bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy, Efficiency and Security of Urea Treatment in the Syndrome of Inappropiate Antidiuretic Hormone Secretion
Authors: Perelló Camacho Eva , Gómez Francisco José Pomares , Penabad Luis López , López Rosa María Mirete , Esteban María Rosa Pinedo , Escribano José Ramón Domínguez 
Published: May 2021

Abstract
Introduction: In the present times, several strategies have been proposed for the treatment of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Urea has demonstrated to be an effective treatment but its use has not been extended. Our work analyzes our experience with urea in the treatment of SIADH. Material and Methods: Observational retrospective analysis of 39 patients with SIADH in which urea has been used in our hospital with pre- and post-analysis of plasmatic sodium concentrations. Results: We included 39 patients with SIADH win a mean age of 76,4 ± 15,8 years. The plasma sodium nadir was 120,0 ± 5,1 mmoL/L and at the initiation of treatment 125,2 ± 4,1 mmoL/L. Total time of treatment was 2,42 ± 3,86 months being the treatment still active in 4 patients. We observed an improvement of sodium in all patients with a mean sodium at the end of treatment of 134.3 + - 5.0 mmol/L being this values statistically significant compared to the initial sodium (p&lt;0.01). As a matter of fact we found significant differences at one week of treatment (p&lt;0.01), keeping sodium stable levels around 135 mmol/L during the treatment period. The treatment was stopped in 3 cases (7.7 %) by the patient, one for mild digestive symptomatology and two for limited palatability. Of them two were treated with tolvaptan and the other did not need any further treatment. There were no adverse events in the rest of the patients. From the economic perspective and considering the duration of treatment, if we compare this to the cost of tolvaptan during the same period and the same number of patients, there was a reduction of cost of 87.9 % in comparison with treatment with tolvaptan. Conclusions: In our experience urea has shown to be a safe and cost effective option in the treatment of hyponatremia caused by SIADH showing improvement in sodium levels from the first week of treatment in all patients. We think it should be considered a valid therapeutic option.
Gonadotropin-Releasing Hormone Agonist Induced Pituitary Apoplexy
Authors: Yu Xiaoling , Guarda Francisco J , Shiraliyeva Naila , Haines Melanie S , Saylor Philip J , Nachtigall Lisa B 
Published: May 2021

Abstract
Background: Gonadotropin-releasing hormone agonists (GnRHa), used in the treatment of prostate cancer (PC) and for reproductive purposes in women, have been implicated as the cause of pituitary apoplexy (PA), a potentially life-threatening condition. The pathophysiology of PA after GnRHa has not been completely elucidated. Proposed mechanisms include a stimulatory effect of GnRHa on pituitary adenoma cell metabolism, causing mismatched blood supply prompting hemorrhage or infarction. Prior documentation of PA associated with GnRHa has been scarce and limited to case reports.
Methods: This is a detailed clinical case series of GnRH-induced PA from a single institution, obtained by a Research Patient Data Repository query. Clinical characteristics of the patients including demographics, detailed history, time interval between GnRHa and PA, physical exam, biochemical data, pituitary imaging and pathology were reviewed. Results: Seven cases were identified between 1990-2020; six men (aged 55 – 83 years) receiving treatment for PC and one woman (aged 22 years) receiving GnRHa for oocyte donation. All patients presented with headache; four within 48 hours of, one &gt;1 month after, and one 5 months after, receiving GnRHa. One patient had insufficient data on time between GnRHa and PA. Most patients (86%) presented with nausea and vomiting. Other symptoms included ophthalmoplegia (43%), visual field defects (17%), and altered consciousness (29%). All patients had sellar masses and/or evidence of hemorrhage on MRI. Five patients underwent pituitary surgery while the others were managed medically. Of those who underwent surgical resection, 80% had positive histopathological staining for gonadotropins. Five patients with reliable hypothalamic-pituitary-adrenal (HPA) axis testing had impairment of this axis after PA; 40% recovered adrenal function. Central hypothyroidism occurred in 60% of whom 66% recovered. Hyponatremia occurred in 43%.
Conclusions: Patients with gonadotrope-secreting adenomas may develop PA in response to GnRHa, more frequently in elderly men who are receiving GnRHa treatment for PC. This may be due to older age and higher prevalence of GnRHa use in this group. However, as demonstrated here and in prior case reports, women are not exonerated from this complication. Headache and adrenal insufficiency are typically present. HPA axis recovers in a subset. While most patients present &lt;48 hours after GnRHa treatment, delayed presentations may occur. Therefore, a history of prior GnRHa exposure should be ascertained in patients presenting with PA. While the incidence of PA after GnRHa is low, this case series and prior case reports suggest that this serious potential complication should be recognized prior to treatment, especially in patients with known pituitary macroadenomas.
Olfactory Performance in Youth With Full and Subthreshold Avoidant/Restrictive Food Intake Disorder
Authors: Stull Madeline Rogers , Harshman Stephanie G , Kuhnle Megan , Wons Olivia , Misra Madhusmita , Eddy Kamryn , Lawson Elizabeth Austen , Thomas Jennifer J 
Published: May 2021

Abstract
Background: Avoidant/restrictive (A/R) food intake disorder (ARFID) is characterized by restrictive eating defined by lack of interest in food, sensory sensitivity, and/or fear of aversive consequences of eating resulting in a failure to meet adequate nutritional and/or energy needs. The complex psychopathology that differentiates ARFID from other eating disorders highlights the need to explore the role of sensory systems in disease etiology. Olfaction has an important role in eating behavior. Specifically, olfactory dysfunction is associated with decreased food intake and appetite. Olfactory performance and associated clinical characteristics have yet to be examined in individuals with ARFID. We hypothesized that higher levels of PYY, which signals satiety, would be associated with poorer olfactory performance; whereas greater food fussiness and A/R eating severity would be associated with stronger olfactory performance. Methods: We evaluated a cross-sectional sample of children and adolescents with full and subthreshold ARFID (n=82, 46.2% female, mean age 15.8±3.8). We measured olfactory performance with the Sniffin’ Sticks test (Burghardt®, Wedel, Germany) which captures odor discrimination, odor identification, and odor threshold. Higher scores on all three indices represent stronger olfactory performance. We also measured fasting serum PYY; severity of A/R eating on the Pica, ARFID and Rumination Disorder Interview (PARDI); and food fussiness as a measure of food-related sensory sensitivity on the Adult Eating Behavior Questionnaire. Statistical analyses included T-test and spearman’s correlations. Results: Greater fasting serum PYY levels were associated with significantly poorer performance on the odor threshold test (r=-0.4, p=0.003). Greater severity of A/R eating (r=-0.3 p=0.008) and food fussiness (r=-0.2, p=0.03) were both associated with significantly poorer performance on the odor discrimination test. Conclusions: As predicted, we found that higher levels of PYY were associated with poorer olfactory performance in youth with full and subthreshold ARFID. However, contrary to hypotheses, we found that greater food fussiness and severity of A/R eating were associated with poorer olfactory performance. Future research should investigate whether high levels of PYY and poor olfactory performance are causes, consequences, or correlates of A/R eating.
Clinical Presentation and Management of Patients With Acromegaly at a University Hospital
Authors: Leao Felipe A , Drummond Juliana B , Bizzi Mariana F , Gainnetti Alexandre , Ribeiro-Oliveira Antonio , Soares Beatriz Santana 
Published: May 2021

Abstract
We conducted a retrospective analysis aiming to evaluate different treatment responses in a cohort of acromegaly patients followed at the Federal University of Minas Gerais Neuroendocrinology Outpatient Clinic who were diagnosed between the years of 1998 and 2020. Results: seventy-two patients with acromegaly were initially identified through chart review. Twelve patients were subsequently excluded from this analysis - nine patients who had been recently diagnosed and were awaiting surgical treatment as well as three patients who had been lost to follow-up. The study sample (n=60) included forty females patients (67%). Mean (range) age at diagnosis was 43.5 years-old (17-76) and mean (range) follow-up time was 107 (1-261) months. At diagnosis, 88.7% of the patients presented with a macroadenoma, and median (range) basal GH and IGF-1 of the studied population were 21.76 (0.89-193) ng/mL and 310 (110-2459) % above the age and sex-adjusted ULN, respectively. Fifty-six (93%) patients underwent transsphenoidal surgery while four patients (6.7%) received primary medical treatment. Amongst patients not cured by surgery (n=42), 37 patients (88%) were sequentially treated with first generation long-acting somatostatin analogues (SSAs) and 3 patients (7%) received cabergoline. Amongst patients sequentially treated with SSAs, 14 (38%) achieved optimal biochemical control, defined as normal age and sex-adjusted IGF-1 levels, under SSAs monotherapy (octreotide LAR maximum dose of 40 mg/28 days or lanreotide autogel maximum dose of 120 mg/28 days) while one out of three patients achieved biochemical control under cabergoline monotherapy (maximum dose of 3 mg/week). All patients who did not achieve biochemical control under SSA or cabergoline monotherapy (n=25) were sequentially treated with SSAs and cabergoline combined therapy and optimal biochemical control was achieved in 13 (52%) of them. Pegvisomant (maximum dose of 30 mg/day) was further added to the therapeutic scheme in seven patients, allowing biochemical control in 4 (57.1%) additional patients. Amongst five patients (8%) patients who were treated with adjuvant radiotherapy, two did not achieved long-term remission, despite combined therapy with SSAs, cabergoline and pegvisomant. Discussion: the high reported prevalence of macroadenomas in our cohort possibly reflects a delay in the diagnosis and may account for the low observed successful surgical rate in comparison to other series, however treatment response rates to SSAs monotherapy as well as combined SSAs and cabergoline therapy here reported are in line with previous reports. Given its low cost and larger availability, cabergolin was amply prescribed as opposed to pegvisomant, which was employed as a third-line treatment showing a disease control rate lower than previously reported in interventional studies but consistent with previous real-world data.
Acute Transcriptional Effects of Dexamethasone on Mouse Adrenal Gland Transcriptome
Authors: Zheng Huifei Sophia , Daniel Jeff , Foradori Chad David , Kemppainen Robert J , Huang Chen-Che Jeff 
Published: May 2021

Abstract
Researchers have long known that dexamethasone causes cellular and functional changes in the adrenal gland. For example, long-term dexamethasone treatment leads to reversible adrenal cortex atrophy. In the adrenal medulla, dexamethasone treatment alters the maturation and function of the neural crest-derived chromaffin cells. Here we aim to study the acute transcriptional effect of dexamethasone on mouse adrenal gland at the transcriptome level. Our data suggested that a one-hour dexamethasone treatment had a cell type-specific effect on the adrenal transcriptome. There were 922 dexamethasone-induced genes and 853 dexamethasone-suppressed genes. GO analysis showed that the upregulated genes were primarily linked to neuronal cell function. Clustered heatmaps further showed that many genes involved in the catecholamine synthesis were upregulated by dexamethasone treatment, whereas most genes involved in the steroidogenesis pathway were downregulated. Interestingly, steroidogenic factor 1 (SF1, encoded by Nr5a1), the critical transcription factor that regulates steroidogenesis, had a &gt;2-fold decrease under the one-hour dexamethasone treatment, suggesting a possible mechanism of the acute suppression of steroidogenic activity. Our findings indicate that the acute effects of dexamethasone stimulate catecholamine synthesis in the medulla, whereas steroidogenesis in the cortex is suppressed by dexamethasone.
Low Risk for All-Cause Mortality Among Patients With Lung Neuroendocrine Tumors Co-Diagnosed With Pituitary Adenoma
Authors: Sinvani Naama Peltz , Percik Ruth , Uri Inbal , Kfir Sapir Kon , Tirosh Amir , Tirosh Amit 
Published: May 2021

Abstract
Context: Lung neoplasm often co-occur with pituitary adenoma (PA). However, whether co-diagnosis of lung neuroendocrine tumors (LNET) and PA constitute unique entity, and the impact of such co-diagnosis on patients outcome is yet to be defined. Objective: To compare the clinical characteristics of patients with LNET to those co-diagnosed with PA. Design: Retrospective, case-control study including patients diagnosed with LNET or PA between 2000 and 2016. Setting: The Surveillance, Epidemiology and End Results database. Patients: 2,947 patients had LNET, including 2,913 with LNET alone (“Sporadic”) and 34 patients with both LNET and PA (“MENx”). Main Outcome Measure(s): All-cause mortality (ACM). Results: PA preceded LNET diagnosis in 85.3% of patients and had higher rates among LNET patients (34/2,947) than with any cancer (p&lt;0.00001) and compared to patients with non-small cell lung cancer (NSCLC) (15/2,378, p=0.047). MENx patients were younger at diagnosis compared with NSCLC patients and PA (p=0.04). Among patients&lt;60 years with LNET, co-diagnosis with PA was associated with lower ACM risk (Log-rank test, p=0.03). Adjusted ACM risk of patients with “MENx” was lower than sporadic LNET (hazard ratio 0.553, 95% confidence interval 0.309-0.99, p=0.046), especially among Caucasians, and a lower overall-mortality risk in patients &lt;60 years with borderline statistical significance (p=0.071). Conclusions: Patients with both LNET and PA constitute a distinct morbidity and mortality profile compared with sporadic LNET possibly suggesting an undefined MEN syndrome. Additional studies to further investigate the natural course and genetic profile of patients with these neoplasms are needed.
Androstenedione Is the Preferred Substrate for Cytochrome P450 11β-hydroxylase Leading to the Production of 11β-Hydroxyandrostenedione in the Adrenal Gland
Authors: Barbier Inge Doney , Gent Rachelle , Du Toit Therina , Swart Amanda C 
Published: May 2021

Abstract
Adrenal cytochrome P450 11β-hydroxylase (CYP11B1) is a mitochondrial enzyme that catalyzes the final step of glucocorticoid synthesis, converting 11-deoxycortisol (S) and deoxycorticosterone (DOC) to cortisol (F) and corticosterone (CORT), respectively. CYP11B1 is predominantly located in the zona fasciculata of the adrenal gland with studies also showing that CYP11B1 catalyzes the conversion of androstenedione (A4) and testosterone (T) to 11β-hydroxyandrostenedione (11OHA4) and 11β-hydroxytestosterone (11OHT), respectively. Adrenal vein sampling in women has shown that 11OHA4 turnover is high, with a marked increase after treatment with ACTH which is known to upregulate CYP11B1 expression. We hypothesized that CYP11B1’s affinity for A4 as a substrate may be favored over glucocorticoids since 11OHA4 is one of the major androgens produced in the adrenalThis study aimed to elucidate the kinetic parameters (Km and Vmax) for A4 and T with respect to CYP11B1. A4 and T (0.2 µM to 5 µM) were assayed in HEK-293 cells transiently transfected with CYP11B1 and the adrenodoxin redox partner. Data was used to generate progress curves and fitted to the Michaelis-Menten equation. A4 had the lowest Km (0.21 μM) with a significantly higher Vmax (315.77 pmol/min/mg protein) in comparison to T, S and DOC. Results suggest that A4 binds more readily to CYP11B1 resulting in the high turnover of substrate. The androgenic activity of CYP11B1 catalyzed steroid products was determined using a luciferase assay conducted in CV1 cells. Both A4 and 11OHA4 showed no androgenic activity, however, the 11βHSD2 product of 11OHA4, 11-ketoandrostenedione (11KA4), elicited a response at 100 nM. 11OHT was an androgen receptor (AR) agonist, however, exhibiting a lower response when compared to T and 11-ketotestosterone over all concentrations tested (1, 10 and 100 nM). As confirmation of CYP11B1 activity in the adrenal, circulatory steroid levels were determined in healthy female subjects (n=88). CORT, F and 11OHA4 were measured at a frequency of 70–100%, compared to 11OHT (40–70%), while 11βHSD2 activity produced 11KA4 (&lt;10%). In conclusion, the catalytic efficiency of CYP11B1 towards A4 is higher compared to T and the classical substrates. The high substrate affinity and turnover provides evidence for 11OHA4 in adrenal vein samples. Concurrently, our analysis suggests that agonism is diminished by the presence of the C11- hydroxyl group, while AR agonistic activity is gained upon its conversion to a keto group. Furthermore, these androgens could perhaps modulate cortisol production in the adrenal due to potential competition between precursor substrates.
Novel Pituitary Organoid Model as Powerful Tool to Unravel Pituitary Stem Cell Biology Across Ages and Disease
Authors: J Vankelecom Hugo E , Laporte Emma , Hermans Florian , Nys Charlotte , Vennekens Annelies 
Published: May 2021

Abstract
The pituitary gland harbors a population of stem cells. However, role and regulation of these cells remain poorly understood. We recently established organoids from mouse pituitary as a novel research tool to explore pituitary stem cell biology (Cox et al., J. Endocrinol. 2019; 240:287-308). In general, organoids represent 3D in vitro cell configurations that develop and self-organize from (single) tissue stem cells under well-defined culture conditions that typically mirror the stem cell niche and/or embryogenic processes. Organoids reliably recapitulate key aspects of the original organ, including of its stem cell compartment. Moreover, organoids are long-term expandable while retaining these properties. We demonstrated that pituitary organoids originate from the resident (SOX2+) stem cells, largely phenocopy these cells and retain the stemness phenotype during expansive culture. Interestingly, the organoids show confident in vivo translatability and, when developed from transgenically damaged gland, recapitulate the activation status of the stem cells as observed in situ following injury. Now, we found that the organoids also mirror the stem cells’ phenotype and biology in physiological conditions in which the stem cell compartment is either activated or compromised. Organoids from the neonatal maturing pituitary reproduce phenotypical and functional aspects of its activated stem cells, whereas organoids from aging gland mimic the declined functional state of the stem cells in old pituitary. Interestingly, this functional decay was found to be reverted during organoid culture, indicating that the old pituitary stem cells retain intrinsic functionality but are in vivo restrained by an obstructive microenvironment, not present in the organoid culture. Indeed, using single-cell transcriptomics and in vivo analysis, we found that the aging pituitary suffers from a prevailing inflammatory state (inflammaging) which appears to raise the threshold for stem cell activation. Interestingly, comparison of young and old pituitary led us to the discovery of pituitary stem cell activators. Finally, we found that activated parameters of organoid formation are also observed when tumorigenesis takes place in the gland, again mimicking the in situ stem cell activation that is occurring in this perturbed, pathological condition. Taken together, we identified, and applied, our new pituitary organoid model as advanced and powerful tool to gain profound insight into pituitary stem cell behavior across life and disease, which is expected to eventually translate into restorative and rejuvenative tactics when pituitary function is compromised by damage or age. In this context, our single-cell transcriptome database has strong potential to unveil appealing targets.
Association Between Dyslipidemia and Helicobacter Pylori Infection
Authors: Hayes Dorado Juan Pablo 
Published: May 2021

Abstract
Introduction: The association between Helicobacter pylori infection and elevated plasma levels of LDL cholesterol and decreased HDL cholesterol has been reported. Objective: To determine the frequency of altered plasma levels of LDL cholesterol, HDL cholesterol and triglycerides in pediatric patients with Helicobacter pylori infection. Materials and Methods: Prospective, observational and analytical study. Pediatric patients with Helicobacter pylori infection, July 2019 - June 2020 period. Exclusion criteria: Obesity, diabetes mellitus, hypothyroidism, hepatopathy, nephropathy, collagen disease, corticotherapy, use of proton pump inhibitors and H2 antihistamines. Antibodies against Helicobacter pylori and plasma levels of total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides were studied. Two groups of patients: Those with Helicobacter pylori infection and the other of uninfected children. Results: Patients attended: 39; studied: 22; excluded: 17. Group of non-infected: 25.Triglyceride levels (mg/dL) were 117 + -21 in patients with Helicobacter pylori and 98 + -19 in those not infected (p = 0.01); HDL cholesterol levels (mg/dL), 39 + -14 in those infected and 47 + -13 in patients without Helicobacter pylori infection (p = 0.03). Conclusions:Patients with Helicobacter pylori infection had a higher frequency of dyslipidemia, compared to the group of uninfected children.