Identification of mitogen-activated protein kinases substrates in Arabidopsis using kinase client assay.

Mitogen-activated protein kinase (MPK) cascades are essential signal transduction components that control a variety of cellular responses in all eukaryotes. MPKs convert extracellular stimuli into cellular responses by the phosphorylation of downstream substrates. Although MPK cascades are predicted to be very complex, only limited numbers of MPK substrates have been identified in plants. Here, we used the kinase client (KiC) assay to identify novel substrates of MPK3 and MPK6. Recombinant MPK3 or MPK6 were tested against a large synthetic peptide library representing in vivo phosphorylation sites, and phosphorylated peptides were identified by high-resolution tandem mass spectrometry. From this screen, we identified 23 and 21 putative client peptides of MPK3 and MPK6, respectively. To verify the phosphorylation of putative client peptides, we performed in vitro kinase assay with recombinant fusion proteins of isolated client peptides. We found that 13 and 9 recombinant proteins were phosphorylated by MPK3 and MPK6. Among them, 11 proteins were proven to be the novel substrates of two MPKs. This study suggests that the KiC assay is a useful method to identify new substrates of MPKs.

Quercetin induces pathogen resistance through the increase of salicylic acid biosynthesis in Arabidopsis.

Quercetin is a flavonol belonging to the flavonoid group of polyphenols. Quercetin is reported to have a variety of biological functions, including antioxidant, pigment, auxin transport inhibitor and root nodulation factor. Additionally, quercetin is known to be involved in bacterial pathogen resistance in Arabidopsis through the transcriptional increase of pathogenesis-related (PR) genes. However, the molecular mechanisms underlying how quercetin promotes pathogen resistance remain elusive. In this study, we showed that the transcriptional increases of PR genes were achieved by the monomerization and nuclear translocation of nonexpressor of pathogenesis-related proteins 1 (NPR1). Interestingly, salicylic acid (SA) was approximately 2-fold accumulated by the treatment with quercetin. Furthermore, we showed that the increase of SA biosynthesis by quercetin was induced by the transcriptional increases of typical SA biosynthesis-related genes. In conclusion, this study strongly suggests that quercetin induces bacterial pathogen resistance through the increase of SA biosynthesis in Arabidopsis.

Dexamethasone suppression for 18F-FDG PET/CT to localize ACTH-secreting pituitary tumors.

BACKGROUND: 18Fluorine-Fluoro-deoxy-glucose (18F-FDG) positron emission tomography (PET) is widely used for diagnosing various malignant tumors and evaluating metabolic activities. Although the usefulness of 18F-FDG PET has been reported in several endocrine diseases, studies on pituitary disease are extremely limited. To evaluate whether dexamethasone (DEX) suppression can improve 18F-FDG PET for the localization of adrenocorticotropic hormone-secreting adenomas in the pituitary gland in Cushing's disease (CD). METHODS: We included 22 patients with CD who underwent PET imaging before and after DEX administration. We compared the success rates of PET before and after DEX suppression, magnetic resonance imaging (MRI), and bilateral inferior petrosal sinus sampling (BIPSS). We determined the final locations of adenomas based on intraoperative multiple-staged resection and tumor tissue identification using frozen sections. Standardized uptake value (SUV) were analyzed to confirm the change of intensity of adenomas on PET. RESULTS: Twenty-two patients were included (age at diagnosis: 37 [13-56] years), and most were women (90.91%). Pituitary adenomas compared to normal pituitaries showed increased maximum SUV after DEX suppression but without statistical significance (1.13 versus. 1.21, z=-0.765, P = 0.444). After DEX suppression, the mean and maximum SUV of adenomas showed a positive correlation with nadir cortisol levels in high-dose DEX suppression test (Rho = 0.554, P = 0.007 and Rho = 0.503, P = 0.017, respectively). In reference sites, mean SUV of cerebellum was significantly decreased (7.65 vs. 6.40, P = 0.006*), but those of the thalamus and gray matter was increased after DEX suppression (thalamus, 8.70 vs. 11.20, P = 0.010*; gray matter, 6.25 vs. 7.95, P = 0.010*). CONCLUSION: DEX suppression did not improve 18F-FDG PET/CT localization in patients with CD.

Role of Immediate Postoperative Prolactin Measurement in Female Prolactinoma Patients: Predicting Long-Term Remission After Complete Tumor Removal.

BACKGROUND: Transsphenoidal surgery is one of the important treatment options in the management of prolactinomas; however, complete resection of the tumor does not always lead to endocrinological remission. While many studies have investigated preoperative factors associated with surgical outcome, little has been known about the relationship between postoperative factors and long-term surgical outcomes; moreover, there is no consistency in results. The aim of this study was to demonstrate the reliability of immediate postoperative prolactin levels as predictors of long-term outcomes. METHODS: A total of 105 female patients who underwent complete removal of their histologically confirmed prolactinomas were included, and their medical records were retrospectively reviewed. To evaluate the predictability of immediate postoperative prolactin levels for long-term remission, prolactin levels were measured at 2, 6, 12, 18, 24, 48, and 72 h after surgery. RESULTS: From the 105 included patients, 95 (90.5%) and 10 (9.5%) belonged to the remission and non-remission groups, respectively. A significant difference was observed in the prolactin level measured 6 h after surgery between the remission and non-remission groups, and this difference stayed apparent until 72 h after surgery. We derived a cut-off value for every postoperative time point that showed a significant relationship with disease remission. CONCLUSION: Our study suggests that immediate postoperative measurement of prolactin levels is a reliable predictor of long-term remission and can contribute to early identification of patients who require adjuvant treatment after surgery.

Surgical Treatment of Prolactinomas: Potential Role as a First-Line Treatment Modality.

PURPOSE: Treatment with dopamine agonists (DAs) has been the first-line standard treatment for prolactinoma, and surgery has been reserved for drug intolerance and resistance for several decades. We evaluated whether surgery plays a primary role in prolactinoma management. MATERIALS AND METHODS: We conducted a retrospective study of 210 prolactinoma patients who had received surgical treatment at our institution. We analyzed the treatment outcomes according to tumor extent, sex, and preoperative DA medication. RESULTS: Overall hormonal remission was achieved in 164 patients (78.1%), and complete removal was achieved in 194 patients (92.4%). When the tumors were completely removed, the remission rate increased to 84.5%. Anterior pituitary function was normalized or improved in 94.6% of patients, whereas only 4.1% of patients showed worsening of hormone control. Hormonal remission was higher in patients who had not received DA preoperatively than in those who had received preoperative DA treatment. Smaller tumor size (<1 cm), no invasion into the cavernous sinus, and female sex were predictors of good surgical outcomes. CONCLUSION: Although DAs remain the first-line standard treatment for prolactinomas, surgery can be an excellent option and should be considered as an alternative primary treatment modality when patients are predicted to achieve a good surgical outcome.

MRI-Based Classification of Rathke's Cleft Cyst and Its Clinical Implication.

BACKGROUND: Rathke's cleft cysts (RCCs) are benign tumors of the pituitary gland. Small, asymptomatic RCCs do not require surgical treatment, whereas surgical treatment is required for symptomatic RCCs. METHODS: We retrospectively reviewed medical records of patients with an RCC who were diagnosed and managed in our institution between April 2004 and April 2020 and generated two different cohorts: the observation (n=114) and the surgical group (n=99). Their initial MRI signal characteristics were analyzed. The natural course focusing on cyst size was observed in the observation group and postoperative visual and endocrine outcomes were evaluated in the surgical group. RESULTS: The characterization of MRI signals of cyst contents in both T1-weighted (T1W) and T2-weighted (T2W) images revealed nine combinations for our 213 patients. Among 115 patients with a high T2W signal, the cysts showed hypo-, iso-, and hyper-intensity on T1W images in 72, 39, and 44 patients, respectively; Type S-low, Type S-iso, and Type S-high. One more major group of 35 patients showed RCCs with hyperintensity on the T1W images and hypointensity on the T2W images named as Type M. In the comparison between observation and surgical groups, we identified only two major groups in which the number of patients in the surgical and observation groups was statistically different: more Type S-low in a surgical group (p<0.001) and more Type M in an observation group (p=0.007). In subgroup analysis, the range of change in the cyst size was the highest in Type S-high in the observation group (p=0.028), and intergroup differences in visual and endocrine outcomes were not evident in the surgical group. CONCLUSION: MRI characteristics help to predict the natural course of RCCs. We identified subgroups of RCCs which are more or less likely to require surgical intervention.

Dual inhibition of CPT1A and G6PD suppresses glioblastoma tumorspheres.

PURPOSE: Limited treatment options are currently available for glioblastoma (GBM), an extremely lethal type of brain cancer. For a variety of tumor types, bioenergetic deprivation through inhibition of cancer-specific metabolic pathways has proven to be an effective therapeutic strategy. Here, we evaluated the therapeutic effects and underlying mechanisms of dual inhibition of carnitine palmitoyltransferase 1A (CPT1A) and glucose-6-phosphate dehydrogenase (G6PD) critical for fatty acid oxidation (FAO) and the pentose phosphate pathway (PPP), respectively, against GBM tumorspheres (TSs). METHODS: Therapeutic efficacy against GBM TSs was determined by assessing cell viability, neurosphere formation, and 3D invasion. Liquid chromatography-mass spectrometry (LC-MS) and RNA sequencing were employed for metabolite and gene expression profiling, respectively. Anticancer efficacy in vivo was examined using an orthotopic xenograft model. RESULTS: CPT1A and G6PD were highly expressed in GBM tumor tissues. Notably, siRNA-mediated knockdown of both genes led to reduced viability, ATP levels, and expression of genes associated with stemness and invasiveness. Similar results were obtained upon combined treatment with etomoxir and dehydroepiandrosterone (DHEA). Transcriptome analyses further confirmed these results. Data from LC-MS analysis showed that this treatment regimen induced a considerable reduction in the levels of metabolites associated with the TCA cycle and PPP. Additionally, the combination of etomoxir and DHEA inhibited tumor growth and extended survival in orthotopic xenograft model mice. CONCLUSION: Our collective findings support the utility of dual suppression of CPT1A and G6PD with selective inhibitors, etomoxir and DHEA, as an efficacious therapeutic approach for GBM.

Asian-specific 3'UTR variant in CDKN2B associated with risk of pituitary adenoma.

BACKGROUND: Previous genomewide association studies (GWASs), single nucleotide polymorphisms (SNPs) on cyclin-dependent kinase inhibitor 2 A (CDKN2A), cyclin-dependent kinase inhibitor 2B (CDKN2B), and cyclin-dependent kinase inhibitor 2B antisense RNA1 (CDKN2B-AS1) were reported as risk loci for glioma, a subgroup of the brain tumor. To further characterize this association with the risk of brain tumors in a Korean population, we performed a fine-mapping association study of CDKN2A, CDKN2B, and CDKN2B-AS1. METHODS AND RESULTS: A total of 17 SNPs were selected and genotyped in 1,439 subjects which were comprised of 959 patients (pituitary adenoma 335; glioma 324; meningioma 300) and 480 population controls (PCs). We discovered that a 3'untranslated region (3'UTR) variant, rs181031884 of CDKN2B (Asian-specific variant), had significant association with the risk of pituitary adenoma (PA) (Odds ratio = 0.58, P = 0.00003). Also, rs181031884 appeared as an independent causal variant among the significant variants in CDKN2A and CDKN2B, and showed dose-dependent effects on PA. CONCLUSIONS: Although further studies are needed to verify the impact of this variant on PA susceptibility, our results may help to understand CDKN2B polymorphism and the risk of PA.

Arachnoid Remodeling by Clipping Technique Facilitates Surgical Maneuverability during Transsphenoidal Surgery for Pituitary Macroadenoma.

OBJECTIVE: Pituitary adenomas frequently extend into the suprasellar space. After a suprasellar tumor is removed, the superiorly extended arachnoid becomes redundant and sinks down into the intrasellar space which often hiders visualization and accessibility to the hidden space behind the evaginated arachnoid. We introduced arachnoid remodeling by clipping technique, and evaluated its usefulness and safety during TSS. METHODS: Total 223 patients who underwent arachnoid remodeling with our new clipping technique were included. Redundant arachnoid was clipped along the dural edge with multiple 2.6-mm titanium clips until the redundant arachnoid membrane no longer blocked the surgical route. To check for possible deterioration of hormonal function by this technique, we assessed anterior pituitary function of 166 patients who underwent arachnoid remodeling by clipping and compared this with those of other 429 control patients. RESULTS: Our technique greatly enhanced the accessibility and visualization of intrasellar and parasellar spaces, both of which are generally hindered by redundant arachnoid during transsphenoidal surgery (TSS). We found no difference in anterior pituitary function between a clip-assisted arachnoid remodeling group and the control group, implying that this technique does not result in hypopituitarism. CONCLUSION: During TSS for pituitary adenomas with suprasellar extension, arachnoid remodeling by clipping technique is very useful and convenient for the management of the redundant arachnoid membrane to enhance visualization and surgical accessibility.

Clinical Relevance of New World Health Organization Classification System for Pituitary Adenomas: A Validation Study With 2-Year Experience.

BACKGROUND: The new World Health Organization (WHO) classification system proposed a cell lineage-based classification scheme for pituitary adenomas in which transcription factors (TFs) play a major role as key classifiers. We aimed to evaluate clinical relevance of the new classification system in a clinical setting. METHODS: TF staining was retrospectively performed for 153 clinically and histologically well characterized pituitary adenomas. Then, 484 pituitary adenomas were prospectively stained for TFs and then for relevant pituitary hormones. TF and hormone stain-based diagnoses were compared, and differences in clinical manifestations were evaluated. RESULTS: The accuracies of antibodies for three TFs were successfully validated and had an overall matching rate was 89.6%. We identified 50 (10.4%) cases with discrepancies between TF and pituitary hormone stains. Gonadotroph adenomas lacking follicle-stimulating hormone and luteinizing hormone stains account for most discrepancies. Null cell adenomas may be more prevalent than reported and may be clinically more aggressive than gonadotroph adenomas. CONCLUSION: The new WHO classification is mostly well matched with the traditional classification. However, until the new classification is further validated and interpreted in the context of long-term clinical outcomes, routine histological examination should include full slate of immunostains for pituitary hormones as well as TFs.

Novel somatic variants involved in biochemical activity of pure growth hormone-secreting pituitary adenoma without GNAS variant.

We aimed to identify somatic genetic alterations in pure growth hormone (GH)-secreting pituitary adenomas without GNAS variants. Patients with GH-secreting pituitary adenoma who underwent transsphenoidal adenomectomy at Severance Hospital, Yonsei University College of Medicine were recruited. Somatic genetic alterations were profiled by whole-exome sequencing (WES) and targeted resequencing. WES was performed using DNA from nine GH-secreting pituitary tumors and corresponding blood samples. Absence of GNAS variant was confirmed by Sanger sequencing. For targeted resequencing of 140 fixed tissues, 48 WES-derived candidate genes and 7 GH-secreting pituitary adenoma-associated genes were included. Forty-eight genes with 59 somatic variants were identified by WES. In targeted resequencing, variants in 26 recurrent genes, including MAST4, PRIM2, TNN, STARD9, DNAH11, DOCK4, GPR98, BCHE, DARS, CUBN, NGDN, PLXND1, UNC5B, and COL22A1, were identified, but variants in previously reported genes were not detected. BCHE, DARS, NGDN, and UNC5B variants were associated with increased GH-secreting pituitary tumor biochemical activity, which was confirmed in vitro. Although recurrent point variants were rare, several somatic variants were identified in sporadic pure GH-secreting pituitary adenomas. Several somatic variants may affect pathways involved in the tumorigenesis and biochemical activities of GH-secreting pituitary adenomas.

Delayed Hyponatremia after Transsphenoidal Surgery for Pituitary Adenomas: A Single Institutional Experience.

BACKGROUND: Hyponatremia is a common complication after transsphenoidal surgery (TSS) for pituitary adenomas. This study retrospectively reviewed various clinical factors of pituitary adenoma patients who underwent TSS and aimed to identify possible risk factors of postoperative hyponatremia. METHODS: Total 1,343 patients who underwent TSS for their pituitary adenomas in a single institution were enrolled to this study. We identified and analyzed 93 patients (6.9%) with postoperative hyponatremia and compared them with other 1,250 patients in a control group. Patients' age, sex, tumor extent based on the modified Hardy classification, tumor size and hormonal type of the tumors were analyzed in comparison between two groups. The results of pre- and post-operative combined pituitary function test and their comparison were analyzed to elucidate a possible association between postoperative hyponatremia and hypopituitarism. RESULTS: The onset of postoperative hyponatremia was 7.8 days after surgery (range: postoperative day 3-13). The initial level of serum sodium (Na) level at the start of treatment was 123.5 mmol/L (range: 114-131 mmol/L) and the duration of treatment was 2.7 days (range: 1-9 days). Female predominance was evident in the hyponatremia group (77.4% vs. 61.4%, p=0.02). Preoperative hypopituitarism (58.5% vs. 71.5%, p=0.007) and postoperative hypocortisolism (33.7% vs. 23.4%, p=0.029) were related to postoperative hyponatremia. Other pre- and post-operative clinical factors were not associated with postoperative hyponatremia. CONCLUSION: Postoperative hyponatremia is a common complication after TSS and is potentially fatal. Female patients were more likely to develop delayed hyponatremia. We demonstrated possible associations of delayed postoperative hyponatremia with preoperative and postoperative pituitary functions, but the mechanism behind it should be further investigated.

Revisiting the Role of Insulin-like Growth Factor-1 Measurement After Surgical Treatment of Acromegaly.

CONTEXT: In the management of growth hormone (GH)-secreting pituitary adenomas, the oral glucose tolerance test (OGTT) has been the gold standard not only for diagnoses but also for the determination of biochemical remission. Insulin-like growth factor-1 (IGF-1) is an essential biomarker, although it should be adjusted for both age and sex. OBJECTIVE: We evaluated whether IGF-1 levels could serve as a reliable alternative to an OGTT for disease monitoring after the surgical treatment of acromegaly. We retrospectively reviewed the medical records of 320 patients who underwent surgical resection of their GH-secreting pituitary tumors at the Severance hospital. Receiver operator characteristic (ROC) analyses were performed to validate the accuracy of IGF-1 levels for the assessment of remission. In addition, regression analyses were performed to identify factors associated with discrepancy between OGTT and IGF-1 levels. RESULTS: Except for 1 week after surgery, ROC analyses showed an area under the curve of greater than 0.8 for IGF-1 at all time points. Of 320 patients, 270 achieved endocrine remission after surgery alone. Among these patients, IGF-1 levels were normalized in 250 patients. The mean duration from surgery to IGF-1 normalization was 4.7 months. Regression analyses demonstrated that risk of failed IGF-1 normalization was increased by 3.1-fold when the tumor invaded the cavernous sinus and increased by 9.0-fold in patients with incomplete tumor removal. CONCLUSION: IGF-1 level is a reliable alternative to OGTT and plays a valuable role in monitoring acromegaly status.

Radiomics With Ensemble Machine Learning Predicts Dopamine Agonist Response in Patients With Prolactinoma.

CONTEXT: Early identification of the response of prolactinoma patients to dopamine agonists (DA) is crucial in treatment planning. OBJECTIVE: To develop a radiomics model using an ensemble machine learning classifier with conventional magnetic resonance images (MRIs) to predict the DA response in prolactinoma patients. DESIGN: Retrospective study. SETTING: Severance Hospital, Seoul, Korea. PATIENTS: A total of 177 prolactinoma patients who underwent baseline MRI (109 DA responders and 68 DA nonresponders) were allocated to the training (n = 141) and test (n = 36) sets. Radiomic features (n = 107) were extracted from coronal T2-weighed MRIs. After feature selection, single models (random forest, light gradient boosting machine, extra-trees, quadratic discrimination analysis, and linear discrimination analysis) with oversampling methods were trained to predict the DA response. A soft voting ensemble classifier was used to achieve the final performance. The performance of the classifier was validated in the test set. RESULTS: The ensemble classifier showed an area under the curve (AUC) of 0.81 [95% confidence interval (CI), 0.74-0.87] in the training set. In the test set, the ensemble classifier showed an AUC, accuracy, sensitivity, and specificity of 0.81 (95% CI, 0.67-0.96), 77.8%, 78.6%, and 77.3%, respectively. The ensemble classifier achieved the highest performance among all the individual models in the test set. CONCLUSIONS: Radiomic features may be useful biomarkers to predict the DA response in prolactinoma patients.

Radiomics model predicts granulation pattern in growth hormone-secreting pituitary adenomas.

PURPOSE: To investigate whether radiomic features from magnetic resonance image (MRI) can predict the granulation pattern of growth hormone (GH)-secreting pituitary adenoma patients. METHODS: Sixty-nine pathologically proven acromegaly patients (densely granulated [DG] = 50, sparsely granulated [SG] = 19) were included. Radiomic features (n = 214) were extracted from contrast-enhancing and total tumor portions from T2-weighted (T2) MRIs. Imaging features were selected using a least absolute shrinkage and selection operator (LASSO) logistic regression model with fivefold cross-validation. Diagnostic performance for predicting granulation pattern was compared with that for qualitative T2 signal intensity assessment and T2 relative signal intensity (rSI) using the area under the receiver operating characteristics curve (AUC). RESULTS: Four significant radiomic features from the contrast-enhancing tumor (1 from shape, 1 from first order feature, and 2 from second order features) were selected by LASSO for model construction. The radiomics model showed an AUC, accuracy, sensitivity, and specificity of 0.834 (95% confidence interval [CI] 0.738-0.930), 73.7%, 74.0%, and 73.9%, respectively. The radiomics model showed significantly better performance than the model using qualitative T2 signal intensity assessment (AUC 0.597 [95% CI 0.447-0.747], P = 0.009) and T2 rSI (AUC 0.647 [95% CI 0.523-0.759], P = 0.037). CONCLUSION: Radiomic features may be useful biomarkers to differentiate granulation pattern of GH-secreting pituitary adenoma patients, and showed better performance than qualitative assessment or rSI evaluation.

Optical Coherent Tomography Predicts Long-Term Visual Outcome of Pituitary Adenoma Surgery: New Perspectives From a 5-Year Follow-up Study.

BACKGROUND: Compressive optic neuropathy is the most common indication for transsphenoidal surgery for pituitary adenomas. Optical coherence tomography (OCT) is a useful visual assessment tool for predicting postoperative visual field recovery. OBJECTIVE: To analyze visual parameters and their association based on long-term follow-up. METHODS: Only pituitary adenoma patients with abnormal visual field defects were selected. A total of 188 eyes from 113 patients assessed by visual field index (VFI) and 262 eyes from 155 patients assessed by mean deviation (MD) were enrolled in this study. Postoperative VFI, MD, and retinal nerve fiber layer (RNFL) thickness were evaluated and followed up. After classifying the patients into normal (>5%) and thin (<5%) RNFL groups, we investigated whether preoperative RNFL could predict visual field outcomes. We also observed how RNFL changes after surgery on a long-term basis. RESULTS: Both preoperative VFI and MD had a linear proportional relationship with preoperative RNFL thickness. Sustained improvement of the visual field was observed after surgery in both groups, and the degree of improvement over time in each group was similar. RNFL thickness continued to decrease until 36 mo after surgery (80.2 ± 13.3 µm to 66.6 ± 11.9 µm) while visual field continued to improve (VFI, 61.8 ± 24.5 to 84.3 ± 15.4; MD, -12.9 ± 7.3 dB to -6.3 ± 5.9 dB). CONCLUSION: Patients with thin preoperative RNFL may experience visual recovery similar to those with normal preoperative RNFL; however, the probability of normalized visual fields was not comparable. RNFL thickness showed a strong correlation with preoperative visual field defect. Long-term follow-up observation revealed a discrepancy between anatomic and functional recovery.

Immediate postoperative measurement of thyroid-stimulating hormone as an early predictor of remission in thyroid-stimulating hormone-secreting pituitary adenomas.

OBJECTIVE: Thyroid-stimulating hormone (TSH)-secreting pituitary adenoma (TSHoma) is a rare type of pituitary adenoma; thus, little is known about TSHomas. The purpose of this study was to analyze clinical characteristics and therapeutic outcomes of TSHomas based on a single-center experience. The authors also searched for reliable preoperative and early postoperative factors that could predict long-term endocrinological remission. METHODS: The clinical, radiological, and pathological characteristics and surgical and endocrinological outcomes of 31 consecutive cases of TSHomas that were surgically treated between 2005 and 2017 were reviewed retrospectively. Preoperative factors were evaluated for their ability to predict long-term remission by comparing remission and nonremission groups. TSH and free thyroxine levels were measured at 2, 6, 12, 18, and 24 hours after surgery to determine whether they could predict long-term remission. RESULTS: Gross-total removal of tumor was achieved in 28 patients (90.3%), and 26 patients (83.9%) achieved endocrinological remission by surgery alone based on long-term endocrinological follow-up (median 50 months, range 32-81 months). The majority of the tumors were solid (21/31, 67.7%), and en bloc resection was possible in 16 patients (51.6%). Larger tumor size and tumor invasion into cavernous sinus and sphenoid sinus were strong predictors of lower rates of endocrinological remission. Immediate postoperative TSH level at 12 hours after surgery was the strongest predictor, with a 0.62 µIU/mL cutoff. Postoperative complications included CSF rhinorrhea in one patient and epistaxis in another patient, who underwent additional surgical treatment for the complications. CONCLUSIONS: Tumor size and extent are major prognostic factors for both extent of resection and endocrinological remission. The consistency of TSHomas was more likely to be solid, which makes extracapsular dissection more feasible. Long-term remission of TSHomas could be predicted even during the early postoperative period.

Lateral supraorbital versus pterional approach for parachiasmal meningiomas: surgical indications and esthetic benefits.

The lateral supraorbital (LSO) approach is a minimally invasive modification of the pterional approach. The authors assess the surgical indications and esthetic benefits of the LSO approach in comparison with the pterional approach for parachiasmal meningiomas. From April 2013 to May 2017, a total of 64 patients underwent surgery for parachiasmal meningiomas. Among them, tumor resection was performed with the LSO approach for 34 patients and pterional approach for 30 patients. A retrospective analysis was done on tumor characteristics, surgical outcome, approach-related morbidity, and esthetic outcome between the two approaches. Gross total resection was achieved in 33 of 34 patients (97.1%) with the LSO approach. There were no differences in tumor size, origin, consistency, internal carotid artery encasement, cranial nerve adhesion, and optic canal invasion between the two approaches. The most common tumor origin was the tuberculum sellae for both the LSO and pterional approaches. For tumors with preoperative visual compromise, immediate visual outcome improved or remained stable in 76% and 80.9% with the LSO and pterional approaches, respectively. Surgery time, surgical bleeding, hospital length of stay, and esthetic outcome were significantly shorter and superior with the LSO approach. There were no differences in surgical morbidity and brain retraction injury between the two approaches. The LSO approach can provide a safe, rapid, and minimally invasive exposure for parachiasmal meningiomas compared with the pterional approach. Surgeons must consider tumor size, origin, and extent in determining the resectability of the tumor rather than the extent of exposure.

Angioleiomyoma in the Orbital Apex: A Case Report.

A 56-year woman presented eyeball pain and blurred vision. MRI revealed a small well-delineated solid tumor in the apex of right orbit with optic nerve compression. Intraoperatively, the tumor was found very fibrous, hypervascular and adhesive to surrounding structures. The tumor was completely removed with the combination of endoscopic and microscopic technique. Patient experienced transient oculomotor nerve palsy, which completely recovered 3 months after surgery. Herein we report a rare case of angioleiomyoma in the orbital apex.

Prevalence of Thyroid Disease in Patients Surgically Treated for Pituitary Disease.

Thyroid disease mainly has a thyroid origin but can occasionally have a pituitary origin. Clinicians face several challenges when these conditions occur together. We aimed to determine the prevalence of thyroid disorders in patients undergoing trans-sphenoidal adenomectomy (TSA) for pituitary disease. We reviewed the medical records of patients undergoing TSA for pituitary disease between 2008 and 2017 at Severance Hospital. Thyroid disorders were categorized using blood test results and medical histories at the time of preoperative evaluation. Among 2202 patients, 44 (2%), 218 (9.9%), and 74 (3.4%) had hyperthyroidism, hypothyroidism, and post-thyroidectomy status before TSA, respectively. Among the 44 patients with hyperthyroidism, 30 (68.2%) had central hyperthyroidism. Among the 218 patients with hypothyroidism, 165 (75.7%) had central hypothyroidism. Central hypothyroidism was more common in patients with adrenocorticotropic hormone-secreting pituitary adenomas (aOR (adjusted odds ratio) 1.85), Rathke's cleft cysts (aOR 2.34), and craniopharyngiomas (aOR 2.58) (all p < 0.05) than in those with nonfunctioning pituitary adenomas. Contrastingly, thyroid cancer had an increased prevalence in patients with growth hormone- (aOR 3.17), prolactin- (aOR 3.66), and thyroid-stimulating hormone-secreting (aOR 6.28) pituitary adenomas (all p < 0.05). Pituitary disease sometimes accompanies thyroid disorders; their characteristics vary according to the type of pituitary disease.