bluuebunny/crossref_metadata_2025_split huggingface dataset:
6525 Alternating Hypothyroidism and Hyperthyroidism Complicated by Thyroid Eye Disease
Authors: Chen A M , Barnett B G 
Published: October 2024

Abstract
Disclosure: A.M. Chen: None. B.G. Barnett: None.
Conversion of hypothyroidism to hyperthyroidism, as well as alternating hypothyroidism and hyperthyroidism, is a rarely described phenomenon believed to be largely mediated by alterations in thyrotropin receptor autoantibodies. A 70-year-old Caucasian woman with a history of glaucoma was diagnosed with primary hypothyroidism in 2004 and had remained biochemically euthyroid on thyroid hormone replacement therapy, taking a combination of daily levothyroxine 100 mcg and desiccated thyroid extract (DTE) 15 mg. In January 2018, she was found to have biochemical thyrotoxicosis on routine thyroid testing. Accordingly, her dose of DTE was stopped by her primary care provider. Her dose of levothyroxine was sequentially decreased and eventually stopped in September 2018. She reported having an upper respiratory tract infection a few weeks before this conversion in thyroid function was observed. She was referred to endocrinology that November, and was noted to have fatigue, hair loss, red and dry eyes, and double vision requiring ophthalmology evaluation. Her home medications included estradiol patch, multivitamin, and cetirizine. Mild proptosis of her left eye was observed. Labs showed subclinical hyperthyroidism and positive thyroid antibody assays: TSH &lt;0.01 mIU/L, free T4 1.32 ng/dL, total T3 115 ng/dL, TSI 374 % basal activity, TBII 4.73 IU/L, and TPO antibody 39 IU/mL. Given her symptoms, the patient was initiated on methimazole 5 mg daily. Repeat labs two months later revealed she had become overtly hypothyroid again. Methimazole was discontinued. A period of biochemical euthyroidism ensued, until she became overtly hypothyroid again in October 2019 and levothyroxine was restarted at 50 mcg daily. Her disease course was complicated by severe thyroid eye disease (TED) with left optic neuropathy and restrictive strabismus. Between 2019 and 2020, her TED was treated with a course of IV methylprednisolone, followed by left 3-wall orbital decompression and subsequent left inferior rectus recession. Of note, she was diagnosed with breast cancer in 2021 and is now status post mastectomy and on anastrozole therapy. The patient has remained biochemically euthyroid on levothyroxine 50 mcg daily since October 2019, based on her age-adjusted TSH reference range. Her TED Clinical Activity Score has improved to 0 from initial pre-treatment score of 2. This case illustrates the potential for a patient with autoimmune hypothyroidism to convert to and from a hyperthyroid state, even after more than a decade interval. It is presumed that she had a predominance of TSH receptor blocking antibodies that caused her previous hypothyroidism, and then shifted to a predominance of TSH receptor stimulating antibodies causing thyrotoxicosis. Clinician awareness and further research into this disease entity is crucial to elucidate its pathogenic basis and identify risk factors and potential treatment options.
Presentation: 6/3/2024
12361 An Unusual Case of Myxedema Coma
Authors: Hasan Nazmul , Yang Daniel , Othman Thaer , Dai-Ju Jenny 
Published: October 2024

Abstract
Disclosure: N. Hasan: None. D. Yang: None. T. Othman: None. J. Dai-Ju: None.
Background: Most cases of Myxedema Coma are associated with primary hypothyroidism with significantly elevated TSH levels. However the presence severe illness can contribute to decreased TSH release even in the absence of central lesions. Case: 60 year old female was found down covered in feces. She was hypothermic to 89°F, with a pulse of 62. Physical exam revealed hair loss, thick tongue, non-pitting edema, and delayed relaxation of brachial reflexes. Labs showed Sodium of 123, blood glucose of 80. Thyroid function testing revealed only a mildy elevated TSH of 13 with free T4 &lt;0.025. Anti-TPO antibodies were elevated at 157. MRI of the Sella was negative any lesions. Thyroid ultrasound showed atrophic bilateral thyroid lobes. Assessment for hypopituitarism did not show any significant deficiencies with Cortisol 45, ACTH 11, LH 0.5, FSH 8.5, IGF-33, and Total Testosterone 10. She was found to have septic shock secondary to perforated sigmoid colon requiring colectomy. She was initially loaded with Dexamethasone 4mg followed by IV Levothyroxine 100mcg, with steroids being discontinued after AI was ruled out. After treating her sepsis she was transitioned to 150mcg of oral Synthroid with improvement of her thyroid function tests to TSH of 2.7 and free T4 of 1.56. Discussion: The majority of Myxedema Coma is associated with primary hypothyroidism. In these cases, TSH levels are markedly elevated, often greater than 100. When the TSH is not as elevated as we would expect, many factors must be considered, the greatest being central hypothyroidism where TSH secretion may be impaired from pituitary tumors, surgery, radiation, and other causes. Our patient however did not have any central lesions on imaging and was found to have anti TPO antibodies with atrophic thyroid lobes on ultrasound suggestive of primary hypothyroidism. This brings us to the effect of acute illness on the balance of thyroid hormones. Conditions such as sepsis stimulates elevations in inflammatory cytokines which disrupt the physiologic response to release TSH. Previous studies involving sepsis revealed the main cytokines implicated are TNF alpha, Interferon gamma, IL-1, and IL-6. The degree of inadequate TSH secretion is often times proportional to the severity of illness and improves after recovery from the illness. Conclusion: Our body's response to critical illness involves complex hormonal changes which affect the HPA axis and can decrease TSH secretion, even in myxedema coma without central lesions.
Presentation: 6/1/2024
7205 Anaplastic Thyroid Carcinoma Presenting as New-Onset Thyrotoxicosis and Hypoparathyroidism in a Young Patient: A Diagnostic Dilemma between Hashitoxicosis and Anaplastic Thyroid Cancer
Authors: Sulehri Muhammad Shahan , Bustamante Eilyn G , Elmaaz Ahmed , Chaudhuri Ajay 
Published: October 2024

Abstract
Disclosure: M. Sulehri: None. E.G. Bustamante: None. A. Elmaaz: None. A. Chaudhuri: None.
Introduction: This case report explores the complex diagnostic challenges encountered in a young patient presenting with anaplastic thyroid carcinoma (ATC) manifested by thyrotoxicosis and hypoparathyroidism. Case report: A 29-year-old male who sought multiple emergency room visits for shortness of breath, was initially misdiagnosed with pneumonia. On the third visit, exacerbated respiratory distress led to intubation, CT of the neck and thyroid US unveiling an infiltrative mass centered within the region of the thyroid gland. Initial thyroid function tests showed TSH &lt;0.02 uIU/mL, free thyroxine 6.91 ng/dL, and total T3 204 ng/dL indicating hyperthyroidism, promptly managed with Methimazole and beta blockade. Elevated TPO antibodies (194 unit/mL) were observed, whereas thyroglobulin antibodies and thyroid receptor antibodies were undetected. Concurrently, hypoparathyroidism was noted, marked by low calcium levels (7.9 mg/dL) with albumin of 3.4 g/dL (corrected Calcium 8.4), and low parathyroid hormone (PTH) (&lt;6 pg/mL). Other labs showed ionized calcium 4.30 mg/dL, phosphate 4.6 mg/dL, magnesium 1.8 mg/dL, and vitamin D 54 ng/dl. The patient received calcium carbonate supplement, calcitriol and IV calcium gluconate. Thyrotoxicosis then transitioned to hypothyroidism and levothyroxine replacement therapy was initiated. Definitive diagnosis was delayed due to the patient's overall condition and a low suspicion of malignancy. Left thyroidectomy and tracheostomy were performed, revealing dense subplatysmal necrosis with tumor involvement of both thyroid lobes and isthmus with multiple enlarged nodes. Final surgical pathology confirmed the presence of anaplastic thyroid carcinoma. Due to poor prognosis, the patient was transferred to hospice care where the patient succumbed to his condition within a day. Conclusion: Anaplastic thyroid cancer is considered one the most aggressive and fastest growing tumors. Although it is usually seen in patients after the age of 60, we present a very rare case of ATC in a young patient in the third decade who was presented with infiltrative thyroiditis and hypoparathyroidism. The case underscores the importance of considering rare etiologies in patients with atypical clinical presentation.
Presentation: 6/1/2024
7272 Antineoplastic Effect of Cabozantinib in Primary and Continuous Human Anaplastic Thyroid Cancer Cells
Authors: Elia Giusy , Ferrari Silvia Martina , Ragusa Francesca , Mazzi Valeria , Patrizio Armando , Balestri Eugenia , Botrini Chiara , Rugani Licia , Barozzi Emilio , La Motta Concettina , Fallahi Poupak , Antonelli Alessandro 
Published: October 2024

Abstract
Disclosure: G. Elia: None. S. Ferrari: None. F. Ragusa: None. V. Mazzi: None. A. Patrizio: None. E. Balestri: None. C. Botrini: None. L. Rugani: None. E. Barozzi: None. C. La Motta: None. P. Fallahi: None. A. Antonelli: None.
Anaplastic thyroid cancer (ATC) is a highly aggressive cancer with a low median survival of about 6-10 months. The standard treatment include surgery, external hyperfractionated radiation therapy, and chemotherapy. However, these therapies are not effective and new therapeutical approaches are needed. Tyrosine kinase inhibitors (TKI) are a class of drugs able to inhibit different pathways that results inappropriately activated in cancer cells.To date no studies evaluated the effect of cabozantinib in primary human ATC cells, and in ATC continuous cell line in vitro. We aimed to test the efficacy of cabozantinib a multiTKI acting against VEGFR 1,2, c-MET, and RET (recently approved for aggressive differentiated thyroid cancer) in primary human ATC cells, and in ATC continuous cell line (8305C, CAL-62) in vitro. Therefore, for primary ATC cells we collected surgical thyroidal tissues from five patients with ATC, from thyroid biopsy at the moment of first surgical operation, and we tested the effect of cabozantinib. Cabozantinib showed its efficacy in inhibiting cell proliferation, and also in increasing apoptosis (p &lt; 0.05) both in primary and in continuous ATC cells. In conclusion, cabozantinib demonstrated a good antineoplastic activity in human ATC cells in vitro. These results open the way for a possible clinical use of cabozantinib in patients with ATC, and are important for a personalized therapeutic approach to be tailored to each patient avoiding the administration of ineffective drugs.
Presentation: 6/1/2024
8049 Beyond Metastasis: Parasitic Thyroid Tissue Mimicking Thyroid Cancer
Authors: Shah Mahabir Singh , Humayon Salman , Mungo Nicolas A 
Published: October 2024

Abstract
Disclosure: M.S. Shah: None. S. Humayon: None. N.A. Mungo: None.
This case study details a complex clinical scenario involving a patient with diaphoresis and a familial history of thyroid cancer. Initial suspicions of functionally active metastatic thyroid cancer led to a thyroidectomy and cervical lymph node dissection, only to reveal unexpected parasitic thyroid tissue. This case highlights the importance of meticulous evaluation and follow up similar presentations, shedding light on the rarity of this phenomenon.The patient, experiencing a year of diaphoresis unresponsive to estradiol therapy, underwent imaging revealing multiple thyroid nodules. A left superior nodule (TI-RADS 4) and a more concerning right mid-posterior nodule (TI-RADS 5) prompted fine needle aspiration (FNA). FNA of the right thyroid nodule exhibited Bethesda category III atypia, no molecular samples were taken at that time, while cervical lymph node FNA yielded nondiagnostic results.Subsequent ultrasound showed no interval change in the right thyroid nodule but raised concerns about increased solid components and decreased echogenicity in other nodules. Due to patient concerns of positive family history of thyroid cancer, the lymph node was biopsied. The result yielded a low cellular sample, but follicular thyroid tissue was present. The patient elected to undergo thyroidectomy as she did not want to continue monitoring. Pathology revealed parasitic thyroid tissue in the lymph node and nodular follicular thyroid disease, with no evidence of papillary thyroid carcinoma in the gland. Notably, the patient had no history of thyroid surgeries, ruling out traumatic rupture or implantation from a follicular adenoma. However, the possibility of follow-up metastatic follicular carcinoma cannot be entirely excluded on histologic grounds.Follow-up tests were recommended, encompassing mutational analysis, whole-body scans, and thyroglobulin (Tg) monitoring. Molecular analysis did not favor cancer. Tg levels remained at (18 ng/ml, n&lt; 35ng/ml) of initial evaluation six weeks post surgery and repeat testing is pending. Ablative radioactive iodine therapy may be appropriate as resection of all parasitic thyroid tissue can prove difficult.This case emphasizes the diagnostic challenges posed by the rare occurrence of parasitic thyroid tissue, often mistaken for metastatic thyroid cancer. The findings contribute to our understanding of uncommon thyroid pathologies. The clinical implications of this case extend to the importance of heightened clinical suspicion in intricate endocrine cases.
Presentation: 6/3/2024
7092 Blocking of Aggressive Tumor Progression of Anaplastic Thyroid Cancer by p53
Authors: Hwang E , Chari R , Kimura T , Cheng S Y 
Published: October 2024

Abstract
Disclosure: E. Hwang: None. R. Chari: None. T. Kimura: None. S. Cheng: None.
Background: Anaplastic thyroid cancer (ATC) is the most aggressive form of thyroid cancer, with very limited treatment options. Patients succumb to death within 6-12 months after diagnosis. It has been observed that mutations of p53, occurring as tumorigenesis progresses, is associated with the aggressiveness of ATC. The present studies tested the hypothesis that wild type p53 (WTp53) could block tumor progression and mitigate its aggressiveness. Methods: We used human 8505C cells as a model, derived from human ATC tumors, harboring BRAFV600E mutation and one allele of mutated p53C742G. We re-expressed WTp53 or mutant p53C742G into 8505C cells (8505C-WTp53 or 8505C-MTp53 cells, respectively) via lentiviral transduction. We analyzed the effects of exogenous expressed WTp53 and mutant p53 on cell proliferation, apoptosis, and migration in vitro and the progression of tumors in vivo mouse xenograft models. Results: We showed that p53 proteins were more abundantly expressed in 8505C-WTp53 or 8505C-MTp53 cells than the parental 8505C cells. Using WTp53 luciferase reporter (PG-13), we demonstrated that the expressed WTp53 was functional as the transcription activity of p53 was higher than the parental 8505C cells. Consistently, in 8505C-MTp53, the reporter activity of PG-13 was not detected. The expressed WTp53 inhibited cell proliferation and decreased cell migration. Immunohistochemical analysis (IHC) showed decreased proliferation marker Ki67 and increased cleaved caspase-3, indicating the induction of apoptosis in 8505C-WTp53 cells. Importantly, we found that the NIS expression was increased in 8505C-WTp53 cells, but not in 8505C-MTp53 cells, as compared with 8505C cells. Xenograft studies showed that tumor progression was inhibited in nude mice injected with 8505C-WTp53 cells as compared with tumors induced by 8505C parental cells and 8505C-MTp53 cells. Consistent with in vitro findings, IHC demonstrated decreased proliferation marker Ki67 and increased cleaved caspase-3 proteins in tumors induced by 8505C-WTp53 cells. Furthermore, the expression of apoptotic regulators such as BAX and PUMA, known as p53 target genes, were elevated in 8505C-WTp53 cultured cells and in 8505C-WTp53-induced tumors, indicating induction of apoptosis. Conclusions: Our findings showed that the aggressiveness of ATC, caused by mutant p53 in late stage of tumor progression, can be mitigated by exogenous expression of WTp53. These results provided new insights into the deleterious actions of mutation of p53 in ATC tumor development. Importantly, our studies revealed that targeting p53 in ATC could be considered as a potential therapeutic opportunity.
Presentation: 6/3/2024
6517 Cardiac Tamponade Secondary to Occult Primary Hypothyroidism
Authors: Javed Laraib , Al jumaili Hamsa , Mahaldar Anshinee , Goyal Itivrita , Shakir Nabeela , Punni Emma 
Published: October 2024

Abstract
Disclosure: L. Javed: None. H. Al jumaili: None. A. Mahaldar: None. I. Goyal: None. N. Shakir: None. E. Punni: None.
Introduction: The incidence of pericardial effusion in hypothyroidism seems to correlate with severity and duration of the condition and ranges from 3% to 37%. Cardiac tamponade resulting from hypothyroidism is exceptionally rare. We present a case of a patient presenting with this complication.Case Summary:A 38-year-old woman presented during a routine clinic visit with symptoms of fatigue and was found to have elevated liver functions enzymes with ALT 107 (N&lt;48 U/L ) and AST 70 (N&lt;47 U/L)Further evaluation through abdominal imaging revealed incidental finding of a partially imaged moderate pericardial effusion. A subsequent echocardiogram showed circumferential pericardial effusion with early tamponade physiology, necessitating immediate referral to the emergency room (ER) for further assessment and management.Upon admission to the ER, the patient reported progressive fatigue, increased sleep and menorrhagia over 8 months. There were no accompanying symptoms of weight gain or constipation. Family history was positive for thyroid disease in her grandmother. Initial vital signs on admission were Blood pressure: 119/86, Pulse: 55, Respiratory Rate: 13, Temp: 36.7 °C. Electrocardiogram showed sinus bradycardia. Laboratory findings were significant for: Hgb 8.7 (N&gt;11.5), MCV 77.5 (N&gt;80 fL), mildly elevated ALT 56, markedly elevated TSH 255 (N&lt;5 IU/mL), low free T4 &lt;0.1 (N ≥ 0.7 ng/dL), low free T3 &lt;0.6 (N ≥2.0 pg/m), and elevated TPO 472 (N 35 IU/mL). Infectious and rheumatologic work-up were negative. Thyroid ultrasound showed heterogenous echogenicity consistent with thyroiditis.Patient underwent urgent pericardiocentesis draining 750 ml of clear yellowish pericardial fluid. Simultaneously, the patient was initiated on daily levothyroxine at a dose of 112 mcg.Stability in hemodynamics and repeat echocardiogram showcasing no pericardial effusion facilitated the patient’s discharge. Notable improvement with reduction in TSH from 260 to 20 was seen at the one-month follow-up in endocrinology clinic. Conclusion: Hypothyroidism should be considered in patients diagnosed with cardiac tamponade presenting with bradycardia, as in this case. It's been observed that hypothyroidism can affect LFTs which typically resolve with thyroid replacement. Treatment of cardiac tamponade depends on the patient's hemodynamic status. For early mildly affected cases of tamponade, a conservative approach involving close monitoring and limiting fluid intake may suffice, but drainage is often necessary. Since the pericardial effusion and tamponade stem from hypothyroidism, there's a high chance of effusion recurring after drainage. Hence, administering levothyroxine is essential, often leading to effusion resolution within 2-12 months without recurrence.
Presentation: 6/3/2024
6602 Classification of TSH Trajectories During Levothyroxine Treatment in the ELSA-Brasil Cohort
Authors: Ettleson Matthew D , Penna Gustavo C E , Wan Wen , Bensenor Isabela M , Laiteerapong Neda , Bianco Antonio C 
Published: October 2024

Abstract
Disclosure: M.D. Ettleson: None. G.C. Penna: Consulting Fee; Self; Ipsen, Bayer, Inc.. W. Wan: None. I.M. Bensenor: None. N. Laiteerapong: None. A.C. Bianco: Consulting Fee; Self; Abbvie.
Classification of TSH Trajectories During Levothyroxine Treatment in the ELSA-Brasil Cohort Introduction: Hypothyroidism is a common endocrine disorder for which levothyroxine (LT4) serves as the primary treatment. Periods during which thyroid stimulating hormone (TSH) levels are outside the normal range have been associated with adverse cardiovascular outcomes, including mortality. In practice, serial TSH levels are measured over time to ensure therapeutic LT4 treatment is maintained. However, there is no measure of the quality of treatment maintenance over time. TSH trajectory classification represents a novel approach to define the adequacy of LT4 treatment for hypothyroidism over time utilizing multiple observation points. Methods: With longitudinal clinical data, including thyroid function from a large prospective study, we aimed to define classes of TSH trajectories and examine changes in cardiovascular (CV) health markers over a 9 year study period with three observation points. Growth mixture modeling (GMM), including latent class growth analysis (LCGA), was used to classify LT4-treated individuals participating in the Longitudinal Study of Adult Health in Brazil (ELSA-Brasil) based on serial TSH levels. Repeated measure analyses were then utilized to measure within-class changes in blood pressure, lipid levels, hemoglobin A1c, and CV-related medication utilization. Results: From the 621 LT4-treated study participants, the best-fit GMM approach identified four TSH trajectory classes, as defined by their relationship to the normal TSH range: 1) High-high normal TSH, 2) Normal TSH, 3) Normal-to-low TSH, and 4) Low-to-normal TSH. Notably, the average baseline LT4 dose was lowest in the high-high normal TSH group (77.7 mcg, p &lt;0.001). There were no significant differences in CV health markers between the classes at baseline. At least one significant difference in CV markers occurred in all classes, highlighted by the low-to-normal class, in which total and HDL cholesterol, triglycerides, and A1c all increased significantly (p = 0.049, p &lt;0.001, p &lt;0.001, and p = 0.001, respectively). Medication utilization increased in all classes over the study period. Conclusion: GMM/LCGA represents a viable approach to define and examine LT4 treatment by TSH trajectory. In the future, more comprehensive datasets will allow for more complex trajectory modeling and analysis of clinical outcome differences between trajectory classes. Defining the adequacy of LT4 treatment using a longitudinal scope could allow clinicians to more accurately communicate treatment progress and identify patients at risk for adverse CV outcomes.
Presentation: 6/3/2024