/l following an oGTT and normalized population matched IGF-1). There were 43 consecutive patients with acromegaly, with 13 (30%) microadenomas and 12 (28%) invasive adenomas. Overall, surgical remission was achieved in 29 (67%) patients. The remission rates were similar between micro (77%), macro (63%) and giant (67%) adenomas. There were nonsignificant trends towards higher remission rates for noninvasive tumours compared with invasive tumours (74%vs 50%) and for patients with a preoperative GH nadir10 μg/l (73%vs 54%) and IGF-1 standard deviation score15 (72%vs 54%). Remission rates for acromegaly surgery have improved following establishment of a specialist surgical service, with a reduction in surgeon numbers. Endoscopic trans-sphenoidal surgery remains an effective first-line treatment for achieving biochemical remission in acromegaly, despite the introduction of the more stringent 2010 consensus guidelines.