bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pituitary Macroprolactinoma Apoplexy in a Prepubertal Girl
Authors: Ribeiro Sabliny Carreiro , Dall agnese Angélica Cristina , Mota Laís Marques , Geremia Cesar , Bressiani Marina , Hertz Michele Teixeira , Marchesan Lucas Bandeira , Coutinho Márcia Khaled 
Published: May 2021

Abstract
Background: Prolactinomas are rare in children, with an incidence of 1: 10.000.000 cases, representing less than 2% of all intracranial tumors in this age group (1). Indeed, only a few cases are reported in prepubertal children.
Clinical Case: Eight-year old female prepubertal child, previously healthy, presented a progressive loss of the visual acuity in the last 5 months and was admitted to the emergency department with an intensive headache associated with nauseas, started 48 hours before the admission. At the physical examination, the patient was eutrophic, with an infantile genitalia and no breast development or galactorrhea. No focal neurologic deficits were detected and presented normal pupils reflex and preserved extrinsic eye movements. The Campimetry evidenced bitemporal heteronymous hemianopsia and the nuclear magnetic resonance of the central nervous system identified a suprasellar and intrasellar expansive lesion measuring 3.2 x 2.6 x 2.3 cm, with bleeding signs and compression of the optic chiasm. The hormonal evaluation showed: free T4 0.55 ng/dL (normal value: 0.93-1.70ng/dL), total T4 4.8ng/dL (5.1-14.1ng/dL), TSH 4.06µUI/mL (0.6-5.4µUI/mL), morning serum cortisol 1.80mcg/dL (6.2-2mcg/dL), ACTH 7.0pg/mL (&lt;46pg/mL), prolactin 3.376ng/mL (4.8-23.3ng/mL). The patient initially started glucocorticoid replacement, subsequently levothyroxine and cabergoline. A diagnosis of macroprolactinoma with pituitary apoplexy and optic nerve compression was performed and confirmed by the Immunohistochemical after the transsphenoidal resection. No history of any neoplasms were reported by family members and calcium abnormalities were excluded in the child. A significant improvement of the visual field was suddenly observed and the prolactin substantially decreased to 35ng/mL within 30 days after the intervention. CONCLUSION: We report a rare case of macroprolactinoma in a prepubertal girl associated with pituitary apoplexy. Complete assessment and prompt intervention were essential to recover the visual field and to prevent major sequelae.
Reference: (1) Yang, A., Cho, S. Y., Park, H., Kim, M. S., Kong, D.S., Shin, H.J., & Jin, D.K. (2020). Clinical, Hormonal, and Neuroradiological Characteristics and Therapeutic Outcomes of Prolactinomas in Children and Adolescents at a Single Center. Frontiers in Endocrinology. 2020; 11:527.
Quality of Life in Children and Young People With Congenital Adrenal Hyperplasia in the United Kingdom - Nationwide Multicentre Assessment
Authors: Lawrence Neil Richard , Bacila Irina-Alexandra , Mahdi Sundus , Albi Sabah , Cheetham Tim D , Crowne Elizabeth C , Das Urmi , Dawson Jeremy , Dattani Mehul Tulsidas , Davies Justin , Gevers Eveline , Krone Ruth , Kyriakou Andreas , Patel Leena , Randell Tabitha , Ryan Fiona , Keevil Brian George , Ahmed Syed Faisal , Krone Nils Peter 
Published: May 2021

Abstract
Introduction: Impaired Quality of Life (QoL) in Congenital Adrenal Hyperplasia (CAH) has been demonstrated in adults, but research in children has yielded variable results. We investigated the impact of CAH on QoL of children and adolescents alongside clinical health outcomes (biometric and biochemical profiles). Method: We collected data from 14 tertiary UK centres to explore current health status of 8-18 year olds with CAH. QoL was assessed by using three different questionnaires; strengths and difficulties questionnaire (SDQ), Paediatric Quality of life (PedsQL) and Self-image profile (SIP), the former two completed by both patients and their parents. Height, weight and blood pressure were converted to age and sex adjusted z-scores. Serum markers included 17OH-progesterone (17OHP), androstenedione (D4), testosterone (T) and 11-ketotestosterone (11KT). Statistical Analysis: Statistical analysis comprised of principal component analysis (PCA) followed by multivariate analysis of variance (MANOVA), and post hoc regression. Results: Of the 107 CAH patients included in the study, median age 12.4 years (IQR 10.0-15.1), 55% were female and 104 completed at least 1 questionnaire. Adequate data for PCA was available from 73/107. Three Principal Components (PCs) with observed eigenvalues &gt; 1 explained 71% of the total variance in the observed variables. PC1 reflected ‘disease control’ comprising 17OHP, D4, T and 11KT. PC2 reflected ‘biometrics’ comprising age, and height and weight z-score. PC3 reflected ‘blood pressure’, comprising systolic and diastolic z-score. PC1 correlated with outcomes in the parent and patient SDQ as well as parent PedsQL. PC2 and PC3 did not correlate with QoL. Regression analysis revealed higher scores (indicating lower QoL) in the SDQ domain of emotional problems and PedsQL domain of emotional health in patients where biomarkers suggested good control or overtreatment. Post hoc regression analysis revealed a rise in Androstenedione of 10nmol/L equated to an improved SDQ emotional problems score of 0.5 points and an improved PedsQL emotional health score of 3 points. Conclusion: The study found an interrelation between QoL and biomarkers of disease control in CAH. There were more emotional problems with higher levels of androgen suppression. Biochemical control within normal ranges did not predict emotional problems. However, unexpectedly, patients with very high levels of androgens were highlighted as reporting fewer problems with their emotional QoL. Further research into QoL in CAH and optimal levels of biochemical control will further understanding.
Erythrocytosis in a Large Cohort of Trans Men Using Testosterone: A Long Term Follow up Study on Prevalence, Determinants, and the Effect of Years of Exposure
Authors: Madsen Milou Cecilia , van Dijk Dennis , Wiepjes Chantal , Conemans Elfi , Thijs Abel , Den Heijer Martin 
Published: May 2021

Abstract
Background: Erythrocytosis is a known side effect of testosterone therapy in hypogonadal men and can increase the risk of thromboembolic events. Erythrocytosis is also seen in trans men (birth-assigned female, male gender identity) receiving testosterone therapy. Currently there are no clinical guidelines for the management of this problem in trans men. Specific aims: 1. To study the prevalence and determinants in the development of erythrocytosis in trans men using testosterone. 2. To study the association between duration of testosterone treatment and hematocrit levels. Methods: A 20 year follow-up study in adult trans men who started testosterone, and had monitoring of hematocrit levels at our center (n=1073). Results: Erythrocytosis (defined as hematocrit levels of &gt;0.50 l/l twice) occurred in 11% of trans men. Multilevel analyses showed former or current smoking (OR 2.2, 95%CI 1.6-3.3), testosterone administration as long-acting intramuscular injection (OR 2.9, 95% CI 1.7-5.0), a higher age at initiation of hormone therapy (up to OR 5.9, 95% CI 2.8-12.3) for people above 40 compared to &lt;18), higher BMI (&gt;30 g/m2 compared to 18.5-25 kg/m2) (OR 3.7, 95% CI 2.2-6.2) and a medical history for chronic pulmonary diseases, sleep apnea or polycythemia vera (OR 2.5, 95% CI 1.4-4.4) as determinants that increased the risk of high hematocrit levels. In the first year of testosterone therapy hematocrit levels increased most: from 0.39 l/l at baseline to 0.45 l/l after 1 year. Although there was only a slight continuation of this increase in the following 20 years (0.45 at 1 year and 0.46 at 20 years), the probability of developing erythrocytosis still increased (10% after 1 year, 38% after 20 years). Conclusion: Erythrocytosis frequently occurs in trans men using testosterone. The biggest increase in hematocrit was seen in the first year, but also after the first years there is a substantial number of people that present with hematocrit &gt;0.50. Because smoking, obesity and use of injection as dosage form are associated with a higher risk for erythrocytosis, a reasonable first step in the care for transmen with erythrocytosis while on testosterone is to advise them to quit smoking and to switch to a transdermal administration type and if BMI is high, to lose weight.
A Simple Algorithm is Created for Identifying Intermenstrual Intervals Containing an Oscillatory LH Pattern That Associates With Vasomotor Symptoms Using Daily Urinary LH Excretion in the Study of Women’s Health Across the Nation (SWAN)
Authors: Lasley Bill L , McConnell Daniel S , Crawford Sybil 
Published: May 2021

Abstract
Background: A specific and unique pattern of luteinizing hormone (LH) excretion has been associated with vasomotor symptoms (VMS) in early menopausal women. Described as “oscillations” of LH excretion, this pattern is consistent with secretory “surges” of LH followed by pituitary “fatigue”. This pattern has not been observed in non-VMS intermenstrual intervals and supports the concept that a breakdown in the hypothalamic-pituitary ovarian axis feed-back loops leads to extreme and cyclic variations in gonadotropin hormone releasing hormone (GnRH) secretion that stimulates collateral nerves to alter core body temperature. Regardless of the precise mechanism, the pattern of LH secretion, as transduced in daily urine as oscillations, provides the basis for the development and validation of a VMS algorithm. Objective: The purpose of this study was to create a simple algorithm to identify intermenstrual intervals exhibiting oscillatory LH, to facilitate investigations into its associations with VMS and other symptoms during the menopausal transition (MT). Methods: As part of the Study of Women’s Health Across the Nation (SWAN), participants in the Daily Hormone Substudy (DHS) were asked to provide daily urine samples - from which LH, E1c, and PdG were measured - and complete a daily symptoms diary for one menstrual cycle (up to 50 days). Analyses included 144 participants whose first DHS collection did not meet the Kassam criterion for evidence of luteal activity; of these, 61 were assessed by an expert as having oscillatory LH and 83 as non-oscillatory LH. Proposed algorithm-based classifications regarding oscillatory LH included number of days with LH at least 50% of the collection maximum LH (number of large-LH days) and number of days with LH no more than twice the collection minimum LH (number of small-LH days). Agreement of these 2 criteria with rater-assigned oscillatory LH was assessed using nonparametric t-tests and binomial logistic regression. Associations of these with VMS frequency were assessed using Spearman correlations. Results: The number of large-LH days was strongly associated with oscillatory LH: median (interquartile range) = 13 (7,22) for oscillatory collections versus 4 (2, 11) for non-oscillatory collections (p&lt;.0001) but number of small-LH days was unrelated (p=.98). Percentage of collection days with VMS was significantly correlated with number of large-LH days (Spearman r=.37, p&lt;.0001) but not with number of small-LH days (Spearman r=.03, p&gt;.05); adjustment for total collection length had negligible impact. Conclusion: A simple algorithm using urinary LH profiles can be used to identify intermenstrual collections that likely contain intervals of VMS.
Adiposity Alters Follicle Dynamics in Women of Reproductive Age With Regular Menstrual Cycles
Authors: Oldfield Alexis , Jarrett Brittany Y , Carter Faith , Brink Heidi Vanden , Lujan Marla Elaine 
Published: May 2021

Abstract
Obesity increases a woman’s likelihood of experiencing adverse reproductive health outcomes, including menstrual cycle irregularity, anovulation, and luteal phase dysfunction. Despite a heightened risk of reproductive dysfunction some women with obesity display ovulatory cyclicity. The degree to which adiposity affects menstrual cycle characteristics in this population is limited to endocrine assessments; evidence supports decreased luteinizing hormone pulse amplitude and reduced luteal phase progesterone. However, these endocrine disruptions have not been linked to alterations in follicular events. The objectives of the present analysis were to evaluate longitudinal changes in follicle size populations and growth kinetics of selectable follicles (6-9mm) and identify endocrine abnormalities associated with obesity in regular cycles. 14 non-obese women (BMI &lt;30 kg/m2) and 15 obese women (BMI≥ 30 kg/m2) with regular cycles were evaluated by serial ovarian transvaginal ultrasonography and venipuncture every-other-day for one complete inter-ovulatory interval (IOI). The number and diameters of all follicles ≥2 mm at each visit were documented offline using the grid method. Growth profiles of individual follicles which grew to &gt;7mm were assessed using the Identity Method. Diagnostic, morphologic, and endocrine features were compared across groups using parametric and non-parametric t-tests (i.e. cross-sectional features) and mixed models (i.e. longitudinal features). Non-obese and obese women with regular cycles showed similar IOI, follicular phase, and luteal phase lengths. The mean number of recruitment events, maximum dominant follicle diameter, and the growth rates of ovulatory follicles over time did not differ between groups, despite confirmation of compromised mean luteal progesterone production (8.23 ng/mL vs. 14.75 ng/mL, p=0.047) and decreased mean luteal FSH levels in women with obesity (2.33 mIU/mL vs. 5.83 mIU/mL, p=0.040). Over the IOI women with obesity showed an increased proportion of 2-5 mm follicles (β=5.3%; p&lt;0.05) and a decreased proportion of 6-9mm follicles (β=-5.0%; p=0.05) versus non-obese women consistent with fewer follicles transitioning from the 2-5 mm pool to the selectable stage. This is the first comparison of follicle dynamics between non-obese and obese women with regular ovulatory cycles. These data suggest that a smaller pool of selectable follicles is present in women with obesity and may result in suboptimal follicle development luteal function. Future studies are needed to understand the impact of altered follicle populations and luteal hormone dynamics on endometrial receptivity and fertility/fecundity.
Anti-Mullerian Hormone Protein-Altering Variants Are Associated With Hypertriglyceridemia in the General Population
Authors: Chang Sydney , Copperman Alan , Dunaif Andrea Elizabeth 
Published: May 2021

Abstract
We found 17 rare PCOS-specific functional protein-altering variants (PAVs) or mutations in the gene, AMH, that decrease the biologic activity of the encoded protein, anti-Müllerian hormone (AMH), in the heterozygous state. Approximately 3% of European ancestry PCOS cases in our cohort of ~700 were affected. Our preliminary studies found evidence for a metabolic phenotype in both PCOS as well as their male first-degree relatives who were heterozygous carriers of these AMH PAVs. We performed this study to test the hypothesis that AMH mutations are associated with metabolic abnormalities in the general population. The Mount Sinai BioMe Biobank is an electronic health record (EHR)-linked biobank, containing anonymized whole exome sequences from 30,813 participants of diverse ancestries. We interrogated the sequence data to identify individuals with PCOS-related AMH PAVs. IRB-approval was obtained to review the linked EHR. Outcomes were the presence of obesity (BMI ≥ 30 kg/m2), type 2 diabetes (hemoglobin A1C ≥ 6.5%), prediabetes (hemoglobin A1C 5.7% - 6.4%), elevated cholesterol (total cholesterol ≥ 200 mg/dL), hypertriglyceridemia (TG ≥ 150 mg/dL), and hypertension (≥2 blood pressure values ≥140/90, or administration of antihypertensive medications). Control subjects were obtained from the National Health and Nutrition Examination Survey using propensity score matching (for sex, age, and BMI) with a 1:4 case:control ratio. A total of 292 individuals with AMH PAVs were identified, resulting in a combined 0.95% prevalence of AMH PAVs in an unselected population (1.07% in Europeans, 0.28% in African Americans, 0.54% in Hispanics, and 0.07% in Asians). After adjusting for age, BMI, and race/ethnicity, there was a statistically significant increased prevalence of hypertriglyceridemia in both women (OR 7.29, 95% CI 3.77-14.00) and men (OR 10.15, 95% CI 4.68-22.00) with AMH
PAVs compared to sex-, age- and BMI-matched controls. There was also a statistically significant increased prevalence of elevated cholesterol in men with AMH PAVs compared to controls (OR 2.48, 95% CI 1.15-5.34). There were no significant differences between individuals with AMH PAVs and matched controls with respect to the other outcomes. These findings suggest that decreased bioactivity of AMH is causally related to dyslipidemia in the general population. TG levels are elevated in both sexes, whereas increases in cholesterol are only seen in men. The mechanisms by which decreases in AMH bioactivity alter circulating lipid levels are of considerable interest since AMH has no known metabolic actions. It is possible that the putative metabolic effects of AMH are mediated by increases in circulating testosterone (T) levels that in turn alter lipid metabolism. Since T levels are not commonly available in EHR, future studies will be needed to investigate this hypothesis as well as to explore metabolic actions of AMH.
Involvement of BMP-15 in Glucocorticoid Actions on Ovarian Steroidogenesis by Rat Granulosa Cells
Authors: Kashino Chiaki , Hasegawa Toru , Nakano Yasuhiro , Iwata Nahoko , Yamamoto Koichiro , Kamada Yasuhiko , Masuyama Hisashi , Otsuka Fumio 
Published: May 2021

Abstract
Glucocorticoid receptor (GR) are known to be expressed in the ovary and glucocorticoids are shown to exert direct effects on granulosa cell functions. In the clinical setting, menstrual abnormality, amenorrhea and hypermenorrhea can be shown in patients with glucocorticoid excess. On the other hand, glucocorticoids can also be used for the treatment of PCOS with hyperandrogenism. However, the effects of glucocorticoids on the reproductive system have not been fully elucidated. In the present study, we investigated the influence of glucocorticoids on follicular steroidogenesis using primary culture of rat granulosa cells, by focusing on the ovarian bone morphogenetic proteins (BMPs) acting as a luteinizing inhibitor. Granulosa cells isolated from female immature rats were treated with follicle-stimulating hormone (FSH) in the presence of dexamethasone (Dex) in serum-free conditions. After treatment with Dex for 48 h, the changes of estradiol (E2) and progesterone (P4) production and cAMP synthesis induced by FSH treatments were measured by ELISA. Total RNAs of granulosa cells treated with FSH, Dex and BMPs were extracted and mRNA levels of steroidogenetic factors and enzymes, BMP receptors and Id-1 were quantified by real-time RT-PCR. Phosphorylation of Smad1/5/9 induced by BMPs was evaluated by Western blotting using cell lysates in the presence or absence of Dex. As a result, it was revealed that Dex treatment decreased FSH-induced E2 production by granulosa cells. In accordance with the steroid results, Dex suppressed FSH-induced P450arom mRNA expression as well as FSH-induced cAMP synthesis by granulosa cells. By contrast, Dex treatment augmented FSH-induced P4 production by granulosa cells in a concentration-dependent manner. Dex treatment was found to enhance basal and FSH-induced mRNA levels of P4-synthetic enzymes including P450scc and 3βHSD. Of note, Dex treatment activated the BMP target gene Id-1 transcription and Smad1/5/9 phosphorylation, in particular, induced by BMP-15 among various BMP ligands including BMP-2, -4, -6, -7, -9 and -15. It was also revealed that Dex treatment increased mRNA levels of ALK-6, a type-I receptor for BMP-15, and that BMP-15 treatment in turn upregulated GR mRNA levels expressed by granulosa cells. Given that BMP-15 acts as an inhibitor for P4 production by suppressing FSH-receptor actions, it was suggested that glucocorticoid is functionally linked to the enhancement of endogenous BMP-15, leading to the negative feedback toward the P4 overproduction induced by FSH and Dex in granulosa cells. Collectively, it was revealed that glucocorticoids elicit differential effects on the ovarian steroidogenesis of E2 and P4, in which GR and BMP-15 actions are mutually enhanced in granulosa cells.
Pre-Eclampsia Strikes: Could It Be Related This Gland?
Authors: Lofters Jason , Flemming Nia , Gayle Latoya , Simmonds Ro-Kaye , Adedoyin Oluwafeyi , Brijmohan Sharmela , Fein Deborah 
Published: May 2021

Abstract
Introduction: Primary hyperparathyroidism (PHPT) is rarely diagnosed in pregnancy and if left untreated has the potential to lead to serious maternal and neonatal complications. We describe a case of PHPT with associated complicated pre-eclampsia. Clinical Case29-year-old primigravida admitted at 33 + 6 weeks with fatigue, 10lbs weight gain and elevated BP. Labs revealed potassium 2.9 (3.5-5.2mmol/L), corrected serum calcium (Ca)11.62 (8.4-10.2mg/dL), ionized calcium 1.69 (1.15-1.33mmol/L), PTH 163.9 (15-65pg/mL) and vitamin D 24.6 (30-100ng/mL). Other labs were normal. Urine studies showed 315mg/24h proteinuria and urine calcium of 129.5 mg/24hrs (100-300mg/24hrs). She was started on magnesium sulphate along with labetalol for BP control, given betamethasone for stimulation of fetal lung maturity as well as potassium repletion. Hypercalcemia (HCa) was initially managed with fluids and Lasix intravenously. At 34 + 2 weeks she developed SOB, orthopnea, headaches with new 9lbs weight gain over 5 days and sustained BP elevation. Urgent C-section was done for pre-eclampsia with severe features. Post-operatively, she suffered from postpartum hemorrhage, managed with transfusion of packed red cells and transient placement of a Bakri balloon. Her HCa worsened with Ca 12.56 and cinacalcet was started after delivery. This coincided with gradual improvement of her BP and Ca to 10.8. She declined additional work-up and was discharged in stable condition. Clinical LessonPHPT often goes undiagnosed in pregnancy, with symptoms of fatigue and constipation mimicking common complaints of pregnancy. Studies have also suggested that up to 25% of patients with PHPT during pregnancy present with hypertension and pre-eclampsia and that there is an association between preeclampsia and the presence of parathyroid adenomas. The pathophysiology is unclear but is thought to be due to endothelial dysfunction triggered by hypercalcemia as well as abnormal placentation. No clear guidelines exist for the management of PHPT during pregnancy, with observation and rehydration being the preferred initial options. The use of cinacalcet as well as curative surgical parathyroidectomy when Ca levels persist &gt;11 in the second trimester have also been described. Our patient presented similarly, with severe pre-eclampsia needing urgent C-section, further complicated by persistent severe HCa. Early diagnosis of PHPT, along with treatment including cinacalcet improved her Ca. It is therefore important that PHPT be considered in patients presenting like ours, progressing to severe pre-eclampsia as early reduction of serum calcium may reduce morbidity and mortality. ReferencesMcCarthy, A., Howarth, S., Khoo, S., Hale, J., Oddy, S., Halsall, D., ... & Samyraju, M. (2019). Management of primary hyperparathyroidism in pregnancy: a case series. Endocrinology, diabetes & metabolism case reports, 2019(1).