Xuefei Shou

Transsphenoidal pituitary macroadenomas resection guided by PoleStar N20 low-field intraoperative magnetic resonance imaging: comparison with early postoperative high-field magnetic resonance imaging.

OBJECTIVETo evaluate the applicability of low-field intraoperative magnetic resonance imaging (iMRI) during transsphenoidal surgery of pituitary macroadenomas. METHODSFifty-five transsphenoidal surgeries were performed for macroadenomas (modified Hardys Grade II–IV) resections. All of the surgical processes were guided by real-time updated contrast T1-weighted coronal and sagittal images, which were acquired with 0.15 Tesla PoleStar N20 iMRI (Medtronic Navigation, Louisville, CO). The definitive benefits as well as major drawbacks of low-field iMRI in transsphenoidal surgery were assessed with respect to intraoperative imaging, tumor resection control, comparison with early postoperative high-field magnetic resonance imaging, and follow-up outcomes. RESULTSIntraoperative imaging revealed residual tumor and guided extended tumor resection in 17 of 55 cases. As a result, the percentage of gross total removal of macroadenomas increased from 58.2% to 83.6%. The accuracy of imaging evaluation of low-field iMRI was 81.8%, compared with early postoperative high-field MRI (Correlation coefficient, 0.677; P < 0.001). A significantly lower accuracy was identified with low-field iMRI in 6 cases with cavernous sinus invasion (33.3%) in contrast to the 87.8% found with other sites (Fishers exact test, P < 0.001). CONCLUSIONThe PoleStar N20 low-field iMRI navigation system is a promising tool for safe, minimally invasive, endonasal, transsphenoidal pituitary macroadenomas resection. It enables neurosurgeons to control the extent of tumor resection, particularly for suprasellar tumors, ensuring surgical accuracy and safety, and leading to a decreased likelihood of repeat surgeries. However, this technology is still not satisfying in estimating the amount of the parasellar residual tumor invading into cavernous sinus, given the false or uncertain images generated by low-field iMRI in this region, which are difficult to discriminate between tumor remnant and blood within the venous sinus.

Diagnosis and minimally invasive surgery for the pituitary abscess: A review of twenty nine cases

OBJECTIVEnThis study aimed to better determine the salient signs and symptoms for diagnosis of a pituitary abscess as well as the determination of the most appropriate treatment.nnnMETHODSnA retrospective analysis was performed using clinical presentations, imaging features, diagnosis and treatment of 29 patients with pituitary abscess in our hospital.nnnRESULTSnWe made the correct diagnosis of pituitary abscess before surgery only in 2 cases (13.3%) out of 15 patients between January 2004 and January 2008. While 12 cases (85.7%) out of 14 patients were correctly diagnosed before surgery between January 2008 and June 2010. All of the patients underwent transnasal-transsphenoidal surgery assisted by the microscope or endoscope. The antibiotic therapy and hormonal replacement were routinely administrated. The postoperative courses were uneventful and all symptoms of the patients were gradually improved one week to six months after surgery. None of the 29 cases were recurrent during the follow-up.nnnCONCLUSIONnWith the increased clinical experience, the correct diagnosis rate of pituitary abscess before surgery has been greatly improved in recent three years. The microsurgical drainage, proper antibiotics and hormonal replacement are the keys to the treatment of pituitary abscess.

Immuno-laser capture microdissection of frozen prolactioma sections to prepare proteomic samples

Laser capture microdissection (LCM) technology combined with immunohistochemistry (immuno-LCM) is a valuable tool to obtain specific target cell populations and therefore this technique enables more accurate proteomic profile. In this study, we optimized the regular immuno-LCM technique to isolate and stain pure prolactin cells from either normal human pituitary (n=6) or prolactioma (n=11). Compared with the routine procedure, more intense and specific staining could be obtained when sections were pretreated with 0.2% Triton X-100 for 4 min. Interestingly, longer pretreatment (0.2% Triton X-100 for 10 min) or higher concentration (2% Triton X-100 for 4 and 10 min) greatly impaired labeling intensity and cell shape. Further scanning electron microscope study revealed that the component extracted from the cell surface by Triton X-100 was lipid. Using the optimized immuno-LCM technique, more pure prolactin cells could be isolated and prepared for further proteomic analysis. Taken together, we reported an optimized immuno-LCM technique that could effectively dissect pure target cells in different type pituitary adenomas for further proteomics analysis.

Gangliocytomas in the sellar region

Gangliocytomas occurring in the sellar region are extremely rare. We examined a cohort of these tumors to examine their clinical presentations and prognoses. Between January 2000 and December 2012, 23 patients were diagnosed with sellar region gangliocytomas in Huashan Hospital. These patients were retrospectively reviewed for medical histories, endocrinological examinations, preoperative magnetic resonance imaging (MRI), pathological findings and follow-ups. Endocrinological tests revealed elevated prolactin (PRL) levels in 10 cases (43.5%) and elevated growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels in 9 cases (39.1%). Scattered ganglion cells admixed with adenomatous components were observed in 16 cases (69.6%). In the remaining 7 cases (30.4%), only fragments with ganglion cells dispersed in the fibrillar matrix without adenohypophyseal components were detected. Immunohistochemistry revealed PRL-positive adenomas in 6 cases (26.1%) and GH-positive adenomas in 8 cases (34.8%). The average follow-up period was 4.2 years (range: 1-12.7 years). Gross total resection was achieved in 20 cases (87.0%). One patient recurred five years after tumor resection (4.3%). One patient died of acute myocardial infarction six years after operation. Gangliocytomas located in the sellar region may represent a unique immunopathological entity. The surgical results and prognoses of the gangliocytomas were comparable with those of pituitary adenomas.

Incidence of Pituitary Apoplexy and Its Risk Factors in Chinese People: A Database Study of Patients with Pituitary Adenoma

Background There are few studies of the incidence and clinical characteristics of pituitary apoplexy (PA) in pituitary adenoma patients, and the findings have been inconsistent. Objective The aim of the study was to retrospectively assess the incidence, clinical presentation, surgical management and postoperative complications of PA in pituitary adenoma patients. Methods A database was specifically designed to collect clinical, therapeutic, prognostic and histological information about pituitary adenoma patients. Using multivariate logistic regression, odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to identify associated factors. Results A total of 2021 pituitary adenoma patients were recruited. 97 (4.8%) patients had PA. The incidence of PA was 10.11% in patients with pituitary macroadenoma, and 0.36% in patients with microadenoma. Variables for the logistic regression model independently associated with PA were sex (male vs. female, OR = 2.54, 95% CI: 1.59~4.07), tumor type (negative staining vs. positive staining, OR = 2.04, 95% CI: 1.29~3.23), and tumor size (macroadenoma vs. microadenoma, OR = 26.46, 95% CI = 9.66~72.46). Headache, visual deterioration, and vomiting were the most common symptoms in patients with pituitary adenoma. Patients with and without PA had similar frequency of visual deterioration, head trauma, acromegalic appearance, galactorrhoea, cold intolerance and Cushingoid appearance, but headache, vomiting, ptosis, diplopia, fever and blindness were significantly more common in patients with PA. Pearson Chi-Square tests revealed a significant difference in surgical approach between patients with and without PA (95.88% vs. 85.57%, P = 0.01). Conclusion Our findings suggest that PA is not a rare event. Male sex, non-functioning tumor, and macroadenoma are associated with an increased risk of PA. Compared with pituitary adenoma patients without PA, patients with PA have more severe symptoms.

Endoscopic endonasal pituitary adenomas surgery: the surgical experience of 178 consecutive patients and learning curve of two neurosurgeons

BackgroundWe aim to study surgical technique and analyze the related factors affecting tumor total removal and postoperative endocrinological remission for endoscopic endonasal pituitary adenomas surgery.MethodsWe retrospectively analyzed 178 endoscopic endonasal pituitary adenomas surgery from March 2011 to May 2014. Endonasal approach included the routine transnasal-sphenoidal approach, transnasal- maxillary sinus approach in four cases and transnasal-clivus approach in one case.ResultsAccording to postoperative imaging data and endocrine examination results, total removal was achieved in 129 patients (72.5%), and endocrinological remission was achieved in 38 patients with functional adenomas (44.1%). Statistical analysis of the clinical data showed that total removal rate was much closely related to tumor volume (Pu2009=u20090.006), and tumor invasiveness (Pu2009<u20090.001).ConclusionsIn this study, we found tumor sizes and invasion of cavernous sinus were related to total removal rate and endocrinological remission rate; the direction and degree of tumor invasion, and the surgeon’s experience were the key influence factors of the endocrinological remission rate for invasive functional pituitary adenomas.

Identification of recurrent USP48 and BRAF mutations in Cushing’s disease

Cushing’s disease results from corticotroph adenomas of the pituitary that hypersecrete adrenocorticotropin (ACTH), leading to excess glucocorticoid and hypercortisolism. Mutations of the deubiquitinase gene USP8 occur in 35–62% of corticotroph adenomas. However, the major driver mutations in USP8 wild-type tumors remain elusive. Here, we report recurrent mutations in the deubiquitinase gene USP48 (predominantly encoding p.M415I or p.M415V; 21/91 subjects) and BRAF (encoding p.V600E; 15/91 subjects) in corticotroph adenomas with wild-type USP8. Similar to USP8 mutants, both USP48 and BRAF mutants enhance the promoter activity and transcription of the gene encoding proopiomelanocortin (POMC), which is the precursor of ACTH, providing a potential mechanism for ACTH overproduction in corticotroph adenomas. Moreover, primary corticotroph tumor cells harboring BRAF V600E are sensitive to the BRAF inhibitor vemurafenib. Our study thus contributes to the understanding of the molecular mechanism of the pathogenesis of corticotroph adenoma and informs therapeutic targets for this disease.In this study the authors report USP48 and BRAF are frequently mutated in USP8 wild-type corticotroph adenomas, and cause Cushing’s disease mainly through promoting the promoter activity of POMC. Inhibition of BRAF may be a promising therapeutic strategy for the treatment of patients with BRAF-mutated corticotroph adenomas.

Surgical outcomes and predictors of glucose metabolism alterations for growth hormone-secreting pituitary adenomas: a hospital-based study of 151 cases

PurposeThe surgical outcome on glucose metabolism in acromegaly patients is not fully understood. We aimed to investigate the impact of surgery on glucose metabolism and identify key factors that influence alterations of glucose metabolic status in acromegaly patients.MethodsOral glucose tolerance test was performed in 151 newly diagnosed acromegaly patients before and 3–12 months after surgery. Insulin resistance and insulin secretion was assessed. Patients were grouped as cured, discordant, and having active disease according to postoperative growth hormone (GH) and insulin-like growth factor-1 (IGF-1) levels. Receiver-operating characteristic curves were generated to determine the optimal cut-off points to predict the impact of surgery on glucose metabolism.ResultsAt baseline, 32.5%, 41.7%, and 25.8% patients were categorized as having normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and diabetes mellitus (DM), respectively. After surgery, improved glucose tolerance was observed in 87.3% patients with IGT and 66.7% patients with DM. Deterioration was observed in 14.3% patients with NGT. Glucose tolerance improved in patients with lower preoperative FBG, 2u2009h-BG, and HbA1c and higher HOMA-β and IGI/IR. The proportion of NGT was significantly increased in surgically cured patients (28.3% vs. 79.2%, Pu2009<u20090.001) and those with normal GH but elevated IGF-1 levels (25.6% vs. 79.5%, Pu2009<u20090.001), but not in patients with active disease (42.9% vs. 57.1%, Pu2009=u20090.131). Baseline FBGu2009<u20096.35u2009mmol/l predicted improved glucose metabolism after surgery.ConclusionsGlucose metabolic status improved in patients with preserved β-cell function. Preoperative FBG was an independent predictor for improved glucose tolerance status after surgery.

Clinical features of patients with pituitary stalk thickening: a review of 159 cases from one medical center

BackgroundPituitary stalk thickening (PST) used as an imaging diagnosis plays a major role in diagnosis and treatment of the hypothalamus and pituitary disease at an early stage. Up until now, several lines of systematic investigations have been conducted among adolescents, and the results indicated that PST is possibly one of the principal early manifestations of sellar region tumor. To characterize the major clinical features of PST and to identify the most effective treatments we conducted this study.MethodsThis was a retrospective review of patients with PST evaluated at Huashan Hospital over an eight-year period between 2007 and 2014. One hundred fifty nine patients who were diagnosed PST were included. The data including demographics, clinical presentations, imaging examinations, laboratory results and surgery were thoroughly reviewed and carefully analyzed. According to their clinical presentations and examinations, relevant treatments were adopted and different prognosis were observed.ResultsOf the 159 patients, 57 were males and 102 were females (median age was 29 and 43.4% were under the age of 21xa0years). And of the patients in the age group between 30 and 35xa0years, 84% were females. “Polydipsia and polyuria” was the most common clinical manifestation observed in 90 cases (>50%). 49.5% of the patients were diagnosed to have at least one anterior pituitary dysfunction. The sellar region MRI (SR-MRI) data showed that patients who had different clinical presentations or pituitary function showed different SR-MRI appearance. Over 60% patients who performed follow-up MRI showed shrunken PST. Fourteen cases who received radiotherapy appeared to be improved as shown by MRI.ConclusionsPST is most commonly seen in the teenagers and the women of reproductive age. Distinct etiology may be identified based on the clinical manifestations, age and SR-MRI, which would help to make the final decision for treatments. Radiotherapy and immuno-suppressed therapy are effective in alleviating clinical symptoms and shrinking the stalk thickening.

Recovery of Hpa Axis Function After Successful Gonadotropin-induced Pregnancy and Delivery in a Woman With Panhypopituitarism: Case Report and Review

AbstractHypopituitarism is defined as the partial or complete defect of anterior pituitary hormone secretion. Patients with hypopituitarism usually need life-long hormone replacement therapy. However, in this case, we report a patient with panhypopituitarism whose hypothalamus–pituitary–adrenal (HPA) axis function was completely recovered after pregnancy and delivery.In this case study, we reported the case management and conducted a review of literature to identify the possible mechanism of pituitary function recovery.The patient who suffered from secondary amenorrhea was found a nonfunctioning pituitary macroadenoma, and the hormone test showed serum cortisol, FT3, FT4, thyrotropic hormone, and prolactin were at normal range. After surgical removal of the tumor which invasion in the sellar region, the patient had panhypopituitarism confirmed by the routine hormone test. Though spontaneous pregnancy is impossible in female patients with panhypopituitarism, the patient was restored fertility by the help of artificial reproductive techniques. After the confirmation of the pregnancy, levothyroixine was increased to 75 &mgr;g daily and readjusted to 150 &mgr;g daily before delivery according to the monthly measurement thyroid function. Hydrocortisone 10u200amg daily replaced cortisone acetate; the dose was increased according to the symptoms of morning sickness. A single stress dose of hydrocortisone (200u200amg) was used before elective cesarean delivery and was tapered to the dose of 10u200amg per day in 1 week. Levothyroixine was reduced to 75 &mgr;g daily after delivery. During follow-up, her hypothalamus–pituitary–adrenal (HPA) axis function was completely recovered. The peak serum cotisol level could increase to 19.08u200a&mgr;g/dL by insulin-induced hypoglycemia. However, growth hormone remained unresponsive to the insulin-tolerance test, and thyroid hormone still needed exogenous supplementation.Hormone replacement therapy needed closely followed by endocrinologist and multidisciplinary cooperation during the pregnancy of patients with hypopituitarism. This case indicates that the pituitary function may partially recover after pregnancy in panhypopituitarism patients.