bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT627 Is Cyberknife Stereotactic Radiosurgery Effective For Treating Cushing’s Disease?
Authors: Wintermyer Gelareh , Villanueva Erika 
Published: October 2023

Abstract
Disclosure: G. Wintermyer: None. E. Villanueva: None.
Patients with pituitary adenoma can often present with endocrine abnormalities. Transsphenoidal surgery(TSS) is the “gold standard” treatment. In patients with recurrent or post-surgery remaining adenoma, stereotactic radiosurgery with CyberKnife (CKRS) has demonstrated to be a good adjuvant therapy. Occasionally patients develop hypopituitarism and adrenal insufficiency (AI) post CKRS. Here is a patient with ACTH-secreting pituitary adenoma with Cushing’s disease who developed remission afterCKRS:52-year-old-male with PMHx of T2DM, hypothyroidism, HTN presented to hospital complaining of fatigue, ataxia, 40-lbs weight loss over four months and mood changes. Due to ataxia, CT of the head was done which revealed an Empty Sella. During the workup, ACTH and cortisol were detected 131 pg/mL and 37.5 ug/dL respectively. After ruling out life-threatening medical conditions, he was discharged with endocrinology referral for Empty Sella syndrome (ESS) and elevated ACTH. During endocrinology evaluation, patient was sent for testosterone, LH, FSH, ACTH, AM cortisol, prolactin and DHEAS tests. Results were as follows: elevated ACTH (91 pg/mL) and Cortisol (33.5ug/dL), elevated DHEAS (401 ug/dL) and prolactin (15 NG/dL), low testosterone (72 NG/dL), within appropriately low LH and FSH. Later, PM Salivary cortisol level, Dexamethasone suppression test(DST), and urine free cortisol (UFC) level were tested. He had pituitary MRI concurrently. Salivary cortisol and UFC were high. There was no suppression of cortisol level after DST. Pituitary MRI demonstrated pituitary tumor. He was diagnosed with Cushing’s disease and was referred to neurosurgery for pituitary tumor TSS. Patient was started on Ketoconazole prior to surgery. Pathology confirmed ACTH-secreting pituitary adenoma. After surgery, Cortisol level normalized, and the patient regained his energy. Post-surgery MRI showed complete resection of adenoma. Ketoconazole was discontinued post-operatively. Two years later, during routine workup, there were elevations in 24-hour and PM salivary cortisol levels. The patient was asymptomatic. He failed his DST. Repeat pituitary MRI showed small hypo enhancement at the bottom of Sella suspicious for pituitary adenoma recurrence. The patient underwent CKRS. Cortisol level and pituitary axis activity remained normal since CKRS. No change was noted in the six-month and one-year surveillance MRI. Even though TSS is a “gold standard” treatment for pituitary adenoma, the likelihood of remaining residues or recurrence of the tumor is high. Frequent pituitary hormone checks can detect recurrence of adenoma before emerging symptoms. CKRS should be considered as a therapeutic option for recurrent adenoma. Clinicians should frequently check patients for hypopituitarism and AI post-CKRS. Clinicians should also recognize that ESS may contribute to MRI-negative Cushing’s disease.
Presentation: Saturday, June 17, 2023
OR2804 Endocrine And Vision Outcomes Following 90Yttrium Therapy For Cystic Sellar Lesions—A Prospective Cohort Study
Authors: MacLean Mark A , Ahmad Syed , Hebb Andrea L O , Tahir Anas , Greene Ryan , Clarke David B , Imran Syed Ali 
Published: October 2023

Abstract
Disclosure: M.A. MacLean: None. S. Ahmad: None. A.L. Hebb: None. A. Tahir: None. R. Greene: None. D.B. Clarke: None. S.A. Imran: None.
Background: Untreated cystic sellar lesions can cause vision loss, endocrine dysfunction, and obstructive hydrocephalus related to growth and mass effect. Microsurgical resection, stereotactic aspiration, and radiation treatment strategies are limited by significant complications and high risk of recurrence. Stereotactic intracavitary irradiation with the beta-emitting isotope 90Yttrium (90Yt) has been proposed as an alternative to mitigate these challenges. Long term-efficacy data is lacking. Here, our objective was to prospectively assess the effect of 90Yt on cyst volume, endocrine, and vision outcomes. Methods: We conducted a Health Canada approved, single-centre, prospective cohort study. Clinical outcome measures included cyst volume measured on magnetic resonance imaging, formal visual field (VF) testing, and hypothalamic-pituitary (HP) hormonal function. All patients provided informed consent and underwent right frontal stereotactic insertion of 90Yt colloid (200 Gy cyst wall). Results: Twenty-two patients (55% females) received 90Yt therapy. Mean age was 63.5 (SD 15.4) years with no difference between genders (p = 0.055). Mean duration of follow-up was 52 months (range 5-113). Cystic lesions included: craniopharyngioma (86%), Rathke’s cleft cyst (9%) and cystic prolactinoma (5%). Mean tumor cyst volumes were reduced by 77% at 12-month follow-up (pre-operative: 5.2, SD 4.5 cc; 12 months post-operative: 1.2, SD 1.5 cc; p = 0.002). Males had larger tumor volumes at baseline (7.7, SD 5.0 cc vs. 3.2, SD 2.8; p = 0.02) and 3 months (4.7, SD 3.4 vs. 1.8, SD 2.0; p = 0.04) but these differences had resolved by 9-month follow-up. Pre-operative clinical features included: VF deficit (36%), VF deficit plus headache (36%), headache alone (9%), hydrocephalus (5%), and 14% were asymptomatic. HP hormone dysfunction was observed in 59% of patients pre-operatively (27% complete; 73% partial) and 68% post-operatively (p = 0.50); specifically, no differences were found pre- and post-operatively for secondary hypogonadism (50% vs. 55%), hypothyroidism (45% vs. 59%), hypoadrenalism (36% vs. 27%), growth hormone deficiency (27% vs. 23%), diabetes insipidus (23% vs. 27%), and hyperprolactinemia (36% vs. 36%) (all p &gt; 0.05). Pre-operative VF deficits were found in 68% of patients, of which 32% normalized and 36% remained stable (p = 0.180). Worsened vision was detected in 9% of patients post-operatively. Treatment failure requiring conventional surgery occurred in 18% of patients. Conclusions:90Yt therapy significantly reduced tumor cyst size and stabilized both endocrine function and vision in patients with cystic lesions of the sellar region.
Presentation: Sunday, June 18, 2023
SAT026 Melanocortin Receptors In The Earliest Chordates?
Authors: Ji Ren-Lei , Jiang Shanshan , Kleinau Gunnar , Scheerer Patrick , Tao Ya-Xiong 
Published: October 2023

Abstract
Disclosure: R. Ji: None. S. Jiang: None. G. Kleinau: None. P. Scheerer: None. Y. Tao: None.
Melanocortin receptors (MCRs) genes have been identified to be functional in the genome of early chordates, e.g. the cyclostomata, around 360 million years ago. Whether it appears in the most ancient chordates, such as cephalochordate and urochordata (500 million years ago), however, remained unknown until now. Herein, therefore, we studied experimentally four putative, sequence based predicted melanocortin-4 receptor (mc4r) like receptors and one putative MC1R-like receptor from urochordata and cephalochordate (from NCBI database), including Styela clava (sc), Ciona intestinalis (ci), Branchiostoma floridae (fl), and Branchiostoma belcheri (bb). No genes coding the endogenous MCR ligands were observed in these species. We further expressed these putative receptor plasmids in HEK293T cells and stimulated with α-melanocyte stimulating hormone (α-MSH) and synthetic MCR ligands to verify whether these receptors are functional MCRs. Our results showed that four receptors (so far named flMC4R, bbMC4R-1, bbMC4R-2, and ciMC1R) had high cell surface expression in HEK293T cells, whereas scMC4R had low cell surface expression. Four receptors (except scMC4R) showed high basal cAMP signaling, suggesting that these receptors are likely coupled to the stimulatory Gs protein. However, no specific binding to the superpotent α-MSH analog, NDP-MSH, were observed at these five receptors, and in accordance they had no α-MSH-induced cAMP signaling coupled to Gs stimulation. Additionally, all five receptors had low basal and no α-MSH-stimulated ERK1/2 signaling. Four human MC4R inverse agonists, including Agouti-related protein and three small molecular compounds (Ipsen5i, MCL0020, and ML00253764), had no effect on cAMP and ERK1/2 signaling of the four predicted MC4R-like receptors. In summary, our results suggested that the four predicted MCR-like receptors (except scMC4R) in ancient chordates are indeed functional receptors, with high constitutive activity, but they are all not MCR-like receptors based on our experimental data with common endogenous and synthetic MCR ligands. We hypothesize that these receptors might be MCR-like receptors, in that receptors might appear earlier than appearance of endogenous ligands; or these receptors might be other ancient G protein-coupled receptors (GPCRs) with other unidentified ligands. However, further studies are needed to identify the ancient GPCR system, which may include studies on the appearance of ligands or precursors.
Presentation: Saturday, June 17, 2023
THU214 Exploratory Study Of The Association Of Genetic Factors With Recovery Of Hypothalamic-Pituitary-Adrenal Axis In Cushing Disease
Authors: Nguyen Matthew H , Zhang Wei , Pankratz Nathan , Lane John , Chittiboina Prashant , Faucz Fabio R , Liu Aiyi , Mills James L , Stratakis Constantine A , Tatsi Christina 
Published: October 2023

Abstract
Disclosure: M.H. Nguyen: None. W. Zhang: None. N. Pankratz: None. J. Lane: None. P. Chittiboina: None. F.R. Faucz: None. A. Liu: None. J.L. Mills: None. C.A. Stratakis: None. C. Tatsi: None.
Successful treatment of endogenous Cushing syndrome (CS) is often followed by a period of adrenal insufficiency of variable duration. Recovery of the hypothalamic-pituitary-adrenal (HPA) axis may range from 6 months to more than 2 years. Previous studies have investigated potential clinical and biochemical factors involved in this process with variable results. We performed an exploratory study on genetic factors potentially involved in HPA axis recovery in patients with Cushing disease (CD). Ninety (90) patients with CD, who were treated with transsphenoidal surgery (TSS), had initial remission, and a follow up of at least 3 months postoperatively, were included in the study. Recovery of the HPA axis was defined as morning cortisol level or peak cortisol during a standard dose (250 mcg) IV corticotropin stimulation test of &gt;18mcg/dL. Genetic data was obtained by whole exome sequencing (WES). Variants 1) in genes potentially involved in the HPA axis, 2) rare in the general population and 3) predicted as possibly or probably damaging in silico, were selected from WES. Statistical analysis was performed for each variant or for each gene (calculating all variants present in the same gene) using a Cox proportional hazard model. Correction for multiple comparisons was assessed with the false discovery rate (FDR) method.We identified 97 variants in 47 genes of interest that met the above criteria. Although five variants showed a trend toward association with shorter duration of postsurgical adrenal insufficiency (AI), no significant association was noted after correction for multiple comparisons. Furthermore, each variant was present in only one patient. At the gene-level, the BAG1 gene showed significant correlation with shorter postsurgical duration of AI (Hazard ratio: 28.7, 95% Confidence Interval: 5.4-151.1, FDR q-value=0.004), but both patients with a BAG1 variant later experienced recurrent disease, which could suggest an independent predictor of shorter recovery time. When we excluded patients with recurrence, no significant association was reported on the gene-level. In this exploratory study, we did not identify a significant genetic modifier of HPA recovery time. Other factors, clinical or surgical, may play a more important role in the recovery process or larger cohort studies may be required.
Presentation: Thursday, June 15, 2023
THU217 Vision-related Quality Of Life In Patients With Childhood-onset Craniopharyngioma - Results Of Hit-Endo And Kraniopharyngeom 2000/2007
Authors: Sowithayasakul Panjarat , Boekhoff Svenja , Beckhaus Julia , Friedrich Carsten , Muller Hermann Lothar 
Published: October 2023

Abstract
Disclosure: P. Sowithayasakul: None. S. Boekhoff: None. J. Beckhaus: None. C. Friedrich: None. H.L. Muller: None.
Quality of life (QoL) has become a critical component of therapeutic outcomes in the survivors of childhood-onset craniopharyngioma (CP). Visual deficiency adversely affects daily functioning and QoL in childhood CP. This cohort study aimed to report the vision-related QoL in CP patients. The primary outcome measure was pediatric QoL (PEDQOL score) in patients with and without visual impairment from presentation at the time of CP diagnosis to three-year follow-up. The risk factors associated with visual impairment were also analyzed. A total of 120 patients were included in this study, with a median age at diagnosis of 10 years (ranging from 1.3 to 16.8 years). The most common presenting symptoms at the time of CP diagnosis were headache (42%), visual impairment (20%), and growth retardation (12%). Visual impairment was found in 87 patients (70%). Ophthalmologic examination and PEDQOL scores, which were grouped into seven domains: physical functioning, cognition, social functioning friends, social functioning family, and body image, were evaluated at the third month, first-year, and third-year after diagnosis. Parents of children with visual impairment report worse social functioning in their families than parents of children without visual impairment, one (p=0.017) and three years (p=0.011) after diagnosis. After three years, children with visual impairment were found to have worse quality of life in the autonomy domain of self- (p=0.029) and parental assessment (p=0.048). High tumor volume (&gt;21 cm³), radiation therapy and extrasellar tumor location were identified as potential risk factors for visual impairment. We conclude that visual impairment has a negative impact on QoL after CP. Early detection of visual impairment, regular QoL assessment, and risk-appropriate follow-up care are recommended.
Presentation: Thursday, June 15, 2023
FRI589 MicroRNAs In Maternal Plasma At 15 Weeks Gestation As Biomarkers For Later Preterm Birth: Evidence For Dysregulated Mirna Biogenesis And Implications For Pregnancy-related Endocrine Signaling Pathways
Authors: Ramzan Farha , Rong Jing , Roberts Claire , O'Sullivan Justin , Perry Jo Kate , Taylor Rennae , McCowan Lesley , Vickers Mark Hedley 
Published: October 2023

Abstract
Disclosure: F. Ramzan: None. J. Rong: None. C. Roberts: None. J. O'Sullivan: None. J.K. Perry: None. R. Taylor: None. L. McCowan: None. M.H. Vickers: None.
Introduction: Preterm birth (PTB) is a leading cause of morbidity and mortality in infants, with rates of PTB increasing globally over the last 20 years. MicroRNAs (miRNAs) have been reported to have widespread involvement in the development of and protection from many diseases, there is increasing interest in their potential role in the aetiology of a range of pregnancy-related disorders, including PTB. Objectives: To investigate differential miRNA abundances in mid-pregnancy plasma samples between mothers with term infants compared with moderate to late preterm infants (spontaneous PTB) and replication across independent cohorts. Method: The Auckland and Adelaide arms of the Screening for Pregnancy Endpoints (SCOPE) study were utilised. miRNAs in plasma at 15 weeks gestation from mothers of term and moderate to late preterm infants (n=54 per group) were quantified using the NanoString nCounter human v2 miRNA expression panel. Gene expression of key mediators of miRNA biogenesis, including Drosha, Dicer and Argonaut were quantified via RT-qPCR. In-silico analysis was performed to investigate the biological pathways associated with the dysregulated miRNAs. Results: Of the 800 miRNAs examined, the top four miRNAs identified were conserved across both cohorts and were significantly downregulated in the plasma of mothers who later experienced a PTB. The gene pathways associated with the top candidate miRNAs were linked to inflammatory processes, mitochondrial biogenesis, apoptosis and regulation of key pregnancy-related hormonal signaling pathways. Moreover, miRNAs were consistently downregulated in the PTB group concomitant with reduced gene expression of key miRNA biogenesis markers. Conclusions: We identified miRNAs in maternal plasma in mid-pregnancy that were highly predictive of later spontaneous PTB and, importantly, were conserved across two independent cohorts. Moreover, in addition to identifying potential early biomarkers for subsequent PTB, we provide evidence for persistent downregulation of miRNAs in those mothers who later delivered preterm, which is likely to have widespread effects on endocrine signaling pathways during pregnancy.
Presentation: Friday, June 16, 2023
FRI591 Association Of TSH Levels And NAFLD Severity In Children And Adolescents
Authors: Untalan Matthew , Crimmins Nancy Abigail , Mencin Ali , Yates Katherine , Stavra Xanthakos , Thaker Vidhu 
Published: October 2023

Abstract
Disclosure: M. Untalan: None. N.A. Crimmins: None. A. Mencin: None. K. Yates: None. X. Stavra: None. V. Thaker: None.
Background: Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation and is now the most common form of chronic liver disease in children and adolescents. Recent studies have indicated an association between subclinical hypothyroidism (SH) and NAFLD. An underactive thyroid gland produces insufficient T3 and T4 involved in hepatic fat metabolism that could contribute to NAFLD. While increased TSH has been documented in individuals with NAFLD, its independent role with NAFLD disease severity is yet to be clarified. Objective: To study the relationship of TSH levels and the severity of NAFLD/NASH, as well as determine whether changes in TSH levels are associated with changes in NAFLD/NASH among children. Methods: This retrospective study used data from two cohorts within the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN). TSH, free and total T4, total T3, TPO antibodies and thyroglobulin (TBG) levels were assessed in samples obtained first at baseline and then at 52-96 weeks. Individuals with overt hypothyroidism, abnormal TPO antibody levels, and those receiving thyroid treatment were excluded from analysis. SH was defined as TSH &gt; 4.4 mIU/L. Linear and multinomial regression models were used to identify the association between TSH, SH and NAFLD severity measured by NAFLD activity score (NAS), fibrosis stage, steatosis level, lobular and portal inflammation and ballooning while adjusting for potential confounders (sex, age, race, BMI-z, HOMA-IR and non-HDL levels). Longitudinal analysis was conducted by mixed-effects model. Analyses were performed with SAS and R statistical software. Results: 218 individuals and 421 observations were included in the cross-sectional and longitudinal analyses, respectively. Children with more severe grades of steatosis were more likely to be younger (p = 0.03) and male (p = 0.02). At baseline, TSH was not significantly associated with any NAFLD histological measures. Longitudinal analyses revealed a positive association of change in TSH and steatosis level after adjusting for covariates, and follow-up time (p = 0.03). Change in SH was associated with change in fibrosis stage (p = 0.01). Adding HOMA-IR and non-HDL levels to the models did not change this relationship. The positive relationship of total T3 and T4 with NAS was explained by TBG. Conclusion: In a large cohort of pediatric patients with biopsy-confirmed NAFLD, high TSH levels correlated with increasing steatosis grade and NAS, and SH with increased liver fibrosis. Markers of impaired thyroid function may help predict disease severity in pediatric patients with NAFLD.
Presentation: Friday, June 16, 2023
THU620 Metastatic Adrenocortical Carcinoma Arising From A Testicular Rest Tumor
Authors: Chozet Luis Edmundo , Bruder Jan M , Flores Raina , Hackman Sarah , Highes Kenneth , Vasquez Libia , Le Guillaume , Cortez Tiffany , Escobar Vasco Maria Adelaida 
Published: October 2023

Abstract
Disclosure: L.E. Chozet: None. J.M. Bruder: None. R. Flores: None. S. Hackman: None. K. highes: None. L. Vasquez: None. G. Le: None. T. cortez: None. M.A. Escobar Vasco: None.
Background: Congenital adrenal hyperplasia (CAH) involves a range of autosomal recessive disorders characterized by abnormalities in the adrenal biosynthesis pathway. Testicular adrenal rest tumors (TARTs) are a complication mostly seen in male patients with congenital adrenal hyperplasia which can lead to infertility. These tumors are known to have benign characteristics. We present a unique case of a male patient with CAH diagnosed with metastatic adrenocortical carcinoma arising from a TART. Clinical Case: A 40-year-old man with poorly controlled congenital adrenal hyperplasia from 21-hydroxylase deficiency and bilateral testicular adrenal rest tumors presented with syncope and worsening left testicular pain for 2 months. Scrotal ultrasound showed enlarged bilateral scrotal masses (left bigger than right). Initial evaluation for his syncopal event included CTA chest which showed an incidental finding of innumerable bilateral solid pulmonary nodules. 17-hydroxyprogesterone levels were elevated at 5273 ng/dL (normal less than 138 ng/dL). Additional biochemical workup of the testicular mass was unremarkable. The patient underwent left radical orchiectomy with pathology showing high-grade carcinoma with adrenocortical differentiation. A right upper lobe lung biopsy was done which demonstrated metastatic carcinoma with adrenocortical differentiation, morphologically similar to the testicular tumor. The initial patient presentation of progressively worsening left testicular pain in the setting of testicular adrenal rest tumors (TARTs) led to the diagnosis of adrenal carcinoma. Conclusion: This case presents a unique presentation of adrenal carcinoma in a patient with congenital adrenal hyperplasia arising in the setting of testicular adrenal rest tumors (TARTs). This case demonstrates a unique presentation of adrenal carcinoma, as malignant degeneration has not been described in patients with TARTs. It also highlights the importance of close monitoring even if these tumors are thought to be of benign origin.
Presentation: Thursday, June 15, 2023