Coexistence of TSH-secreting adenoma and primary hypothyroidism: a case report and review of literature.

BACKGROUND: Thyrotropin-secreting adenoma (TSHoma) is the least common type of pituitary adenoma, these patients often present with symptoms of hyperthyroidism. When TSHoma patients combined with autoimmune hypothyroidism, it is critically difficult to diagnose for the specific confusion in the results of thyroid function test. CASE PRESENTATION: One middle-aged male patient was presented with a sellar tumor on cranial MRI for headache symptoms. After hospitalization, a significant increase in thyrotropin (TSH) was revealed by the endocrine tests, while free thyronine (FT3) and free thyroxine (FT4) decreased, and the diffuse destruction of thyroid gland was revealed by thyroid ultrasound. Based on the endocrine test results, the patient was diagnosed as autoimmune hypothyroidism. After the multidisciplinary discussion, the pituitary adenoma was removed by endoscopic transnasal surgery, until the tumor was completely excised, for which TSHoma was revealed by postoperative pathology. A significant decrease of TSH was revealed by the postoperative thyroid function tests, the treatment for autoimmune hypothyroidism was conducted. After 20 months of follow-up, the thyroid function of patient had been improved significantly. CONCLUSION: When the thyroid function test results of patients with TSHoma are difficult to interpret, the possibility of combined primary thyroid disease should be considered. TSHoma combined with autoimmune hypothyroidism is rare, which is difficult to diagnose. The multidisciplinary collaborative treatment could help to improve the outcomes of treatment.

Impact of three surgical approaches on the therapeutic efficacy of intraventricular craniopharyngiomas: a single-center retrospective analysis.

This study aimed to investigate the therapeutic efficacy of three different surgical approaches for the treatment of intraventricular craniopharyngiomas (IVCs). The three surgical approaches investigated in this study were the endoscopic endonasal approach (EEA), pterional trans-lamina terminalis approach (PTA), and interhemispheric trans-lamina terminalis approach (ITA). Patient demographics, preoperative symptoms, endocrine and hypothalamic status, tumor characteristics, and surgical outcomes were analyzed and compared among the different surgical groups. A total of 31 patients with IVCs were included in the analysis, with 12 patients in the EEA group, 8 patients in the ITA group, and 11 patients in the PTA group. The mean follow-up time was 39 ± 23 months. Statistical analysis of the data revealed significant differences in the gross total resection (GTR) rate among the three surgical groups (P = 0.033). The GTR rate for the EEA group was 100%, that for the ITA group was 88%, and that for the PTA group was 64%, which was the lowest rate observed. After surgery, only 8.3% of the patients in the EEA group did not experience new postoperative hypopituitarism, while the percentages in the ITA and PTA groups were 75% and 73%, respectively (P = 0.012). Finally, we found that postoperative hypopituitarism may be related to the transection of the pituitary stalk during the operation (P = 0.020). Based on the results of this study, we recommend using the EEA and the ITA instead of the PTA for the surgical resection of IVCs. Furthermore, the appropriate surgical approach should be selected based on the tumor's growth pattern.

Comprehensive Analysis of 34 Edible Flowers by the Determination of Nutritional Composition and Antioxidant Capacity Planted in Yunnan Province China.

The main purpose of this study was to reveal the nutritional value and antioxidant activity of 34 edible flowers that grew in Yunnan Province, China, through a comprehensive assessment of their nutritional composition and antioxidant indices. The results showed that sample A3 of Asteraceae flowers had the highest total flavonoid content, with a value of 8.53%, and the maximum contents of vitamin C and reducing sugars were from Rosaceae sample R1 and Gentianaceae sample G3, with values of 143.80 mg/100 g and 7.82%, respectively. Samples R2 and R3 of Rosaceae were the top two flowers in terms of comprehensive nutritional quality. In addition, the antioxidant capacity of Rosaceae samples was evidently better than that of three others, in which Sample R1 had the maximum values in hydroxyl radical (·OH) scavenging and superoxide anion radical (·O2-) scavenging rates, and samples R2 and R3 showed a high total antioxidant capacity and 2,2-diphenyl-1-pyridylhydrazine (DPPH) scavenging rate, respectively. Taken together, there were significant differences in the nutrient contents and antioxidant properties of these 34 flowers, and the comprehensive quality of Rosaceae samples was generally better than the other three families. This study provides references for 34 edible flowers to be used as dietary supplements and important sources of natural antioxidants.

A MEMS modulator-based dual-channel mid-infrared laser heterodyne radiometer for simultaneous remote sensing of atmospheric CH4, H2O and N2O.

The performance of a micro-electro-mechanical system (MEMS) modulator-based dual-channel mid-infrared laser heterodyne radiometer (MIR-LHR) was demonstrated in ground-based solar occultation mode for the first time. A MEMS mirror was employed as an alternative modulator to the traditional mechanical chopper, which makes the system more stable and compact. Two inter-band cascade lasers (ICL) centered at 3.53 µm and 3.93 µm, were employed as local oscillators (LO) to probe absorption lines of methane (CH4), water vapor (H2O) and nitrous oxide (N2O). The system stability greater than 1000 s was evaluated by Allan variance. The experimental MIR-LHR spectra (acquired at Hefei, China, on February 24th 2022) of two channels were compared and were in good agreement with simulation spectra from atmospheric transmission modeling. The mixing ratio of CH4, H2O and N2O were determined to be ∼1.906 ppm, 3069 ppm and ∼338 ppb, respectively. The reported MEMS modulator-based dual-channel MIR-LHR in this manuscript has great potential to be a portable and high spectral resolution instrument for remote sensing of multi-component gases in the atmospheric column.

Tractography of the stria terminalis in the human brain.

The aim of this study was to investigate the trajectory of the stria terminalis and develop a protocol for mapping the stria terminalis using multi-shell diffusion images based tractography. The stria terminalis was reconstructed by combining one region of interest at the amygdala with another region of interest at the bed nucleus of stria terminalis. In addition, one region of avoidance was placed on the fornix at the interventricular foramen and another was set at the anterior perforated substance. The fiber-tracking protocol was tested in a Human Connectome Project-842 template, 35 healthy subjects from Massachusetts General Hospital, and 20 healthy subjects from the Human Connectome Project using generalized q-sampling imaging based tractography. The stria terminalis was reconstructed in the Human Connectome Project-842 template, 35 Massachusetts General Hospital healthy subjects, and 20 Human Connectome Project healthy subjects with our protocol. The stria terminalis originated from the amygdala and traveled parallel to the fornix. Then, the stria terminalis followed a C-shaped trajectory around the inferior, posterior, and dorsal surfaces of the thalamus before projecting to the bed nucleus of stria terminalis between the thalamus and caudate nucleus. There were no significant differences in the quantitative anisotropy and fractional anisotropy values between the left and right stria terminalis. The stria terminalis was accurately visualized across subjects using multi-shell diffusion images through generalized q-sampling imaging based tractography. This method could be an important tool for the reconstruction and evaluation of the stria terminalis in various neurological disorders. One Sentence Summary The visualization of the stria terminalis through the multi-shell diffusion images using generalized q-sampling imaging based tractography.

Tractography of the ansa lenticularis in the human brain.

The aim of this study was to make a thorough investigation of the trajectory of the ansa lenticularis (AL) and its subcomponents using high-resolution fiber-tracking tractography. The subcomponents of the AL were reconstructed from one region of interest (ROI) in the area of the globus pallidus combined with another ROI in the red nucleus, substantia nigra, subthalamic nucleus, or thalamus. This fiber-tracking protocol was tested in an HCP-1065 template, 35 healthy subjects from Massachusetts General Hospital (MGH), and 20 healthy subjects from the human connectome project (HCP) using generalized q-sampling imaging (GQI)-based tractography. Quantitative anisotropy and fractional anisotropy were also computed for the AL subcomponents. The subcomponents of the AL could be reconstructed in the HCP-1065 template, 35 MGH healthy subjects, and 20 HCP healthy subjects. The AL descends from the globus pallidus and joins the ansa peduncularis for a short distance, subdividing later into fibers that continue separately to the red nucleus, substantia nigra, subthalamic nucleus, and thalamus. The study demonstrated the trajectory of the ansa lenticularis and its subcomponents using GQI-based tractography, improving our understanding of the anatomical connectivity between the globus pallidus and the thalamo-subthalamic region in the human brain. One Sentence Summary The investigation of the ansa lenticularis and its subcomponents using high-resolution diffusion images based tractography.

The trajectory of the medial longitudinal fasciculus in the human brain: A diffusion imaging-based tractography study.

The aim of this study is to investigate the trajectory of medial longitudinal fasciculus (MLF) and explore its anatomical relationship with the oculomotor nerve using tractography technique. The MLF and oculomotor nerve were reconstructed at the same time with preset three region of interests (ROIs): one set at the area of rostral midbrain, one placed on the MLF area at the upper pons, and one placed at the cisternal part of the oculomotor nerve. This mapping protocol was tested in an HCP-1065 template, 35 health subjects from Massachusetts General Hospital (MGH), 20 healthy adults and 6 brainstem cavernous malformation (BCM) patients with generalized q-sampling imaging (GQI)-based tractography. Finally, the 200 µm brainstem template from Center for In Vivo Microscopy, Duke University (Duke CIVM), was used to validate the trajectory of reconstructed MLF. The MLF and oculomotor nerve were reconstructed in the HCP-1065 template, 35 MGH health subjects, 20 healthy adults and 6 BCM patients. The MLF was in conjunction with the ipsilateral mesencephalic part of the oculomotor nerve. The displacement of MLF was identified in all BCM patients. Decreased QA, RDI and FA were found in the MLF of lesion side, indicating axonal loss and/or edema of displaced MLF. The reconstructed MLF in Duke CIVM brainstem 200 µm template corresponded well with histological anatomy. The MLF and oculomotor nerve were visualized accurately with our protocol using GQI-based fiber tracking. This GQI-based tractography is an important tool in the reconstruction and evaluation of MLF.

Predictors of Immediate Remission after Surgery in Cushing's Disease Patients: A Large Retrospective Study from a Single Center.

OBJECTIVE: Transsphenoidal surgery (TSS) is the first-line treatment of patients with Cushing's disease (CD). However, biochemical remission rates after TSS for CD vary from 59 to 95%, and the predictors of surgical outcomes remain unclear. The aim of this study was to identify the predictors of early outcomes in patients with CD treated with TSS. METHODS: The clinical features and outcomes of CD patients who underwent TSS between February 2000 and September 2019 at the Peking Union Medical College Hospital were collected from medical records and analyzed. Uni- and multivariate odds ratio (OR) analyses were performed to identify the predictors of early outcomes in patients with CD. RESULTS: A total of 1,045 patients were included. The median age at TSS was 34.0 years (IQR 26.0-45.0), with a female:male ratio of 4.2:1 (844/201). The median duration of symptoms was 46.0 months (IQR 24.0-72.0). After surgery, the overall postoperative immediate remission rate was 73.3%, and 26.7% of patients had persistent hypercortisolism. Univariate analysis demonstrated that the number of operations was correlated with a lower immediate remission rate (OR 0.393, 95% CI 0.266-0.580, p = 0.000), as was tumor size (OR 0.462, 95% CI 0.334-0.639, p = 0.000), the duration of disease (OR 0.996, 95% CI 0.993-0.999, p = 0.003), and preoperative ACTH concentration (0.998, 95% CI 0.996-0.999, p = 0.003). Cavernous sinus invasion has also been identified as an important factor associated with a lower immediate remission rate (OR 0.275, 95% CI 0.166-0.456, p = 0.000). No correlations were detected between the immediate outcomes and age, gender, BMI, the combination of a low- and high-dose dexamethasone suppression test, preoperative morning serum cortisol level, or 24-h urinary free cortisol level (all p > 0.05). The results of multivariate analysis were similar to those of univariate analysis. Preoperative ACTH ≤67.35 ng/L predicted remission with 60.9% sensitivity and 49.5% specificity (AUC 0.553; p = 0.008). A cutoff of ≤64.5 months for disease duration predicted immediate remission with 40.5% sensitivity and 71.0% specificity (AUC 0.552; p = 0.01). CONCLUSION: Early outcomes of TSS in CD patients can be predicted by factors including the number of operations, duration of disease, tumor invasion, tumor size, and preoperative ACTH concentration. These predictors can be used to improve the perioperative management of CD patients.

Deep-Learning Approach to Automatic Identification of Facial Anomalies in Endocrine Disorders.

BACKGROUND: Deep learning has the potential to assist the medical diagnostic process. We aimed to identify facial anomalies associated with endocrinal disorders using a deep-learning approach to facilitate the process of diagnosis and follow-up. METHODS: We collected facial images of patients with hypercortisolism and acromegaly, and we augmented these images with additional negative samples from public databases. A model with a pretrained deep-learning network was constructed to automatically identify these hypersecretion statuses based on characteristic facial changes. We compared its performance to that of endocrine experts and further investigated key factors upon which the best performing model focused. FINDINGS: The model achieved areas under the receiver operating characteristic curve of 0.9647 (Cushing's syndrome) and 0.9556 (acromegaly), accuracies of 0.9593 (Cushing's syndrome) and 0.9479 (acromegaly), and recalls of 0.7593 (Cushing's syndrome) and 0.8089 (acromegaly). It performed better than any level of our endocrine experts. Furthermore, the regions of interest on the part of the machine were primarily the same as those upon which the humans focused. INTERPRETATION: Our findings suggest that the deep-learning model learned the facial characters based merely on labeled data without learning prerequisite medical knowledge, and its performance was comparable with professional medical practitioners. The model has the potential to assist in the diagnosis and follow-up of these hypersecretion statuses.

Outcomes of Transsphenoidal Surgery in Cushing Disease Patients with Negative Pituitary Magnetic Resonance Imaging Findings: A Single-Center Experience.

OBJECTIVE: Transsphenoidal surgery (TSS) is a first-line treatment for Cushing disease (CD). However, a subset of patients with CD have no visible adenoma on magnetic resonance imaging (MRI), and whether MRI results affect surgical outcomes is controversial. The aim of this study was to compare the surgical outcomes of CD patients with negative MRI findings to those of patients with positive MRI findings. METHODS: The clinical features and outcomes of CD patients who underwent TSS between January 2000 and July 2019 at Peking Union Medical College Hospital were collected from medical records. The clinical, endocrinologic, histopathologic, surgical outcomes, and a minimum 12-month follow-up of 125 consecutive CD patients with negative MRI findings were compared with those of 1,031 consecutive CD patients with MRI-visible adenomas. RESULTS: The total remission rate was 73.3% after TSS, and 11.8% of patients experienced recurrence. Of 1,031 patients with MRI-visible adenomas, postoperative remission was achieved in 762 patients (73.9%), and the recurrence of CD was observed in 94 (12.3%) patients. Of the 125 patients with negative MRI findings, postoperative remission was achieved in 85 (68%) patients, and recurrence was observed in 6 (7.1%) patients. The remission rate and recurrence rate were not significantly different between patients with negative MRI findings and those with positive MRI findings (all P>.05). The remission rate was not significantly different between patients who did or did not undergo bilateral inferior petrosal sinus sampling (BIPSS) in patients with negative MRI findings (P>.05). In the patients with negative MRI findings who underwent BIPSS, the remission rate of patients with positive BIPSS results was not different from that in patients with negative BIPSS results (P>.05). The lack of prior TSS, the detection of a tumor during operation, and pathologic confirmation of adenoma were associated with a higher surgical remission rate in patients with negative MRI findings (all P<.05). Similar results were observed in the patients with positive MRI findings (all P<.05). In addition, the major perioperative complications, including intraoperative cerebrospinal fluid leakage, hypopituitarism, and transient diabetes insipidus, were not related to the MRI results (all P>.05). CONCLUSION: The remission rate and recurrence rate were not different between patients with negative MRI findings and those with positive MRI findings. If CD is clearly diagnosed according to biochemical tests, radiologic examinations, and BIPSS, we recommend TSS as the first-line treatment for patients, even if the MRI results are negative.

Effect of TIPA on mechanical properties and hydration properties of cement-lithium slag system.

Effect of triisopropanolamine (TIPA) on compressive strength and hydration properties of cement-lithium slag (LS, 30%) paste was studied. The results demonstrated that the addition of TIPA is advantageous for compressive strength at 7 d, 28 d and 60 d. The reason was related to the pore complexity and hydration process of cement and LS. TIPA reduced the total porosity, and increased the fractal dimension, making the pore structure more complicated. In addition, TIPA promoted the pozzolanic reaction of LS and the hydration of cement, expediting the formation of C-S(A)-H gel. TIPA accelerated the dissolution of aluminate ions, silicate ions and ferric ions in the pore solution, thereby accelerating the pozzolanic reaction of LS. During the hydration of cement-LS paste, TIPA facilitated the conversion of ettringite to the AFm-like phase and produced more C-A-S-H gel by promoting the dissolution of aluminate ions.

Prediction of Recurrence after Transsphenoidal Surgery for Cushing's Disease: The Use of Machine Learning Algorithms.

BACKGROUND: There are no reliable predictive models for recurrence after transsphenoidal surgery (TSS) for Cushing's disease (CD). OBJECTIVES: This study aimed to develop machine learning (ML)-based predictive models for CD recurrence after initial TSS and to evaluate their performance. METHOD: A total of 354 CD patients were included in this retrospective, supervised learning, data mining study. Predictive models for recurrence were developed according to 17 variables using 7 algorithms. Models were evaluated based on the area under the receiver operating characteristic curve (AUC). RESULTS: All patients were followed up for over 12 months (mean ± SD 43.80 ± 35.61). The recurrence rate was 13.0%. Age (p < 0.001), postoperative morning serum cortisol nadir (p = 0.002), and postoperative (p < 0.001) and preoperative (p = 0.04) morning adrenocorticotropin (ACTH) level were significantly related to recurrence. AUCs of the 7 models ranged from 0.608 to 0.781. The best performance (AUC = 0.781, 95% CI 0.706, 0.856) appeared when 8 variables were introduced to the random forest (RF) algorithm, which was much better than that of logistic regression (AUC = 0.684, p = 0.008) and that of using only postoperative morning serum cortisol (AUC = 0.635, p < 0.001). According to the feature selection algorithms, the top 3 predictors were age, postoperative serum cortisol, and postoperative ACTH. CONCLUSIONS: Using ML-based models for prediction of the recurrence after initial TSS for CD is feasible, and RF performs best. The performance of most of ML-based models was significantly better than that of some conventional models.

Metformin inhibits growth and prolactin secretion of pituitary prolactinoma cells and xenografts.

Metformin (MET) is a diabetes drug that activates AMP-activated protein kinase (AMPK), and is suggested to have anticancer efficacy. Here, we investigated the role of AMPK signalling in prolactinoma (PRLoma), with particular respect to MET and bromocriptine (BC) as a PRLoma treatment. We analysed AMPK phosphorylation, dopamine D2 receptor (D2R), and oestrogen receptor (ER) expression in both BC-sensitive and -resistant PRLoma samples; effects of the AMPK agonist MET (alone or with BC) on in vitro proliferation and apoptosis, xenograft growth and prolactin (PRL) secretion of BC-sensitive and -resistant cells, and ER expression in xenografts. Some BC-resistant PRLomas showed high D2R expression but extremely low AMPK activation. MET significantly inhibited proliferation of cultured PRLoma cells; MET + BC notably restrained their PRL secretion. MET + BC further decreased tumour growth and serum PRL levels in xenografts than BC treatment alone. ER was down-regulated after AMPK activation in both cultured cells and xenografts. Together, we propose that the AMPK signalling pathway down-regulates ERα and ERß, and suppresses PRLoma growth as well as PRL secretion. Combined MET + BC is a potential treatment for PRLomas.

Tumour lateralization in Cushing's disease by inferior petrosal sinus sampling with desmopressin.

BACKGROUND: Bilateral inferior petrosal sinus sampling (IPSS) with corticotropin-releasing hormone (CRH) is currently the gold standard in the diagnosis of Cushing's disease (CD) and has also been used in tumour lateralization. Our objective was to determine the diagnostic value and lateralization accuracy of IPSS with desmopressin. METHODS: We retrospectively analysed 91 patients with Cushing's syndrome who had either negative findings on pituitary dynamic enhanced magnetic resonance imaging (MRI) or nonsuppressed high-dose dexamethasone suppression tests (HDDST). Thin-slice thoracoabdominal computed tomography (CT) and octreotide receptor imaging of whole body were also negative to rule out ectopic adrenocorticotropin hormone (ACTH) syndrome. All patients went through IPSS with desmopressin. Afterwards, transsphenoidal pituitary surgery, light microscope pathology and immunohistological staining for ACTH were performed in all patients. RESULTS: Diagnosis of CD. Among the 91 patients included, 90 were confirmed with CD, of whom 89 had positive IPSS findings, therefore the sensitivity was 98.9%. The one patient who was negative for CD also had negative IPSS findings, therefore the specificity was 100%. Tumour lateralization. Among the 51 patients who were ultimately diagnosed with CD and whose lateralization by IPSS and surgery was either left or right, 37 had IPSS lateralization in concordance with surgery, therefore the concordance rate was 72.5%. Patients in the concordant group had a higher frequency of right lateralization by surgery. CONCLUSIONS: IPSS with desmopressin is a sensitive approach in the diagnosis of CD and has moderate accuracy in tumour lateralization, making it an alternative choice to IPSS with CRH.

[Influence of Nasal Disinfection on Nasal Bacterial Colonization through the Transsphenoidal Approach].

Objective To explore the influence of the iodine disinfection on nasal bacterial colonization through the transsphenoidal approach. Methods Totally 133 pituitary adenoma patients who underwent transsphenoidal surgery in our department from January to August 2017 were enrolled in this study. Before disinfection,pharyngeal swabs of inferior turbinate root secretions were taken for bacterial culture. After iodine disinfection,pharyngeal swabs were taken again at the same site. Changes in the nasal bacterial spectrum before and after disinfection were compared. Patients were followed up for three months after the surgery,during which any intracranial infection/bacteraemia was recorded,and its correlation with nasal bacteria colonization was analyzed. Results Nasal bacterial colonization was detected in 45 (33.8%) of 133 patients before iodine disinfection and in only 6 cases (4.5%) after iodine disinfection (χ2=34.5,P=0.000). Thus,iodine disinfection eliminated 86.7%(39/45) of the colonized bacteria. The most common nasal bacterium was Staphylococcus aureus (24.4%,11/45),followed by Klebsiella pneumoniae (24.4%,11/45),and Staphylococcus epidermidis (13.3%,6/45). One patient had high fever and chills 2 days after surgery,but blood culture and cerebrospinal fluid culture showed negative Results . After the administration of third-generation cephalosporins,the symptoms disappeared after two days. Conclusion sThere are colonized bacteria in nasal cavity. Iodine disinfection of nasal cavity can effectively clear most of the nasal bacteria. The possibility of intracranial infection/bacteremia after transsphenoidal approach is low.

[Unusual Isolated Sellar Spindle Cell Carcinoma:Report of One Case].

Sellar malignant tumors are uncommon and usually reported as metastatic diseases from breast or lung cancers. Spindle cell carcinoma (SCC) is a rare malignancy and has been found in breast,oral cavity,lungs,kidneys,and hepatobiliary pancreatic system but not in sellar region. We report here the first case of isolated sellar SCC with aggressive features in Peking Union Medical College Hospital. This patient was referred to our hospital on September 9,2015 and discharged on October 16,2015. We described the clinical manifestations,imaging findings,and pathological features of this rare disease.

Extended transsphenoidal approach for pituitary adenomas invading the cavernous sinus using multiple complementary techniques.

PURPOSE: Transsphenoidal surgery is the treatment of choice for most pituitary adenomas (PA), except prolactinomas. Difficulties achieving radical resection with this method are encountered in patients with PAs invading the cavernous sinus (CS), due to the inability of the standard transsphenoidal approach to expose all tumors adequately. This study analyzed methods to resect PAs invading the CS and factors influencing the degree of tumor resection and occurrence of complications. METHODS: Outcomes were retrospectively analyzed in 52 patients with PA invading the CS who underwent surgery via the extended transsphenoidal approach utilizing multiple techniques, including microscopy, endoscopy, neuronavigation, and intraoperative Doppler ultrasonography. RESULTS: Gross-total resection (GTR) was achieved in 33 patients (63.5 %). GTR rate was significantly higher in patients with Knosp Grade 3 than Knosp Grade 4 (92.3 vs. 53.8 %) and in patients undergoing initial surgery than reoperation (77.1 vs. 35.3 %). One patient (2.9 %) undergoing initial surgery experienced transient cranial nerve palsy, without other postoperative complications. Postoperative complications were significantly higher after reoperation. Firm tumor consistency was significantly more frequent in patients undergoing reoperation than initial surgery (52.9 vs. 8.6 %). CONCLUSION: Extended transsphenoidal surgery incorporating multiple complementary techniques was highly effective for PAs invading the CS. Postoperative complications rates were relatively low, especially for patients undergoing initial surgery and those with Knosp Grade 3 tumors. Total resection of PAs invading the CS remains challenging, especially in patients undergoing reoperation or having firm tumors.

Phenotype-Genotype Association Analysis of ACTH-Secreting Pituitary Adenoma and Its Molecular Link to Patient Osteoporosis.

Adrenocorticotrophin (ACTH)-secreting pituitary adenoma, also known as Cushing disease (CD), is rare and causes metabolic syndrome, cardiovascular disease and osteoporosis due to hypercortisolism. However, the molecular pathogenesis of CD is still unclear because of a lack of human cell lines and animal models. Here, we study 106 clinical characteristics and gene expression changes from 118 patients, the largest cohort of CD in a single-center. RNA deep sequencing is used to examine genotypic changes in nine paired female ACTH-secreting pituitary adenomas and adjacent nontumorous pituitary tissues (ANPT). We develop a novel analysis linking disease clinical characteristics and whole transcriptomic changes, using Pearson Correlation Coefficient to discover a molecular network mechanism. We report that osteoporosis is distinguished from the phenotype and genotype analysis. A cluster of genes involved in osteoporosis is identified using Pearson correlation coefficient analysis. Most of the genes are reported in the bone related literature, confirming the feasibility of phenotype-genotype association analysis, which could be used in the analysis of almost all diseases. Secreted phosphoprotein 1 (SPP1), collagen type I α 1 chain (COL1A1), 5'-nucleotidase ecto (NT5E), HtrA serine peptidase 1 (HTRA1) and angiopoietin 1 (ANGPT1) and their signalling pathways are shown to be involved in osteoporosis in CD patients. Our discoveries provide a molecular link for osteoporosis in CD patients, and may open new potential avenues for osteoporosis intervention and treatment.

[Use of inferior petrosal sinus sampling during the perioperative periodtreatment of Cushing's disease with negative magnetic resonance imaging].

OBJECTIVE: To analyze inferior petrosal sinus sampling (IPSS) in diagnosis and treatment of Cushing's disease with negative magnetic resonance imaging (MRI). METHODS: We retrospectively reviewed 79 cases of Cushing's disease with negative MRI in the Department of Neurosurgery of Peking Union Medical College Hospital from August 2012 to August 2014. Of the 79 patients, 58 underwent IPSS. There were 16 males and 42 females in this study, with age 12 to 65 years old. All 58 patients underwent endocrine assessment before transsphenoidal surgery, and pathology specimens were examined. RESULTS: The IPSS results of all the 58 patients suggested the excessive secretion of ACTH was from pituitary. Of the 58 patients, visible tumor was found in 56 cases during intraoperative exploration (96.6%). In 29 (50%) cases, the side of pituitary where tumor was located predicted by IPSS was the same with intraoperative exploration. Typical tumor was seen in 47 cases during exploration, and the endocrine remission rate was 83.0% after operation. Suspicious tumor was seen in 9 cases, and endocrine response rate was 44.4%. No tumor was found in two cases who had no remission after operation. Pituitary adenoma was confirmed in 41 patients (70.7%) by pathological exam. And anterior or posterior lobe of pituitary was reported in 12 cases, pituitary hyperplasia in 5 cases. CONCLUSIONS: IPSS is recommended in Cushing's disease patients with negative MRI, and it is helpful to judge whether the excessive secretion of ACTH is from pituitary, while its value in predicting the lateralization of tumor is low. If IPSS results are positive, transsphenoidal surgery should be performed.