Relacorilant, a Selective Glucocorticoid Receptor Modulator in Development for the Treatment of Patients With Cushing Syndrome, Does Not Cause Prolongation of the Cardiac QT Interval.

OBJECTIVE: To assess the effect of relacorilant, a selective glucocorticoid receptor modulator under investigation for the treatment of patients with endogenous hypercortisolism (Cushing syndrome [CS]), on the heart rate-corrected QT interval (QTc). METHODS: Three clinical studies of relacorilant were included: (1) a first-in-human, randomized, placebo-controlled, ascending-dose (up to 500 mg of relacorilant) study in healthy volunteers; (2) a phase 1 placebo- and positive-controlled thorough QTc (TQT) study of 400 and 800 mg of relacorilant in healthy volunteers; and (3) a phase 2, open-label study of up to 400 mg of relacorilant administered daily for up to 16 weeks in patients with CS. Electrocardiogram recordings were taken, and QTc change from baseline (ΔQTc) was calculated. The association of plasma relacorilant concentration with the effect on QTc in healthy volunteers was assessed using linear mixed-effects modeling. RESULTS: Across all studies, no notable changes in the electrocardiogram parameters were observed. At all time points and with all doses of relacorilant, including supratherapeutic doses, ΔQTc was small, generally negative, and, in the placebo-controlled studies, similar to placebo. In the TQT study, placebo-corrected ΔQTc with relacorilant was small and negative, whereas placebo-corrected ΔQTc with moxifloxacin positive control showed rapid QTc prolongation. These results constituted a negative TQT study. The model-estimated slopes of the concentration-QTc relationship were slightly negative, excluding an association of relacorilant with prolonged QTc. CONCLUSION: At all doses studied, relacorilant consistently demonstrated a lack of QTc prolongation in healthy volunteers and patients with CS, including in the TQT study. Ongoing phase 3 studies will help further establish the overall benefit-risk profile of relacorilant.

Colorectal carcinoma to pituitary tumour: tumour to tumour metastasis.

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.

Quantitative Magnetic Resonance-Derived Biomarkers as Predictors of Function and Histotype in Adenohypophyseal Tumours.

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.

Value of Early Post-Operative Growth Hormone Testing in Predicting Long-Term Remission and Residual Disease after Transsphenoidal Surgery for Acromegaly.

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 <0.4 µg/L during an OGTT and normalized population-matched IGF-1). Forward stepwise logistic regression was used to determine factors associated with remission. 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 <0.4 (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.

Venous thromboembolism chemical prophylaxis after endoscopic trans-sphenoidal pituitary surgery.

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.

Long-term oncological outcomes after haemorrhagic apoplexy in pituitary adenoma managed operatively and non-operatively.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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 epithelial-myoepithelial carcinoma of the pituitary gland.

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.

Pre- and postoperative need for pituitary hormone replacement in non-adenomatous sellar and parasellar lesions: importance of the sellar encroachment score.

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.

Ectopic Cushing's syndrome secondary to olfactory neuroblastoma.

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.

Lymphocytic hypophysitis: modern day management with limited role for surgery.

PURPOSE: 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. METHODS: 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). RESULTS: 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 was <1 month, 1-6 months or >6 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. CONCLUSIONS: 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.

Sphenoid sinus mucosal thickening in the acute phase of pituitary apoplexy.

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 < 0.001). 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 0.012-0.16; p < 0.001). In multivariate analysis of the PA group alone, a shorter time from symptom onset to presenting MRI scan (OR 0.12, 95% CI 0.026-0.54; p = 0.006) and a more severe grade of apoplexy (OR 7.29, 95% CI 1.10-48.40; p = 0.04), were associated with SSMT. CONCLUSION: The incidence of SSMT is higher in patients with PA, especially during the acute phase of PA. The aetiology of SSMT in PA is unclear and may reflect inflammatory and/or infective changes.

The prevalence of growth hormone deficiency in survivors of subarachnoid haemorrhage: results from a large single centre study.

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 < 0.0001 and p < 0.0001 respectively). 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.

Pituitary apoplexy - bespoke patient management allows good clinical outcome.

OBJECTIVE: 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.

Acromegaly surgery in Manchester revisited--the impact of reducing surgeon numbers and the 2010 consensus guidelines for disease remission.

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 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. METHODS: 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 nadir <0·4 µg/l following an oGTT and normalized population matched IGF-1). RESULTS: 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 nadir <10 µg/l (73%vs 54%) and IGF-1 standard deviation score <15 (72%vs 54%). CONCLUSIONS: 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.

Extraventricular neurocytoma of the sellar region.

OBJECTIVE: 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. CLINICAL PRESENTATION: 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. INTERVENTION: 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. CONCLUSION: 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.

Anabolic-androgenic steroids abuse-induced seizures: A case report in a young male bodybuilder.

None.

Endoscopic transsphenoidal surgery for biochemically and clinically non-functioning adenohypophyseal tumours in the elderly: experience from a single UK centre.

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.

Nasal symptoms following endoscopic transsphenoidal pituitary surgery: assessment using the General Nasal Patient Inventory.

OBJECT: The endoscopic approach for pituitary tumors is a recent innovation and is said to reduce the nasal trauma associated with transnasal transsphenoidal surgery. The authors assessed the temporal changes in the rhinological symptoms following endoscopic transsphenoidal surgery for pituitary lesions, using the General Nasal Patient Inventory (GNPI). METHODS: The GNPI was administered to 88 consecutive patients undergoing endoscopic transsphenoidal surgery at 3 time points (presurgery, 3-6 months postsurgery, and at final follow-up). The total GNPI score and the scores for the individual GNPI questions were calculated and differences between groups were assessed once before surgery, several months after surgery, and at final follow-up. RESULTS: Of a maximum possible score of 135, the mean GNPI score at 3-6 months postsurgery was only 12.9 ± 12 and was not significantly different from the preoperative score (10.4 ± 13) or final follow-up score (10.3 ± 10). Patients with functioning tumors had higher GNPI scores than those with nonfunctioning tumors for each of these time points (p < 0.05). Individually, a mild increase in symptom severity was seen for symptoms attributable to the nasal trauma of surgery, with partial recovery (nasal sores and bleeding) or complete recovery (nasal blockage, painful sinuses, and unpleasant nasal smell) by final follow-up (p < 0.05). Progressive improvements in symptom severity were seen for symptoms more attributable to tumor mass preoperatively (for example, headaches and painkiller use [p < 0.05]). In total, by final follow-up 8 patients (9%) required further treatment or advice for ongoing nasal symptoms. CONCLUSIONS: Endoscopic transsphenoidal surgery is a well-tolerated minimally invasive procedure for pituitary fossa lesions. Overall patient-assessed nasal symptoms do not change, but some individual symptoms may show a mild worsening or overall improvement.

Low-grade CSF leaks in endoscopic trans-sphenoidal pituitary surgery: efficacy of a simple and fully synthetic repair with a hydrogel sealant.

BACKGROUND: Intra-operative CSF leak during endoscopic trans-sphenoidal surgery is not uncommon. Surgical repair with a variety of autologous grafts, rigid buttresses and CSF diversion techniques that add time and complexity have been reported. OBJECTIVE: To describe a simple and purely synthetic closure for low-grade CSF leaks following endoscopic trans-sphenoidal pituitary surgery. METHODS: A retrospective review of all endoscopic trans-sphenoidal surgery undertaken for pituitary pathology between 2005 and 2010 was carried out. The grade of CSF leak and success of graded repair was noted. Patients with no CSF leak (grade 0) had gelatin sponge placed in the tumour cavity. In those with low-grade CSF leak through small arachnoid defects (grade 1), repair was carried out using gelatin sponge and hydrogel sealant overlay. CSF diversion was not employed for low-grade CSF leaks. RESULTS: Of the 255 endoscopic trans-sphenoidal surgeries, 158 (62%) had no leak (grade 0) and 74 (29%) had a low-grade leak (grade 1). Repairs in all cases were of grade 0, and all but two cases of grade 1 CSF leak were successful at a mean follow-up of 29 months. The 2 (2.7%) post-operative CSF leaks were seen within 6 weeks of surgery. Both cases were related to bouts of sneezing and were repaired using further trans-sphenoidal surgery and/or lumbar CSF diversion. CONCLUSIONS: A simple purely synthetic repair of low-grade CSF leaks is described. This repair is safe and comparable in efficacy whilst avoiding the morbidity related to more complex sellar reconstructions previously described.

Pituitary adenoma and incidental superior hypophyseal aneurysm.

In patients with pituitary adenomas, intra-cranial aneurysms can be an incidental finding, and are usually located outside the pituitary region. The authors describe the multi-modal management of a rare case of an aneurysm of the supraclinoid carotid that encroached into a pituitary macroadenoma.