bluuebunny/crossref_metadata_2025_split huggingface dataset:
FRI171 Can 11-Dehydrodexamethasone Improve The Salivary Dexamethasone Suppression Test?
Authors: Marshall David , Issa Basil George , Keevil Brian George 
Published: October 2023

Abstract
Disclosure: D. Marshall: None. B.G. Issa: None. B.G. Keevil: None.
Background: The 1 mg overnight dexamethasone suppression test (ONDST) is recommended as a first-line test for the investigation of Cushing Syndrome. Measurement of dexamethasone alongside cortisol in a 9am serum sample has been credited with improving diagnostic sensitivity of the test. Previous studies have also looked at the utility of salivary dexamethasone and have observed poor correlation with serum dexamethasone. Herein we introduce the concept of measuring 11-dehydrodexamethasone: a dexamethasone metabolite produced in the salivary duct through metabolism with 11β-hydroxysteroid dehydrogenase type 2 (11Β-HSD2). Methods: Paired 9am serum and saliva samples (n=44) were collected post ONDST. The saliva samples were analysed utilising a novel in-house LC-MS/MS assay which measured cortisol, cortisone, dexamethasone and 11-dehydrodexamethasone. Serum cortisol and dexamethasone had previously been analysed separately by LC-MS/MS. Results were compared and correlations were assessed using Pearson regression. Results: Serum and salivary dexamethasone exhibited poor correlation (R-squared = 0.16), supporting what has been observed previously. Salivary dexamethasone and 11-dehydrodexamethasone also showed poor correlation (R-squared = 0.19). Serum dexamethasone and salivary 11-dehydrodexamethasone yielded a positive correlation with an R-squared of 0.65. However, at higher concentrations the correlation appeared non-linear. Conclusion: Correlation of serum dexamethasone with 11-dehydrodexamethasone is a novel finding, which to the author’s knowledge, has not been previously established/investigated. It is hypothesized that the non-linear correlation might be due to saturation kinetics of the enzyme 11Β-HSD2 in the salivary duct, a similar relationship was observed when comparison of salivary cortisol and cortisone was assessed. The development of this LC-MS/MS assay for salivary measurement of 11-dehydrodexamethasone opens the possibility for a fully remote DST, whereby patients could administer the drug and take a 9am saliva sample. Further sample comparisons are required to develop a 11-dehydrodexamethasone cut-off which equates to a serum dexamethasone concentration of 3.3 nmol/L.
Presentation: Friday, June 16, 2023
FRI174 Spectrum Of Presentation Of Adrenal Incidentalomas : Is The Distribution Changing? Experience From A Tertiary Care Centre Of Eastern India
Authors: Mishra Ipsita , Vivek Marrapu Venkata , Baliarsinha Anoj Kumar 
Published: October 2023

Abstract
Disclosure: I. Mishra: None. M.V. Vivek: None. A.K. Baliarsinha: None.
Spectrum of presentation of adrenal incidentalomas : Is the distribution changing? Experience from a tertiary care centre of Eastern India Abstract: Incidentally discovered adrenal masses have become a common clinical problem. An adrenal mass is uncovered in up to 4% -10% of patients imaged for non-adrenal disease. Incidentalomas are uncommon in patients younger than 30 years of age but increase in frequency with age; more frequently in females, especially in the sixth and seventh decades. Functioning tumors with a clear clinical phenotype (pheochromocytomas and those secreting cortisol, aldosterone, or sex steroids) and carcinomas account for around 28%- 32% of all adrenal incidentalomas. We reviewed last three year records of all the patients with the diagnosis of adrenal incidentaloma presenting to our institute and data regarding the clinical profile and outcomes of all the patients were analysed. The data obtained was entered into Microsoft Excel Worksheet and analysed using Statistical Package for Social Sciences (SPSS, IBM Corp. Released 2020.IBM SPSS Statistics for Windows, Version 20.0.Armonk,NY: IBM Corp.).Total 44 patients of adrenal incidentalomas were reviewed. In our case series, incidentalomas frequency were found to be increasing with age, most common in the 5th and 6th decades with equal frequency between male and females. Functioning tumours accounted for 54.5%(n=24), non functioning in 38.6%(n=17) and adrenal deficiciency in 6.8%(n=3)respectively. Most commonly encountered tumour was Pheochromocytoma(n=14,31.8%)followed by benign adenoma(n=10, 22.7%), adrenalcarcinoma (n=7,15.9%), myelolipoma(n=5,11.3%), aldosterone producing adenoma (n=3,6.8%), adrenal haemorrhage (n=1,2.2%), angiomyolipoma (n=1,2.2%), adrenal cyst (n=1,2.2%), and adrenal granuloma (n=2,4.5%) respectively. Amongst benign adenomas 40%(n=4) were functional( cortisol excess) and 60%(n=6) were non functional.Amongst adrenal carcinomas 42.8% (n=3) were functional and 57.2%(n=4) were non functional. Adrenal haemorrhage and adrenal granulomas had features of adrenal deficiency. The present work demonstrates that the distribution of adrenal incidentalomas is equal in both males and females, with functioning tumour Pheochromocytoma being more common than other variants. Hence the importance of complete biochemical investigation of adrenal incidentalomas is warranted. The probable changing pattern in the distribution of etiologies of adrenal incidentolomas can be further elucidated by analyzing data of a large cohort of patients with adrenal incidentolomas. Reference: Mansmann G, Lau J, Balk E, Rothberg M, Miyachi Y, Bornstein SR. The clinically inapparent adrenal mass: update in diagnosis and management. Endocr Rev. 2004 Apr;25(2):309-40. doi: 10.1210/er.2002-0031. PMID: 15082524.
Presentation: Friday, June 16, 2023
FRI425 BIUXX
Authors: Mendonça Macedo Daniel , Casanova João , Guerra Adalgisa , Francisco Rosário 
Published: October 2023

Abstract
Disclosure: D.M. Macedo: None. J. Casanova: None. A. Guerra: None. R. Francisco: None.
Title: Hyperandrogenism due to post-menopausal ovarian stromal hyperplasia. Introduction: Severe and rapidly progressive installation of hyperandrogenism in women after menopause should be carefully investigated. Stromal hyperplasia of the ovaries, which etiology is not completely understood, is a rare and benign cause of excess androgen production. In addition to hyperandrogenism, it is usually associated with hyperinsulinism, obesity, metabolic syndrome and acanthosis nigricans. Clinical case: A 60 year old overweight female patient with a history of type 2 diabetes mellitus, dyslipidemia, polycystic ovarian syndrome and menopause at 53 years old, reported the recent onset of hirsutism on the face and back, alopecia and increased libido. The laboratory evaluation revealed: total testosterone 89.6ng/dL (&lt;35.9), free testosterone 5.13pg/mL (&lt;4.2), sex hormone-binding globulin 22.9nmol/L (18-144), LH 21.3mIU/mL (14-52), FSH 27.4mIU/mL (26-135) and E2 &lt;19.0pg/mL. The remaining androgens did not show alterations and hypercortisolism was excluded. Abdominal and pelvic ultrasound was performed and revealed enlarged ovaries with homogeneous echotexture and reduced echogenicity. A pelvic MRI was also performed and showed solid lesions in both ovaries, with moderate T1 and T2 hypointensity, suspicious of bilateral androgen-producing ovarian tumors. After multidisciplinary discussion, the patient underwent total hysterectomy with bilateral oophorectomy. Histopathology was compatible with bilateral stromal hyperplasia of the ovaries. Three months after surgery, the patient presented with a reduction of the facial and back hirsutism and slight improvement in alopecia. The laboratorial evaluation revealed a marked reduction in total testosterone (18.0ng/dL) and free testosterone (1.07pg/mL). Conclusions: New-onset hyperandrogenism in postmenopausal women is very uncommon and a diagnostic challenge. After excluding iatrogenic causes, hypercortisolism or adrenal tumor, the differential diagnosis between virilizing ovarian tumor and bilateral stromal hyperplasia is difficult to establish. Although the imaging distinction is possible, the definitive diagnosis is histopathologic and total hysterectomy with bilateral oophorectomy should be performed. In this case, although MRI was suspicious of bilateral ovarian tumors, the definitive diagnosis was stromal hyperplasia of the ovaries. Three months after surgery, the patient presented marked clinical and biochemical improvement.
Presentation Date: Friday, June 16, 2023
SAT004 A Novel Therapeutic Target Of Mitochondrial Protein To Prevent Steroid-induced Muscle Atrophy Through Regulation Of Proteolysis And Myogenesis
Authors: Kim Min-Ji , Singh Sinam Ibotombi , Kim Saehan , Siddique Zerwa , Hee Kwon So , Jeon Jae-Han , Lee In-Kyu 
Published: October 2023

Abstract
Disclosure: M. Kim: None. I.S. Sinam: None. S. Kim: None. Z. Siddique: None. S. Kwon: None. J. Jeon: None. I. Lee: None.
Objectives: Muscle atrophy, defined as a progressive loss of muscle mass and function induced by various etiology. Steroids is well-known muscle atrophy-inducible drug by enhancing of muscle catabolism and proteolysis. Pyruvate dehydrogenase kinase (PDK), a mitochondrial protein that inhibits the pyruvate dehydrogenase complex, is highly upregulated in metabolic diseases, especially pathologic muscle conditions associated with enhanced muscle proteolysis and aberrant myogenesis. Here, we investigated the role of PDK on proteolysis and myogenesis in steroid-induced muscle atrophy. Methods & Materials: Human skeletal (gluteus-maximus) muscles obtained from patients who underwent hip replacement surgery according to steroid administration were used for evaluated at the molecular level by expression of key genes and proteins involved in myogenesis. Steroid-induced muscle atrophy models were developed administered with glucocorticoid (GC) 25 mg/kg, intraperitoneally, for 10 days. Muscle dysfunction was studied in vivo in wild-type and PDK4 knockout mice treated with GC. We used C2C12 myotubes treated with GC for 24 h for in vitro study. Results: The expression of PDK4, as well as muscle-specific E3 ligases: muscle RING finger 1(MuRF1) and muscle atrophy F box (MAFbx), are significantly increased in skeletal muscle of steroid-user. In mouse model of steroid-induced muscle atrophy, expression of PDK4 and MAFbx are also upregulated, whereas knockdown of PDK4 reduces MAFbx expression and ameliorated steroid-induced muscle atrophy; increased muscle strength and muscle fibers. In C2C12 myotubes, knockdown of PDK4 was also associated with reduction of myogenin induction and MAFbx expression. To find out the mechanism, we used coimmunoprecipitation and liquid chromatography-mass spectrometry analysis and found that myogenin is novel substrate of PDK4. Mechanistically, this result suggests that PDK4 promotes MAFbx recruitment to catalyze muscle atrophy-induced MYOG ubiquitination and degradation. Conclusion: Taken together, the results suggest that PDK4-dependent activation of the ubiquitin degradation pathway appears to underly the promotion of muscle atrophy by directly targeting the muscle-specific MAFbx. Therefore, the inhibition of PDK4 represents as a novel therapeutic target to alleviate steroid-induced muscle atrophy.
Presentation: Saturday, June 17, 2023
OR33-05 Glucocorticoids Instigate Transcriptional Waves To Maintain Temporally Organized Fuel Production During Fasting
Authors: Goldberg Dana , Goldstein Ido 
Published: October 2023

Abstract
Disclosure: D. Goldberg: None. I. Goldstein: None.
Most animals are well equipped to endure prolonged fasting periods by converting energy stores into available biochemical fuel. This is achieved by the hepatic production of two fuel types supplying other tissues: glucose (originating from gluconeogenesis or glycogen breakdown) and ketone bodies (produced via ketogenesis). The adaptive response to fasting involves several hormones that together maintain homeostasis in the face of energy shortage. Glucocorticoids (GCs) are principal hormonal cues regulating the transcriptional response to fasting and were shown to augment both glucose and ketone production. We aimed to decipher how GCs control both the gluconeogenic and ketogenic programs. We profiled the transcriptional response and genome-wide enhancer dynamics of primary mouse hepatocytes to GC treatment. In addition to the induction of the expected fasting metabolism genes, we were surprised to find that GCs induced various genes encoding transcription factors (TFs). In fact, 13% of GC-induced genes were TFs, many of which were similarly induced in livers of fasted mice. Perturbation experiments and chromatin immunoprecipitation sequencing (ChIP-seq) showed that GCs induced these TFs via the glucocorticoid receptor (GR) which bound to DNA regulatory elements of the genes. We found that GCs induce two groups of TFs. The first group are TFs that maintain the early gluconeogenic fasting response. Indeed, knock-down of GC-induced TFs (C/EBPβ, MAFB or KLF15) reduced gluconeogenic gene expression. The second group are TFs which dictate a secondary transcriptional wave serving to produce fuel in prolonged fasting. Notably, GCs Initiate a TF cascade in which GR induces the expression of the Ppara gene, leading to increased PPARα protein. Upon subsequent ligand stimulation of PPARα, a ketogenic gene program is activated. We show that a dual treatment of GCs with a PPARα agonist leads to synergistic induction of ketogenic genes and that this induction is dependent on protein synthesis. We have analyzed the transcriptomic result of this TF cascade and found that dozens of ketogenic genes are synergistically induced. Genome-wide analysis of enhancer dynamics revealed numerous enhancers activated by the GR-PPARα cascade. These enhancers are proximal to ketogenic genes, are enriched for the PPARα binding motif and show increased PPARα binding as profiled by ChIP-seq. Taken together, our work reveals a GC-induced program whereby the expression of TFs increases during fasting, serving to rapidly support gluconeogenic capacity in short-term fasting and initiate a delayed ketogenic program brought about in prolonged fasting. These two regulatory modules may dictate the well-known temporal organization of the fasting response whereby gluconeogenesis predominates in early fasting but is gradually replaced by ketogenesis as fasting persists.
Presentation: Sunday, June 18, 2023
THU654 The Use Of Plasmapheresis In A Severe Case Of Amiodarone Induced Thyrotoxicosis
Authors: Moazezi Tina , Koh Chung-Kay 
Published: October 2023

Abstract
Disclosure: T. Moazezi: None. C. Koh: None.
Thyroid storm is an endocrine emergency that results in a hypermetabolic state due to excess levels of circulating thyroid hormone and carries a high mortality rate. Therapeutic plasma exchange (TPE) can be used in cases of thyrotoxicosis refractory to medical management to achieve hemodynamic and clinical stability. We present a case of a 74-year-old male with severe amiodarone-induced thyrotoxicosis who presented with altered mentation and ultimately required intubation and intensive care for management of thyroid storm. Standard medical therapy for treatment was initiated immediately with antithyroid drugs, beta blockers, glucocorticoids, potassium iodide solution, and cholestyramine. However, the patient remained unresponsive and intubated with worsening biochemical parameters with increased total T3 levels and sustained elevated levels of free T4 even after five days of maximal medical therapy. Due to the lack of a clinical and biochemical response to conventional medical therapy, the patient was started on plasmapheresis and underwent a total of seven cycles of plasmapheresis over a period of ten days. He significantly improved with TPE and was successfully bridged to a total thyroidectomy, which was completed without complications. Our case demonstrated a decrease in total T3 concentration of roughly 45% after one session of plasmapheresis and roughly 76% with seven sessions of plasmapheresis by the time of thyroidectomy. Free T4 levels remained elevated above reference range until the day after the fifth session of plasmapheresis. This case is important because the literature surrounding the use of TPE in thyroid storm is sparse, and there have only been case reports and retrospective studies published on the subject. Ultimately, while TPE is not conventionally used as part of routine treatment for thyroid storm, endocrinologists should keep this tool at the forefront of their management strategies to deliver quicker treatment to critically ill patients and prevent complications of thyroid storm. Nonetheless, more research is needed to delineate concrete guidelines and specific protocols for use of TPE in thyroid storm.
Presentation: Thursday, June 15, 2023
THU662 Poor Response To Medical Treatment In A Patient With Amiodarone-induced Hyperthyroidism: A Therapeutic Dilemma
Authors: Ahmed Asiri Alanood , Sulimani Riad , Alkhidady Wijdan 
Published: October 2023

Abstract
Disclosure: A.A. Asiri: None. R. Sulimani: None. W. Alkhidady: None.
Introduction: Hyperthyroidism is a well-known complication of amiodarone therapy. An incidence of 3% is reported in North America1, and even higher percentages in amiodarone deplete areas of about 10%.2 Treatment of amiodarone-induced hyperthyroidism (AIH) is challenging, it depends on various factors including the type of AIH, dependence of the patient’s cardiac condition on amiodarone therapy, other complications or comorbidities of the patient such as hepatic injury or dysfunction and the response of the patient to antithyroid therapy. Clinical Case: We present a case of a 32-year-old lady with a therapeutic dilemma in treating type I AIH, resistant to medical therapy. Our patient first had acquired COVID-19-induced myocarditis in 2020 and subsequently developed sustained ventricular tachycardia and was treated with amiodarone and placed on an implantable cardioverter-defibrillators (ICD) device. Two years later in 2022, the patient developed type I amiodarone-induced hyperthyroidism, with a free T4 reaching 100 pmol/L (Reference range 15-22 pmol/L) and complicated with transaminitis. She was unresponsive to medical therapy including: anti-thyroid medications, IV high-dose hydrocortisone, potassium iodide drops, and cholestyramine. She also developed adverse events with two of the antithyroid medications, Carbimazole and PTU; where she had elevated liver enzymes more than five time upper limit of normal and a generalized skin rash with PTU. Plasmapheresis was not an option as some of her cardiac medications drug levels could be affected. She underwent an emergent total thyroidectomy with dual beta blockade (Propranolol and Sotalol) successfully without any post op events. Her T4 level normalized within 8 days of her operation and her liver enzymes normalized within 2 weeks. Conclusion: We report the success and safety of surgical management in a patient with a cardiac arrhythmia and uncontrolled severe amiodarone-induced hyperthyroidism in the setting of adequate beta blockade. References: 1. Goldschlager N, Epstein AE, Naccarelli G, et al. Practical guidelines for clinicians who treat patients with amiodarone. Practice Guidelines Subcommittee, North American Society of Pacing and Electrophysiology. Arch Intern Med. 2000;160:1741–8. 2. Martino E, Aghini-Lombardi F, Mariotti S, et al. Environmental iodine intake and thyroid dysfunction during chronic amiodarone therapy. Ann Intern Med. 1984;101:28–34.
Presentation: Thursday, June 15, 2023
FRI186 Differences Of Body Composition And Comorbidities In Patients With Primary Aldosteronism According To Sex And Subtypes
Authors: Park Seung Shin , Ahn Chang Ho , Seo Sookkyeong , Kim Sang Wan , Yoon Ji Won , Kim Jung Hee 
Published: October 2023

Abstract
Disclosure: S. Park: None. C. Ahn: None. S. Seo: None. S. Kim: None. J. Yoon: None. J. Kim: None.
Background: Primary aldosteronism (PA) is associated with metabolic risks such as diabetes and obesity. However, controversy exists as to which subtype of PA has a higher metabolic risk between idiopathic hyperaldosteronism (IHA) and aldosterone-producing adenoma (APA). We aimed to assess the body composition of two PA subtypes according to sex and evaluate autonomous cortisol secretion (ACS) and its contribution to comorbidities. Methods: A total of 400 patients with PA and 1:10 age- and sex-matched healthy controls (n=4,000) were enrolled. Clinical and biochemical data were reveiwed. The skeletal muscle area (SMA), subcutaneous fat area, and visceral fat area (VFA) at the third lumbar spine were calculated using abdominal computed tomography-based body composition analysis. Results: In both sexes, a higher body mass index (BMI) was observed in patients with IHA than in those with APA (P&lt;0.001 in men and P=0.049 in women). Hemoglobin A1c (HbA1c) level and the prevalence of diabetes were higher in female patients with IHA than in those with APA (6.0±0.9 vs. 5.6±0.5%, P=0.005 for HbA1c; 19.0% vs. 6.8%, P=0.016 for diabetes). The VFA/BMI ratio was significantly higher in patients with IHA than in patients with APA (5.77±2.69 vs. 4.56±2.35, P&lt;0.001 in men; 4.03±2.58 vs. 2.53±2.05, P&lt;0.001 in women). In subgroup analysis, decreased SMA was observed in PA patients with ACS compared with those without ACS. Compared with age- and sex-matched healthy controls, all patients with IHA and female patients with APA showed significantly higher VFA and VFA/BMI. Conclusion: Patients with IHA were more obese and had higher visercal adiposity than those with APA. This metabolically unfavorable body composition may contribute to a higher metabolic risk in patients with IHA. The role of adipose tissue in pathogenesis of IHA remains to be elucidated.
Presentation: Friday, June 16, 2023