bluuebunny/crossref_metadata_2025 huggingface dataset:
OR11-06 Biological Activity Of Lumisterol Hydroxymetabolites And Their Mechanism Of Action
Authors: Slominski Andrzej T , Kim Tae-Kang , Podgorska Ewa , Janjetovic Zorica , Stefan Joanna , Ravichandran Senthilkumar , Slominski Radomir M , Song Yuwei , Song Yuhua , Szpotan Justyna , Mobley Alisa A , Raman Chander , Tang Edith K Y , Jetten Anton M , Holick Michael F , Tuckey Robert C
Published: October 2023

Disclosure: A. Slominski: None. T. Kim: None. E. Podgorska: None. Z. Janjetovic: None. J. Stefan: None. S. Ravichandran: None. R.M. Slominski: None. Y. Song: None. Y. Song: None. J. Szpotan: None. A. Mobley: None. C. Raman: None. E. Tang: None. A.M. Jetten: None. M.F. Holick: None. R. Tuckey: None.

While the role of vitamin D3 in body homeostasis is well established, the functions of its photoderivative, lumisterol (L3), are gradually being appreciated. Previously, we reported that L3 can be metabolized by CYP11A1 and CYP27A1 to mono- and dihydroxy-L3. Furthermore, we have shown that 7DHC reductase (DHCR7) does not act on L3 and its metabolites [(OH)nL3]. In the current study, we show the presence of CYP27A1-derived 25(OH)L3, (25R)27(OH)L3 and (25S)27(OH)L3 in human epidermis and serum, and the capability by human keratinocytes to generate them from L3 substrate. Furthermore, these metabolites inhibited keratinocyte proliferation and stimulated cell differentiation. They, together with CYP11A1-derived (OH)nL3 acted as ligands on the human aryl hydrocarbon (AhR), liver X (LXR α and β), and peroxisome proliferator-activated (PPARγ) receptors as demonstrated by functional assays, molecular modeling, and activation of the CYP1A1 and CYP1B1, which are downstream of the AhR. These findings indicate that these hydroxyderivatives can regulate physiological functions by acting on AhR, LXRs and PPARγ receptors and activate respective downstream signaling pathways. Thus, L3 produced in the skin by UVB, can act as a pro-hormone that is metabolized into biologically active metabolites by CYP11A1 and CYP27A1 that can not only regulate skin functions but also other biological functions after their entry into the systemic circulation. These findings open, previously unanticipated, exciting new areas of research on the physiological role of (OH)nL3, and L3 through action on AhR, LXRs and PPARγ receptors.

Presentation: Friday, June 16, 2023
SAT001 Membrane Progesterone Receptors Induce Glycogenolysis In Uterine Epithelial Cells
Authors: Berg Malia , Dean Matthew
Published: October 2023

Disclosure: M. Berg: None. M. Dean: None.

In humans and cattle, 40-60% of pregnancies fail, with most losses occurring prior to or during implantation. Throughout this time, the developing embryo needs glucose to survive. The demand for glucose increases dramatically at the morula stage as the embryo enters the uterus. Yet, how glucose is regulated to match the changing needs of the embryo is unclear. Glycogen is composed of thousands of glucose molecules and is present in the uterine epithelium of many species. Our lab has shown that the glycogen content of the bovine uterine epithelium was lower during the luteal phase than at estrus. Therefore, our objective was to elucidate the role of progesterone in glycogenolysis of uterine epithelial cells. Bovine uterine epithelial (BUTE) cells were treated with insulin-like growth factor 1 (IGF1) to stimulate glycogenesis, followed by treatment for 48 hours. Progesterone decreased glycogen levels in BUTE cells by 99% (P=0.0002). RU486 did not block progesterone's effect, indicating that the effect of progesterone was not mediated by nuclear progesterone receptors (nPR). Thus, we hypothesized that the effect of progesterone is mediated by membrane progesterone receptors (mPRs). RT-PCR confirmed that BUTE cells expressed all five mPRs (α, β, γ, δ, and ε). Like progesterone, a specific mPR agonist (Org OD 02-0) decreased glycogen levels in BUTE cells by 99% (P<0.0001). Indicating a potential for mPRs to regulate glycogen in vivo, immunohistochemistry showed that the bovine uterine epithelium expressed high levels of mPRα. These results validate that progesterone is acting through mPRs to stimulate glycogen breakdown in BUTE cells. Once progesterone binds to the mPR, two signaling pathways can be activated, cAMP and AMPK. Neither progesterone nor Org OD 02-0 changed intracellular cAMP concentrations. In agreement, the adenylyl cyclase activator forskolin increased cAMP concentration but did not decrease glycogen. BUTE cells treated with progesterone had increased pAMPK levels at 24 hours compared to the control (P=0.0001). BUTE cells treated with an AMPK activator (D942) had a decrease in glycogen (P=0.0051). Supporting these results in vivo, pAMPK levels in the uterine epithelium were high in the bovine uterine epithelium during the luteal phase when glycogen levels were low. In a human model, progesterone and Org OD 02-0 decreased glycogen levels to a similar extent in Ishikawa cells that express mPRs but not nPRs (P=0.0027). In conclusion, progesterone acting through the mPR and AMPK to stimulate glycogenolysis may play a crucial role in providing glucose to endometrial tissue or the growing embryo.

Presentation: Saturday, June 17, 2023
SAT012 In Vivo Mapping Of Subcellular Proteomes In Mice
Authors: Kim Kwang-eun , Park Isaac , Kim Jeesoo , Kim Jong-Seo , Rhee Hyun-Woo , Myoung Suh Jae
Published: October 2023

Disclosure: K. Kim: None. I. Park: None. J. Kim: None. J. Kim: None. H. Rhee: None. J. Suh: None.

To facilitate the understanding of metabolic changes associated with aging and disease processes we have developed new in vivo tools that enable tissue-specific profiling of subcellular proteomes. First we describe a method to profile in vivo mitochondrial proteomes utilizing transgenic mice expressing mitoAPEX, a peroxidase-based proximity labeling enzyme containing a mitochondrial matrix targeting sequence. Upon label activating conditions, mitoAPEX rapidly (<1 min) catalyzes production of biotin radicals which biotinylate proteins within a 20 nm radius. Mass analysis of biotinylated proteomes from proximity labeled mitoAPEX mouse tissues confirmed specific and efficient labeling of the mitochondrial proteome and revealed tissue-specific patterns of the matrix proteome. The labeled muscle proteomes from young and old mitoAPEX mice revealed significant changes in the quantity and composition of protein species. Of these, RTN4IP1, was shown to be downregulated in muscle tissue of old mice. However, in contrast to previous reports, our analysis of RTN4IP1 shows RTN4IP1 is localized to the mitochondrial matrix and not the outer membrane. In addition to the mitoAPEX mice, we generated another in vivo proximity labeling tool iSLET (in situ Secretory protein Labeling via ER-anchored TurboID) which labels secretory pathway proteins, via proximity labeling activity by ER lumen targeted TurboID, an engineered biotin ligase. We expressed iSLET in the mouse liver and demonstrate efficient labeling of the liver secreted proteome which could be tracked and identified within circulating blood plasma. We expect mitoAPEX and iSLET mice will facilitate our understanding of mitochondrial function and interorgan communication networks in aging and associated disease processes.

Presentation: Saturday, June 17, 2023
OR22-01 Sex Differences In Enterohepatic Circulation Mediated By Hepatic FXR And SHP Depletions In Mice
Authors: Reichardt Francois , Galuke Christopher A , Anakk Sayeepriyadarshini
Published: October 2023

Disclosure: F. Reichardt: None. C. Galuke: None. S. Anakk: None.

Bile acids are transported via the portal vein to the liver after their absorption through the distal intestine mucosa. In hepatocytes, they activate the nuclear receptors, Farnesoid-X-receptor (FXR) and Small Heterodimer Partner (SHP), which exert negative feedback on bile acids synthesis. The aim of this project is to decipher how hepatic FXR/SHP deletion impact BA composition, enterohepatic circulation, and its cross talk with the gut microbiota. Enterohepatic circulation was investigated by measuring total bile acids in intestinal, hepatic tissues and fecal tissues and in portal and systemic blood, using 3-5 months-old fed female and male wildtype (WT) and LDKO (liver specific FXR/SHP depletions) mice. We also examined if intestinal dysmotility mediated the alteration in bile acids absorption by following methylene blue dye progression in overnight fasted WT and LDKO mice. Portal and systemic total bile acids concentrations were higher in LDKO mice compared to WT, despite of no significant change in hepatic and intestinal levels. Sex differences were seen only in LDKO mice with higher systemic and portal concentrations in females compared to males. Intestinal transit time and fecal total bile acids were equivalent between all mice. Intriguingly, we observed that portal bile acids levels correlated to the liver weight to body weight ratio and to cecum weight to body weight ratio, suggesting that bile acids alterations within the enterohepatic loop could be associated to cecal dysbiosis. These preliminary findings highlight altered BA recirculation in LDKO mice compared to WT, but also between females and males LDKO. We hypothesize that these sex-specific modifications are associated with intestinal dysbiosis impacting bile acid compositions, and to test this we will be analyzing the influence of sex, and BA composition on the microbiome. Further investigations using fasted or HFD-fed LDKO and WT mice will help us to better understand the role of hepatic FXR and SHP in bile acids circulation between intestine and liver. Acknowledgement: University of Illinois Urbana-Champaign, American Cancer Society and Cancer Center at Illinois Seed grant

Presentation: Saturday, June 17, 2023
OR22-02 Sex Differences In 11-Oxyandrogen Correlations With Adipose Tissue Compartments
Authors: Turcu Adina F , Lee Chaelin , Joseph Auchus Richard
Published: October 2023

Disclosure: A.F. Turcu: None. C. Lee: None. R.J. Auchus: None.

Background: Adrenal-derived 11-oxygenated C19 steroids (11-oxyandrogens) are mediators of adrenarche and several disorders of androgen excess. 11β-hydroxyandrostenedione (11OHA4), a major adrenal product, is converted to the bioactive androgen 11-ketotestosterone (11KT) via 11β-hydroxysteroid dehydrogenase type 2 (HSD11B2) and aldo-keto reductase 1C3 (AKR1C3). The adipose tissue expresses both AKR1C3 and the type 1 isoenzyme HSD11B1, which participate in modulating peripheral androgen production. The impact of adipose tissue compartments on circulating 11-oxyandrogens in men and women is not well understood. Setting and Participants: A subset of participants in the population-based, multiethnic cohort of the Dallas Heart Study, phase 2 were included. Measurements: All participants underwent subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) measurements by abdominal magnetic resonance imaging (MRI). Testosterone (T), androstenedione (A4), and four 11-oxyandrogens were quantified simultaneously in peripheral blood using liquid chromatography-tandem mass spectrometry. Associations between adipose tissue compartments and androgens were assessed by Pearson correlation tests, stratified by sex. Results: Of the 498 participants included, 282 (56.6%) were women, 49% were Black, 32% White, 18% Hispanic. The mean age of study participants was 54.3 +/- 10.7 years, and mean BMI was 30.9 +/- 6.9 kg/m2. There was no difference in age and race distribution between men and women. 11OHA4, 11β-hydroxytestosterone (11OHT), and 11KT correlated positively with BMI in women (R2 = 0.15-0.18, p<0.01) but not in men. Conversely, T correlated negatively with BMI only in men (R2 = -0.26, p<.0001). 11OHA4 and 11OHT correlated directly with both SAT and VAT in women (R2 = 0.14-0.18, p<0.05), and a similar correlation was observed between 11OHT and VAT in men. Conversely, T and A4 displayed an inverse correlation with SAT and/or VAT in both sexes. 11KT and 11-ketoandrostenedione (11KA4) displayed no association with adipose tissue compartments. Conclusions: 11OHA4 and 11OHT, but not their respective 11-keto metabolites correlate with all adipose tissue compartments in women, while T correlates inversely with adiposity in men, particularly with SAT. Sexual dimorphism in adipose tissue and impact on androgen modulation might contribute to sex differences in cardiometabolic morbidity.

Presentation: Saturday, June 17, 2023
OR33-03 Circadian Analysis Of Nuclear Receptor Protein Expression In Mouse Liver Reveals Peak COUP-TFII, EAR2, LXRa, LXRb And TR4 Expression At The End Of The Mouse Active Cycle ZT0
Authors: Fadi Saikali Michael , Xu Li Jia , Cummins Carolyn L
Published: October 2023

Disclosure: M.F. Saikali: None. J. Li: None. C.L. Cummins: None.

Nuclear Receptors (NRs) are a family of ligand-mediated transcription factors that control the expression of genes involved in a wide range of physiological processes. The ability to study NRs quantitatively at the protein level has been hindered by the poor quality of available antibodies, as well as the lack of available high throughput methods to study more than a few receptors at a time. To address this need, we have developed a mass spectrometry based targeted proteomic assay to quantify the absolute amounts of NR protein in mouse livers over a circadian period. C57Bl6 mice were sacrificed at 12 weeks every 4 hours from zeitgeber time ZT0 to ZT20. Their livers were processed using a transcription factor extraction protocol1. For each sample, 100 µg nuclear protein was processed using the NR assay described previously2. Briefly, the lysate is digested following the Multi-Enzyme Digestion Filter Aided Sample Preparation protocol. The sample is then spiked with 50 fmol of our internal standard mix. This mix is composed of 66 carefully selected peptides that account for 49 NRs, 11 histone peptides, and 6 circadian clock proteins. The resulting digest that contains the internal standards is desalted on C18 tips, followed by separation on an EASY-Spray C18 column (75 um x 50 cm, 3Å), and analyzed on a Thermo QExactive HF mass spectrometer in parallel reaction monitoring mode. We used this assay to quantify the changes in NR protein expression in mouse livers for 9 receptors; RORα, CAR, COUP-TFII, EAR2, GR, LXRα, LXRβ, PPARα, and TR4. RORα showed peak nuclear expression at ZT0, with a peak-to-trough change of 2.2-fold. COUP-TFII, EAR2, LXRα, LXRβ, and TR4 also showed peak expression at ZT0 (the end of the active phase) with changes of 3.3, 2.4, 1.7, 2.0, and 1.6-fold respectively. GR showed peak nuclear expression at ZT12 with a 1.8-fold change. CAR showed 2.3-fold peak expression at ZT16. COUP-TFII, EAR2, and TR4 are considered orphan receptors with no known endogenous ligands. These data will be used to uncover endogenous tissue-specific ligands by analyzing extracts isolated at the zeitgeber time that the receptor is maximally expressed. Sources of Research Support: This project has been supported by the J. P. Bickell Foundation and the Canadian Institutes of Health Research New Frontiers Research Fund and International Development Research Fund. 1.Gillespie, M. A. et al. Absolute Quantification of Transcription Factors Reveals Principles of Gene Regulation in Erythropoiesis. Mol Cell (2020) doi:10.1016/j.molcel.2020.03.031.2.Saikali, M. F. & Cummins, C. L. Quantifying the Protein Levels of All Nuclear Hormone Receptors by Mass Spectrometry. J Endocr Soc5, (2021).

Presentation: Sunday, June 18, 2023
THU659 Plasmapheresis As A Therapy For Amiodarone-induced Thyrotoxicosis: A Case Report And Literature Review
Authors: Loughner Chelsea L , Lynn Bononi Patricia
Published: October 2023

Disclosure: C.L. Loughner: None. P.L. Bononi: None.

Introduction: Amiodarone-induced thyrotoxicosis (AIT) is a common cause of hyperthyroidism. Treatment consists of stabilizing the thyroid followed by thyroidectomy1. Plasmapheresis has been suggested as a temporary measure when illness severity precludes standard therapy. Here, we review current literature and provide a case of AIT treated with plasmapheresis. Clinical Case: A 71-year-old male was seen for progressive subclinical hyperthyroidism, diagnosed several years prior. Three years ago, he started taking amiodarone for paroxysmal ventricular tachycardia. One month prior to admission, he was admitted for decompensated heart failure and had TSH 0.02 mcU/mL (n 0.4-4.4 mcU/mL), free T4 4.48 ng/dL (n 0.7-1.9 ng/dL), and free T3 2.58 pg/mL (n 2.0-4.4 pg/mL). Amiodarone was halved after being diagnosed with AIT. Methimazole and prednisone were started. He was readmitted one month later. TSH was undetectable at admission and free T4 was 4.04 ng/dL. Amiodarone was discontinued. His hepatic enzymes were elevated, necessitating the discontinuation of methimazole. His heart failure precluded thyroidectomy. Due to the limitation of treatment options, the patient was given three rounds of plasmapheresis to reduce thyroid hormone levels. His free T4 dropped to 2.81 ng/dL. The patient underwent total thyroidectomy once stable. His free T4 was 1.73 after and was started on levothyroxine. Clinical Lesson: When patients are unable to have standard treatment of AIT, other options must be considered. While there are some case reports3,4, there are currently no RCTs for plasmapheresis for AIT. In the case of this patient with cardiac complications from AIT and concurrent hepatic impairment, plasmapheresis provided stability of thyroid hormones until surgical correction could be achieved.

References: 1. Tizianel I, Sabbadin C, Censi S, et al. Therapeutic Plasma Exchange for the Treatment of Hyperthyroidism: Approach to the Patient with Thyrotoxicosis or Antithyroid-Drugs Induced Agranulocytosis. J Pers Med. 2023;13(3):517. Published 2023 Mar 13. doi:10.3390/jpm13030517. 2. Padmanabhan A, Connelly-Smith L, Aqui N, et al. Guidelines on the Use of Therapeutic Apheresis in Clinical Practice - Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Eighth Special Issue. J Clin Apher. 2019;34(3):171-354. doi:10.1002/jca.217053. Miller A, Silver KD. Thyroid Storm with Multiorgan Failure Treated with Plasmapheresis. Case Rep Endocrinol. 2019;2019:247584. 3. Published 2019 Oct 9. doi:10.1155/2019/24758434. Zhu L, Zainudin SB, Kaushik M, Khor LY, Chng CL. Plasma exchange in the treatment of thyroid storm secondary to type II amiodarone-induced thyrotoxicosis. Endocrinol Diabetes Metab Case Rep. 2016;2016:160039. doi:10.1530/EDM-16-0039.

Presentation: Thursday, June 15, 2023
THU660 Pericardial Effusion Secondary To Uncontrolled Hypothyroidism
Authors: Deniz Cain Gozde , Goldsmith Daniel , Ruel Ewa
Published: October 2023

Disclosure: G.D. Cain: None. D. Goldsmith: None. E. Ruel: None.

Introduction: Hypothyroidism is an endocrine disorder that can effect multiple organ systems. Pericardial effusion is a rare but significant complication of hypothyroidism. Early diagnosis and management of the pericardial effusion is important to prevent progression to cardiac tamponade and hemodynamic instability. We present a case of pericardial effusion in a 62-year-old female with hypothyroidism and medication non-compliance. Case Presentation: A 62-year-old female with past medical history of hypothyroidism and hypertension presented to the emergency department due to altered mental status. Patient's family reported that she had a progressive decline in her speech for more than a month, until she became completely aphasic on day of presentation, which prompted them to call EMS. Patient had diminished exercise capacity, dyspnea on exertion, bilateral pedal edema over the past couple of months. Family also reported that the patient had been depressed and negligent of her health following the passing of her husband three years ago. She was not taking her medications including levothyroxine. In the ED, patient was hypertensive, blood pressure was 190/100. CT head stroke protocol did not show stroke. Chest x-ray showed massive cardiac enlargement. 2D-Echo confirmed a large pericardial effusion without cardiac tamponade. Thyroid function panel showed high TSH of 77, free T4 was undetectable. Pericardial effusion was most likely secondary to hypothyroidism. Myxedema coma was suspected due to patient's progressive mental deterioration. Patient also had myxedema of bilateral lower extremities. IV levothyroxine and hydrocortisone were started with improvement in her symptoms. A pericardial window was performed by the thoracic surgeon for her large pericardial effusion. Patient had large amounts of drainage from JP pericardial drain for more than two weeks following the surgery. JP drain was removed after the amount of drainage decreased to less than 100 ml a day. Cultures and cytology for malignancy were sent and all came back negative. Patient’s symptoms improved with treatment and the she was discharged on levothyroxine 137 mcg daily. Patient was counseled to take her medication regularly. Follow-up appointments were arranged with primary care provider and endocrinology. Discussion: Pericardial effusion is a rare complication of hypothyroidism, more likely to be seen in severe, untreated hypothyroidism such as in this case. The mechanism of pericardial effusion in hypothyroidism is through increased capillary permeability in heart and decreased lymphatic drainage of albumin, resulting in accumulation of fluid in the pericardial space. The effusion develops over time and patients can have large amounts of volume at the time of diagnosis without tamponade physiology. Early diagnosis is important to avoid tamponade and hemodynamic instability.

Presentation: Thursday, June 15, 2023
THU667 Severe Hypothyroidism With Paradoxically Elevated Direct Free T4 Due To Anti-thyroxine Antibodies
Authors: Magvanjav Oyunbileg , John McPhaul Michael , Choucair Ibrahim , Holt Elizabeth
Published: October 2023

Disclosure: O. Magvanjav: None. M.J. McPhaul: None. I. Choucair: None. E. Holt: None.

Introduction Laboratory interference may cause abnormal thyroid function test (TFT) results, leading to misdiagnosis and inappropriate patient care. There are several major types of interference. Here, we describe a hypothyroid patient with an elevated thyroid stimulating hormone (TSH) level with a paradoxically elevated direct free thyroxine (FT4) level caused by interference from anti-thyroxine autoantibodies (THAAB). Clinical Case Our patient is a 38-year-old man who was found to have markedly elevated TSH and FT4 levels during an outpatient workup for Lyme disease. The patient was overall well-appearing but reported some symptoms suggestive of hypothyroidism including excessive fatigue, non-pitting edema, and dry skin. Physical exam was notable elevated blood pressure (systolic blood pressure of 150 mmHg and diastolic blood pressure of 95 mmHg), normal temperature, normal heart rate (72 bpm), regular heart rhythm, and normal body mass index. He had non-tender thyromegaly without nodules, non-pitting edema of bilateral hands and legs, decreased leg hair over bilateral shins, and coarse, dry skin of his hands. Initial TSH level was >150 mIU/ml, with a paradoxically elevated direct FT4 of 10 ng/dl (normal range 0.80-1.70 ng/dL). The FT4 level by equilibrium dialysis was <0.2 ng/dl. Outside laboratory testing to eliminate the effect of heterophile antibodies using two different assays again returned with elevated FT4 levels. Screening for macro TSH confirmed the markedly elevated TSH level. Further investigations at a second outside laboratory revealed that he had THAAB. A repeat FT4 level by dialysis confirmed the markedly low FT4 levels. He was empirically started on low dose levothyroxine and after increasing the levothyroxine dose, he showed improvement in clinical symptoms and the expected decline in TSH. Conclusions Here we present a rare case of THAAB that caused laboratory interference during thyroid function testing, leading to falsely elevated thyroid hormone levels on immunoassays. This case shows the importance of suspecting interference when there is a discrepancy between clinical symptoms and laboratory results or between results obtained from different testing methods. Our patient likely had a genetic predilection for autoimmunity, and Lyme disease is a known trigger for various autoimmune conditions. Our case also emphasizes the importance of taking a systematic approach to investigate the cause of the laboratory interference. This will help prevent misdiagnosis of thyroid disorders that may lead to additional unnecessary testing and treatment.

Presentation: Thursday, June 15, 2023
THU677 Performance Of American Thyroid Association And American College Of Radiology Scoring Systems In The Evaluation Of Pediatric Thyroid Nodules
Authors: Garabet Diramerian Linda , Douek Michael , Tse Gary , Iskander Paul , Li Shanpeng , Yeh Michael W , Livhits Masha J , Leung Angela M , Chiu Harvey K , Wu James X
Published: October 2023

Disclosure: L. Garabet Diramerian: None. M. Douek: None. G. Tse: None. P. Iskander: None. S. Li: None. M.W. Yeh: None. M.J. Livhits: None. A.M. Leung: None. H.K. Chiu: None. J.X. Wu: None.

Background: The underlying malignancy rate of thyroid nodules is higher in pediatric patients compared to adults. Ultrasound scoring systems developed for adult thyroid nodules may not be applicable to pediatric populations. Objective: To evaluate the performance characteristics of adult American Thyroid Association (ATA) and American College of Radiology Thyroid Imaging and Reporting Data System (TIRADS) scoring systems in risk-stratifying pediatric thyroid nodules. Methods: This was a retrospective chart review of pediatric patients aged ≤18 years with thyroid nodules at UCLA Health from 2002-2022. Patients with no available ultrasound images or cytopathology results (fine needle aspiration [FNA] or surgical pathology) were excluded. Each thyroid nodule was scored according to the ATA and TIRADS systems through independent, blinded review by two study radiologists; discordances were arbitrated by a third. For patients who did not undergo thyroid surgery, we considered thyroid nodules benign if their size was stable on repeat ultrasound or if a repeat FNA was benign. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated for each system. Sensitivity analyses were performed to determine the optimal size cut-off to recommend FNA biopsy while maintaining a sensitivity equivalent to that of adults. Results: There were 77 patients (median age, 15 years [range 2-18]); 71.4% female) with 115 thyroid nodules. The underlying malignancy rate was 27.8%. Using adult-size cut-offs for FNA biopsy, the ATA scoring system would have failed to recommend biopsy for 11 of 32 malignant nodules, and had the following performance: sensitivity 66%, specificity 55%, NPV 81%, and PPV 36%. The TIRADS scoring system would have failed to recommend biopsy for 15 of 32 malignant nodules and had the following performance: sensitivity 53%, specificity 87%, NPV 83%, and PPV 61%. In sensitivity analyses, the optimal size cut-offs for FNA using the ATA scoring system were: 2 cm for very low risk, 1 cm for low risk, and 0.5 cm for intermediate and high risk categories (sensitivity 94%; specificity 33%). The optimal size cut-offs for FNA using TIRADS were: 3 cm for TIRADS-2, 0.8 cm for TIRADS-3 and TIRADS-4, and 0.5 cm for TIRADS-5 (sensitivity 91%; specificity 59%). Conclusion: The adult ATA and TIRADS ultrasound scoring systems have low sensitivity for thyroid cancer in pediatric thyroid nodules. Lowering the size cutoffs for recommending thyroid FNA biopsy increases sensitivity to >90% for both ATA and ACR TIRADS scoring systems.

Presentation: Thursday, June 15, 2023
THU682 Long-term Outcomes Of Prophylactic Lateral Neck Dissection In Papillary Thyroid Carcinoma
Authors: Matsui Ai , Kuga Yoko , Saito Yoshiyuki , Yoshioka Kana , Masaki Chie , Akaishi Junko , Yamada Hames Kiyomi , Tomoda Chisato , Suzuki Akifumi , Matsuzu Kenichi , Kitagawa Wataru , Sugino Kiminori , Ito Koichi
Published: October 2023

Disclosure: A. Matsui: None. Y. Kuga: None. Y. Saito: None. K. Yoshioka: None. C. Masaki: None. J. Akaishi: None. K.Y. Hames: None. C. Tomoda: None. A. Suzuki: None. K. Matsuzu: None. W. Kitagawa: None. K. Sugino: None. K. Ito: None.

Background: Prophylactic lateral neck dissection for papillary thyroid carcinoma is no longer recommended in guidelines of each country. Since 2010, it is not employed at our hospital as well. Thereafter, however, no long-term study has been conducted to investigate the differences in postoperative lymph node recurrence rate between patients who underwent prophylactic lateral neck dissection and those who did not; in this study, we have re-examined these differences. Object and Methods: There were 1732 cases of papillary thyroid carcinoma with no distant metastasis operated between January 2010 and December 2011. Among them, 1542 cases, excluding the cases with clinical lateral neck lymph node metastasis, were included in this study. Lymph node metastases were confirmed based on the diagnosis via cytological or histopathological examination. No exclusion criteria were established for the extent of thyroidectomy, and cases with lobectomy and total or subtotal thyroidectomy were included. Of the 1542 cases, 140 cases had lateral neck dissection (Group A) and 1402 cases did not have prophylactic lateral neck dissection (Group B), and both were compared. The study design was a retrospective study, comparing each group using the Kaplan-Meier method with lymph node recurrence as the endpoint. Results: Comparing the backgrounds of Group A and Group B, respectively, significant differences for age (49.2 years vs. 52.9 years, P = 0.003), macroscopic tumor invasion into the perithyroidal soft tissues (13 [9.3%] vs. 27 [1.9%], P < 0.001), and tumor size (24.8 mm vs. 13.1 mm, P < 0.001), were observed. And significant differences were observed in the 10-year postoperative lymph node recurrence-free rates (92.6% vs. 96.6%, P = 0.012) in Group A and Group B, respectively. When the backgrounds were matched by age, sex, macroscopic tumor invasion into the perithyroidal soft tissues, and tumor size using propensity score matching (138 matched pairs), no significant differences were observed in the 10-year recurrence-free rates (92.5% vs. 95. P = 0.208) in both groups. Conclusions: The results of this study showed no significant difference in postoperative lymph node recurrence rates between the two groups, suggesting that the presence or absence of prophylactic lateral neck dissection does not affect postoperative lymph node recurrence during the long-term observation period.

Presentation: Thursday, June 15, 2023
THU683 TERT Promoter Mutations, But Not BRAFV600EMutation, Correlate With The American Thyroid Association And TNM Staging Systems And Predict Outcome Of Differentiated Thyroid Cancer
Authors: Mukhtar Noha , Alhamoudi Kheloud , Alswailem Meshael , Al-Hindi Hindi , Murugan Avaniyapuram K , Alghamdi Balgees , Saeed Alzahrani Ali
Published: October 2023

Disclosure: N. Mukhtar: None. K. Alhamoudi: None. M. Alswailem: None. H. Al-Hindi: None. A.K. Murugan: None. B. Alghamdi: None. A.S. Alzahrani: None.

Context: The American Thyroid Association risk stratification (ATA) and the American Joint Committee on Cancer Tumor Node Metastases (TNM) predict recurrence and mortality of differentiated thyroid cancer (DTC). BRAFV600E and TERT promoter mutations have been shown to predict DTC outcome. Our objectives were to study these molecular markers in terms of their interaction and potential incremental prognostic values over the ATA and TNM staging systems. Patients and Methods: We studied 315 non-selected patients, 229 females, 86 males with a median age of 36 years (IQR 24-49). Data were extracted from medical records. BRAFV600E and TERT promoter mutations were tested by PCR-based Sanger sequencing. Persistent disease (PD) included all patients in structurally or biochemically incomplete and indeterminate response as defined by the 2015 ATA guidelines. Data were analysed using Chi-Square and Fisher Exact test and Kaplan Meier analysis. Results: Of 315 patients tested, 138 (43.8%) had BRAFV600E-positive tumors and 77 (24.5%) were positive for TERT promoter mutations. The BRAFV600E mutation did not correlate with the ATA and TNM staging, being non-significantly different in various stages of these systems and did not predict the development of PD (P 0.11). Unlike BRAFV600E, TERT promoter mutations were more frequent in the ATA high-risk than in intermediate- or low-risk tumors (P 0.01) and in TNM stages III and IV than in lower stages (P <0.001). TERT promoter mutations also predicted the outcome being present in 36.4% of patients with PD compared to only 15.6% in those without evidence of disease (P <0.0001). The same pattern was also seen when BRAFV600E and TERT promoter mutations were combined. TERT promoter mutations alone or TERT promoter + BRAFV600E mutations predicted the development of PD in 100% of patients in TNM stage IV or high-risk ATA stage. Conclusions:TERT promoter mutations alone or in combination with BRAFV600E mutation, but not BRAFV600E mutation alone, correlated well with the ATA and TNM staging and predicted development of PD, especially in higher stages of these systems. The combination of high-risk ATA or TNM stage IV with TERT promoter mutations is highly predictive of development of PD predicting PD in 100% of cases with these combinations.

Presentation: Thursday, June 15, 2023
FRI464 Subacute Thyroiditis Related To COVID-19 Vaccines- A Case Series
Authors: Mejia Hery , Gillis Funderburk Sheri Anita , Raj Thomas Sunil
Published: October 2023

Disclosure: H. Mejia: None. S.A. Gillis Funderburk: None. S.R. Thomas: None.

Background: Subacute thyroiditis (SAT) has been reported following SARS-COV-2 viral infection, as well as in recipients of the mRNA vaccines for SARS-COV-2. Patients present with palpitations, tremors and weight loss as well as low grade fevers and a tender thyroid. It is a self-limited condition that typically follows a triphasic course that may include thyrotoxicosis, hypothyroidism and return to normal thyroid function. Clinical features and sonographic findings can provide a specific diagnosis, and a radioactive iodine uptake study is often not required. Report: In 2021, 123 patients were referred to our outpatient service for evaluation of thyrotoxicosis. Among them, we identified 9 women without history of thyroid disease who presented with clinical findings of SAT with thyrotoxicosis. Patients with history of thyroid dysfunction and thyroid nodules were excluded. The symptoms began between 4-27 days after the first or second dose of either the Pfizer Bio-NTech or the Moderna COVID-19 mRNA vaccine. All tested negative for TSI and had no nodules on ultrasound. 2 patients had thyroid uptake scans which confirmed thyroiditis. All 9 patients improved with symptomatic treatment and thyroid functions normalized with time. Discussion: Since the mRNA vaccines for SARS-COV-2 became nationally available, several adverse reactions have been reported including SAT. The mechanism for post-vaccination SAT or thyroid dysfunction remains unknown. Transmembrane protease serine-2 (TMPRSS-2) and ACE-2 receptors allow the SARS-CoV-2 to enter human cells. ACE-2 and TMPRSS-2 are expressed in thyroid follicular cells, and their expression is higher than in lung cells, especially in women. These situations may explain why SARS-CoV-2 causes SAT in women more frequently. Inactive virus vaccines contain many proteins belonging to the pathogen virus and similar antigenic parts. The increased affinity of the SARS-CoV-2 towards the thyroid suggests that inactive vaccine may also affect the thyroid tissue. In the past, SAT has been reported after an inactive virus vaccine- seasonal influenza vaccine, H1N1 vaccine and hepatitis B vaccine. In addition, the COVID-19 vaccine contains aluminum hydroxide as an adjuvant. Autoimmune inflammatory syndrome induced by adjuvants (ASIA syndrome) was previously reported following various vaccines. A recent article describes a patient with COVID-19 vaccine related ASIA syndrome and SAT. In some cases, elevated proinflammatory markers and cytokines after receiving the vaccine may play a major role, as it can stimulate a significant response from our immune system. Hence, SAT should be included as a possible side effect of receiving these vaccines. Conclusion: Our case series highlights a possible relationship between the COVID-19 mRNA vaccines and subacute thyroiditis which has been previously underreported or not recognized by healthcare providers.

Presentation: Friday, June 16, 2023
FRI474 Panhypopituitarism And Central Hypothyroidism Presenting As Myoclonus And Hyperreflexia, An Unusual Presentation Likely Related To Thyrotropin-releasing Hormone
Authors: Nadeem Ifrah , Khan Wahab J , Thapa Sudan
Published: October 2023

Disclosure: I. Nadeem: None. W.J. Khan: None. S. Thapa: None.

Introduction: Panhypopituitarism may present with symptoms of predominantly one or more hormonal deficiencies. The thyrotropin-releasing hormone has been described as causing neuromuscular hyperexcitability via its modifying role in synaptic functions in addition to its effect on the pituitary. We present a panhypopituitarism due to macroadenoma presenting with weakness, tongue fasciculation, hyperreflexia, and myoclonic jerks. Case Presentation: A 78-year-old woman with a medical history of essential hypertension came to ER with generalized weakness, twitching of her tongue, and involuntary jerking movements of her lower limbs for the past month. On admission, vital signs were normal. Neurological examination revealed tongue fasciculation and bilateral lower extremity myoclonus. Her visual field testing was normal. CT scan of the head showed an apparent seller mass but ruled out any acute pathology. Further neurologic, infectious, and rheumatologic work-up revealed negative results. In addition, an MRI of the cervical, thoracic, and lumbar spine was negative for any mass effect. The pituitary showed a 2.0 x 1.5 x 2.3 cm sellar mass, deforming the optic chiasm and deviating the infundibular stalk to the right side. Laboratory work-up revealed secondary adrenal insufficiency, central hypothyroidism, hypogonadotropic hypogonadism, and hyperprolactinemia. The patient was diagnosed with non-functioning pituitary macro adenoma. Myoclonus significantly improved after initiating the hormone replacement with levothyroxine and a stress hydrocortisone dose, gradually tapered to a physiological dose, and cabergoline. Repeat MRI after three months showed a stable 1.5 x 2.0 x 2.3 cm sellar mass. Surgery was not recommended due to no visual compromise. Instead, she will be followed in the clinic with a 6-month head imaging and hormone testing. Discussion: Usual clinical manifestations of hypothyroidism are the same regardless of etiology. However, there may be additional findings related to hypothalamic or pituitary dysfunction in the case of secondary or tertiary hypothyroidism due to non-thyroidal illness. Muscle fasciculations are common with hypothyroidism. But myoclonus and hyperreflexia are the findings in hyperthyroidism except for one hypothyroid state, i.e., Hashimoto encephalopathy (HE). TRH plays an important role in the pathophysiology of myoclonus and hyperreflexia in patients with HE and without HE. Our patient had tertiary hypothyroidism with likely elevated TRH in the presence of low FT4 and TSH. Therefore, we propose a high level of TRH in central hypothyroidism as the reason for her hyperreflexia and myoclonus.

Presentation: Friday, June 16, 2023
FRI486 Overactive Thyroid And Overactive Mind - An Intervened Relationship
Authors: Bilichodu Rangappa Sushma , Avula Sreekant , Anderson Zachary A , Kumar Ameya
Published: October 2023

Disclosure: S. Bilichodu Rangappa: None. S. Avula: None. Z.A. Anderson: None. A. Kumar: None.

Introduction: Traditionally, psychiatric symptoms were thought to be common manifestation of hypothyroidism. However, in the recent times the trend has changed. Various studies have shown a strong association of hyperthyroidism and psychosis. Thyrotoxicosis is associated with various psychiatric symptoms such as anxiety, restlessness, emotional liability, depression, mania, and rarely acute psychosis. Association between thyroid and mental health is a long-known entity but poorly understood pathophysiology. Here we present a case of graves disease presenting as acute psychosis as initial presentation. Clinical Case: A 45-year-old male with no significant past medical history was brought to emergency department (ED) by police after he was found to be walking in front of a shopping mall and was severely agitated. On arrival to ED, he was found to be very restless, irritable, and aggressive. Patient was found to have persecutory delusions and auditory hallucinations. His blood pressure was elevated, and he had tachycardia. He was given Haloperidol to calm down. Patient was evaluated with blood work and urine toxicology. Blood work up showed thyroid stimulating hormone (TSH) of <0.01m IU/L, Free T4 of 4 ng/dl and Total T3 of 380 ng/dl. Patient was started on Methimazole and propranolol. On further work up for thyrotoxicosis there was elevated thyroid stimulating immunoglobulin (TSI) which was consistent with Grave’s disease. Ultrasound thyroid revealed diffuse enlarged thyroid with increased vascularity. Once the patient was stable, he was further interviewed, he gave a history of palpitations, increased anxiety, and weight loss for two months, but he didn’t seek any medical attention. By the time of discharge, he symptomatically improved and his Free T4 and total T3 trended down. Patient was discharged on methimazole 10 mg daily along with propranolol. Conclusion: Graves’s disease can mimic psychosis. Psychosis may develop in the wake of thyroid hormone excess. Future research is warranted to find out the relation between psychotic disorders and excess thyroid hormone and the pathological process involved. It also helps in having clear treatment guidelines which will reduce the morbidity and improves the quality of life. Identifying somatic causes for psychiatric issues will help in treating them and might lead to complete recovery and not needing any further psychiatric medications.

Presentation: Friday, June 16, 2023
FRI517 BIUX2X2
Authors: Dash Kalpana , Ayyagari Usha
Published: October 2023

Disclosure: K. Dash: None. U. Ayyagari: None.

A Rare Presentation of Solitary Thyroid Nodule - Microfilaria: Case reportDash Kalpana,* Ayyagari Usha***Department of Endocrinology & Metabolism, Apollo Hospitals, Bilaspur. Chhattisgarh, India.** Smriti Speciality Klinics, Chennai, IndiaTel: +919827143474, Email: drkdash@rediffmail.com. Introduction: Filariasis is a debilitating public health problem in the tropics most commonly presenting with asymptomatic microfilaremia. Clinical manifestations include lymphangitis/lymphadenitis in lower limbs(elephantiasis), peritoneum, scrotum(hydrocele), and rarely in breast (breast lump), pleural effusion, bone marrow, and thyroid (painless nodule or thyroiditis). Diagnosis is by demonstrating microfilaria in peripheral blood or tissue biopsy or detection of filarial antigen/antibody in blood. Adult worms are found in lymphatics, subcutaneous tissue, peritoneal and pleural fluid, heart, brain, scrotum, breast, and rarely, thyroid. Filariasis may rarely present as superficial swellings at unusual sites. We present a case of filarial thyroid nodule, a rare manifestation of filarial disease. Clinical Case: Female, 72, presented with painless swelling over the thyroid for 6 months. She had no significant past medical history, was otherwise asymptomatic, clinically and biochemically euthyroid, with normal hemogram, RFT, and LFT. Clinical examination revealed a firm, non-tender nodule measuring 35x45mm, moves with deglutition. On USG of neck, a nodular hypoechoic lesion of 41x45mm was seen over right lobe of thyroid with calcification. FNAC was done for suspected carcinoma & showed histiocytes, hurthle cells, giant cells and a single viable Microfilarial form of Wuchereria bancrofti. She was treated with Diethylcarbamazine citrate & made a full recovery with resolution of the nodule. Discussion: We report a rare manifestation of filarial disease as a painless thyroid nodule. Circulating microfilaria reach the thyroid tissue, followed by rupture of vasculature causing local inflammatory reaction and subsequent nodular transformation. Diagnosis presents challenges as the endemic species in India exhibit nocturnal periodicity and it is difficult to find microfilariae in blood and fine-needle aspirates during the day. Case reports of microfilaria in thyroid aspirates from nodules or thyroiditis are rare. Clinical Lesson: The differential diagnosis for a painless thyroid nodule includes possible malignant disease, with the associated stress of further investigation and treatment. However, accurate diagnosis of filarial disease, rare as it may be, even in endemic areas, obviates the need for surgery as evidenced by the resolution of the nodule with medical treatment in our case.

Presentation: Friday, June 16, 2023
FRI520 Disparities In Available Surgeons And Specialty Physicians Providing Endocrine-related Health Care Coverage To Populations In South Texas And The Rio Grande Valley
Authors: Sampson Alia Valentine , Wong Alvarado Ed , Diaz Edward M , Reinhart Henry
Published: October 2023

Disclosure: V. Alia: None. E.W. Alvarado: None. E.M. Diaz: None. H. Reinhart: None.

Introduction: The Rio Grande Valley and South Texas is home to some of the most medically underserved populations in the nation, with gaps in health care ranging from low rates of adequately insured individuals, to the amount of primary and specialty healthcare services available [1]. Populations living in these areas near the Texas-Mexico border have some of the highest incidence of metabolic and endocrine-related disease in the U.S., while paradoxically having a large deficit in endocrine-specialists available to meet the medical and surgical needs of the community [1,2,3]. Methodology: We analyzed data from the National Center for Health Workforce Analysis (NCHWA), as well as data from the Texas department of state health services (TDSHS) to determine current and projected endocrine-related healthcare coverage needs in South Texas and the Rio Grande Valley (RGV) between 2013 to 2025 and 2018 to 2032 respectively [2,3]. Results: Analysis of the data provided by the NCHWA revealed that by 2025 the southern region of the U.S. is projected to have the largest shortage of full-time equivalent (FTE) surgical specialty physicians in the entire country with a deficit of 10,210 [3]. ​Additionally, data displaying critical-shortages provided by the TDSHS stated that in 2018 the percent demand met (PDM) for FTE endocrinologists in South Texas was only 76.6% with a projected decline to 65.7% by 2032 [2]. Noteworthy data from the TDSHS also stated that in 2018 the RGV specifically had a significant deficit in endocrinologists with a PDM of only 53.6%, while simultaneously having a projected increase to 66.4% by 2032 [2]. The TDSHS classified specialties in South Texas to be critically short when they are projected to have a deficit of ≥100 FTEs and <80% of the physician demand being met [2]. Conclusion: The collection of data analyzed led us to effectively identify significant disparities in endocrine-related healthcare coverage in the South Texas region, specifically the RGV. Additionally, new multidisciplinary healthcare institutions built in the RGV are striving to improve patient access to primary and subspecialty care by recruiting and training physicians in the area, but further action is still needed to counteract the described critical-shortages in physicians responsible for the long-term management of endocrine-related diseases.

Presentation: Friday, June 16, 2023