bluuebunny/crossref_metadata_2025_split huggingface dataset:
SAT550 Warthin-like Variant of Papillary Thyroid Carcinoma: An Even Rarer Presentation
Authors: Kunadia Jessica , Chablani Sumedha 
Published: October 2023

Abstract
Disclosure: J. Kunadia: None. S. Chablani: None.
Introduction: We present a rare case of Warthin-like variant of papillary thyroid carcinoma (WLPTC) with later development of a second primary malignancy. Clinical Case: A 56 year old female with hypertension, hyperlipidemia, ulcerative colitis, asthma, and a strong family history of cancer presented in 2017 for evaluation of an enlarged thyroid gland noted by her primary care provider. Patient was asymptomatic and denied prior thyroid disease and head or neck radiation. Labs demonstrated normal TSH and free T4 levels. TPO antibodies were elevated to 1,155 IU/mL (reference range 0.0 – 5.5 IU/mL). Thyroid US was notable for a diffusely enlarged thyroid gland containing a 1.4 x 0.6 x 1.0 cm solid, hypoechoic nodule without calcifications in the upper pole of the right lobe. Shared decision-making resulted in a plan for continued surveillance. Repeat thyroid US in 2018 demonstrated that this nodule had increased in volume by 56.25%, now measuring 1.4 x 0.75 x 1.25 cm. Fine needle aspiration (FNA) biopsy was performed and positive for papillary thyroid carcinoma (PTC). Patient underwent total thyroidectomy; pathology revealed a 1.2 x 1 x 0.9 cm WLPTC and 0.2 cm papillary thyroid microcarcinoma. There was no evidence of extrathyroidal extension, angioinvasion, or lymph node involvement. Follow-up neck US in 2020 demonstrated a 0.4 cm hypoechoic ovoid structure in the left thyroid bed and an enlarged but morphologically normal-appearing right level II lymph node. Repeat neck US in 2021 showed the appearance of a new 2.8 cm right level II lymph node; FNA was positive for malignancy with negative thyroid transcription factor-1 staining and undetectable thyroglobulin. Patient underwent an excision biopsy of the lymph node, and pathology was consistent with metastatic adenoid cystic carcinoma (ACC). A right submandibular gland lesion detected on subsequent MRI head and neck was resected and confirmed to be the primary source of ACC. Patient was treated with adjuvant radiation therapy with adequate response to therapy. Conclusion: WLPTC is a rare subtype of PTC that accounts for 0.2-1.9% of cases and carries a strong association with Hashimoto’s thyroiditis. It is histologically characterized by papillary architecture, oncocytic changes, nuclear features of PTC, and dense lymphoplasmacytic infiltration of the papillary cores. WLPTC is considered to have a favorable prognosis given its low frequency of lymphovascular invasion and low recurrence risk. This case also highlights the importance of keeping a broad differential when evaluating new findings on neck US in patients with a history of thyroid cancer. Metastases to cervical lymph nodes most commonly occur from head and neck tumors. However, to date, only one other case of PTC with second primary malignancy of salivary ACC has been reported.
Presentation Date: Saturday, June 17, 2023
SAT551 Significantly Elevated Thyroglobulin Levels with Negative Whole-Body Scan and PET/CT After Treatment of Thyroid Cancer: A Case Report
Authors: Bassatne Aya , Chaiban Joumana T 
Published: October 2023

Abstract
Disclosure: A. Bassatne: None. J.T. Chaiban: None.
Background: Thyroglobulin (Tg) levels are used to monitor recurrence or persistence of disease after treatment of differentiated thyroid cancer. Some cases may have persistently elevated Tg and negative whole-body scans (WBS). We present a case of substantially elevated Tg levels despite negative WBS and PET/CT after thyroidectomy and radioactive iodine (RAI) treatment in a patient with papillary thyroid carcinoma (PTC). Clinical Case: A 66 years old lady was referred to the endocrinology clinic almost 5 years ago after incidental findings of calcified thyroid nodules on CT. Thyroid US confirmed 2cm aggregate calcified nodules. FNA revealed PTC for which she underwent thyroidectomy. Pathology showed a unifocal 3.5 cm left lobe conventional PTC without angioinvasion nor extrathyroidal extension, 3/13 positive lymph nodes (LN) on the lateral dissection of the left neck as well as multiple small LN on the central dissection. 6 days postop, her Tg was still significantly high at 40.5ng/mL (Ref 1.2-35 ng/mL) and then increased to 397ng/mL after thyrogen preparation for RAI ablation, antithyroglobulin antibodies were negative. WBS post RAI was negative except for the physiologic neck uptake. Almost a year later, a diagnostic WBS after thyrogen stimulation was still negative but the stimulated Tg increased again to 235 ng/mL with negative thyroglobulin antibodies. Tg result were confirmed by LC-MS method. Heterophile Antibodies were negative. Patient confirmed that every single time she followed at least 2 weeks of low iodine diet in preparation for the WBS. Unfortunately, we were not able to get a 24 hour urine collection for iodine. A PET/CT was reassuring. CT neck/chest did not show any suspicious metastases. TSH was maintained at an adequately suppressed level all through and Tg levels were ranging around 6-8 ng/mL. After another year, a stimulated Tg was 302.4 ng/mL with a TSH of 198 mcU/mL (Ref 0.35-5.0 mcU/mL). At that time, a repeat WBS was negative and a repeat PET/CT demonstrated an interval development of a small thyroid focus thought to be consistent with recurrence of malignancy. However, a CT of neck/chest did not reveal any abnormal thyroid findings or metastases. Patient received 100 mCi of RAI after thyroid hormone withdrawal. Subsequent WBS was negative. Currently her Tg levels are stable at around 8-9ng/mL for the past 6 months with a suppressed TSH. Patient had another PET/CT through her breast surgeon to follow on a previous breast lesion and no thyroid abnormality was noted. Conclusion: Elevated Tg levels despite negative imaging may be seen in patients with PTC as illustrated in this case. We are reporting it due to the extent of elevation of Tg levels seen on more than one occasion in the absence of structural recurrence. Evaluation and treatment of such patients remain controversial.
Presentation Date: Saturday, June 17, 2023
SAT308 An Assessment Of Prognostic Markers To Predict Metastatic Pheochromocytoma/Paraganglioma
Authors: Lundholm Michelle D , Berber Eren , Rao Pratibha P R 
Published: October 2023

Abstract
Disclosure: M.D. Lundholm: None. E. Berber: None. P.P. Rao: None.
Introduction: Pheochromocytoma/paraganglioma (PCC/PGL, or PPGL) are rare neuroendocrine tumors arising from chromaffin cells. Early identification of PPGL with metastatic potential is a diagnostic challenge. More data are needed on features and scoring markers used to predict PPGL metastasis. Methods: A single-center, retrospective observational study was performed of consecutive patients with pathology-confirmed PPGL from 2005 to 2022. Features associated with metastasis were identified and Pheochromocytoma of the Adrenal gland Scaled Score (PASS), Age, Size, Extra-adrenal location and Secretory type (ASES) score, and Size, Genetic, Age, and PASS (SGAP) score were calculated. Results: We identified 371 patients with PPGL (251 PCC, 120 PGL), age 52.2±15.4yrs, 60.6% female, 69.8% incidental. Metastatic disease was reported in 13.2% (N=49; 30 PCC, 19 PGL) associated with younger age (47.3 vs 53.0yrs, p=0.029), larger tumor size (6.3 vs 4.0cm, p&lt;0.001), histologic findings of necrosis (26% vs 2.5%, p&lt;0.001) and vascular invasion (42.1% vs 19.6% p=0.038), hyperadrenergic symptoms at diagnosis (38.8% vs 22.0%, p=0.038), norepinephrine-only secreting tumors (59.6% vs 30.1%, p&lt;0.001), extra-adrenal location (51.0% vs 32.0%, p=0.009), presence of genetic mutations (72.4% vs 38.5%, p&lt;0.001), particularly SDHx (31.0% vs 12.2%, p=0.020) and VHL mutations (24.1% vs 3.8%, p=0.001). There were no significant differences by gender, race, other histologic criteria from PASS, or other mutations such as RET or NF-1. ASES was positive (≥2) in 27.2% (N=100/371) with sensitivity (SN) 79.6%, specificity (SP) 81.1%, positive predictive value (PPV) 39.0%, and negative predictive value (NPV) 96.3% for predicting metastatic disease. PASS and SGAP could only be applied to patients with PCC: PASS was positive (≥4) in 29.7% (N=55/185) with SN 60.0%, SP 73.9%, PPV 21.8%, and NPV 93.8%. SGAP was positive (≥5) in 27.6% (N=32/116) with SN 56.3%, SP 77.0%, PPV 28.1%, and NPV 91.7%. Discussion: Metastatic PPGL is associated with age, tumor size and location, select histologic findings, symptomatic presentation, hormone-secreting pattern, and select genetic mutations. PPGL scoring markers ASES, PASS, and SGAP were all effective at identifying cases with low likelihood of metastasis, but had poor PPV. ASES outperformed PASS and SGAP in test metrics and practicality as the only clinically-derived marker which could be applied to all cases of PPGL. ASES can also be used pre-operatively. Most histologic features and genetic mutations included in PASS and SGAP were not strongly correlated with metastasis, though limited by lower prevalence in the study population. Conclusion: Our data supports the use of ASES alongside data on necrosis, vascular invasion, SDHx and VHL mutations where available to fine-tune our prediction of metastatic potential for PPGL.
Presentation: Saturday, June 17, 2023
THU298 Effect Of SGLT2 Inhibition On Metabolic, Cardiac And Renal Outcomes In Heart Transplant Recipients (EMPA-HTx study): Protocol And Study Design
Authors: Raven Lisa M , Muir Christopher A , Kessler Iglesias Cassia , Kotlyar Eugene , Muthiah Kavitha , Bart Nicole K , Macdonald Peter S , Hayward Christopher S , Jabbour Andrew , Greenfield Jerry R 
Published: October 2023

Abstract
Disclosure: L.M. Raven: None. C.A. Muir: None. C. Kessler Iglesias: None. E. Kotlyar: None. K. Muthiah: None. N.K. Bart: Advisory Board Member; Self; Bristol-Myers Squibb. Grant Recipient; Self; Pfizer, Inc. Speaker; Self; Pfizer, Inc. P.S. Macdonald: Speaker; Self; Boehringer Ingelheim, AstraZeneca. C.S. Hayward: None. A. Jabbour: None. J.R. Greenfield: Speaker; Self; Boehringer Ingelheim, AstraZeneca.
Background: Heart transplantation (HTx) is standard of care for treatment of end-stage heart failure. Immunosuppression medication, required to prevent rejection, can result in adverse metabolic and renal effects. Clinically significant post-transplant complications include metabolic (diabetes, weight gain), renal impairment and cardiac disease, such as allograft vasculopathy and myocardial fibrosis. Sodium glucose co-transporter 2 inhibitors (SGLT2i) may have positive effects on all of these post-transplant complications. SGLT2i have been observed to improve metabolic parameters in patients with type 2 diabetes following cardiac and renal transplantation, but their benefit and safety in HTx has not been evaluated in randomised prospective studies. Aims: The overall aim of this project is to study the safety and efficacy of empagliflozin in HTx recipients. The primary end point will be improvement in glycaemic control assessed by change in glycosylated hemoglobin (HbA1c) and/or fructosamine, with secondary endpoints of cardiac fibrosis assessed by cardiac magnetic resonance, and renal function assessed by serum creatinine. Methods: Randomised, placebo-controlled trial of empagliflozin 10 mg daily versus placebo in recent HTx recipients. One hundred participants will be randomised 1:1. They will commence the study medication within 6-8 weeks of transplantation. Follow up will be 12 months after transplantation. Results from routine pre-HTx assessment will be reviewed to assess for pre-HTx diagnosis of diabetes. Routine laboratory tests, including full blood count, biochemistry, glucose, lipids and liver function as well as HbA1c, fructosamine, beta-hydroxybutyrate and urine albumin creatinine ratio, will be measured at baseline prior to receipt of study drug or placebo. Patients will be reviewed monthly during the study until 12 months post-HTx and data will be collected for each patient at each study visit. Cardiovascular magnetic resonance will be measured at baseline and 12 months after HTx. This study has been approved by St Vincent’s Hospital Human Research Ethics Committee (2021/ETH12184). Trial registration: ACTRN12622000978763. Discussion: This study will, for the first time, determine the efficacy and safety of SGLT2i in HTx recipients.
Presentation: Thursday, June 15, 2023
OR12-03 The Pancreatic Islet Alpha Cell Arginine Transporter SLC7A2 Regulates Arginine-induced Glucagon Secretion and Glycemia
Authors: Stanley Jade E , Reuter Austin , Sellick Katelyn , Attie Alan D , Keller Mark P , Dean E Danielle 
Published: October 2023

Abstract
Disclosure: J.E. Stanley: None. A. Reuter: None. K. Sellick: None. A.D. Attie: None. M.P. Keller: None. E. Dean: None.
Glucagon secreted from pancreatic islet α cells stimulates both hepatic glycogenolysis and gluconeogenesis resulting in the fractional extraction of amino acids from the blood. Thus, glucagon stimulates hepatic glucose output and raises blood glucose. When liver glucagon signaling is impaired, amino acid accumulation (hyperaminoacidemia) promotes subsequent α cell hyperplasia and hyperglucagonemia via this liver-α-cell axis, an endocrine feedback loop. We show that high levels of both glutamine and recently arginine are required to stimulate α cells to proliferate. Arginine also potently stimulates glucagon secretion, but the mechanisms behind this are not well defined. We find that the cationic amino acid transporter, SLC7A2/CAT2 is the most highly expressed amino acid transporter in human pancreatic α cells and three-fold higher in α cells than it is in β-cells in both mouse and human islets. We also find two SNPs in the human SLC7A2 locus are strongly associated with HbA1c (rs142010226 (A/G) - chr8: 17,367,112; p=9.11e-18; β=0.0113 and rs2517232 - chr8: 17,367,421; p=2.553e-14; β=-0.0283). Both SNPs are in the first intron of SLC7A2 but appear to exert opposite effect on HbA1c and associated with distinct haplotype blocks. ATAC-Seq analyses of human islets show that these SNPs are within 1 kb of binding sites for MAFB and FOXA2 transcription factors, both critical for α cell gene expression. To test if α cell expression of SLC7A2 plays a role in both glycemia and arginine-stimulated glucagon secretion, we generated α cell-specific Slc7a2-/- (α7A2KO) mice. Blood glucose and glucagon levels were not significantly different after a 6-hour fast in α7A2KO and 7A2WTCre+ mice. After a 6-hour fast, mice were administered an arginine bolus (2g/kg) via intraperitoneal injections and their blood glucose and glucagon levels were measured 15 minutes post-injection. α7A2KO mice had a significantly higher blood glucose level than 7A2WTcre+ mice after stimulation with arginine (arginine-stimulated blood glucose - 7A2WTCre+ 124.3 ± 26.7 mg/dl vs. α7A2KO 159.6 ± 32.1 mg/dl n=23-25 p=0.0019). However, glucagon secretion was significantly lower after stimulation with arginine in the α7A2KO mice compared to the 7A2WTCre+ mice (arginine-stimulated glucagon - 7A2WTCre+ 321.8 ± 171.9 pM vs. α7A2KO 74.6 ± 22.8 pM n=4-6; p&lt;0.0001). Together, these data indicate that SLC7A2 mediates arginine’s effects in α cells and plays an important role in regulating glycemia.
Presentation: Friday, June 16, 2023
OR12-05 Blunting Of Sympathetic Activation Of Pancreas As A Cause For Hypoglycemic Unawareness In Hypoglycemia Associated Autonomic Failure
Authors: Thakkar Keya , Hampton Rollie , Jimenez Gonzalez Maria , Espinoza Diego , Stanley Sarah 
Published: October 2023

Abstract
Disclosure: K. Thakkar: None. R. Hampton: None. M. Jimenez Gonzalez: None. D. Espinoza: None. S. Stanley: None.
Introduction: Hypoglycemia activates the autonomic nervous system to suppress pancreatic insulin and increase glucagon release, restoring blood glucose levels to normal. These effects occur partly via sympathetic innervation of pancreatic islets. Recurrent hypoglycemia leads to a blunted autonomic response known as Hypoglycemia Associated Autonomic Failure (HAAF), which further exacerbates hypoglycemia. The mechanisms underlying HAAF are not well-understood, but changes in pancreatic innervation may contribute. Hypothesis: Decreased activity and remodeling of sympathetic innervation to the pancreas contribute to autonomic dysfunction with repeated hypoglycemia. Methods: To examine pancreatic sympathetic innervation with repeated hypoglycemia, C57Bl6 mice were treated with 0, 1, or 5 episodes (0, 1x, or 5x) of insulin-induced hypoglycemia. Pancreata, sympathetic celiac ganglia, and brains were harvested. Pancreatic tissue was immunostained for insulin, glucagon, and tyrosine hydroxylase (TH), a marker for sympathetic innervation. Samples were then cleared using iDISCO+, imaged, and analyzed using Imaris to examine the 3D distribution of innervation and islets. To determine if pancreatic sympathetic nerve function is altered in HAAF, we used viral delivery to express activating chemogenetic constructs specifically in pancreas-projecting sympathetic nerves. We assessed the effects of chemogenetic activation of pancreatic sympathetic innervation during insulin tolerance testing (ITT) in C57Bl6 mice with or without previous recurrent hypoglycemia. Results: 3D image analyses suggest acute hypoglycemia (1x) upregulates islet glucagon staining intensity. By comparison, recurrent hypoglycemia (5x) ​decreases pancreatic TH+ innervation and may blunt hypoglycemia-induced increases in islet glucagon staining intensity. Chemogenetic activation of pancreas sympathetic nerves in mice with repeated hypoglycemia increased blood glucose during an ITT while activation in mice without previous hypoglycemia did not significantly alter blood glucose. These data suggest reduced activity in pancreatic sympathetic innervation with recurrent hypoglycemia that can be restored by chemogenetic activation. Conclusions: Our data suggest repeated episodes of hypoglycemia may remodel the structure and function of peripheral pancreatic sympathetic innervation as compared to one episode of hypoglycemia. Restoring activity in pancreatic sympathetic innervation may partially reverse the severity of hypoglycemia in HAAF. Staining and analysis of celiac ganglia and sympathetic outflow circuits in the CNS will allow determination of the level at which blunting of sympathetic activation and/or remodeling of innervation occurs.
Presentation: Friday, June 16, 2023
OR18-02 Mammary Insulin Sensitivity Increases At The Onset Of Lactation And Promotes Metabolic Pathways Supporting Breast Milk Synthesis
Authors: Meng Xin , Rostom Hussam , Fry Alexandria , Elajnaf Taha , Hannan Fadil 
Published: October 2023

Abstract
Disclosure: X. Meng: None. H. Rostom: None. A. Fry: None. T. Elajnaf: None. F. Hannan: None.
The initiation of lactation during postpartum days 1-4 is hormonally regulated and critical for successful breastfeeding. Insulin represents a key lactogenic hormone as evidenced by women with diabetes mellitus who have delayed lactation onset. However, the role of insulin in lactation and its influence on mammary cells are unclear. We utilised clinical and cellular approaches to investigate this, and recruited n=38 healthy pregnant women (age range 26-42 years) following informed consent and measured serum insulin at 36 weeks’ gestation and during post-partum days 1-4 (1). Serum insulin progressively decreased from 36 weeks’ gestation to day 4 post-partum (244±33pmol/L vs 37±4pmol/L, p&lt;0.0001). Moreover, reverse transcription-quantitative PCR (RT-qPCR) of lactating human mammary epithelial cells (HMECs) isolated from breast milk showed a &gt;20-fold increase in insulin receptor expression compared to non-lactating HMECs (p&lt;0.01, n=4). These findings indicated an increase in both systemic and mammary insulin sensitivity at lactation onset. We hypothesised that insulin promotes lactation by influencing mammary metabolism and used cultured HMECs to evaluate this. Stimulation of HMECs with 10nM insulin caused a &gt;7-fold increase (p=0.001, n=5) in the phosphorylation of Akt, a signalling protein required for initiating lactation. Akt influences oxidative phosphorylation and glycolysis, and we assessed these processes by measuring oxygen consumption rate (OCR) and extracellular acidification rate (ECAR), respectively. Cultured HMECs treated with 10nM insulin for ≤18hrs showed increased OCR (22±0.9 vs. 17±0.4pmol O2/min/106 cells for control HMECs, p&lt;0.05, n=4) and ECAR (0.23±0.003 vs. 0.18±0.002mpH/min/106 cells for control HMECs, p&lt;0.001, n=4), consistent with increased oxidative phosphorylation and glycolysis. HMECs treated with 10nM insulin for 8hrs had significant upregulation of genes encoding glycolytic enzymes, namely hexokinase 2 (&gt;4-fold increase, p&lt;0.0001, n=4) and pyruvate kinase M1/2 (1.4-fold increase, p&lt;0.05, n=4). However, RT-qPCR analysis of HMECs showed that insulin did not increase expression of genes mediating oxidative phosphorylation, suggesting an Akt-mediated post-transcriptional mechanism. In summary, increased mammary insulin sensitivity together with insulin-stimulated oxidative phosphorylation and glycolysis may support mammary function and milk component synthesis at the onset of lactation.
Reference: (1) Rostom, H. et al. Protocol for an observational study investigating hormones triggering the onset of sustained lactation: the INSIGHT study. BMJ Open 12, e062478.
Presentation: Saturday, June 17, 2023