bluuebunny/crossref_metadata_2025_split huggingface dataset:
RF35 | PSAT257 The Severity of Subacute Thyroiditis Depends on Its Causative Agent
Authors: Brancatella Alessandro , Viola Nicola , Sgrò Daniele , Casula Mauro , Santini Ferruccio , Latrofa Prof Francesco 
Published: November 2022

Abstract
We retrospectively evaluated 402 patients referred to of the University Hospital of Pisa because of a SAT from January 2011 to December 2020. Neck pain was present in all patients; in 92 patients it was bilateral. A previous symptomatic involvement of the upper airways was reported by 97 patients. 32 patients did not receive pharmacological treatments, 16 were treated with non-steroidal anti-inflammatory drugs (NSAIDs) and 354 with glucocorticoids; the most common initial dose of prednisone was 25 mg (in 286 patients); the majority (n. 277 patients) were treated for 90 days. 88 patients experienced permanent hypothyroidism. Free thyroxine (FT4) values ​​correlated with those of the C reactive protein (CRP), erythrocyte sedimentation rate (ESR) and thyroglobulin (Tg) ​​(p &lt;0.001 for all). Tg values ​​correlated with the severity of thyrotoxicosis and the levels of inflammatory markers. Values ​​of FT4, Tg, ESR and CRP in patients experiencing hypothyroidism were higher compared to those observed in patients who remained euthyroid after SAT. Values ​​of FT4, Tg, and CRP and incidence of hypothyroidism were higher in patients with bilateral neck pain compared to those experiencing unilateral neck pain. Similar differences were observed comparing patients who had respiratory symptoms prior to SAT to those who did not. Glucocorticoid treatment was associated with a shorter duration of neck pain (14 days) compared to those treated with NSAIDs (28 days) and those left untreated (28 days) (p &lt;0.001). The initial dose of 25 mg (lower than that recommended by the recent guidelines of the American Thyroid Association - 40 mg/day) was sufficient to control the pain. The annual incidence of SAT was similar throughout the entire period of observation. The third quarter of the year was characterized by the highest number of cases compared to the other quarters in all years except 2012 and 2015, when there was a higher incidence in the first quarter, and in 2020, when most of the SAT cases occurred in the second and fourth quarters. In these peculiar periods thyrotoxicosis and inflammatory markers were higher and permanent hypothyroidism more common. The clusters of SAT in 2020 occurred within a month of the Covid-19 waves, while in the winter seasons 2011-12 and 2014-15 in Italy there was a higher incidence of the influenza virus A.H3N2. In conclusion, the severity of SAT depends upon the causative virus.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 1:06 p.m. - 1:11 p.m.
OR29-2 Comprehensive Steroid and Global Metabolome Analysis by Mass Spectrometry and Machine Learning to Understand Metabolic Risk in Benign Adrenal Tumours With Mild Autonomous Cortisol Secretion
Authors: Prete Alessandro 
Published: November 2022

Abstract

Background
Benign adrenal tumours are found in 3-10% of adults and can be non-functioning (NFAT) or associated with adrenal hormone excess. Analysing 1305 prospectively recruited patients with benign adrenal tumours, we recently demonstrated that 45% of patients had mild autonomous cortisol secretion (MACS), i.e. biochemical evidence of cortisol excess without distinct signs of Cushing syndrome (CS). We found that MACS increases the prevalence and severity of type 2 diabetes and hypertension and primarily affects women (Ann Int Med. 2022 Doi: 10.7326/M21-1737). Here we analysed the cohort's steroid metabolome and non-targeted global metabolome to reveal underlying metabolic processes.

Methods
We analysed 24-h urine samples from 1305 patients (649 NFAT, 591 MACS, 65 CS) using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) multi-steroid profiling assay. In addition, we performed non-targeted serum metabolome analysis in a representative sub-cohort (104 NFAT, 140 MACS, 47 CS) employing two complementary LC-MS assays, HILIC and C18-lipidomics. The steroid and global metabolome data were analysed by two supervised machine learning approaches, generalized matrix learning vector quantization and ordinal regression, to identify the most relevant metabolic changes.

Findings
Urine steroid metabolome analysis revealed an increase in glucocorticoid excretion from NFAT over MACS to CS, whereas androgen excretion decreased. Increased glucocorticoid metabolites were also the major differentiators between MACS patients with and without type 2 diabetes and hypertension, respectively. Lipidome analysis by machine learning identified glycerophospholipids, lysoglycerophospholipids, triacylglycerides, ceramides, sphingolipids, and acylcarnitines as the most relevant metabolite classes exhibiting gradually progressive changes with increasing cortisol excess (NFATInterpretation: We show a gradual change in the lipidome towards lipotoxicity with increasing cortisol excess. MACS patients with type 2 diabetes and hypertension had higher glucocorticoid output than other MACS patients, suggestive of a causative contribution of cortisol excess to their increased cardiometabolic burden. Observed changes may hold promise for risk stratification in MACS, a highly relevant and previously largely overlooked metabolic risk condition.
Presentation: Tuesday, June 14, 2022 10:00 a.m. - 10:15 a.m.
RF35 | PSAT263 Efficacy of Teprotumumab for Thyroid Eye Disease in Hypothyroid Patients
Authors: Smith Terry J , Choudhary Chitra , Bhattacharya Rajib J , Holt Robert 
Published: November 2022

Abstract

Background
Thyroid eye disease (TED) is an autoimmune inflammatory process that can lead to eye-bulging (proptosis) and double-vision (diplopia). Teprotumumab, an insulin-like growth factor-I receptor inhibitory antibody, has demonstrated improvements in proptosis and diplopia. Thyroid dysregulation has been linked to increased TED severity1 and may trigger TED flares,2 thus, treatment efficacy of hypo- or hyperthyroid patients with teprotumumab is of interest. This post-hoc analysis of pooled phase 2 and 3 trial data3 examined teprotumumab efficacy in patients with low baseline FT4 levels.

Methods
Patients from Phase 2 and 3 teprotumumab trials with low baseline FT4 (≤11.5 pmol/L) were included. Patients received teprotumumab or placebo for 24 weeks (8 infusions). Proportions of proptosis (≥2 mm reduction), clinical activity score (CAS, 7-point scale, CAS 0 or 1), and diplopia (≥1 Gorman diplopia scale grade improvement) responders were determined at Week 24. Additionally, the Graves’ ophthalmopathy- quality of life (GO-QOL) questionnaire measured quality of life.

Results
Nine teprotumumab-treated patients (6 female [67%], 54.6±10.7 years old) and 8 (6 female [75%], 50.0±14.9 years old) patients made up the teprotumumab and placebo groups, respectively. Mean baseline proptosis in the study eye was 25.1±3.9 mm in teprotumumab patients and 21.9±3.8 mm in placebo patients. At Week 24, 78% (7/9) teprotumumab-treated vs. 38% (3/8) placebo-treated patients were proptosis responders. Further, mean proptosis reduction was 2.9±0.6 mm with teprotumumab vs. 1.2±0.7 mm with placebo. 67% (6/9) vs. 13% (1/8) of teprotumumab vs. placebo patients were CAS responders at Week 24. Of those with baseline diplopia, 86% (6/7) vs. 40% (2/5) were diplopia responders, respectively. In the teprotumumab group, the least square mean change from baseline in overall GO-QOL score improved by 23.4±6.4, which was a large clinical change. In contrast, the placebo group improved by 6.9±7.4.

Conclusions
After 24 weeks, responses to teprotumumab were greater versus placebo in patients with low baseline FT4 in two clinical trials. Responses in these mildly hypothyroid patients in this study were consistent with those in the overall pooled population as follows: Proptosis response: 78% and 77%, respectively; mean proptosis reduction: 2.9 mm and 3.14 mm; diplopia response 86% and 70%; CAS response 67% and 62%, respectively. Thus, pretreatment hypothyroid status does not affect clinical responses to teprotumumab in TED.

References
Bartalena L. Best Pract Res Clin Endocrinol Metab 2012; 26: 371-379. Patel P, et al. Ophthalmic Plast Reconstr Surg 2015; 31(6): 445-448. Kahaly et al. Lancet Diabetes and Endocrinol 2021; 9(6): 360-372
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 12:26 p.m. - 12:41 p.m.
LBODP107 Real World Performance Of The Afirma Xpression Atlas In Bethesda III And IV Thyroid Nodules. A Private Practice Experience
Authors: Ortega Dayron , Mhaskar Rahul , Pinero-Pilona Antonio 
Published: November 2022

Abstract
Fine Needle Aspiration (FNA) has modified all methods for diagnosing thyroid cancer; and in conjunction with the Bethesda System and the genomic sequencing classifiers (GSC), clinicians can objectively identify the risk of malignancy of thyroid nodules prior to surgical interventions. To further characterize these thyroid nodules, the Afirma Xpression Atlas (XA), a form of The Cancer Genome Atlas, was created and launched in May 2018. In November 2019 and March 2020, the Afirma XA panel was expanded to include 905 genomic variants and 235 fusions from 593 genes. Post-validations studies for the Afirma XA have been developed in well recognized large academic centers with unclear applicability or extrapolation to small endocrinology centers, which may have a different patient's population and thyroid cancer prevalence. This study was designed to analyze and objectively measure the performance of the Afirma XA in Bethesda III and IV thyroid nodules classified as GSC suspicious in our private endocrinology practice. We conducted a retrospective cohort analysis comparing all indeterminate and GCS suspicious nodules with their respective final surgical pathology results between June 2018 to October 2021. Forty-two thyroid nodules were studied, and the Bethesda III category was the predominant cytopathology discovered, representing 69% of all indeterminate nodules. Afirma XA was able to identify genomic alterations in only 40% of all included nodules. We found a 35% (CI: 15%-59%) sensitivity, 54% (CI: 32%-75%) specificity, 47% (CI: 35%-59%) of negative predictive value, and 41% (CI: 25%-60%) of positive predictive value when a 47% of cancer prevalence is applied. Based on this data, we conclude that Afirma XA cannot be used exclusively as a rule-out or a ruled-in test in GSC suspicious, Bethesda category III and IV thyroid nodules in small private endocrinology practices.
Presentation: No date and time listed
LBSUN255 Recurrent Hypoglycemia In A Patient With Beckwith-Wiedemann Syndrome Secondary To Insulinoma
Authors: Akcan Tugce , Shariff Julia Rose R 
Published: November 2022

Abstract

Background
Beckwith-Wiedemann Syndrome (BWS) is a genetic condition characterized by macrosomia, childhood tumors, and neonatal hypoglycemia and hyperinsulinemia. The cause of this hyperinsulinemic hypoglycemia is unknown, but it is believed to be caused by chromosomal mutations at 11p15.5 and genes encoding beta-cell ATP-sensitive potassium channels. In our case, we have an adult patient with a history of BWS who is experiencing hypoglycemia due to a different cause: an insulinoma. This is the first report of insulinoma in an adult with this syndrome.

Case Presentation
The patient is a 53-year-old male with a history of BWS. Due to shortness of breath, the patient was admitted and discovered to have new and severe systolic heart failure. Patient was started on beta blockers by cardiology. During his hospital stay, he developed hypoglycemia, with glucose levels in the 20s. As the hypoglycemia became more frequent, he was placed on dextrose. Dextrose was turned off to obtain hypoglycemia labs such as insulin, proinsulin, C-peptide, and hydroxybutyrate, but his blood sugar never fell below 80mg/dL. His hypoglycemia was attributed to a beta-blocker side effect or rebound from a dextrose infusion. He was discharged from hospital and sent home. After a loss of consciousness episode at home two weeks later, the patient was readmitted. When he arrived at the emergency department, his blood glucose level was 18mg/dL, and he was given dextrose. After being admitted to the hospital, dextrose was again discontinued, and blood glucose levels dropped to 45mg/dL on serum testing. At the time, C-peptide levels were elevated at 25.7ng/mL, B-hydroxybutyrate levels were 0. 06mmol/L, and insulin levels were above 700uIU/mL. At the time, the choice was between insulin autoantibody syndrome and insulinoma. The patient then had an abdominal computed tomography scan, which revealed a 3.7×2.9cm neuroendocrine tumor in the distal pancreas. Changes in the liver were found to be alarming for metastases, thus an MRI was conducted to confirm this. There was no sign of liver metastases on the MRI. In the interim, the patient was started on subcutaneous octreotide 50 mcg twice daily. Given the patient's underlying heart problems, diazoxide was not pursued. Octreotide was increased to 100mcg subcutaneously three times daily throughout his hospital stay, and he was discharged home with a continuous glucose monitor and intentions to operate later that month.

Conclusions
Although BWS has been linked to a higher risk of childhood malignancies, it's uncertain whether BWS could be a predisposing factor for the development of insulinoma. Because this is such a rare disorder, there is a paucity of information on predisposition or risk factors. However, the link between macrosomia and tumor growth in BWS suggests that there may be a predisposition to insulinoma that has yet to be investigated.
Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.
ODP548 Fatty acid metabolism-related factors in breast and endometrial cancers
Authors: Miki Yasuhiro , Naraoka Hiyori , Iwabuchi Erina , Sato Ai , Takagi Kiyoshi , Sasano Hironobu , Ishida Takanori , Suzuki Takashi , Ito Kiyoshi 
Published: November 2022

Abstract
Obesity is a well-known risk factor for gynecological malignant tumors such as breast and endometrial cancers. In the cancer microenvironment, the interaction between cancer cells and adipocytes reportedly contributes to the malignant behavior of cancer. In breast cancer, the fatty acid transporter CD36, also known as fatty acid translocase, has been shown to mediate fatty acid uptake into cancer cells and activate signaling pathways that promote tumor progression. Fatty acids are speculated to play important roles in breast and endometrial cancer; however, detailed mechanisms remain unclear. In the present study, we first examined the expression of CD36 and acyl-CoA dehydrogenase long chain (ACADL) in breast (30 cases) and endometrial (35 cases) cancer tissues using immunohistochemistry. CD36 is a membrane protein that transports long-chain fatty acids, and ACADL catalyzes the initial β-oxidation reaction. We detected no correlation between the CD36 status and clinicopathological factors, including the estrogen receptor status in breast cancer tissues. CD36 status revealed a significant positive correlation with lymph node metastasis in endometrial cancer. There was no immunoreactivity for CD36 in morphologically normal mammary glands. Otherwise, CD36 immunoreactivity was detected in the endometrial glandular cells. In both cancers, ACADL expression did not correlate with any clinicopathological factor. Both CD36 and ACADL showed higher positivity rates in endometrial cancer than in breast cancer. In addition, the effect of lipid addition on cell proliferation was examined using breast (T-47D) and endometrial (AN3CA) cancer cell lines exhibiting equivalent CD36 levels. Lipid (Refeed JNS) was obtained from Remembrane, Italy. Lipid addition promoted cell proliferation in both T-47D and AN3CA cells. Intracellular fatty acid β-oxidation (FAO) was visualized using FAOBlue (Funakoshi, Tokyo, Japan), a nonanoic acid (C9) derivative of coumarin, a blue fluorescence dye. Following FAOBlue decomposition in the fourth FAO cycle, coumarin is released from propionic acid, and released coumarin shows strong blue fluorescence excited at 405 nm. T-47D cells showed blue fluorescence in the lipid-supplemented medium, indicating β-oxidative activity. Conversely, AN3CA cells exhibited weak fluorescence under the same conditions. It can be postulated that intracellular lipid uptake and subsequent β-oxidation are mediated via a specific pathway in breast and endometrial cancers. Lipid-mediated effects differ between breast and endometrial cancers, and further investigations are needed to elucidate intracellular signals mediating these effects.
Presentation: No date and time listed
ODP549 From Positive to Negative, a Histidine to Aspartic Acid Change in SDHB is Breaking Bad in Cardiac Paraganglioma
Authors: Harbuz-Miller Inga , Carafone Lindsay , Archibald William , Victor Adrienne 
Published: November 2022

Abstract

Introduction
Cardiac paraganglioma (PGL) are extremely rare tumors. They are derived from chromaffin cells of the neural crest. Up to 40% of PGL foster germline mutations, while some bear somatic mutations. Here, we describe a sympathetic paraganglioma presenting as a cardiac mass, found to have a novel mutation of SDHB.

Clinical Case
A 64-year-old man with uncontrolled type 2 diabetes mellitus presented with chest pain, progressive fatigue and unintentional weight loss. An echocardiogram demonstrated a right atrial mass. Cardiac magnetic resonance imaging showed a 6.9×5.8×4.9 cm mass in the lateral right atrial wall and right atrioventricular groove, encasing the right coronary artery. Surgical removal was attempted and aborted due to involvement of the tricuspid valve. Incisional biopsy was consistent with paraganglioma. Plasma free normetanephrine was elevated at 1.87 nmol/L (ULN 0.89 nmol/L) and plasma free metanephrine was normal at 0.14 nmol/L (ULN 0.49 nmol/L). Chromogranin A was elevated at 1,038 ng/mL (normal &lt;93 ng/mL). Iodine-123 meta-iodobenzylguanidine scan demonstrated increased and persistent MIBG activity of the cardiac mass. Ga-68 DOTATATE PET/CT scan revealed DOTATATE avidity of the mass without evidence of distant metastatic disease. Next-generation sequencing of the specimen revealed a variant of unknown significance of SDHB H244D at a variant allele frequency of 62.2%. This missense mutation replaces the histidine to aspartic acid, resulting in changes in charge of the side chain from positive to negative. Systemic treatment with tyrosine kinase inhibitor (TKI) cabozantinib was initiated due to unresectable tumor. Three month surveillance with Ga-68 PET/CT DOTATATE scan revealed partial response to treatment. Chromogranin A and normetanephrine are trending down, suggesting biochemical response.

Conclusion
Cardiac PGL are rare and SDHB mutations are associated with worse prognosis. This is the first case of a missense mutation of SDHB at H244D, which may be clinically relevant in characterizing cardiac paraganglioma and potential response to TKI therapy.
Presentation: No date and time listed
ODP555 In-vitro Combo Treatments of Human Melanoma (1205Lu, WM238) Cell Lines with Curcumin, Vitamins and Steroids
Authors: Ramaraj Pandurangan , Chiu Albert 
Published: November 2022

Abstract

Previous combo treatment experiments on BLM human melanoma cell line identified two combos vit-A + RU-486 and Cur+P+RU as the best combinations to decrease melanoma cell growth as well as IL-8 secretion in -vitro. In order to confirm this finding, experiments were repeated on two other human melanoma cell lines 1205Lu and WM238. Initial single or solo compound treatment on 1205Lu cells resulted in cell growth in the range of 37–59% compared to untreated control 1205Lu cell growth at 100%. A double combo treatment with combinations such as D+P, D+RU, A+P, A+RU, A+D resulted in cell growth in the range of 17 to 37% on the 1205Lu cell line. Whereas on WM238 cell line resulted in cell growth in between 18–22%. A triple combo such as combinations of three compounds (Cur+P+RU, Cur+A+P, Cur+D+RU) resulted in cell growth in the range of 19-30% on 1205Lu cells, whereas on WM238 cells resulted in between 19–20% cell growth. Elisarray of the supernatants from the combos which showed a significant decrease in cell growth revealed the regulation only in IL-8 secretion. IL-8 secretion in the supernatants of combos treated with A+RU and Cur+P+RU was17.5 and 8. 0 pg/ml respectively on the 1205Lu cell line. Whereas, IL-8 secretion was 0.515 and 0.926 pg/ml respectively in the supernatants of A+RU and Cur+P+RU combo treatments on the WM238 cell line.

Conclusion
Based on cell growth, Elisarray and IL-8 quantitation, two combos A+RU and Cur+P+RU also fared well on the two other cell lines 1205Lu and WM238.
Presentation: No date and time listed
ODP556 Krüppel-like factor 9 (KLF9) Links Hormone Dysregulation and Circadian Disruption to Breast Cancer Pathogenesis
Authors: Ybañez Weand , Bagamasbad Pia 
Published: November 2022

Abstract
Circadian disruption is an emerging driver of breast cancer (BCa), with epidemiological studies linking shift work, chronic jet lag, and undue exposure to light at night to increased cancer risk. Indeed, several clock genes participate in the gating of mitotic entry, regulation of DNA damage response, metabolite sensing, and epithelial-to-mesenchymal transition, thus impacting BCa etiology. Dysregulated estrogen (E2) and glucocorticoid (GC; hydrocortisone, CORT) signaling prevalent in BCa may further contribute to clock desynchrony by directly impacting the expression and cycling dynamics of genes comprising the local breast oscillator. In this study, we identified the tumor suppressor gene, KLF9, as an important point of crosstalk between hormone signaling and the circadian molecular network and further established its functional role in BCa. We determined that KLF9is a direct GC receptor (GR) target gene in mammary epithelial cells, and that induction is likely mediated through coordinate transcriptional activation from multiple CORT-responsive enhancers in the KLF9 locus. Interestingly, the clock-controlled rhythmic expression of KLF9observed in normal MCF10A cells was abolished in the highly aggressive TNBC MDA-MB-231 line. As a transcription factor, in turn, KLF9 modulated the baseline mRNA levels of several clock genes and influenced the GC/E-induced alterations in clock gene expression indicating that KLF9 may function as a feedback regulator of the core clock machinery. We then characterized the functional role of KLF9 in context of the hormone-circadian axis in BCa using cellular assays on survival, proliferation, apoptosis, and migration. We determined that KLF9 plays a tumor-suppressive role in BCa regardless of molecular subtype. In addition, KLF9 overexpression potentiated the anti-tumorigenic effects of CORT in ER+ luminal MCF7 cells, while it played a converse effect in triple-negative MCF10A and MDA-MB-231 cells by restraining CORT-enhanced proliferation and survival. Taken together, our findings suggest that dysregulation of KLF9expression and oscillation in BCa may impinge on circadian network dynamics, thus ultimately aggravating BCa oncogenic landscape.
Presentation: No date and time listed