bluuebunny/crossref_metadata_2025_split huggingface dataset:
FRI596 Randomized Clinical Trial Of Theophylline For Treatment Of Pseudohypoparathyroidism Type 1a
Authors: Shoemaker Ashley Hall , Tamaroff Jaclyn , Jueppner Harald 
Published: October 2023

Abstract
Disclosure: A.H. Shoemaker: None. J. Tamaroff: None. H. Jueppner: None.
Background: Pseudohypoparathyroidism type 1A (PHP1A) is a rare, genetic disorder caused by heterozygous inactivating mutations involving the maternal GNAS allele, the gene that encodes the stimulatory G protein (Gsα). Due to tissue specific reduced paternal Gsα expression, several tissues, particularly proximal renal tubules and thyroid, show decreased Gsα-coupled receptor function. Resultant hormone resistances can be treated, but other aspects of PHP1A such as early-onset obesity and short stature are without effective treatment options. Gsα-coupled receptor signaling cascade begins with agonist-stimulated increase in cAMP, the second messenger which is rapidly degraded by phosphodiesterase (PDE). Given that PHP1A patients have reduced, but not completely absent, cAMP production, this clinical trial will test the hypothesis that the non-selective PDE inhibitor theophylline will improve Gsα-coupled receptor signaling. We describe the study design and baseline characteristics of PHP1A patients enrolled in a double-blind, randomized, placebo-controlled clinical trial of theophylline. Methods: A single center will enroll 34 patients. Inclusion criteria: age &gt;=2 years old, diagnosis of PHP1A and obesity. Exclusion criteria include seizure disorder, uncontrolled hormone resistance, pregnancy, and other significant medical problems. Enrollment starts with the oldest age group (&gt;=13 years) and safety/efficacy is reviewed by the DSMB after each block of 6 patients before opening to the next age block (7-12 and 2-6 years). Patients are randomized to theophylline vs. placebo using a permuted-block randomization (2:1) stratified by age and gender. Theophylline levels guide dosing with a goal level of 10-19 mcg/mL. Unblinded study staff review theophylline levels and the dosing protocol includes sham placebo dose adjustments. The primary outcome is change in BMI, expressed as % of the 95th %ile (BMI95), to account for age and gender. Secondary endpoints include changes in glucose tolerance and insulin secretion (insulinogenic index), rate of epiphyseal closure and hormone replacement doses. Results: To date we have screened 27 and enrolled 24 patients. Enrollment in the youngest age block (2-6 years) opened in December 2022. Enrolled patients range from 4 to 55 years old (mean 16.0 ± 10.4 years, 18 pediatric patients), 92% are female, 100% are white and 13% are Hispanic. All patients were obese with a mean BMI95 130.8 ± 23.8%. Three adult patients withdrew due to headaches, nausea/difficulty swallowing pills or travel difficulties. The most common adverse event related to study drug was transient nausea/vomiting. Conclusion: This randomized clinical trial designed to test safety and efficacy of theophylline for PHP1A is ongoing. Thus far the study drug and procedures have been safe and well tolerated.
Presentation: Friday, June 16, 2023
THU624 Opioid Induced Adrenal Insufficiency (OIAI) Presenting With Altered Mental Status
Authors: Bondarenko Darya , Ahmad Mobeen , McGrath Glenn Alan 
Published: October 2023

Abstract
Disclosure: D. Bondarenko: None. M. Ahmad: None. G.A. McGrath: None.
Background: Opioid suppression of the hypothalamic-pituitary-adrenal (HPA) axis via inhibition of corticotropin releasing hormone secretion leading to secondary adrenal insufficiency (AI) has been described in literature. Biochemical secondary AI is evident in 6-50% of patients on chronic opioids; fewer cases are reported presenting with clinical AI.1 We present a rare case of symptomatic opioid-induced AI (OIAI) with clinical improvement on initiation of hydrocortisone. Clinical Case: A 49-year-old female on daily buprenorphine (20 mg) and naltrexone (5 mg) presented to the hospital with syncope and hypotension (79/49 mmHg). AM cortisol was 6.2 mcg/dL, a cosyntropin stimulation test was performed, but there was technical difficulty with the results. She was started on midodrine 2.5 mg three times daily and referred to outpatient endocrinology for follow up. Weeks later, outpatient cosyntropin stimulation test showed baseline cortisol of 18 mcg/dL with increase to 26 mcg/dL. Simultaneous adrenocorticotrophic hormone (ACTH) was 16.9 pg/mL. AI was ruled out. Seven years later she presented with acute lethargy, confusion, and memory loss over several days. AM cortisol was 1.6 mcg/dL and cosyntropin stimulation test increased cortisol to 15.1 mcg/dL (normal response being 18 mcg/dL or greater). ACTH was 24 pg/mL. The abnormal cosyntropin stimulation test results are consistent with AI, and lack of elevation of morning ACTH is consistent with secondary AI.2 Hydrocortisone therapy was started and midodrine was held due to elevated blood pressure after initiation of steroids. She was discharged on hydrocortisone 15 mg each morning and 5 mg each afternoon. Within 10 days of initiation of glucocorticoid replacement therapy her neurologic symptoms improved and midodrine discontinued. Prescription Drug Monitoring Program (PDMP) review shows reduction of buprenorphine (16 mg) and naltrexone (4 mg). Conclusion: Data on management of OIAI and recovery of the HPA axis with or without cessation of opioid therapy is limited. This case highlights that opioids should be considered as a potential cause of secondary AI. Further follow-up of this case and other OIAI cases would provide insight into management of opioid therapy, continuation of glucocorticoid therapy, and recovery of HPA axis. This data could provide basis for OIAI management recommendations. Reference: (1) Fountas, A., Prof, S.V.U., Karavitaki, N. Opioid-induced endocrinopathies. Lancet Diabetes Endocrinol. 2020;8(1);68-80. (2) Bornstein, S.R., Allolio, B., Arlt, W., et al. Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline. J. Clin. Endocr. 2016;101(2);364-389.
Presentation: Thursday, June 15, 2023
FRI428 VTE And Testosterone Therapy: What Is The Risk?
Authors: Cheatham Callie , Colburn Jeffrey , Kemm Matthew 
Published: October 2023

Abstract
Disclosure: C. Cheatham: None. J. Colburn: None. M. Kemm: None.
Testosterone replacement therapy (TRT) to treat hypogonadism from a variety of underlying etiologies remains increasingly prevalent within the United States. While VTE is a known potential risk, the prevalence, underlying mechanism, and associated risk factors remain incompletely understood. Men initiating TRT for hypogonadism often do not receive adequate pre-treatment evaluation or have therapy initiated despite normal testosterone levels. While a 2021 meta-analysis 1 did not demonstrate significantly increased VTE risk associated with TRT, the wide confidence interval, reported low quality of evidence, and lack of studies examining VTE as a primary outcome with data obtained via adverse event reporting demonstrates the importance of further investigation.
Case 1: 55-year-old male with unilateral orchiectomy and associated primary hypogonadism started on TRT 10years prior presented to the hospital with acute onset chest pain and shortness of breath. CT angiography demonstrated right lower lobe segmental pulmonary emboli with parenchymal infarction. At the time of presentation, he was on IM testosterone cypionate 200mg weekly and anastrozole with total testosterone970 ng/dL, free testosterone 298 pg/mL, undetectable estradiol, and hematocrit 41.5%. His testosterone and anastrozole were discontinued at discharge, and he had a negative hypercoagulability workup by a hematologist.
Case 2: 61-year-old male with history of OSA, obesity, and TRT initiated 8 months prior for erectile dysfunction presented to the hospital with dyspnea. CT angiography demonstrated large bilateral pulmonary artery emboli with right heart strain consistent with submassive PE. Review of clinical records preceding TRT initiation indicate normal testosterone values of 533 ng/dL with free testosterone 60.6 pg/dL. At the timeof presentation, his total testosterone was 685 ng/dL, free testosterone 139 pg/mL, and hematocrit of 54%with history of polycythemia since TRT initiation and no documented intervention. He was treated withIR thrombectomy and anticoagulation, and TRT was discontinued at discharge. His hematocrit normalized at follow-up and, after negative hypercoagulability evaluation by a hematologist, TRT was felt to be the most likely etiology of his VTE.
These reported cases of VTE in men of different ages, underlying pathology, testosterone levels at time of event, presence of polycythemia, and time since testosterone initiation highlights the importance of further investigation on the true risk of thrombotic events in TRT patients and necessity of increased patient counseling of potential adverse outcomes.
1. Ayele HT, Brunetti VC, Renoux C, Tagalakis V, Filion KB. Testosterone replacement therapy and the risk of venous thromboembolism: A systematic review and meta-analysis of randomized controlled trials. Thromb Res. 2021;199:123-131. doi:10.1016/j.thromres.2020.12.029
Presentation: Friday, June 16, 2023
SAT351 Utilization of Emergency Services by Transgender People in the United States, 2006-2018
Authors: Stroumsa Daphna , Marsh Erica Elizabeth , Pfeiffer Paul N , Jiang Charley , Vrolijk Aaron , Moravek Molly Bennette 
Published: October 2023

Abstract
Disclosure: D. Stroumsa: None. E.E. Marsh: None. P.N. Pfeiffer: None. C. Jiang: None. A. Vrolijk: None. M.B. Moravek: None.
Bridging the Gap: Utilization of Emergency Services by Transgender People in the United States, 2006-2018Introduction: Transgender or nonbinary (Trans) people face significant health disparities, including in access to primary and preventive care. These disparities are driven by structural, interpersonal, and individual stigma, which lead to barriers accessing care and avoidance of primary care, and to increased reliance on emergency care. We aimed to characterize ED use by Trans patients, and changes in such use over time. Methods: Data was obtained from the Nationwide Emergency Department Sample (NEDS) , which is a weighted stratified sample of hospital-based ED visits. Using gender-dysphoria related ICD-9 and ICD-10 diagnostic codes, we compared visits among trans people to those without such a diagnosis, adjusting for age, region, urbanicity, primary payer, and income quartile. We evaluated rates of chronic condition and mental health conditions as primary diagnosis at presentation and at admission. Presence of chronic conditions was assessed using the ICD-9 Chronic Condition Indicator for 2006-2014. Results: There was a rapid temporal increase in the proportion of visits with a trans-related diagnosis, from 0.001% of visits in 2006 to 0.016% in 2018. There were significant demographic differences between trans people and others. Trans people were significantly more likely to be admitted, adjusting for payment, age group, region, income and mental health condition (overall 52.4% vs. 17.3%, adjusted OR= 7.368 95% CI (6.771, 8.017)). A large proportion of ED visits by trans individuals was associated with a mental health diagnosis (28.7%, compared with 3.9% for others, p&lt;0.001; adjusted OR =2.01, 95% CI 1.91-2.11) and/or with a chronic condition (58.2% vs. 19.2%, p&lt;0.001; adjusted OR =3.65, 95% CI 3.61-3.69). Similarly, hospital admission among trans people was much more likely to be linked to a mental health condition (37.2% vs. 5.3% , p&lt;0.001; adjusted OR = 2.78, 95% CI 2.44-3.16) or chronic condition (67.3% vs 41.3%, p&lt;0.001; adjusted OR = 2.21, 95% CI 1.78-2.75) Discussion: The high admission rates, and high proportion of trans people with a chronic condition or with mental illness, may represent worse overall health due lack of primary care, or a delay in seeking emergency care among Trans people. Lastly, these findings could be a manifestation of a higher likelihood of a trans-related diagnostic code being charted among trans people at admission, or bias towards higher likelihood of trans people receiving a mental-health related diagnosis. There is a need for increasing access to affirming primary and mental health care among trans people, and increased training of emergency clinicians.
Presentation Date: Saturday, June 17, 2023
FRI165 BIUXX
Authors: Haider Adnan , Sadiq Mehjabeen , Shakesprere Jon , Sidhu Gurmanpreet K 
Published: October 2023

Abstract
Disclosure: A. Haider: None. M. Sadiq: None. J. Shakesprere: None. G.K. Sidhu: None.
Background: Syndrome of inappropriate anti-diuretic hormone (ADH) secretion (SIADH) is characterized by inappropriate ADH secretion causing hyponatremia due to free water retention. Plasma volume expansion leads to renin inhibition by the renal juxtaglomerular complex, resulting in decreased aldosterone secretion with inappropriate natriuresis. However, when autonomous renin-independent aldosterone production is present, natriuresis can be suppressed, causing normal sodium levels despite inappropriately high ADH. Case: 58-year-old male with history of resistant hypertension & bipolar disorder on Oxcarbazepine presented with dizziness, lightheadedness, and severe hypokalemia (2.7 mmol/L, n 3.5-5.0 mmol/L). CT Adrenals revealed an incidental 1.2 cm left-sided adrenal adenoma [HU 6, 40% washout]. Serum aldosterone and plasma renin activity (PRA) were obtained in the supine position via LC/MS/MS assay; concurrent serum K+ was 3.4 mmol/L. Spironolactone was started and titrated to 50 mg BID for blood pressure control due to high suspicion of hyperaldosteronism. The patient was continued on Oxcarbazepine 900 mg BID. A 3 mg Dexamethasone suppression test showed suppressed morning cortisol (1.0 μg/dL, n &lt;1.8 μg/dL). Urine catecholamines and metanephrines were obtained and normal. 3-4 days after starting Spironolactone, the patient developed severe subacute hyponatremia (119 mmol/L, n 135-145 mmol/L) from an admission level of 137 mmol/L. No active renal or GI losses, diuretic use, or untreated hypothyroidism were documented. Serum osmolality was low (262 mOsm/kg, n 275-295 mOsm/kg) with urine osmolality of 357 mOsm/kg (n 50-1200 mOsm/kg) and urine sodium of 92 mEq/L (n &gt;20 mEq/L). Serum aldosterone and PRA levels returned with normal aldosterone (7 ng/dL, n 2-9 ng/dL) but suppressed PRA (0.07 ng/mL/hr, n 0.7-3.3 ng/mL/hr) and elevated aldosterone-renin ratio (100 ng/dL per ng/mL/hr, n ≤ 30 ng/dL per ng/mL/hr). As renin was very low despite mild hypokalemia and active Losartan use at the time of testing, these findings were suggestive of primary aldosteronism. In-hospital 24-hour urine aldosterone collection showed urine aldosterone of 29.3 mcg/24 h (n 5-19 mcg/24 h) with urine sodium of 93 mmol/ 24 h (n 40-220 mmol/24 h). Oxcarbazepine was subsequently tapered off; Spironolactone was intermittently held until complete discontinuation. Fluid restriction and oral salt repletion were started and the patient’s sodium ultimately normalized. Outpatient saline suppression testing and adrenal vein sampling were scheduled. Conclusion: Oxcarbazepine was likely causing high ADH release but co-occurring untreated hyperaldosteronism inhibited natriuresis. Use of Spironolactone unmasked natriuresis by blocking aldosterone activity on the intercalated cells of the renal nephron. Stopping Oxcarbazepine ultimately resulted in hyponatremia resolution.
Presentation Date: Friday, June 16, 2023
OR11-05 High-throughput Screening Identifies TR4 Modulators For Potential Therapeutic Application
Authors: Khowal Sapna , Zhang Dongyun , Damoiseaux Robert , Javaherian Keanu , Heaney Anthony P 
Published: October 2023

Abstract
Disclosure: S. Khowal: None. D. Zhang: None. R. Damoiseaux: None. K. Javaherian: None. A.P. Heaney: None.
Cushing Disease (CD), due to an adrenocorticotropic hormone (ACTH)-secreting pituitary tumor, leads to excess cortisol and is a life-threatening “orphan disease”. Although surgical removal can be effective, CD frequently recurs. Thereafter, repeat surgery, radiation therapy and/or bilateral adrenalectomy are not always successful and cause significant morbidity. Medical therapy has significantly improved but there is a clear unmet need for efficacious and safe therapies that target the pituitary corticotroph tumor itself to offer biochemical and tumor control. We previously demonstrated that the orphan testicular receptor 4 (TR4) regulates pro-opiomelanocortin gene transcription and ACTH secretion. Herein, we used the Flexi Vector system to identify TR4 modulators by fusing the TR4 LBD (380-615aa) to a 3’ GAL4 DBD to generate a chimeric fusion plasmid, pBIND-TR4-LBD. The pBIND-TR4-LBD construct and an exogenous luciferase reporter construct pGL4.35 (luc2P/9XGAL4UAS), containing 9 copies of a GAL4 responsive upstream activating sequence (UAS), were then transiently transfected into human embryonic kidney (HEK293) cells. Following treatment with TR4 ligands or modulators, our TR4-LBD undergoes a conformational change and recruits additional cofactors and RNA polymerase II to the complex to drive GAL4-directed firefly luciferase expression. In a high throughput screen (HTS) of 27,705 chemicals, we identified several potential “hit” TR4 modulators that induced or inhibited TR4 LBD-directed GAL4UAS-directed luciferase expression by &gt;3 -fold. Compounds from the HTS included ATP-sensitive K+ and calcium channel blockers, steroid hormones and modulators of cell proliferation and inflammation and several agonist and antagonist “hit” compounds induced TR4 &gt;10 fold or inhibited TR4 by 90% respectively with minimal cell toxicity (&lt;10%). In silico analysis of interactions between the TR4 LBD and these potential ligands indicated that the GLU-534 & ARG-565 may be crucial residues involved in TR4 ligand binding. Dose-response curves to calculate EC50 of these potential TR4 hit compounds and mode-of-action characterization are in progress. Our studies have identified several potent TR4 agonistic and antagonistic compounds and lay the framework for the discovery of safe and efficacious lead TR4 ligands that can be further advanced as potential drug therapies for CD and other diseases.
Presentation: Friday, June 16, 2023
SAT002 Liver-specific Loss Of The Nuclear Receptor Co-regulator ARGLU1 Protects Against Diet-induced Obesity In Female Mice Independent Of Food Intake And Energy Expenditure
Authors: Cash Sarah B , Magomedova Lilia , Tsai Ricky , Cummins Carolyn L 
Published: October 2023

Abstract
Disclosure: S.B. Cash: None. L. Magomedova: None. R. Tsai: None. C.L. Cummins: None.
Arginine and glutamate rich 1 (ARGLU1) has been shown to be a co-regulator for several nuclear receptors including ER, GR and the peroxisome proliferator-activated receptors (PPARs), which are key modulators of nutrient metabolism. We have previously reported that loss of ARGLU1 in the liver protects aged male mice against high-fat diet induced obesity and type 2 diabetes [1]. Here, we assessed the importance of ARGLU1 in lipid and carbohydrate metabolism in aged female mice and used indirect calorimetry to understand the metabolic basis of the resistance to weight gain observed with liver-specific loss of ARGLU1. Aged (11-month-old) female wildtype floxed-Arglu1 mice (Arglu1fl/fl) and liver-specific Arglu1-null mice (Arglu1LKO) were fed a high fat, high cholesterol diet (HFD, 42% calories from fat, TD.88137 Envigo) for 12-weeks (N=7-17). Female mice were housed in Promethion Metabolic Cages (Sable Systems) at room temperature for 5 days during which their food intake, water intake, physical activity, O2 consumption, and CO2 production were measured (N=5-7). Female mice were also subjected to a glucose tolerance test and insulin tolerance test (N=4-8). In agreement with our previous results in male Arglu1LKO mice [1], female Arglu1LKO mice were resistant to diet-induced obesity with final body weights compared to HFD-fed Arglu1fl/fl mice of 30.6 ± 0.9 g vs 35 ± 1 g (P&lt;0.05). Likewise, female Arglu1LKO mice were more glucose tolerant and insulin tolerant compared to HFD-fed Arglu1fl/fl mice. The metabolic cage data showed no change in food intake, locomotor activity or energy expenditure between HFD-fed Arglu1fl/fl and Arglu1LKO mice when accounting for body mass as a covariate (ANCOVA, CalR). Surprisingly, HFD-fed female Arglu1LKO mice had significantly higher water intake compared to HFD-fed Arglu1fl/fl mice (P&lt;0.02). These data support the conclusion that resistance to diet-induced obesity in Arglu1LKO mice is independent of sex. To our surprise, based on the metabolic cage data, we conclude that the mechanism by which Arglu1LKO mice are resistant to diet induced obesity is not due to enhanced energy expenditure or decreased food intake. Future studies will explore whether differential intestinal lipid absorption (independent of food intake) could account for the differences we observed in weight gain between the genotypes. [1] Magomedova, L., Tsai, R., & Cummins, C. L. (2017, April). Hepatic Ablation of the Nuclear Receptor Coactivator, ARGLU1, Is Protective Against the Development of Type 2 Diabetes and Fatty Liver in High-Fat Diet Fed Mice. In 99th Annual Meeting of the Endocrine Society. Endocrine Society.
Presentation: Saturday, June 17, 2023
FRI192 Serum Steroid Biomarkers For The Differential Diagnosis Of Adrenocortical Carcinoma (ACC) And Adrenocortical Adenoma (ACA)
Authors: van Rooyen Desmaré , Scheske Rachel , Lerario Antonio Marcondes , Rainey William E , Auchus Richard Joseph , Hammer Gary D , Else Tobias 
Published: October 2023

Abstract
Disclosure: D. van Rooyen: None. R. Scheske: None. A.M. Lerario: None. W.E. Rainey: None. R.J. Auchus: None. G.D. Hammer: None. T. Else: None.
Background: Adrenal tumors are very common, with the vast majority being benign adrenocortical adenomas (ACA). Adrenocortical carcinomas (ACC) represent only a very small proportion of adrenal tumors. Distinction between the common ACA and rare ACC relies on invasive and costly protocols which are often inconclusive. Research into the use of steroid biomarkers as a non-invasive alternative diagnostic tool has been the focus of various steroid metabolomics studies. In this study, we aimed to identify serum steroid biomarkers to distinguish ACA from ACC. Methods: This study population was comprised of 103 patient samples, including 45 (31 female) and 58 (40 female) respective samples from ACA (age 32-90) and ACC (age 16-77) patients presenting with disease at the time of sampling. No ACC patients studied had been treated with mitotane. Serum steroid levels (4 sulfates and 25 Δ4 steroids) were measured using liquid-chromatography tandem mass spectrometry (LCMS/MS) with comparisons made between steroid profiles in ACA vs ACC and between males and females within each group (ACA and ACC). Data were analyzed to obtain the geometric means with 95% CIs, and statistical significance was determined using a two-tailed Mann-Whitney test. Results: ACC patients were characterized by significantly elevated levels of pregnenolone-sulfate, 17hydroxypregnenolone-sulfate, 11-deoxycorticosterone, 17hydroxyprogesterone, and androstenedione when compared to ACA patients. In addition, steroid levels differed between male and female samples, with dehydroepiandrosterone-sulfate (p&lt;0.01), androstenediol-3-sulfate (p&lt;0.05), 11deoxycortisol (p&lt;0.0001), cortisol (p&lt;0.05) and testosterone (p&lt;0.01) significantly increased in female ACC patients when compared to male counterparts. Conclusion: Significant differences in plasma steroids were observed in ACC vs ACA patients, with more steroids altered in female patients. Serum steroid profiles, particularly steroid sulfates, might serve as an adjunct, easy to obtain diagnostic tool to differentiate ACA and ACC.
Presentation: Friday, June 16, 2023