bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT008 Elucidating The Role Of Small Heterodimer Partner In Injury Associated Hepatic Proliferation
Authors: Shaw Ryan P 
Published: October 2023

Abstract
Disclosure: R.P. Shaw: None.
Small Heterodimer Partner (SHP) is an atypical nuclear receptor that is involved in the regulation of several metabolic pathways but lacks the typically conserved DNA binding domain seen in other nuclear receptors. Several studies have found that SHP expression is drastically lower due to epigenetic silencing in human hepatocellular carcinoma (HCC), the fourth most fatal cancer worldwide, indicating a crucial role for SHP in controlling liver proliferation. SHP can modulate the cell cycle by inhibiting cyclin D1, and remarkably, SHP knockout mice develop tumours at 12 to 15 months of age. The underlying mechanism(s) of this tumorigenesis may be consequential to increases in cyclin D1, yes associated protein (YAP), and decreases in apoptosis when SHP expression is reduced. Furthermore, excessive bile acid (BA) levels in cholestatic liver diseases are cytotoxic and in large quantities, can induce hepatic injury and subsequent hepatic proliferation. We have confirmed that in male mice, loss of hepatic SHP leads to increased systemic BA levels, suggesting these mice may also have increased hepatic injury and proliferation. Moreover, BAs have been identified as upstream regulators of YAP. YAP is a transcriptional coactivator that regulates genes involved in cellular proliferation and differentiation and is also overexpressed in hepatic cancers. In addition to BAs, YAP has also been shown to be activated upon treatment with 0.1% DDC (3,5-Diethoxycarbonyl-1,4-Dihydrocollidine) diet, a chemical-based biliary injury model. We have recently demonstrated that male LSHPKO mice exhibit significantly increased hepatic proliferation, inflammation, and cyclin B1 & B2 mRNA expression in response to the DDC challenge. We have also characterized apoptotic pathways and cell death using TUNEL staining in these mice and characterized how the downregulation of YAP in LSHPKO mice affects hepatic proliferation. These results, in tandem with previous studies of YAP, suggest that hepatic SHP may play a role in mediating hepatic proliferation after injury. It is possible that SHP may act as a repressor for YAP-mediated function.
Presentation: Saturday, June 17, 2023
SAT011 Neonatal Endotoxin Exposure Has Long-term Effects On Glucocorticoid Regulation In Blood And Lymphoid Organs Of Mice
Authors: Mazurenko Anna , Salehzadeh Melody , RY Lim Sarah , Soma Kiran K 
Published: October 2023

Abstract
Disclosure: A. Mazurenko: None. M. Salehzadeh: None. S.R. Lim: None. K.K. Soma: None.
Glucocorticoids (GCs) are steroid hormones that play vital roles in immunity. GCs are produced by the adrenal glands and also by lymphoid organs, such as bone marrow, thymus, and spleen. There is a period of decreased adrenocortical activity in neonatal humans and mice termed the stress hyporesponsive period (SHRP), which protects developing tissues from high circulating GCs and allows for fine-tuning of GC levels in lymphoid organs. In neonatal mice, GC levels increase acutely in response to the bacterial endotoxin, lipopolysaccharide (LPS). Yet, it is not known how early-life LPS exposure affects systemic and local GC levels in adulthood. We assessed whether LPS administration during the SHRP (‘first hit’) affects GC regulation in blood and lymphoid organs in adulthood when challenged again with LPS (‘second hit’). We administered LPS (50 μg/kg i.p.) or saline (vehicle control) to male and female C57BL/6J neonatal mice (PND 4 and 6, within the SHRP). We then split the mice into two groups and administered LPS (50 μg/kg i.p.) or saline to adults (PND90) (2x2 design). We collected whole blood, bone marrow, thymus, and spleen 4 hr after LPS administration at PND90. We used liquid chromatography tandem mass spectrometry (LC-MS/MS) to measure 7 steroids, including 11-deoxycorticosterone (DOC; corticosterone precursor), corticosterone (main active GC in mice), and 11-dehydrocorticosterone (DHC; corticosterone metabolite). Preliminary results show that neonatal LPS treatment altered LPS-stimulated corticosterone levels (but not baseline corticosterone levels) in adult mice. Specifically, neonatal LPS treatment increased blood corticosterone levels in LPS-treated adult males, but not females. In contrast, neonatal LPS treatment increased thymus and spleen corticosterone levels in LPS-treated adult females. There were no effects of neonatal LPS treatment on DOC and DHC levels in adult males. In contrast, neonatal LPS treatment increased thymus DOC and spleen DHC levels in LPS-treated adult females. Altogether, our results suggest that LPS exposure during the SHRP has long-term effects on GC regulation in the blood and lymphoid organs when challenged with a ‘second hit’ in adulthood. This research offers vital insights into understanding the development and regulation of the immune and endocrine systems. Critically, this study demonstrates that lymphoid organs modulate local GC levels independently of circulating GC levels. More generally, these data elucidate the long-lasting programming effects of an immunological stressor, such as neonatal sepsis, early in life.
Presentation: Saturday, June 17, 2023
FRI180 Prevalence Of Vertebral Fractures In Patients With Adrenal Adenomas
Authors: Han Hye Jeong , Lam Han , Rao Sudhaker D , Athimulam Shobana 
Published: October 2023

Abstract
Disclosure: H. Han: None. H. Lam: None. S.D. Rao: None. S. Athimulam: None.
Background: Approximately 5% of adults undergoing cross-sectional imaging are reported to have an adrenal adenoma. Although most adenomas are considered non-functioning (NFAT), up to 48% can present with mild autonomous cortisol secretion (MACS). Published studies have reported an increased prevalence of vertebral fractures (VFx) in MACS. However, findings are limited by sample size, selection bias and lack of diversity in patient population. Objective: To determine the prevalence of vertebral fractures and associated risk factors in patients with adrenal adenomas Design: Retrospective cross-sectional study of patients with adrenal adenomas over a 10-year period (Jan 2012 - Dec 2021). Setting: Academic primary and tertiary care setting Main outcomes measured: 1) MACS was diagnosed based on cortisol level ≥ 1.8cmg/dL after overnight 1mg dexamethasone suppression testing (DST) and NFAT if cortisol &lt; 1.8mcg/dL. Patients who did not undergo 1mg DST were categorized as unknown cortisol status (UCS).2) Bone mineral density (BMD), T- and Z-scores of the lumbar spine (LS). 3)Vertebral morphometry, as assessed by Genant scale, to identify asymptomatic vertebral fractures. Results: Preliminary results included 198 patients with adrenal adenomas [(135 women (67%) with a median age of 67y, 106 Black (54%), 83 White (42%) and 9 other races (4%)]. 74 patients (37%) were diagnosed with NFAT, 42 (21%) with MACS, and 82 (41%) with UCS. Prevalence of vertebral fractures by vertebral morphometry assessment was 6%. (n=12, 5 Black, 7 White). In those with VFx (8 UCS, 2 MACS, 2 NFAT), Black patients had lower BMD (Mean BMD ± SD in Black vs Caucasians: 0.85 ± 018 vs 1.02 ± 0.24 g/cm2, p=0.26). Overall, there was no significant difference in mean LS BMD ± SD (0.97 ± 0.23 vs 1.03 ± 0.20 g/cm2, p=0.41) and mean T-score LS ± SD (-1.11 ± 2.28 vs -0.60 ± 1.71, p=0.49), in patients with and without vertebral fractures, respectively. Conclusions: Patients with adrenal adenoma are at risk of vertebral fractures despite normal or osteopenic BMD. Black patients with adrenal adenomas and vertebral fractures have lower BMD compared to White patients. 41% (n=82, 61% AA, 30% Caucasians, 2% Other) of patients were classified as unknown cortisol status indicating further need to educate health care professionals on evaluation of adrenal adenomas to improve health care outcomes and disparities in management.
Presentation: Friday, June 16, 2023
FRI496 A Rare Case Of Thyroid Hormone Resistance Beta
Authors: Kaur Rai Harpreet , Man Pradhan Rubin , Chaudhuri Ajay 
Published: October 2023

Abstract
Disclosure: H.K. Rai: None. R.M. Pradhan: None. A. Chaudhuri: None.
Background: Genetic mutation in the thyroid hormone receptor leads to the reduced affinity of hormone binding; thus, causing thyroid hormone resistance. It is characterized by a wide range of phenotypic variations and subsequent diagnostic and treatment challenges. Here, we present a case of resistance to the thyroid hormone Beta, with a rare genetic abnormality, that was misdiagnosed as hyperthyroidism. Case: A 46-year-old woman diagnosed with hyperthyroidism s/p RAIA resulting in hypothyroidism on levothyroxine therapy (112mcg daily, weight: 55kg), presented with ten pounds of weight gain, constipation, and cold intolerance for the past six months. TFTs were as follows: TSH: 6.493 mcUnits/ml (normal: 0.400-5.00 mcUnits/ml), and free T4: 1.83 ng/dL (normal: 0.80-1.80 ng/dL). The patient was clinically hypothyroid despite having an elevated FT4 and TSH level. She was also on metoprolol succinate 25 mg daily for sinus tachycardia for the past 1 year. Upon inquiring about further details, the patient informed that at the age of 22, she had significant weight loss, palpitations, and anxiety, but also reported dry skin. The patient was seen by multiple endocrinologists and was provided with contradictory diagnoses. She had RAI scan which was significant for increased uptake and subsequently underwent RAIA. The patient was seen by multiple physicians in the past, levothyroxine dose was adjusted on various occasions but her TFTs never normalized. Post-ablation, she continued to require a higher than the weight-based dose of levothyroxine. Upon review of family history, the patient reported that her father, sister, and daughter had a similar pattern of TFTs with elevated FT4 and TSH values. All of them had palpitations and anxiety that were not severe enough to seek medical care. Family history was also significant for ADHD and hyperlipidemia present in the daughter and father. All affected family members have short stature. The levothyroxine dose was slowly titrated based on the clinical presentation. She was euthyroid with 150 mcg daily of levothyroxine with TSH of 4.869 mcUnits/ml and free T4: 1.85 ng/dl. Given her presentation and suspicion of thyroid hormone resistance, we decided to proceed with genetic testing. The result was positive for the THRB (Resistance to thyroid hormone beta) variant c.904A&gt;G.p.(IIe302Val), which is classified as a variant of uncertain significance, as there is currently insufficient evidence to support its disease-causing role. However, there is a strong association between the gene and the patient's phenotype. Conclusion: The distinctive feature of RTH beta is high levels of free T4 while TSH concentration is normal or elevated, with a combination of hypothyroid and hyperthyroid symptoms. Such patients are often misdiagnosed. We herein describe a novel pathogenic RTH beta gene variant causing thyroid hormone resistance that needs to be further explored.
Presentation: Friday, June 16, 2023
FRI557 Don’t Forget The Incidental Thyroid Nodule In Graves’ Disease. A Case of Marine-Lenhart Syndrome
Authors: Andino-Lebrón Katira Nicole , Martinó-Morales Alejandro , M Janet 
Published: October 2023

Abstract
Disclosure: K.N. Andino-Lebrón: None. A. Martinó-Morales: None. J.M. Colón-Castellano: None.
Marine-Lenhart syndrome (MLS) was initially described by Charkes in 1972 as he observed patients with Graves’ disease (GD) and incidental functioning thyroid nodules. He named the disease Marine-Lenhart syndrome based on a paper published by Marine and Lenhart in 1911. MLS is a variant of GD now described as the coexistence of GD and autonomous functional thyroid nodules (AFTN); thus, patients present with thyrotoxicosis due to GD and AFTN. MLS is very rare, and prevalence is estimated to be around 0.8%-2.7%. Here, we present a case of MLS in a 79-year-old female. A 79-year-old Hispanic woman with history of breast metaplasia s/p chemoprevention with tamoxifen for 5 years, atrial premature contractions on metoprolol, among other medical conditions was referred to Endocrinology clinics by her primary care physician (PCP) because of abnormal thyroid function tests and ultrasound. She reported feeling anxious with associated palpitations, she denied weight loss. Physical examination was remarkable for regular rate and rhythm, no goiter, no palpable nodules, no proptosis, and deep tendon reflexes +1. Laboratory testing revealed a suppressed TSH of 0.224 uIU/mL, normal free T4 at 1.17 ng/dL, normal total T3 at 142.5 ng/dL, and positive thyroid stimulating immunoglobulins at 345%. Thyroid ultrasound showed a normal size gland with multiple complex nodules. In the right lobe there was a mixed cystic and solid nodule, measuring 1.48x1.21x1.71cm, wider than tall, with internal vascularity and punctate calcifications. In the left lobe there was an isoechoic and solid nodule measuring 0.7x0.5x0.7cm, wider than tall, without calcifications. Thyroid uptake scan with SPECT-CT demonstrated a focus of increased tracer uptake on the upper pole of the right thyroid lobe that corresponds to the one found on CT scan and a diminished and nonuniform uptake of the tracer in the reminders of the thyroid gland. The 24-hour radioactive iodine uptake was 17.5%. Diagnosis of MLS was made, and the patient was started on methimazole 5mg daily, which she has been tolerating well. Follow up laboratories show a biochemically euthyroid state. Marine-Lenhart syndrome is a rare entity of Graves’ disease which is currently defined as GD and accompanying functioning nodule(s). To establish the diagnosis, it is important the evaluation with scintigraphy and autoimmune testing. Multiple treatment options are available and patients with GD should be evaluated for the presence of thyroid nodules and their functional status to achieve optimal therapy. Patients with GD have a chance of remission when treated with antithyroid drugs. Due to the pathophysiology of AFTN, patients with MLS (concurrent GD and AFTN) have lower remission rates with antithyroid drugs and may require definitive management therapy with radioactive iodine or surgery.
Presentation: Friday, June 16, 2023
FRI562 Not JUST Severe Hypothyroidism: Recognizing Autoimmune Polyglandular Syndrome
Authors: Jafarian-Kerman Scott R , Razzeto Alejandra , Saini Gagandeep , Siddiqui Mariah , Islam Mohammed , Behman Daisy , Carson Michael 
Published: October 2023

Abstract
Disclosure: S.R. Jafarian-Kerman: None. A. Razzeto: None. G. Saini: None. M. Siddiqui: None. M. Islam: None. D. Behman: None. M. Carson: None.
Background: Recognizing Autoimmune Polyglandular Syndrome (AIPS) in a patient who has chronic hypothyroidism, specifically with a non-classic presentation, is challenging. Clinical Case: A woman in her 50’s with hypothyroidism presented with one week of progressive dizziness and weakness. Medications include levothyroxine 125 μg weekly (per the patient, her PCP started this dose 8 months ago based on lab results). On physical examination: BP 101/74 mmHg; HR 56 bpm; T: 98.1 F (36.7 C); RR: 23/min; O2 Sat: 98%. Skin: vitiligo. Lab results demonstrated TSH: 839.6 μIU/mL (0.5-4.5) from 0.28 one year ago, free T4: 0.15 ng/dL (0.4-4.5), phosphorus: 2.3 mg/dL (2.7-4.5), vitamin D: 17.4 ng/dL (&gt;30). She was started on daily levothyroxine 125 μg and intravenous fluids. On day 3 of admission, Rapid Response was called for blood pressure 54/39 mmHg. Myxedema coma was unlikely as she lacked altered mental status, hypothermia, hypoventilation, hyponatremia, or hypoglycemia; CT head was normal. On the same day, hydrocortisone 100 mcg q8h started due to high suspicion of adrenal insufficiency given low normal cortisol [7.1 ug/dL (6-20)] and hypotension. Due to the history of hypothyroidism, vitiligo, and the new diagnosis of adrenal insufficiency, we suspected AIPS. two days later, primary adrenal insufficiency was established by a positive Cosyntropin stimulation test (1 hour cortisol of 14.8 ug/dL; not reaching &gt;18 μg/dL), elevated ACTH 72 pg/mL (6-50), Aldosterone &lt;1 ng/dL (3-16), and low DHEA of 52 ng/dL (345-2030). Other labs were as follow: normal FSH 85.7 mIU/mL (23-116), elevated PTH 153 pg/mL (16-77) which decreased to 62 pg/mL with vitamin D supplementation, normal Vitamin B12, and negative renin and intrinsic factor antibodies. A diagnosis of AIPS was established and she was discharged on levothyroxine, fludrocortisone, and hydrocortisone. Conclusion: AIPS is typically idiopathic and may affect endocrine organ systems either simultaneously or sequentially. The 3 classic patterns are: Type 1 (most common): younger women, presents with candidiasis, hypoparathyroidism, and Addison’s disease. Type 2: middle-aged women, Addison’s disease, autoimmune thyroid disease and/or Type 1 diabetes. Type 3: Type 1 diabetes, pernicious anemia, vitiligo or alopecia, and normal adrenal cortical function. This patient is unique in that she has characteristics of both type 1 and 3 AIPS, but not diabetes. In this case, the combination of hypotension even in the setting of profoundly undertreated hypothyroidism, prompted the expanded evaluation. While isolated hypothyroidism is common among our internal medicine patients, those with additional symptoms, or in this case unexplained hypotension, should be evaluated for AIPS.
Presentation: Friday, June 16, 2023
FRI567 Insulin Autoimmune Syndrome And Grave’s Disease
Authors: Skariah Annie M , Porter Tama 
Published: October 2023

Abstract
Disclosure: A.M. Skariah: None. T. Porter: None.
Background: Insulin autoimmune syndrome (IAS), also known as Hirata’s disease, is a rare condition characterized by immune mediated post prandial hypoglycemia, due to presence of high titers of insulin autoantibodies (IAA). Most cases reported in Asian population with strong association with HLA-DR4 and specifically with the DRB1*0406. Clinical case: Patient is 36-year-old Asian female with no significant past medical history got evaluated by primary care physician because of fatigue, weight loss and neck swelling. Her symptoms are consistent with hyperthyroidism, got evaluated and found to have elevated thyroid hormone levels and suppressed TSH. At the time of diagnosis, free T3 2922 pg/dl(230-420pg/dl), free T4 &gt; 7.7 ng/dl (0.9-1.7 ng/dl), TSH &lt; 0.01uIU/ml (3-4uIU/ml), total T3 599 ng/dl (80-195 ng/dl), total T4 19.6Ug/dl (5-11 Ug/dl). Patient was started on methimazole, and beta blocker. Other labs including autoimmune panel were positive for TSI (2.8 with normal &lt;1.3) and thyroid receptor antibody &gt;40 (&lt;15.5 IU/l) confirming Graves' disease. 4 weeks after starting treatment with methimazole, patient was experiencing episodes of hypoglycemia, related to food intake. She checked her blood sugar and the lowest blood sugar she noticed was 53 mg/dl. She had no history of diabetes and never used insulin or any other oral diabetic medications. Insulin levels &gt;1000 uIU/ml (2.6-24.9uIU/ml), insulin antibody levels &gt;625 uU/ml (&lt;5 uU/ml), C-peptide as high as 9.5ng/ml (1.1-4.4 ng/ml), Insulin/C-peptide ratio 105, proinsulin elevated 40.3pmol/l (0.0-10 pg/l), and oral hypoglycemic agent screening negative. With the lab results, diagnosis of Hirata’s syndrome was made, Management discussed with the patient. Since patient still having labs consistent with hyperthyroidism, continued methimazole and started on diet interventions including low-carb diet and including complex carbohydrates in the diet. Patient gradually responded to dietary interventions with decrease episodes of hypoglycemia. Never required acarbose or steroids. Follow-up labs shows that patient is responding decrease in the levels of insulin antibodies 116 uU/ml and insulin levels 19.5 uIU/ml. Patients’ hyperthyroidism responded to methimazole, and dose reduced eventually to 5 mg daily with latest labs of free T4 1.21 ng/dl, Free T3 2.7 pg/ml and TSH 2.010 uIU/ml. Conclusion: Association between methimazole and IAS has been already reported before. When a patient is presenting outside Asian countries with similar symptoms, differential of IAS can be missed due to its rarity. But because of globalization; people from all races are seen in every part of the world. It will be beneficial to screen patients for IAS which can decrease cost of work up and treatment, when considering imaging modalities which were included as the part of the work up.
Presentation: Friday, June 16, 2023
FRI570 Repatha Induced Thyroid Storm
Authors: Sepulveda-Garcia Luis Ruben , Madera Marin Luis Norberto , Musa Penna Laurianne El , Medina-Torres Wilnelia , Ortiz-Rivera Monica Alexandra , Rosado-Burgos Alexandra , Alvarado Milliette , Ramirez Margarita , Alejandra Gonzalez-Rodriguez Loida 
Published: October 2023

Abstract
Disclosure: L.R. Sepulveda-Garcia: None. L.N. Madera Marin: None. L. El Musa Penna: None. W. Medina-Torres: None. M.A. Ortiz-Rivera: None. A. Rosado-Burgos: None. M. Alvarado: None. M. Ramirez: None. L.A. Gonzalez-Rodriguez: None.
Introduction: Proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors are an effective medical therapy for lowering plasma LDL-cholesterol and enhancing the LDL-cholesterol ability of statins. In 2020, a case of transient hyperthyroidism secondary to evolocumab was reported. We present a case of impending thyroid storm after a patient received evolocumab. Patient description: 60 y/o female patient with medical history remarkable for hyperlipidemia, anti-TPO positive non-toxic multinodular goiter, hypertension, fibromyalgia, and coronary artery disease who presented with heat intolerance, palpitations, tremors, and insomnia after second dose of evolocumab. At physical exam found with tachycardia, hypertension, anxious mood, tremors, leg pitting edema +1 bilateral, and deep tendon reflexes +3 in lower extremities, although no palpable or painful goiter. Laboratories compatible with hyperthyroidism [TSH &lt; 0.008 uIU/mL (0.3 – 3.0 uIU/mL), Free T4 4.29 ng/dL (0.89 – 1.76 ng/dL), Total T4 20.03 ug/dL (4.5-12 ug/dL)] and clinically with severe thyrotoxicosis. Patient was sent to ED for further evaluation and management. Case outcomes: Upon admission patient presented with a tonic-clonic seizure with short post ictal state. Burch-Wartofsky scale Point Scale 35, consistent with impending thyroid storm. Thyrotoxicosis management given requiring high doses of PTU, hydrocortisone and propranolol, including the need to add cholestyramine to the regime. By day 9 of therapy, patient was transitioned to methimazole 30mg daily with discontinuation of hydrocortisone and cholestyramine. Upon discharge, 2 weeks later, thyroid function tests had normalized to a FT4 of 1.39 ng/dL and a Total T4 of 9.6 ug/dL. Case discussion: A case of transient hyperthyroidism with PCSK9 inhibitor was previously reported requiring only symptomatic treatment. In this case a patient presented with severe thyrotoxicosis after she received her second dose of evolocumab. PCSK9 inhibitor therapy immunological influence on thyroid remains unknown. This case shows the importance of thyroid function test follow up in patients on PCSK9 inhibitor therapy and the possibility of immunological influence on the thyroid.
Presentation: Friday, June 16, 2023