bluuebunny/crossref_metadata_2025_split huggingface dataset:
Copeptin Levels Before and After Transsphenoidal Surgery for Cushing Disease: A Potential Marker of Remission
Authors: Flippo Chelsi L , Tatsi Christina , Sinaii Ninet , Sierra Maria de la Luz , Belyavskaya Elena , Lysikatos-Lyssikatos Charalampos , Keil Margaret , Scientist Nurse , Spanakis Elias , Stratakis Constantine A 
Published: May 2021

Abstract
Objectives: Chronic hypercortisolemia suppresses AVP secretion. Copeptin makes up the C-terminal portion of the AVP precursor pre-pro-AVP, is released in stoichiometric amounts with AVP, and is a stable surrogate marker of AVP.A post-operative increase in plasma copeptin was hypothesized to be a marker of remission of Cushing Disease (CD).
Methods: Plasma copeptin was obtained in patients with CD before and daily in the first week after transsphenoidal surgery (TSS), measured using the Brahm Kryptor Compact PLUS sandwich immunofluorescent assay. Urine output, serum sodium, urine specific gravity, and urine/serum osmolality were used to determine development of central diabetes insipidus (DI) and/or syndrome of inappropriate anti-diuretic hormone secretion (SIADH). Change in copeptin reflects pre-TSS to peak post-TSS copeptin levels. Statistical analyses were completed using non-parametric tests. Results are presented as median (inter-quartile range).
Results: Forty-four patients (64% female, 7-55 years old) were included. After TSS, 8 (18%) developed DI, 13 (30%) developed SIADH, 4 (9%) developed both DI and SIADH, and 19 (43%) developed neither. Thirty-three patients had a follow-up at 3-6 months. Overall, there was no difference in peak post-TSS copeptin for patients in remission versus those not in remission [6.1 pmol/L (4.3-12.1) vs. 7.3 pmol/L (5.4-8.4), p=0.88]. There was, also, no difference in the copeptin change for those in remission versus not in remission [2.3 pmol/L (-0.5-8.2) vs. 0.1 pmol/L (-0.1-2.2), p=0.46]. When we excluded patients who developed a water balance disorder postoperatively, there was a difference in peak post-TSS copeptin for those in remission [10.2 pmol/L (6.9-21.0)] vs. those not in remission [5.4 pmol/L (4.6-7.3), p=0.032], but not in the change in copeptin for those in remission vs. not in remission [5.1 pmol/L (0.3-19.5) vs. 1.1 pmol/L (-0.1-2.2), p=0.39].
Conclusions: Post-TSS plasma copeptin may be a useful early marker to predict remission of CD after TSS. However, the utility of this test may be limited to those who do not develop water balance disorders post-operatively. Additional studies with larger sample sizes are needed to confirm these findings and to determine a post-operative plasma copeptin cutoff level that may predict remission of CD.
Endocrine Dysfunction in Covid-19
Authors: Das Liza , Dutta Pinaki , Bhadada Sanjay Kumar , Rastogi Ashu , Walia Rama , Mukherjee Soham , Puri Goverdhan Dutt , Bhansali Anil 
Published: May 2021

Abstract
Introduction: Evidence pertaining to new-onset endocrine dysfunction in patients with COVID-19 is currently limited and extrapolated from prior SARS epidemics. Further, identifying whether the quantum of this dysfunction is associated with the severity of disease in patients with COVID-19 is unknown. We aimed to to comprehensively explore the prevalence, nature and degree of endocrine dysfunction stratified based on disease severity at a dedicated COVID care centre.
Patients and Methods: Consecutive patients enrolled at PGIMER Chandigarh, were stratified on the basis of disease severity as: group I (moderate to severe disease including oxygen saturation &lt;94% on room air or those with comorbidities) and group II (mild disease, with oxygen saturation &gt;94% and without comorbidities). Hypothalamo-pituitary-adrenal, thyroid, gonadal axes and lactotroph function were evaluated. Inflammatory and cell-injury markers were also analysed.
Results: Patients in group I had higher prevalence of hypocortisolism (38.5 vs 6.8%, p=0.012), lower ACTH (16.3 vs 32.1pg/ml, p=0.234) and DHEAS (86.29 vs 117.8µg/dl, p= 0.086) as compared to group II. Low T3 syndrome was a universal finding, irrespective of disease severity. Sick euthyroid syndrome (apart from low T3 syndrome) (80.9 vs 73.1%, p= 0.046) and atypical thyroiditis (low T3, high T4, low or normal TSH) (14.3 vs 2.4%, p= 0.046) were more frequent in group I than group II. Male hypogonadism was also more prevalent in group I (75.6% vs 20.6%, p=0.006) than group II, with higher prevalence of both secondary (56.8 vs 15.3%, p=0.006) and primary (18.8 vs 5.3%, p=0.006) hypogonadism. Hyperprolactinemia was observed in 42.4% patients, without significant difference between both groups.
Conclusion: COVID-19 can involve multiple endocrine organs and axes, with a greater prevalence and degree of endocrine dysfunction in those with more severe disease. Involvement of multiple axes, particularly at hypothalamo-pituitary level suggests the possibility of hypophysitis as an underlying etiology. We also observed less characterised findings like atypical thyroiditis and normal DHEAS despite secondary hypocortisolism. Follow-up surveillance of these patients at periodic intervals and estimation of anti-pituitary antibodies could be considered to elucidate viral cytopathic effect or inflammation as the major underlying mechanism of endocrine dysfunction.
Oxytocin Levels in Response to Pituitary Provocation Tests in Healthy Volunteers
Authors: Sailer Clara Odilia , Winzeler Bettina Felicitas , Urwyler Sandrine Andrea , Schnyder Ingeborg , Refardt Julie , Eckert Anne , Verghese Nimmy , Fassnacht Martin , Chifu Irina Oana , Lawson Elizabeth Austen , Verbalis Joseph G , Fenske Wiebke Kristin , Christ-Crain Mirjam 
Published: May 2021

Abstract
Background: Oxytocin, secreted into the circulation through the posterior pituitary, regulates lactation, weight, and socio-behavioral functioning. Oxytocin deficiency has been suggested in patients with hypopituitarism, however, diagnostic testing for oxytocin deficiency has not been developed. Known stimuli used in the diagnosis of pituitary deficiencies - the hypertonic saline and arginine infusion tests stimulating copeptin levels, and the oral macimorelin test stimulating growth hormone levels - have also been shown to stimulate oxytocin secretion in animal models. We hypothesized that these provocation tests would stimulate plasma oxytocin levels in humans.
Methods: Basal plasma oxytocin levels were measured for all three tests. Stimulated plasma oxytocin was measured once plasma sodium &gt;150 mmol/l for the hypertonic saline and after 45 minutes for the arginine infusion and the oral macimorelin test, expected peak of copeptin and growth hormone levels, respectively. Primary outcome was change between basal and stimulated oxytocin levels using a paired t-test.
Results: Median (IQR) age of all participants was 24 years (22, 28), 51% were female. As expected, copeptin increased in response to hypertonic saline from 4.0 pmol/L [3.3, 6.7] to 34.2 pmol/L [23.2, 45.4] (p-value &lt;0.001) and in response to arginine infusion from 4.6 pmol/L [3.2, 6.2] to 8.3 pmol/L [6.4, 10.8] (p-value &lt;0.001). Growth hormone increased in response to oral macimorelin from 1.6 ng/mL [0.3, 17.2] to 106.0 ng/mL [73.3, 127.2] (p-value &lt;0.001). Oxytocin levels increased in response to hypertonic saline infusion from 0.3 pg/mL [0.3, 0.5] to 0.6 pg/mL [0.4, 0.7] (p-value 0.007), while there was no change in response to arginine infusion (basal 0.4 pg/mL [0.4, 0.6], stimulated 0.4 pg/mL [0.3, 0.6], p-value 0.6), nor to oral macimorelin (basal 38.7 pg/mL [31.1, 66.9], stimulated 34.2 pg/mL [31.2, 48.2], p-value 0.3).
Conclusion: We found that hypertonic saline infusion results in doubling of oxytocin levels. Further research will be important to determine whether this test could be used diagnostically to identify patients with oxytocin deficiency. In contrast to animal data, arginine and macimorelin did not stimulate oxytocin.
Relationship Between Oxytocin Levels and Brain Volume in Anorexia Nervosa Compared to Healthy Controls
Authors: Sailer Clara Odilia , Breithaupt Lauren , Lyall Amanda E , Vessey Brynn , Plessow Franziska , Kahn Danielle L , Slattery Meghan , Holsen Laura , Eddy Kamryn T , Misra Madhusmita , Lawson Elizabeth Austen 
Published: May 2021

Abstract
Background: A disruption in food motivation pathways has been described in females with anorexia nervosa (AN), a psychiatric disorder characterized by food restriction despite low weight. We have shown that in AN and healthy controls (HC), levels of oxytocin (OXT), a hormone involved in lactation, social behavior and weight regulation, decrease after a meal. In HC, we identified a relationship between postprandial change in OXT and subjective appetite, yet this association was absent in females with AN, suggesting a disconnect between OXT and appetite regulation in AN. Prior studies have shown that gray matter volume of the amygdala and hippocampus, areas rich in OXT receptors, correlate with OXT levels in HC. Furthermore, these regions play a central role in food reward and decreased volume has been reported in AN. We hypothesized that the relationship between postprandial change in OXT and amygdala and hippocampal gray matter volume would differ between AN and HC.
Methods: We performed a cross-sectional study of 51 females (23 restrictive AN; 28 HC). We drew blood for OXT levels fasting and 60 min after a standard meal and performed T1-weighted MRI scans of the brain in the fasted state. MRI data was quality controlled and processed with FreeSurfer. Average gray matter brain volumes were extracted from the bilateral amygdala and hippocampus for each subject. Linear regression models were used to determine differences between AN and HC of postprandial percent change in OXT on amygdala and hippocampus gray matter volume.
Results: Median [IQR] age was higher in females with AN (20.6 years [19.3, 21.5]) than HC (18.8 years [IQR 17.6, 20.3], p=0.02), and percentage of ideal body weight was lower in AN (75.5%) than HC (97.4%, p&lt;0.01). Right hippocampus volume, adjusted for age and total intracranial volume, was significantly lower in AN (estimated difference -188 dm3 [95%-CI -360, -17], p=0.04). Percent change in OXT was not different (p=0.5) but there was a trend for a positive interaction effect (p=0.08) for AN and percent change in OXT on right hippocampus volume. Posthoc exploratory analysis indicated a positive correlation in AN (R2=0.41, p=0.02) and no correlation in HC (R2=0.17,p=0.4) between percent change in OXT and right hippocampus volume. There was no significant between group difference in volume nor postprandial change in OXT for the bilateral amygdala or left hippocampus between groups.
Discussion: Our results indicate smaller right hippocampus volume and a trend towards a positive association with postprandial change in OXT in AN compared to HC. Future studies will be important to better define the relationships between OXT secretion and food motivation brain regions and the impact on eating behavior in AN.
Assessment of the Severity of Carpal Tunnel Syndrome in Patients With Acromegaly: A Focus on Clinical, Biochemical and Image Outcomes
Authors: Paredes Vinueza Diego Fernando , Socorro Gómez-Caballero María del , Solis-Pazmino Andrea Paola , Salazar-Vega Jorge Luis 
Published: May 2021

Abstract
This is a descriptive cross-sectional study designed to analyze the prevalence and severity of carpal tunnel syndrome (CTS) in addition to its association with clinical, biochemical, and imaging variables in a cohort of patients with acromegaly. Data collection was performed by entering them in our database and we subsequently analyzed in the SPSS system. Of the 71 patients registered with acromegaly, 68 met the inclusion criteria. Among the results, 97.8% presented CTS evidenced by electroconduction. Of these, 43 (63.1%) showed moderate involvement, followed by 17 severe cases (25%) and 6 mild cases (8.8%). The level of GH in serum, the years of delay in diagnosis, and the size of the adenoma were related to the presence and severity of CTS (p less than 0.05). The multivariate analysis showed that severe grade had a significant association with these variables compared with moderate and mild grade.
Cardiac Remodeling in Patients with Childhood-Onset Craniopharyngioma - Results of HIT-Endo and KRANIOPHARYNGEOM 2000/2007
Authors: Sowithayasakul Panjarat , Buschmann Leona Katharin , Boekhoff Svenja , Muller Hermann Lothar 
Published: May 2021

Abstract
Hypothalamic obesity caused by childhood-onset craniopharyngioma results in long-term cardiovascular morbidity. Knowledge about clinical markers and risk factors is rare. A cross-sectional study on transthoracic echocardiographic parameters was performed to determine the associations with clinical and anthropometric parameters in 36 craniopharyngioma patients recruited in HIT-Endo and KRANIOPHARYNGEOM 2000/2007. BMI correlated with the thickness of interventricular septum in diastole (IVSd) (r=0.604, p&lt;0.001) and left ventricular posterior wall thickness in diastole (LVPWd) (r=0.460, p=0.011). In multivariate analyses on risk factors for cardiac remodeling, sex hormone replacement therapy, BMI and male gender were positively correlated with increased left ventricular internal diameter in diastole (LVIDd), R2=0.596, F=10.323, p&lt;0.001. BMI and insulin resistance were selected as significant independent determinants of IVSd, produced R2=0.655, F=29.441, p&lt;0.001. Due to wide range of disease duration, 17 pediatric and 19 adult patients were analyzed separately. In the adult subgroup (age at study ≥18 years), BMI correlated with IVSd (r=0.707, p=0.003), LVPWd (r=0.592, p=0.020) and LVIDd (r=0.571, p=0.026). In the pediatric subgroup (age at study &lt;18 years), no correlation between cardiac parameters and BMI was observed. Only LVIDd correlated with disease duration (r=0.645, p&lt;0.001). All cardiac functions were within the normal range, indicating no association with functional impairments. We conclude that cardiac remodeling in patients with childhood-onset craniopharyngioma correlated with the degree of hypothalamic obesity, disease duration, sex hormone replacement therapy, male gender and insulin resistance. As echocardiography has limited sensitivity in patients with obesity, further research on more sensitive techniques for cardiac diagnostics in craniopharyngioma patients is warranted.
Cerebral Infarction in Childhood-Onset Craniopharyngioma Patients - Results of KRANIOPHARYNGEOM 2007
Authors: Boekhoff Svenja , Bison Brigitte , Genzel Daniela , Eveslage Maria , Otte Anna , Friedrich Carsten , Flitsch Joerg , Muller Hermann Lothar 
Published: May 2021

Abstract
Purpose: Cerebral infarction (CI) represents a vascular complication following treatment of suprasellar tumors. Risk factors for CI, incidence rate, and long-term prognosis are unknown for patients with childhood-onset craniopharyngioma (CP). Methods: MRI of 242 CP patients, recruited 2007-2019 in KRANIOPHARYNGEOM 2007, were reviewed for CI. Risk factors for CI and outcome after CI were analyzed. Results: Twenty-eight of 242 patients (11%) presented with CI based on reference assessment of MRI. One CI occurred before initial surgery and one case of CI after release of pressure via intracystic catheter. 26 of 28 CI were detected after CP resecting surgical procedures at a median postoperative interval of one day (range: 0.5-53 days). Surgical intraoperative vascular lesions were documented in 7 cases with CI. There was a trend (p=0.069) towards higher initial presurgical tumor volume in CI patients (21.7 cm3, range: 0.01-187.6 cm3) compared with non-CI patients (15.5 cm3, range: 0.01-286.3 cm3). The CI rate was lower in cases operated via transsphenoidal approach (4%) when compared with transcranial approach (13%). CP patient load of neurosurgical centers as a potential measure of surgical expertise was not associated with CI. In 12 irradiated patients, CI occurred before irradiation in all cases. Multivariate analyses showed that hydrocephalus and gross-total resection (GTR) at the time of primary diagnosis/surgery were independent risk factors for CI. Two-years progression-free survival rate was lower (p=0.023) after CI (0.310±0.095) when compared with the subgroup of patients without CI (0.604±0.034). After CI, quality of life (PEDQOL) and functional capacity (FMH) were impaired when compared with patients without CI. Conclusions: CI occurs in about 11% of CP cases mainly after surgery. Degree of resection and increased intracranial pressure are risk factors, which should be considered in the planning of surgical procedures for prevention of CI.
Effects and Side Effects of Pasireotide Treatment in Cushing’s Disease: Experience of a Single Tertiary Center
Authors: Ozkaya Hande Mefkure , Sahin Serdar , Kerimova Güler , Durcan Emre , Sulu Cem , Kadioglu Pinar 
Published: May 2021

Abstract
Context: Cushing’s disease (CD), when uncontrolled despite surgery, requires medical treatment. In this vein, treatments with long-term effectiveness and safety profiles are needed. We aimed to evaluate the effects and side effects of pasireotide treatment in Cushing’s disease in the real world. Methods: Patients who were followed up for Cushing’s disease and treated with pasireotide between 2001-2019 at Cerrahpaşa Medical Faculty Endocrinology, Metabolism and Diabetes Department were evaluated. Pasireotide efficacy and side effects were evaluated. Results: Thirty-four patients were included in the study. The mean duration of treatment was 24.59 (SD ± 15.21) months. Urinary free cortisol (UFC) decreased in 40.59 % of the patients and normalized in 33.3 %. A total of %71.4 of the patients who were in remission at the 3rd month of the treatment preserved their remission status at last follow-up. A significant difference was found between pre-treatment and final UFC (p = 0.001), but the absence of remission at 3 months did not predict final remission (p = 0.274). ACTH decreased by 9.16 % (SD ± 46.67). A significant difference was found between ACTH levels at 3rd, 6 months, and last control (p = 0.014, 0.017, and 0.017, respectively). Serum cortisol decreased by 13.89 %. A significant difference was found between pre-treatment and 3rd month, pre-treatment and final cortisol (p = 0.034 and 0.013, respectively). The body weight decreased by an average of 5.5 [IQR (0.0-11.5)] kg. Cholecystectomy was performed in 3 patients (9%). The percentage of patients requiring antidiabetic medication increased from 33.3% at diagnosis to 81.8% at the last follow-up visit. A significant difference was found between pre-treatment and 3rd month fasting plasma glucose levels ​​(p = 0.008). HbA1c increased by 17 %. There was a positive correlation between UFC and 3rd month HbA1c. All patients with hyperglycemia were controlled with effective antidiabetic therapy. Conclusion: Pasireotide treatment in CD is effective and safe, remission occurs in the first months of treatment and continues for a long time. Although hyperglycemia is the most common side effect, it is successfully controlled with antidiabetic medication.
Genome-Wide DNA Methylation Differences in Patients With Non-Functioning Pituitary Adenomas With or Without Postsurgical Intervention
Authors: Hallén Tobias , Johannsson Gudmundur , Dahlén Rahil , Andersson-Assarsson Johanna C , Glad Camilla A , Örndal Charlotte , Engvall Angelica , Carén Helena , Skoglund Thomas , Olsson Daniel S 
Published: May 2021

Abstract
Background: More than half of all surgically treated patients with non-functioning pituitary adenomas (NFPA) experience tumor progression during their follow-up, with some of these adenomas exhibiting locally aggressive behavior. Tumor progression is strongly associated with excess morbidity and mortality. Tumor control is, therefore, of vital importance for the patient outcome. There is no reliable method to predict tumor behavior after the initial surgical treatment. The aim of this study was therefore to study associations between DNA methylation patterns and tumor progression in patients with NFPA. Methods: In a case-controlled trial, 43 patients operated for NFPA with immunohistochemical characteristics of gonadotroph subtype were selected. Cases included patients who needed reintervention due to tumor progression (Reintervention group, n = 26), and controls had residual tumor without tumor progression during at least five years of follow-up (Radiologically stable group, n = 17). Genome-wide methylation analysis of the tumor tissue from each patient was performed on the Infinium MethylationEPIC BeadChip platform. Results: Principal component analysis (PCA) showed that clinical course was a strong contributor to the difference in DNA methylation profiles between the two groups. Also, unsupervised hierarchical clustering of the top 5,000 most variable CpG sites revealed three methylation profiles corresponding to, (1) the Reintervention group, (2) the Radiologically stable group, and (3) a mix of the two groups. Although the overall average methylation levels in the two groups did not differ (P = 0.16), 142,521 Differentially Methylated Positions (DMPs) were identified. Of these, 650 showed a difference in beta value methylation larger than 0.2. Interestingly, among the genes harboring the most significantly DMPs was GABRA1, and among the genes containing the largest number of DMPs were GATA2, NUP93, and LGALS1. In addition, the three most hypomethylated and the three most hypermethylated DMPs were all significantly (P &lt;0.05) independently associated with tumor progression free survival (Log-rank test, data not shown). Conclusion: In this novel explorative study, we found a methylation pattern associated with postoperative tumor progression requiring reintervention in patients with NFPA. Among the differently methylated genes we identified, some have previously been described to be involved in pituitary adenoma differentiation or cancer development. Our study is a step towards deciphering epigenetic mechanisms involved in tumor progression and finding epigenetic signatures that might be used to predict postoperative tumor progression in NFPAs.