bluuebunny/crossref_metadata_2025_split huggingface dataset:
ODP583 Screening for Pheochromocytoma in a Cohort of Patients with Takotsubo Cardiomyopathy: New insights on Prevalence and Screening Tests Reliability Surrounding the Acute Cardiac Event
Authors: Bitton Yoel , Bourdeau Isabelle , Gagnon Nadia , Legault Jonathan , Mansour Samer , Guay-Gagnon Martin 
Published: November 2022

Abstract

Background
According to Takotsubo cardiomyopathy (TCM) diagnostic criteria, pheochromocytoma and paraganglioma (PPGL) should be excluded as secondary causes. However, it is unclear whether PPGL screening in the setting of acute TCM is reliable. We aimed to assess the prevalence of PPGL and the reliability of PPGL screening in a cohort of patients with TCM. Method: We retrospectively reviewed data from patients admitted in a tertiary hospital between August 2012 and January 2021 with a diagnosis of TCM proven by typical echocardiography findings and no acute occlusion on coronarography, who were screened for PPGL by plasma metanephrines/normetanephrines (M/NM). If the first screening was positive, a second plasma M/NM sample was used for confirmation. Time between TCM diagnosis and PPGL screening was collected.

Results
Among 64 patients identified with TCM, 42 underwent plasma M/NM screening. 81. 0% were female, and the mean age was 67.4 ± 9.9 years old. Ten patients (23.8%) had a positive result. Of those, 8 patients had a weakly positive result (1-2×upper limit of normal [ULN]) and 2 had a strongly positive result (&gt;2×ULN). Of those 10 patients, 6 underwent a second screening: 5 had a normal result and 1 had a weakly positive result (plasma NM 1. 06×ULN). This patient underwent a third screening that was negative. In addition, an abdominal CT showed normal adrenal glands, and their chromogranin A levels were normal. Four patients had a positive initial PPGL screening, but they did not undergo a second screening: 3 died of causes unrelated to TCM before a second plasma M/NM sample was taken and one patient was lost to follow-up (his plasma NM was weakly positive at 1.29×ULN). They all had an abdominal CT that showed normal adrenal glands. Average time between TCM diagnosis and PPGL screening in all patients and in patients with a positive initial screening was 4.57 ± 3.91 and 3.38 ± 2.12 days, respectively. A linear regression model suggested an inverse relationship between plasma M/NM and time between TCM diagnosis and screening, with R2 = 0.2275.

Conclusion
TCM occurring as the initial presentation of PPGL is rare. All patients with a positive screening ended up being false positives in our study. The ratio of false positive results when screening for PPGL in the setting of acute TCM seems to be higher than in the general population, which could be explained by a hyperadrenergic state. It is unclear whether a shorter delay between TCM diagnosis and PPGL screening may be associated with more false positives. More research is needed to determine what is the optimal timing for PPGL screening in acute TCM and if higher cut-offs should be used to minimize false positive results.
Presentation: No date and time listed
LBSAT311 Rhabdomyolysis: A Rare Presentation Of Hashimoto Thyroiditis In An Adolescent Boy
Authors: Saroufim Rita , Eugster Erica A 
Published: November 2022

Abstract

Introduction
Hashimoto thyroiditis is the most common cause of hypothyroidism and is associated with a wide range of clinical presentations in children and adolescents. Hypothyroidism-induced rhabdomyolysis without precipitating factors is extremely rare, particularly in pediatric patients. We describe a previously healthy adolescent boy who came to our institution with vague symptoms and was found to have rhabdomyolysis secondary to hypothyroidism due to Hashimoto thyroiditis.

Clinical Case
A 16 year old boy presented to the emergency department at Riley Hospital for Children due to a two week history of bilateral eye and lip swelling. Additional symptoms included fatigue, sleepiness, slowing of speech, decreased attention span and weight gain. He was not on any medications and had no history of allergies. There was no family history of endocrine or neuromuscular disorders. Physical exam revealed a height of 177 cm (75th tile), weight of 118.4 kg (99th %tile) and BMI at the 99th %tile. Exam was significant for slow generalized movements, facial edema, and delayed deep tendon reflexes in all extremities. The thyroid gland was normal. Laboratory evaluation revealed Creatinine-1.46 mg/dL (0.3-1.2), ALT-88 Units/L (7-52), AST-254 Units/L (13-39), TSH-32.2 mcU/mL (0.4-4.2), fT4 &lt;0.2 ng/dL (0.6-1.5) and CK 20,500 Units/L (30-223). Thyroid peroxidase antibody was elevated at 686.1 IU/mL. A renal and bladder ultrasound showed trace intra-abdominal ascites and decreased echogenicity of the bilateral psoas muscles favoring edema and consistent with rhabdomyolysis. He received IV hydration and was started on levothyroxine 25 mcg daily that was increased over a 10 month period to achieve euthyroidism. Genetic testing for rhabdomyolysis revealed two variants of unknown significance. Acyl carnitine and carnitine profiles were normal ruling out a metabolic myopathy. His symptoms improved significantly after treatment with levothyroxine although his CK levels plateaued around 1,000 Units/L. Liver and kidney function normalized during follow up.

Conclusion
Rhabdomyolysis is a rare but serious complication of hypothyroidism, the pathogenesis of which is unclear. Proposed hypotheses include impaired mitochondrial oxidative metabolism, decreased muscle carnitine and switching of muscle fibers from fast-twitching type II to slow-twitching type I due to thyroxine deficiency ultimately leading to myolysis and release of intracellular muscle contents into the circulation. It is important for clinicians to have a high index of suspicion for hypothyroidism in children who present with muscle weakness and high creatinine kinase levels. The etiology of the disproportionately mild elevation of TSH in the setting of an unmeasurable free T4 and severe clinical hypothyroidism in our patient remains a mystery.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
ODP447 A Case of Hidden Grave's After Total Thyroidectomy
Authors: Baghel Annavi , Ortega Lucy 
Published: November 2022

Abstract

Introduction
A Sub-sternal goiter is a condition where there is an abnormal enlargement of thyroid gland that extends into the chest. The most commonly accepted definition is when &gt;50% of the volume of a goiter extends into the thoracic inlet. We present an interesting case of a Sub-sternal goiter emerging as a cause of Grave's disease, years after Total Thyroidectomy.

Clinical Case
The Patient is a 75 year old female with PMH of endometrial cancer, who initially underwent total thyroidectomy due to Thyromegaly causing dysphagia, and was started on Levothyroxine therapy after surgery. Three years later, a sub-sternal mass, was incidentally found via CT chest, which measured 3.7cm in largest diameter. Nuclear Medicine uptake and scan confirmed thyroid origin of this mass with an increased uptake but no percentage uptake was provided. Patient's Thyroid functions tests remained within normal range on levothyroxine. But over the next 2 years,the patient needed declining doses of LT4, then became euthyroid, off of levothyroxine and eventually became hyperthyroid, with positive Thyroid stimulating immunoglobulin. She also developed symptoms of tremors and tachycardia, and developed Atrial fibrillation as well. Noophthalmopathyor dermopathy was found on exam. Repeat CT chest showed the sub-sternal goiter had increased to a partially calcified mass of 5.6 cm. NM uptake scan showed 38.6%, at 24 hour, generalized uptake of this mass. Radioactive Iodine Ablation was performed with 30.1mCi and she subsequently became hypothyroid again until 1 year ago when she had episodes of A-fib again, and was found with TSH of 0. 09(0.45-5.33mIU/L) and FT40.9 (0.6- 1.2 ng/dl) and free T3 of 6.4 (pg/dl), off of levothyroxine. NM uptake and scan was repeated which indicated recurrence of Grave's disease from the same source. The Patient chose to initiate Methimazole therapy while contemplating surgical resection.
Clinical Lesson: This is a unique case of Sub-sternal goiter, presenting as grave's disease, years after total thyroidectomy. This case emphasizes on the importance of identifying and treating sub-sternal goiter, as it can cause severe Grave's disease and thyrotoxicosis. Especially in this case, since Grave's caused by this sub-sternal goiter was recurrent after Radioactive iodine ablation.
Presentation: No date and time listed
ODP451 A Case of Papillary Thyroid Cancer Presenting with Marantic Endocarditis and Recurrent Stroke
Authors: Karuppasamy Gowri , Elhadd Tarik 
Published: November 2022

Abstract
Marantic endocarditis or non-bacterial thrombotic endocarditis (NBTE) is characterized by the presence of vegetations on cardiac valves, which consist of fibrin and platelet aggregates and are devoid of inflammation or bacteria. The hypercoagulable state associated with malignancy is well known to be associated with NBTE. Here we report a rare case of Papillary Thyroid Cancer presenting with Marantic Endocarditis and Recurrent Stroke. A 52-year-old lady, with medical background of hypertension, presented to the Emergency Department with history of sudden onset of difficulty in speaking for 3 days. On examination she had slurred speech and tongue deviation to the right side. Neurological examination was otherwise normal. Imaging revealed left frontal, right frontal and left cerebellar infarcts. Transthoracic Echocardiogram showed a large, highly mobile vegetation 18 mm in size, attached to the posterior mitral valve leaflet as well as severe Mitral Regurgitation. She was diagnosed as a case of Cardioembolic ischemic stroke due to endocarditis. She completed a course of empiric antibiotic therapy. However, her blood cultures and fungal culture revealed no growth. After 5 years, she again presented to the hospital with acute stroke. Trans esophageal Echocardiography now revealed multiple filamentous vegetations on the atrial surface of mitral valve, largest measuring 20 mm×4 mm. Her inflammatory markers were negative and 3 sets of blood cultures were again negative. A question was raised, as to whether the filamentous masses represent prolapsing ruptured chordae tendinae rather than vegetations. FDG PET-CT scan was thus performed and revealed: Left thyroid lobe focal uptake seen with an FDG-avid left parajugular lymph node. Ultrasound neck was then performed, which showed bilateral thyroid nodules with high suspicion ultrasound pattern per American Thyroid Association: ill-defined nodule seen in the lower pole measuring 8×8×7 mm with multiple foci of macrocalcification. Thyroid function tests were normal. Ultrasound guided thyroid fine needle aspiration (FNA) biopsy of the left thyroid nodule was performed. The cytology report was consistent with papillary thyroid carcinoma. She is planned for total thyroidectomy, after undergoing mitral valve replacement surgery. This case illustrates one of the paraneoplastic syndromes associated with thyroid cancer. A hypercoagulable state has been observed in several types of thyroid cancer, although the pathogenesis has not been well studied. The etiology of cancer-associated coagulopathy is complex, related to an imbalance in the hemostatic system and abnormal levels of coagulation factors. Further studies on the occurrence of thrombosis in different types of thyroid cancer would help to inform clinical practice in the management of thyroid cancer, including the need for anticoagulation in certain situations.
Presentation: No date and time listed
ODP465 BRAF V600 and NRAS Q61 mutations in thyroid fine-needle aspiration (FNA) with indeterminate cytology in Argentina
Authors: Repetto Esteban M , Fernandez Lucia , Lambertini Roberto , Jaen Ana Del Valle , Vega Veronica Ruda , Moldes Sofia , Aranda Claudio , Faure Eduardo , Oneto Adriana 
Published: November 2022

Abstract

It is known that thyroid cancer initiation and progression occurs because of gradual accumulation of genetic and epigenetic alterations at cell level. Many mutations associated with this disease have been reported to be present in genes encoding proteins in the mitogen-activated protein kinase (MAPK) signaling pathway, specifically BRAF and RAS genes, as well as in the PI3K/Akt signaling pathway, among others. In particular, molecular alterations in follicular cells in the BRAF or NRAS genes have been reported to be associated with the process of carcinogenesis. Previously we found BRAF and NRAS mutations are observed in a significant number of papillary and follicular thyroid carcinomas in our population, respectively. In this study, we tested the diagnostic performance of BRAF and NRAS mutation in thyroid carcinoma in fine-needle aspiration (FNA) specimens with indeterminate cytology. In total, residual material from 73 FNA samples was used (n= 16, Bethesda III; n=48, Bethesda IV and n=9 Bethesda V). BRAF codon 600 mutation and NRAS codon 61 mutations were investigated using qPCR and melting curve analysis was carried out. Diagnosis of malignancy was confirmed by histology on paired surgical specimen in 54 cases.

Results
In the cytologically indeterminate categories, 9.6% of specimens were BRAF V600 mutated: 1 of 16 were subcategorized as atypia of undetermined significance or follicular lesion of undetermined significance (6.3%); 2 of 48 as follicular neoplasm or suspicious for follicular neoplasm (4.1%); and 4 of 9 as suspicious for malignancy (44.4%). NRAS Q61 mutation was found in 4 patients (2 with Bethesda IV and 2 with cytology V). The BRAF V600 mutations were associated with carcinoma in 100% of cases (n = 7), whereas only 75% (n = 3) of the nodules with NRAS were associated with carcinoma. BRAF V600 and NRAS Q61 mutations had high specificity in predicting malignant carcinoma (96.8%); the sensitivity was 43.5% with a positive predictive value of 90.9% and a negative predictive value of 69.8%. In specific categories of indeterminate cytology, the pre-test risk of malignancy was 38%, 33% and 88% while the post molecular test risk of malignancy was 100%, 75% and 100% respectively.

Conclusions
BRAF V600 and NRAS Q61 molecular test in residual FNA samples improve diagnostic accuracy of the cytology analysis in our population and may help to better select patients for avoid inadequate or unnecessary surgeries.
Presentation: No date and time listed
ODP474 Critical Analysis of the Thyroid Cytopathologic Diagnosis of Atypia of Undetermined Significance and Associated Clinical Outcomes
Authors: LaRoe Matthew , Godfrey Sean , Kalia-Reynolds Shelly , Sheth Krupa , Yesaulava Mila , Demirtas Esra , Drake Almond 
Published: November 2022

Abstract

Introduction
FNA is the optimal test for classifying concerning thyroid nodules. Approximately 15-30% of FNAs are indeterminate, representing diagnostic challenge with intra- and inter-observer variability among cytologists. The Bethesda System (BS) for cytopathology was created in 2007 to standardize thyroid cytology with corresponding malignancy risk. Our goal is to identify the incidence of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/ FLUS) and the percent of malignant AUS/FLUS cases at our institution.

Methods
Chart review of 3068 adult patients with FNA performed from 2003 to 2015 was completed, with attention to reports considered "indeterminant". BS for reporting thyroid cytology was not in use at our institution during that time. Cytopathology reports were evaluated for key descriptors concerning for AUS, FLUS, or follicular neoplasm.

Results
461 cytology reports included language consistent with possible "indeterminate" cytology. These reports were reviewed with our institution's cytopathologist and retrospectively assigned an equivalent BS category. 241 cases were consistent with BS category III (7.86% of all thyroid nodule FNAs done during this time period). Molecular marker studies were not being performed at our institution on indeterminate thyroid cytology specimens during this time period. Of the patients who had indeterminate cytology consistent with BS category III, 66.3% (160/241) went for surgery. The malignancy rate was 27.5% (44/160) in the BS category III group.

Conclusion
Our data demonstrated that category III nodules in some practice settings may have a higher risk of malignancy than traditionally believed, and that guidelines recommending repeat FNA or observation merit reconsideration. Molecular marker testing on indeterminate thyroid cytology specimens has been shown to be helpful in determining cases for surgery and is now being utilized at our institution.
Presentation: No date and time listed
ODP476 Does Levothyroxine Intake at Breakfast Matter for Patients With Hypothyroidism? A Meta- Analysis of Randomized Control Trials
Authors: Cheng Ce , Sun Chenyu , Rizwan Tehlil , Ramanathan Shrungavi , Pendergrass Merri 
Published: November 2022

Abstract
The American Thyroid Association recommends taking levothyroxine consistently, "either 60 minutes before breakfast or at bedtime." However, clinicians typically opt to recommend taking levothyroxine on an empty stomach, rather than offering the option of bedtime or with breakfast. Many patients find it cumbersome to take levothyroxine in the morning without food. A meta-analysis was performed to evaluate the effects of taking levothyroxine (LT4) before breakfast (BB) vs. with breakfast (AB) on thyroid function tests in our included four clinical trials. Four randomized controlled trials involving 243 patients were retrieved from PubMed, according to established inclusion criteria. The Standard Mean Difference (SMD) of thyroid-stimulating hormone (TSH), free T4 (FT4), and free or total T3 (F/TT3) with their 95% confidence intervals between AB vs. BB were calculated. Random effect or fixed-effect model was used based on heterogeneity significance. Then a subgroup analysis of liquid levothyroxine and tablet levothyroxine was performed. Sensitivity analysis and publication bias detection were performed. All statistical analysis was performed using RevMan software (v5.4; Cochrane library) and R Core Team (2016, Vienna, Austria), and all p-values were two-tailed, and the significance level was 0. 05. No statistically significant differences of TSH (Mean 1.45-3.74 vs. 1.26-3. 00, SMD 0.25; 95% CI: -0. 06, 0.56; p=0.11, I2=65%), FT4 (Mean 1. 03-1.35 vs. 1. 02-1.24, SMD 0.14; 95% CI: -0.33,0.62; p=0.55, I2=78%), and F/TT3 (SMD -0. 06; 95% CI: -0.28,0.15; p=0.57, I2=0%) between AB vs. BB were found. The subgroup analysis showed that no statistically significant difference of TSH between AB vs. BB when patient took liquid form of levothyroxine (1.45-2.59 vs. 1.26–3. 00; SMD=0. 03; 95% CI: -0.21, 0.27; p=0.81, I2=0%). Although TSH was significantly higher with AB vs. BB when patient took tablet form of levothyroxine (2.89-3.74 vs. 1.54 -1.9; SMD=0.64; 95% CI: 0.24, 0.103; p=0. 001, I2=49%), TSH was within normal limits in both groups. This meta-analysis demonstrates that TSH of patients taking levothyroxine with breakfast is non-inferior to those taking it before breakfast. Although AB group taking levothyroxine by tablet has a significantly higher TSH level than the BB group, both groups have well-controlled levels. Limitations of this study include limited sample size and number of studies. It also was unable to differentiate patients with hypothyroidism from benign or malignant diseases. We also were not able to assess adherence to the prescribed regimen. Patient satisfaction and adherence with treatment may be improved by letting patients know to take LT4 consistently at a time of their choice.
Presentation: No date and time listed
ODP479 Equilibrium Dialysis ID-LC/MS/MS Procedure for Routine Measurement of Free Thyroxine in Serum
Authors: Zhang Li , Ribera Ashley , D’Zio Zachary , Sugahara Otoe , Tse Cindy , Danilenko Uliana , Hubert Vesper 
Published: November 2022

Abstract
Free thyroxine (FT4) test is essential for diagnosis of thyroid diseases. Most FT4 tests used in patient care are immunoassays (IAs). However, concerns about the accuracy of FT4 IAs have been raised in the clinical laboratory community. Reference measurement procedure (RMP) for FT4 based on well-defined equilibrium dialysis (ED) of serum has been established and are well recognized. While FT4 RMP is highly accurate and precise, it is not intended for routine clinical use. Our aim is to develop an ED-based FT4 assay that is traceable to the RMP and suitable for routine measurements such as investigations in epidemiologic studies. The described assay is based on ED-LC-MS/MS. FT4 in serum was isolated from protein-bound T4 in serum according to the CLSI C45-A guideline. FT4 levels achieved equilibrium in a commercially available micro-ED plate after 18 hours. The dialysate was collected and spiked with internal standard (13 C 6 -T4). The IRMM-468 certified primary reference material (JRC, Belgium) of T4 was used for assay calibration. FT4 in dialysate was extracted with ISOLUTE-96-well C18 SPE plates (Biotage) before LC-MS/MS analysis. T4 could be resolved from Triiodothyronine (T3), reverse triiodothyronine (rT3), and other interferences in the dialysate on a C18 UPLC column with an elution time of less than 8 min. Selective reaction monitoring in positive electrospray ionization mode was used for detection. The measuring range covered 1-100 pg/mL of FT4. The assay sensitivity allowed detection of 0.5 pg/mL FT4, which is sufficient for detection of FT4 in normal and hypothyroid patient samples. The difference of this method to the CDC FT4 RMP was within ±5%. The imprecision of the routine assay, evaluated over four different days, was less than 10% CV. The slopes of calibration curves in dialysate matrix and water were comparable with each other indicating no significant matrix effect on FT4 quantification. The use of micro-ED plates in combination with an automated liquid handling system allows for effective automation of the procedure. The stability of T4 calibrator stock and working solutions were confirmed at various conditions. Currently, a comprehensive comparison study is underway between the newly developed routine method and the CDC FT4 RMP. The described routine FT4 assay can significantly improve throughput. The sensitivity, precision, and accuracy are suitable for routine FT4 measurements in clinical laboratories and conducting large epidemiologic studies. Applying this FT4 routine method to generate population data will support the use of standardized FT4 measurements and to address data needs on FT4 in general population.
Presentation: No date and time listed