bluuebunny/crossref_metadata_2025_split huggingface dataset:
PSAT334 An Unusual Case of Thyroid Storm in a Patient with Schizophrenia-A Diagnostic Dilemma
Authors: Markovic Nikolina , Umar Rehan , Raghuwanshi Maya 
Published: November 2022

Abstract

Introduction
Thyroid storm represents life threatening endocrine disorder that requires early recognition and treatment due to significant mortality rates. Case reports in which diagnosis of thyroid storm was delayed secondary to acute psychotic symptoms mainly consisting of auditory hallucinations, delusions, and violent behavior have been published. This case serves to illustrates that even in patients with schizophrenia acute psychiatric disorder can be early manifestation of life-threatening endocrine disorder.

Clinical case
We present a case of 25-year-old male with history of schizophrenia who was brought to hospital after he was found down, disoriented, with auditory hallucinations. Associated symptoms included diarrhea and abdominal pain. On physical exam patient was found to have altered mental status, proptosis, tachycardia, diaphoresis, and warm and moist skin. Due to suspicion for worsening schizophrenia patient was evaluated by psychiatry and was found to have active suicidal ideation. Thyroid function tests (TFTs) was significant of elevated fT4 and T3 (fT4 &gt; 5.0 ng/dl, T3 6.5 ng/dl) and suppressed TSH (0.020 µIU/ml). Burch-Wartofsky Point Scale was suggestive of impending thyroid storm and endocrinology was consulted after which treatment with methimazole, dexamethasone, propranolol, and potassium iodide (Lugol's solution) was started. On second day of treatment patient had significant improvement in mental status with resolution of auditory hallucination, suicidal ideation, and tachycardia with complete return to his baseline mental status on the third day of hospital stay. At the end of hospital course TFTs also showed decrease in fT4 and T3 and patient was discharged on methimazole and propranolol as well as paliperidone for treatment of schizophrenia. When patient was seen during outpatient follow-up, he was free of any psychiatric symptoms.

Conclusion
Mental status changes due to thyroid storm versus acute worsening of schizophrenia is hard to differentiate. Our case shows that even in the patients with prior psychiatric history, thyroid storm should be highly on differential diagnosis especially when patients are presenting with acute worsening of symptoms. In this case high suspicion for thyroid storm and early treatment in first 24h of the presentation lead to favorable outcome of this life-threatening condition. As thyroid storm is clinical diagnosis, high suspicion, use of Burch-Wartofsky Point Scale and early measurement of TFTs can help physicians distinguish thyroid storm from primary neuropsychiatric presentation.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
RF11 | PSAT234 Deep learning analysis of thyroid nodule ultrasound images has high sensitivity and negative predictive value to rule-out thyroid cancer
Authors: Clark Toshimasa , Cohen Trevor , Haugen Bryan R , Subramanian Devika , Pozdeyev Nikita , Dighe Manjiri , Barrio Martin , Leu Michael G 
Published: November 2022

Abstract

Purpose
To evaluate deep learning analysis of thyroid nodule ultrasound images as a rule-out test for thyroid malignancy.

Methods
Supervised deep learning (DL) classifier of thyroid nodules was trained on 32,545 thyroid US images from 621 nodules representing all major benign and malignant types of thyroid lesions and tested on an independent set of 145 nodules collected at a different healthcare system in the United States. The Big Transfer BiT-M ResNet-50×1 convolutional neural net architecture was modified to contain 3, 4, 6 and 3 PreActBottleneck units per block 1 through 4. Weights pretrained on the ImageNet-21k dataset were loaded and weights for blocks 3 and 4 were fine-tuned for the binary classification task of distinguishing benign and malignant thyroid nodules.

Results
The deep learning thyroid nodule classifier achieved an area under receiver operating characteristic curve (AUROC) of 0.889 on five-fold cross-validation. The AUROC improved when images were scaled by nodule size and six randomly selected cine clip frames were added to the training set per epoch. GradCAM class activation heatmaps revealed that microcalcifications and spongiform appearance were reliably recognized by the classifier as malignant and benign features, respectively. Spongiform nodules were found to be benign even when microcystic spaces constituted less than 50% of nodule volume.
To investigate the clinical relevance of the benign vs. malignant classifier, the binary classification threshold for the probability of malignancy generated by model was set at 7% to achieve sensitivity and negative predictive value (NPV) comparable to that of the fine needle aspiration biopsy (FNA). At this threshold, cross-validated deep-learning model achieved a sensitivity of 90%, specificity of 63%, positive predictive value (PPV) of 46% and negative predictive value of 94%. When tested on an independent image set that includes 18 classic papillary thyroid cancers (PTC), 5 follicular variant PTC, 4 medullary thyroid cancers, 3 follicular thyroid cancers (FTC), and 1 Hurthle cell thyroid cancer, the DL classifier achieved AUROC of 0.88, sensitivity of 97%, specificity of 61%, PPV of 40% and NPV of 99%. A single minimally-invasive FTC that had no suspicious features on thyroid ultrasound was incorrectly classified as benign.

Conclusions
This study demonstrates that the ultrasound-based deep-learning classifier of thyroid nodules achieves sensitivity and negative predictive value comparable to that of thyroid fine needle aspiration (FNA). Clinicians may use this tool to augment clinical judgment when determining whether to perform FNA procedures.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Saturday, June 11, 2022 1:06 p.m. - 1:11 p.m.
RF35 | PSAT262 Comparative Study of Hertel Exophthalmometer and Luedde Exophthalmometer Versus Computed Tomography for Measurement of Proptosis in Normal Subjects
Authors: Traiwanatham Sirinapa , Sirinvaravong Sirinart , Plengvidhya Nattachet , Wongsripuemtet Jitsupa , Lertlam Supassa 
Published: November 2022

Abstract

Background
Clinical evaluation of proptosis is measured by an exophthalmometer. Hertel exophthalmometer has long been considered a standard instrument for measurement of eye protrusion. The reading may be subject to error while the examiners read through the integral reflection mirrors. Luedde exophthalmometer, which is a ruler correcting for parallax, is easier to use and less expensive than Hertel exophthalmometer. Since CT scan of orbits or brain provides the most objective assessment of proptosis measurements, we aim to study the correlation between Luedde and Hertel exophthalmometers in comparison with the CT scan for the evaluation of proptosis in normal subjects.

Methods
This prospective study was carried out between November 2020 and January 2021. Sixty-three patients were enrolled from a single tertiary hospital. All patients underwent CT scan of brain for medical reasons. On the same day, proptosis was measured with Hertel and Dual Luedde exophthalmometer by two independent examiners. Measurement of proptosis from CT scan was performed by one experienced neuroradiologist, using 2 reference measurement techniques. Correlation coefficients between proptosis values measured by each exophthalmometer and CT scan were compared.

Results
The mean age of the participants was 63 years old and 54% were female. For the right eye, mean proptosis measurement was 14.9+/-1.6 mm by Hertel exophthalmometer, 14.1+/-2.3mm by Luedde exophthalmometer, 16.6+/-2.3 mm by first CT technique, and 13.1 +/- 2.2 mm by second CT technique. For the left eye, mean proptosis measurement was 15.5 +/-1.5mm by Hertel exophthalmometer, 13.7+/-2.3 mm by Luedde exophthalmometer, 16.6+/-2.3 mm by first CT technique and 13.1 +/- 2.2 mm by second CT technique. The Intraclass correlation coefficient (ICC) of Hertel exophthalmometer for proptosis measurement compared to first CT technique and second CT technique were 0.63 and 0.60 for right eye; 0.61 and 0.55 for left eye, respectively. The ICC of Luedde exophthalmometer for proptosis measurement compared to first CT technique and second CT technique were 0.78 and 0.74 for right eye; 0.77 and 0.74 for left eye, respectively.

Conclusion
There is a good correlation between Hertel and Luedde exophthalmometers in evaluation of proptosis. However, proptosis measured by Luedde exophthalmometer shows superior correlation with CT scan. The result suggests that Luedde exophthalmometer can be routinely used for measurement of proptosis in place of Hertel exophthalmometer, given the simplicity and the inexpensiveness of the instrument.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 12:30 p.m. - 12:35 p.m.
RF35 | PSAT268 Reversal of Graves’ Disease Associated Facial Volume Expansion and Eyelid Changes Following Teprotumumab Therapy
Authors: Ugradar Shoaib , Douglas Raymond 
Published: November 2022

Abstract

Background
Thyroid eye disease (TED) causes orbital soft tissue expansion. Teprotumumab, a monoclonal antibody to the IGF-1R reduces orbital soft tissue swelling in TED. In this study, we quantified the changes to pan facial soft tissue volumes, following treatment with Teprotumumab.

Methods
In this prospective longitudinal study, all patients presenting at our institution for the treatment of TED were considered for study eligibility. Patients who were currently on any other medical therapy for TED were excluded. Further, patients who had any plans to embark on a weight loss regime, or medications that might cause weight loss were excluded. The primary outcome measure was a change in soft tissue volume of the face from baseline to within 3 weeks of the final infusion. Secondary outcome measures included changes in proptosis, clinical activity score and body weight. All patients had 3D facial imaging using the Vectra H2 (Canfield, USA). The use of this system to quantify volumetric change in facial soft tissue has previously been shown to be reliable and accurate.
We also used the Mimics (Materialise) software to build 3D reconstructions of the face from CT scans, allowing us to calculate the volume of muscle and fat tissue pre and post treatment. Relationships between continuous variables were analyzed using bivariate and multivariate analysis. Intraobserver and Interobserver variability was calculated by two observers doing all calculations twice on two separate days.

Results
Forty-three patients with confirmed euthyroid status at the time of study were included. The mean duration of TED was 30 months (34). Following Teprotumumab therapy, the mean (SD) decrease in volume for each region was 0.74 mL (0.82) in the upper face, 1.9 mL (1.2) in the periorbital region, 0.18 mL (0.6) in the temples, 1.73 mL (2.2) in the midface and 2.84 mL (4.7) in the lower face. The mean (SD) decrease in the volume of the full face was 8.4 mL (8.5) (figure 2). There was a significant correlation between 3D facial imaging and volumetric study using CT scans (p &lt; 0.05). Mean (SD) weight prior to therapy was 75 kg (12) and 69 kg (15) following therapy (p &lt; 0.05). There was no relationship between previous steroid use and total body weight reduction and changes in facial volume.

Conclusion
The results of this study expand the borders of TED, suggesting its sequelae may reach beyond that of the orbit and periorbital tissues, to include changes across the entire face. Teprotumumab significantly reduces these changes.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Monday, June 13, 2022 12:42 p.m. - 12:47 p.m.
ODP545 Ectopic Cushing's Syndrome in Small Cell Lung Cancer: A Frequently Missed Diagnosis
Authors: Iqbal Qasim , Martinez Valerie 
Published: November 2022

Abstract
A 61-year old woman, heavy smoker (40 pack-years) with a medical history of type 2 diabetes was brought to the hospital with the chief complaint of altered mental status. She had been recently diagnosed with stage IV small cell lung cancer two weeks prior but had not started chemotherapy. Physical examination was consistent with scattered petechiae and violaceous striae in bilateral upper extremities, chest, and trunk. On arrival, the patient had a blood glucose of 506 mg/dl, K 2.5 mmol/L, bicarb 23, pH 7.5, and beta-hydroxybutyrate 5.3. Further workup revealed an AM cortisol &gt;110 and extremely elevated urine and salivary cortisol at 21000 ug/dl and 97200 ug/dl, respectively. Other remarkable labs were ACTH 480 and low TSH (0.288), free T4 (0.53), and free T3 (1.5). MRI abdomen showed bilateral adrenal masses characteristic of metastatic disease. MRI brain did not show signs of pituitary pathology. The patient was started on Ketoconazole 200 mg twice daily, Octreotide 100 mg IV every 6 hours, and Spironolactone 25 mg twice daily. Spironolactone was increased to 50 mg and later to 100 mg due to significant hypokalemia. At the same time, she was also started on urgent inpatient chemotherapy with Cisplatin/Etoposide and completed one cycle. Cortisol levels started to improve and eventually normalized. Her mental status improved as well. Although the patient symptomatically improved, her extensive-stage small cell lung cancer makes her prognosis poor in the long term.
Presentation: No date and time listed
ODP558 Steroid Receptor Coactivators Promote Non-Small Cell Lung Cancer Tumorigenesis by Inhibiting Differentiation Factors, C/EBPα and NF-κB
Authors: Mendelson Carole , Mishra Ritu 
Published: November 2022

Abstract
The steroid receptor coactivator (SRC) family comprises three members, SRC-1 (NCOA1), SRC-2 (NCOA2), and SRC-3 (NCOA3). These SRC family members modulate diverse gene expression programs both by nuclear receptors and other transcription factors to drive physiological and pathophysiological processes. Notably, SRC-1, -2 and -3 also were found to be involved in different aspects of tumorigenesis. SRC-1 and SRC-3 overexpression has been observed in endometrial, ovarian, prostate, colorectal, gastric, lung, pancreatic and liver cancers. SRC-2 expression is elevated in patients with metastatic prostate cancer. This suggests that SRC family members are involved in signaling pathways critical for cancer cell proliferation and tumorigenesis. In the present study, we have begun to elucidate the mechanisms by which SRC members play a role in non-small cell lung cancer (NSCLC). We used the potent small-molecule SRC inhibitor, SI-2, which significantly impedes primary tumor growth in a breast cancer mouse model [1]. SI-2 selectively reduces cellular protein levels of SRC-1, SRC-2 and SRC-3 post transcriptionally. We observed that treatment of the NSCLC lines A549 and H1299 with SI-2 significantly induced protein expression of CCAAT/enhancer-binding protein-α (C/EBPα). C/EBPα is a basic leucine zipper transcription factor that is highly expressed in differentiated fetal lung epithelial cells, where it controls differentiation-dependent gene expression and inhibits cell proliferation. C/EBPα was found to be inactivated in various types of cancers, providing evidence for a possible tumor suppressor function of the C/EBPα (CEBPA) gene. We found that activation of C/EBPα in SI-2 treated NSCLC (A549 and H1299) was associated with a decline in the levels of histone deacetylases, HDAC-2 and-4. This suggests that inhibiting SRC family members in lung cancer cells causes reactivation of the epigenetically suppressed CEBPA gene by inhibiting histone deacetylase expression. We also observed that SI-2 increased expression of nuclear factor-κB (NF-κB) p65 protein in both A549 and H1299 cells. Previously, we found that NF-κB activates signaling pathways leading to enhanced fetal lung epithelial cell differentiation by decreasing HDAC-2 and -4 expression and binding to promoters of differentiation-inducing genes. Overall, we speculate that the SRC inhibitor, SI-2, blocks NSCLC proliferation and tumorigenesis by enhancing histone acetylation and transcriptional activation of putative tumor suppressors, C/EBPα and NF-κB, to increase lung epithelial cell differentiation. References1. Song, X., et al., Development of potent small-molecule inhibitors to drug the undruggable steroid receptor coactivator-3. Proceedings of the National Academy of Sciences, 2016. 113(18): p. 4970-4975.
Presentation: No date and time listed
RF27 | LBSUN362 Germline CDKN1B Variants Type And Site Are Associated With Specific Phenotype In Multiple Endocrine Neoplasia 4
Authors: Halperin Reut , Tirosh Amit 
Published: November 2022

Abstract

Background
The latest of the multiple endocrine neoplasia (MEN) syndromes described is MEN4, caused by germline CDKN1B tumor suppressor gene mutation. The main clinical manifestations of MEN4 are primary hyperparathyroidism (PHPT), neuroendocrine tumors (NET) and pituitary adenomas (PitAd). CDKN1B codes for the nuclear protein p27, a key regulator of cell cycle. This protein is an intrinsically unstructured protein, that folds upon interacting a putative interactor. It is comprised of two major domains: a kinase inhibitory domain (CDKi) that binds to cyclins and cyclin dependent kinase (CDK), and a scatter domain. p27 acts by inhibiting complexes of cyclins and CDKs, thus preventing the transition between phases of the cell cycle. Less than sixty cases of MEN4 syndrome were described thus far, with clinical manifestations resembling in part to a late onset of MEN1.

Hypothesis
Specific alterations in p27 protein will result in distinct clinical phenotypes.

Methodology Case report
We collected published and unpublished data on all currently known patients with MEN4 worldwide, including newly identified kindreds from our clinic, and performed a thorough genotype-phenotype analysis of the various MEN4 manifestations. Whole exome sequencing was performed, revealing a germline CDKN1B frameshift variant (p.Q107fs*12), that was further verified by Sanger sequencing. A detailed literature review, including requests of unpublished clinical data from past studies was undertaken. Based on the data we performed a time-dependent risk analysis for the three main manifestations of MEN4 by various genotype-related parameters: variant type (single-nucleotide variant vs. indels) and site (variant- and domain-specific analyses). Major results Of 73 cases, 53.4% developed PHPT, 28.8% had PitAD and 19.2% - NET. PitAd developed earlier (age, 34.4±21.4 years) compared with PHPT (50.6±13.9 years) and NET (52.9±13.9 years). The risk to develop PHPT, PitA and NET in patients with MEN4 were 53.4%, 23.2% and 16.2% by age 60 years, respectively.CDKN1B variants clustered in genetic locations, or "hotspots" (i.e., codon 41 frameshift: n=13, codon 107 frameshift: n=11, c.-29-(-26)AGAG deletion: n=4). Although founder effect is relevant, this finding is in contrast to MEN1 genotype. We then performed time-dependent risk analysis for developing clinical manifestation by each gene domain alteration (either point mutation or upstream indel). We found a higher risk to develop PHPT or PitAd with variants affecting codons 94-96 (Log-rank, p values 0.014 and 0.047, respectively), and trend towards higher risk for PHPT for Scatter domain variants (p=0.09). Moreover, indels were associated Conclusions: MEN4 genotype is distinct than MEN1, by the presence of hotspots, and genotype-phenotype association. Further, the risk for PHPT is lower than MEN1, with a lower penetrance, and older age at diagnosis.
Presentation: Monday, June 13, 2022 1:12 p.m. - 1:17 p.m.
PSUN299 GLP-1 Contribution to Insulin Secretory Response to Protein Ingestion and Insulin Kinetics Following Gastric Bypass and Sleeve Gastrectomy
Authors: Rayas Maria , DeFronzo Ralph A , Gastaldelli Amalia , Salehi Marzieh 
Published: November 2022

Abstract
Rapid passage of ingested nutrients to the gut after Roux-en-Y gastric bypass (GB) and sleeve gastrectomy (SG) results in hyperinsulinemia after glucose ingestion, in part due to an enhanced glucagon-like peptide-1 (GLP-1)-induced insulin secretory response (ISR) and reduced metabolic clearance rate of insulin (MCRI). The effect of endogenous GLP-1 on insulin kinetics is unknown, and so is GLP-1 contribution to insulin secretory response to non-glucose nutrient ingestion. In non-surgical subjects, protein ingestion enhances insulin secretion and reduces MCRI. We hypothesized that protein ingestion enhances GLP-1-induced ISR and alters MCRI in proportion to changes in nutrient influx after GB and SG.
To test this hypothesis ISR, β-cell sensitivity to glucose (BGS), MCRI, and oral glucose insulin sensitivity (OGIS) were measured on 3 days during 50 g glucose ingestion as well as 50 g protein ingestion with and without GLP-1R antagonist, exendin (9-39) [Ex-9] infusion. Ten GB-treated subjects, 9 SG-treated, and 7 non-operated controls (CN) were enrolled. The 3 non-diabetic groups were matched for age, BMI, fat-free mass, HbA1c; surgical groups were matched for weight loss and time post-surgery.
Fasting glucose, insulin, and ISR were similar among the 3 groups and among the 3 studies but fasting MCRI was greater in surgical groups than CN (p&lt;0.05). Compared to glucose, protein ingestion led to larger BGS in 3 groups despite smaller overall ISR response (AUCISR3h) (p&lt;0.05). Blocking GLP-1R during protein ingestion decreased AUCISR3h only in surgical subjects (p&lt;0.05 for interaction), whereas BGS was reduced similarly in 3 groups during Ex-9 infusion (p&lt;0.05). OGIS was smaller during protein than glucose ingestion in 3 groups (p&lt;0.05). GLP-1R blockade did not affect insulin sensitivity. Following nutrient ingestion in parallel with increase in insulin secretion MCRI was reduced to nadir values at 40 minutes, but then gradually increased approaching premeal values at different pace among surgical and non-surgical subjects (p&lt;0.05). The slope of MCRI: Insulin (0-40 min) was smaller after protein ingestion than glucose, and after protein with Ex-9 infusion than without in 3 groups (p&lt;0.05). Blocking GLP-1R had no effect on MCRI values in the latter phase of protein ingestion when insulin secretion reduced approaching premeal values. There was no association between parameters of insulin sensitivity and insulin clearance during glucose or protein ingestion.
Our findings indicate that the regulation of insulin secretion and clearance during protein ingestion is altered after GB and SG. Further, endogenous GLP-1 contribution to insulin secretory response to protein ingestion after GB and SG is enhanced, but GLP-1 effect on insulin kinetics is trivial.
Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.