bluuebunny/crossref_metadata_2025 huggingface dataset:
8141 A Rare Case of Follicular Adenoma with Osseous Metaplasia and Mature Bone Formation- Is Surveillance Important?
Authors: Madani Kulsum , Al-Khazraji Yamama , Sacoto Daniel Hernan , Rai Gur Kiratt K , Belokovskaya Regina , Franco-Akel Alberto A
Published: October 2024

Disclosure: K. Madani: None. Y. Al-Khazraji: None. D.H. Sacoto: None. G.K. Rai: None. R. Belokovskaya: None. A.A. Franco-Akel, MD: None.

Osseous metaplasia and mature bone formation (MBF) are common in malignant thyroid and parathyroid tumors. It is very unusual to have MBF in a benign tumor-like follicular adenoma, as in the case we describe. We found only twelve such cases reported in the literature, and none addressed the cancer risk or need for surveillance for the development of potential malignancy. Thus, further studies are required to investigate the need for surveillance in patients not undergoing excision and in those with remnant thyroid tissue post-removal of the adenoma for recurrence. A 43-year-old female with history of hyperlipidemia and hypothyroidism had an incidental finding of midline neck mass during the evaluation of a left upper extremity lipoma. Ultrasound of the neck showed two nodules in the Left (L) thyroid lobe: a complex nodule measured 2.2 x 1.2 x 2.1 cm and a calcified nodule measuring 1.5 x 0.8 x 0.6 cm. MRI of the neck revealed a 1.9 cm heterogeneously enhancing nodule in the mid to lower pole of the L thyroid lobe. The patient had symptoms suggestive of compression, such as dysphagia, odynophagia, and hoarseness; thus, left hemothyroidectomy was performed. Tissue biopsy was notable for follicular adenoma with osseous metaplasia and mature bone formation. The patient remained clinically and biochemically euthyroid, with only mildly elevated thyrotropin level, and treatment with levothyroxine 25 mcg once daily was initiated. On post-surgical follow-up, there was a lack of data to support close monitoring modality and strategy for the remnant thyroid lobe and neck nodal compartments. We concluded with the patient to follow up in a clinical visit for a physical exam of the neck and to obtain a follow-up sonogram at an interval of six months, in addition to monitoring TSH levels to guide hypothyroidism therapy. Osseous metaplasia has not been established as a premalignant condition, but in certain tissues like the esophagus, metaplasia is a risk factor for malignant conversion, for instance, in Barrett’s esophagus leading to esophageal adenocarcinoma. Moreover, MBF in thyroid tissue has been attributed to the activity of basic fibroblast growth factor (bFGF) and bone morphogenetic protein-2 (BMP-2), which are linked with mitogenesis and tumorigenesis. Thus, the question arises if post-excision surveillance is required in patients with a history of osseous metaplasia in remnant thyroid tissue post-lobectomy or partial thyroidectomy. At this point, more epidemiological data on similar cases may help us understand the true risk of this clinical scenario, in order to develop a reasonable approach for surveillance.

Presentation: 6/3/2024
8471 A Rare Case of Graves' Disease in a Three-Year-Old
Authors: Rajesh Archa , Ravari Ary , Kimball-Ravari Laura Elizabeth , Roan Heather
Published: October 2024

Disclosure: A. Rajesh: None. A. Ravari: None. L.E. Kimball-Ravari: None. H. Roan: None.

Graves’ Disease (GD) is an autoimmune disease that causes hyperfunctioning of the thyroid gland which may be triggered by environmental factors such as infection or stress. Though the leading cause of hyperthyroidism in both adult and pediatric populations is GD, it is extremely rare in children under the age of four years old. Some studies show the incidence to be 1 per 1,000,000 cases[1],2. Detecting GD in children early is very important as untreated GD poses a risk for failure to thrive. There have also been cases of young children suffering from psychomotor delays, craniosynostosis, and language delays because their suspected diagnosis of GD had not been detected for one to two years. In this article, we report the case of a previously healthy three-year-old Caucasian female who presented to the pediatric endocrinologist after collapsing from an episode of hypoglycemia; plasma glucose 47 mg/dL (71-180) . The patient was diagnosed with Graves’ Disease due to her significantly elevated free T3 and T4, decreased TSH, positive thyroid peroxidase (TPO) antibodies, and elevated TSIg. She was started on methimazole treatment; however, she did not respond after six months of ATD and underwent total thyroidectomy. Her hypoglycemia was attributed to abnormal proinsulin processing and glucose metabolism, which has been associated with hyperthyroidism; thyroid hormones can produce increased GLUT2 transporters3. This case report demonstrates the importance of recognizing the signs and symptoms of GD early, as well as discuss the importance of increasing the recognition of autoimmune diseases in the pediatric population. References: 1. Lee HS, Hwang JS. The treatment of Graves’ disease in children and adolescents. Annalsof Pediatric Endocrinology & Metabolism. 2014;19(3):122. doi:https://doi.org/10.6065/apem.2014.19.3.1222. 2. Alex-Ann Beliard K, Shyamkumar S, Brar PC, Rapaport R. Graves disease in infancy: a patient presentation and literature review. Endocrinology, Diabetes & Metabolism Case Reports. 2021;2021. doi:https://doi.org/10.1530/edm-20-0162 3. Hage M, Zantout MS, Azar ST. Thyroid Disorders and Diabetes Mellitus. Journal of Thyroid Research. 2011;2011:1-7. doi:https://doi.org/10.4061/2011/439463

Presentation: 6/3/2024
8135 A Rare Case of Late Recurrence of Graves’ Disease Decades After Radioactive Iodine Therapy: Is it Really a Definitive Treatment?
Authors: Hill Kelly S , Osman Radwa
Published: October 2024

Disclosure: K.S. Hill: None. R. Osman: None.

Graves’ disease (GD) is the most common cause of hyperthyroidism in the US and worldwide. Radioactive iodine (RAI) therapy has excellent success rates in treatment of GD. Studies have demonstrated that RAI successfully treats GD with a single session in the majority of cases. Recurrence after RAI, if it occurs, is most commonly seen in the first year after RAI. However, this is rare particularly in patients who have developed evidence of successful treatment in the form of post-ablative hypothyroidism. Only a few case reports have demonstrated recurrence of GD more than 10 years after treatment of GD with RAI and development of post-ablative hypothyroidism. We report a case of GD recurrence approximately 30 years after ablation. A 69 y/o woman presented for evaluation of hyperthyroidism and newly discovered thyroid nodule. Her history was significant for GD with orbitopathy diagnosed in the early 1990s and treated with RAI. Following the ablation, she developed hypothyroidism and was managed for over 20 years on levothyroxine therapy. In recent years she began to develop symptoms of palpitations and heat intolerance with biochemical evidence of thyrotoxicosis despite reductions in her levothyroxine dose. She also developed recurrence of her orbitopathy, confirmed by ophthalmology. During this time, a neck CT incidentally described an atrophic thyroid gland with a 9 mm soft tissue nodule in the left thyroid bed. Follow up ultrasound showed a 1.1 cm nodule with increased vascularity in the left thyroid bed with an otherwise atrophic gland and no lymphadenopathy. Her levothyroxine was stopped for one month in preparation for a thyroid uptake scan, during which TSH increased to 15 mcU/mL. Scan showed overall severely decreased radioactive iodine uptake of the gland consistent with prior ablation although there was a faint uptake most focally conspicuous on the left side inferiorly. Thyroid stimulating immunoglobulin (TSI) was elevated at 1.35 IU/L (Ref 0.00-0.55). ﻿After discussion with the patient, the decision was made for surgical treatment with thyroidectomy. Pathology was benign. She was continued on her prior dose of levothyroxine 75 mcg daily however now with clinical and biochemical evidence of hypothyroidism requiring continued increase in levothyroxine dose to normalize TSH levels. GD is the most common cause of hyperthyroidism and RAI therapy is the most common definitive treatment for GD in the US. Recurrence of GD after ablative hypothyroidism is rare, particularly in the case of late recurrence decades after ablation. Only a few cases are reported in the literature, ours with the longest interval-to-relapse. Recurrence of orbitopathy may be the first clue. Our case highlights the need to continue to monitor clinically for recurrence of Graves’ disease long after RAI use.

Presentation: 6/3/2024
7045 A Rare Case of Lyme-Associated Thyroiditis in an Otherwise Healthy Patient
Authors: Windham Mary , Majumdar Sachin K
Published: October 2024

Disclosure: M. Windham: None. S.K. Majumdar: None.

Introduction: Lyme disease, a common tick-borne illness, causes multiorgan inflammation and dysfunction. It commonly affects the musculoskeletal, neurologic, cardiovascular, and integumentary systems. The endocrine system is rarely involved. We report a case of Lyme-associated thyroiditis in an otherwise healthy 41-year-old man. Case: A 41-year-old man with a history of hypertension, gastroesophageal reflux and a known BRCA2 mutation presented to the emergency department due to one week of frequent palpitations, fatigue, dyspnea on exertion, and dry cough. Laboratory testing revealed thyrotoxicosis with an undetectable TSH (n 0.270—4.200 µIU/mL), FT4 of 7.04 ng/dL (n 0.80—1.70 ng/dL), and TT3 of 253 ng/dL (n 92.0—224 ng/dL). He denied any recent illnesses or pain in his thyroid. Further work up revealed negative TSI and TPO but did show an elevated high sensitivity CRP of 4.3 mg/L (n <1.0 mg/L) and a sedimentation rate of 33 mm/hr (n 0—20 mm/hr). A thyroid uptake and scan showed markedly decreased uptake suggestive of thyroiditis. The patient was started on a prednisone taper with improvement in his TFTs. At his follow up visit approximately one month later, he reported increasing stiffness in his bilateral jaw and continuing palpitations with movement despite near normalization in his FT4 and TT3, suggestive of possible underlying cardiac conduction defects. He did not recall a tick bite but lived in an area with endemic Lyme disease. Lyme antibodies were sent and returned with a positive Lyme IgG and an indeterminate Lyme IgM, which would be consistent with an active Lyme disease infection at the time of his initial presentation. Treatment for Lyme disease was prescribed. Conclusion: Between 1991 and 2021, the incidence of Lyme disease in the United States doubled due to the combined effects of climate change, increasing host species populations, and human encroachment on animal habitats. People who live in areas with endemic Lyme disease, such as the Northeast and upper Midwest regions of the United States, are at risk even if they do not recall a specific exposure. Although Lyme thyroiditis is extremely rare, its incidence is expected to increase as the overall incidence of Lyme disease increases. Therefore, it is important to consider Lyme disease in the differential when a patient from an endemic area presents with unexplained thyroiditis.

Presentation: 6/2/2024
8161 A Rare Case of Malignant Melanoma Metastatic to the Thyroid Gland
Authors: Ferri-Guerra J , Abdulhussein O , Kasper-Guerra E , Madrigal Loria G , El Hage L
Published: October 2024

Disclosure: J. Ferri-Guerra: None. O. Abdulhussein: None. E. Kasper-Guerra: None. G. Madrigal Loria: None. L. El Hage: None.

69 yo female presented with neck swelling in 2014. TSH was normal. Thyroid ultrasound showed multiple nodules with a right 2.9 x 2.3 x 2.1 cm that was cold on subsequent thyroid uptake scan. FNA of the right nodule in 08/2014 showed malignant cells with spindle cell pattern thought to be medullary thyroid cancer. She was scheduled for total thyroidectomy but presented with small bowl obstruction prior to her surgery and was diagnosed with metastatic melanoma (BRAF +). Initial PET scan showed a 4.1 x 2.8 x 2.8 cm hypermetabolic right thyroid lobe lesion in addition to other multiple hypermetabolic lesions consistent with known melanoma. The thyroid FNA specimen correlated with the small bowel excision specimen and showed similar features diagnosing metastatic melanoma to the thyroid gland.She was started on ipilimumab with subsequent scan in 04/2015 showing increase in right thyroid mass size to 5.4 x 4.2 x 9 cm with mixed results of other metastatic locations. She was switched to pembrolizumab and later dobrafenib/trametinib in 05/2015. Imaging thereafter showing significant improvement including a decrease in the right thyroid nodule size to 1.6 cm x 2.5 cm x 2.4 cm with no hypermetabolic activity on further PET scans. Repeat thyroid ultrasound in 2021 showed multiple nodules with a 2.2 x 1.5 x 1 cm nodule in the right. Repeat FNA of the right nodule was benign. Last imaging in 2023 showed stable nodules. Conclusion: metastasis to thyroid gland from malignant melanoma is a rare finding and should be considered in rapidly growing thyroid nodules. These lesions can be treated with targeted therapy that can spare affected individuals surgery.

Presentation: 6/1/2024
8042 A Rare Case of Papillary Thyroid Carcinoma in a Patient with Li-Fraumeni Syndrome
Authors: Bakhtawar K M , Jaiswal G
Published: October 2024

Disclosure: K.M. Bakhtawar: None. G. Jaiswal: None.

Li-Fraumeni syndrome (LFS) is an autosomal dominant syndrome with a high lifetime probability of cancer at an early age. The spectrum of cancers primarily includes osteosarcoma, soft tissue sarcoma, breast cancer, brain tumors, leukemia, and Adenoid cystic carcinoma. Prior studies have estimated the cumulative cancer risk to be about 50% by age 40 and as high as 90% by age 60. As screening for TP53 mutations has improved and more patients are identified, the LFS cancer spectrum has expanded to include thyroid cancer. However, the occurrence of thyroid cancer in LFS has not been extensively assessed in the literature. A recent study examined cancer patients carrying the Brazilian p.R337H TP53 mutation which demonstrated that out of 101 patients, 11 had thyroid cancer (10.9%). In our case, a 45-year-old female with a past medical history of Li-Fraumeni syndrome, Von Willebrand disease, Pulmonary embolism, HER-2 positive invasive ductal carcinoma of the left breast status post chemotherapy, and bilateral mastectomy presented for evaluation of papillary thyroid carcinoma (PTC). An enlarged thyroid was initially identified on physical exam by the PCP with a follow-up thyroid ultrasound showing bilateral nodules. The right upper pole 1.9 x 1.3 x 1.6 cm nodule was biopsied revealing PCT. Following neck ultrasound demonstrated mildly enlarged lymph nodes on the right side, level 2A 1.5 cm and level 3 1.6 cm. The patient subsequently underwent total thyroidectomy and lymph node dissection. The pathology report revealed a 1.4 cm PTC in the upper right pole, a 0.9 cm PCT in the isthmus, and a 0.8 cm PTC in the left midpole. 4/62 lymph nodes were positive with the largest deposit of 1 cm. All margins were negative for carcinoma with no angioinvasion or lymphatic invasion. She was staged as T1bN1bM0. We are awaiting post-operative Thyroglobulin level to assess the need for Radioactive iodine. BRAFV600E and P53 mutation was identified. The patient carries known heterozygous mutation p.R1755H in the TP53 gene with an estimated lifetime cancer risk of 93%. This particular mutation has not been associated with thyroid cancer in prior studies. Although thyroid cancer is an uncommon manifestation of LFS, this case begs the importance of further studies to explore this association which may then lead to early screening and treatment of thyroid cancer in individuals with founder TP53 mutations.

Presentation: 6/1/2024
8747 A Rare Receptor Resistance with Paradoxical Outcomes!
Authors: Patoli I , Batool S , Gill A S , Makdissi A
Published: October 2024

Disclosure: I. Patoli: None. S. Batool: None. A.S. Gill: None. A. Makdissi: None.

Introduction: Resistance to thyroid hormone receptor is an uncommon cause of abnormal TFTs. (1) We present an interesting case of THRB resistance with cardiac arrhythmia (CA). Clinical Case: 46-year-old man with history of atrial fibrillation (Afib) was referred to endocrinology for evaluation of abnormal TFTs and thyroid nodule. He had a recent hospital admission for Afib with rapid ventricular response; 3 years ago, he was treated with amiodarone for 2 months. TFTs revealed normal TSH of 1.375, elevated FT4 of 2.76 (normal ranges 0.55-4.78 and 0.89-1.76, respectively). Neck CT scan showed large peripherally enhancing centrally necrotic mass with calcification encompassing nearly the entirety of left thyroid lobe measuring 2.2 x 3.6 x 4.6 cm. A 0.8 cm hypodensity within right thyroid lobe also visualized. Thyroid ultrasound showed nodules bilaterally with the largest one in the lower pole of left lobe. FNA biopsy showed Bethesda category- II benign, benign appearing follicular cells and abundant colloid. Repeat labs showed similar results with persistently elevated free T4 (2.56) with equilibrium dialysis, normal alpha subunit, normal TSH (2.14) with human anti-mouse antibody (HAMA) antibody was negative. Alpha subunit:TSH ratio was <1. He remained clinically euthyroid over the course of 1.5 year but repeat labs at that time indicated that TSH had increased to 17 with elevated free T4 (2.6) . MRI brain ruled out TSH secreting adenoma. He reported thyroid abnormalities in son and brother but was unable to provide details. He was referred for genetic screening which showed THRB with pathogenic variant: c.9628> G (p.Y321C). Conclusion: THRB resistance is an uncommonly diagnosed modality in endocrinology. The genes encoding thyroid hormone receptors are THRα gene and THRβ gene (2). Patients with inherited THRB pathogenic variants present with resistance to thyroid hormone and often enlarged thyroid gland. Interestingly, despite having receptor resistance, patients may manifest with CA. This is hypothesized to be due to elevated T4 and T3 concentration in the heart which primarily has higher expression of THRA (3). The diagnosis of thyroid hormone resistance is important to avoid treating asymptomatic patients where treatment is not warranted. References: 1. Larsen CC, et al. Incidental identification of a thyroid hormone receptor beta (THRB) gene variant in a family with autoimmune thyroid disease. Thyroid. 2013 Dec;23(12):1638-43. 2. Ortiga-Carvalho TM, et al. Thyroid hormone receptors and resistance to thyroid hormone disorders. Nat Rev Endocrinol. 2014;10(10):582-591. 3. Wikström L, et al. Abnormal heart rate and body temperature in mice lacking thyroid hormone receptor alpha 1. EMBO J. 1998 Jan 15;17(2):455-61.

Presentation: 6/2/2024
6671 A Recurrent Mass After Thyroid Cancer Treatment
Authors: Sekhon Navharsh , Win Kyaw Z
Published: October 2024

Disclosure: N. Sekhon: None. K.Z. Win: None.

Background: Differentiated thyroid cancers have an excellent prognosis if completely resected and their recurrence rate varies depending on the nature and type of the thyroid tumor. We report a case of symptomatic recurrent mass 1.5 years after hemithyroidectomy for a small locally invasive follicular thyroid cancer. The recurrent mass mimicked malignancy on ultrasound but was pathologically determined to be a suture granuloma. Case: A 62-year-old male with history of follicular thyroid cancer s/p left thyroidectomy presented with a symptomatic neck mass, dysphagia, voice change, and worsening snoring. Thyroid tumor pathology was reported as follicular carcinoma pT1bpNX, 1.4 cm in size, clear margins, no vascular invasion with one focus of transcapsular invasion. He had normal surveillance investigations including thyroglobulin and thyroid ultrasound. He had a normal esophagogastroduodenoscopy which was performed for dysphagia and choking. The thyroid ultrasound showed an indeterminate solid heterogeneous and hypoechoic ovoid soft tissue node measuring 6 mm x 3 mm x 5 mm just right of midline and a 4 mm left neck hypoechoic nodule with no central fatty hilus located lateral to the jugular vein. The lymph node morphology was not typically benign and the patient underwent fine needle aspirate of the mass suggestive of a benign mass. This was followed by surgical removal of the mass and pathologic identification of a suture granuloma. There was resolution of dysphagia after removal of the mass. Discussion: Thyroid tumor recurrence rate is about 15% and is usually seen in aggressive forms or in incomplete resections due to the unrecognized extent of the tumor. Recurrences can be local, regional or distant. Suture granuloma is a rare complication after thyroidectomy and reflects an inflammatory response to retained foreign material. It develops slowly after the thyroidectomy and presents as a painless mass mimicking malignancy or lymph node metastasis. Other lesions that can mimic thyroid cancer on ultrasonography include chronic granulomatous lesions, traumatic neuroma and surgical clip. Conclusion: Our case highlights that suture granuloma should be considered in addition to malignant recurrence in cases of painless mass at the site of thyroidectomy. References: 1. Javalgi AP, Arakeri SU. Post thyroidectomy suture granuloma: a cytological diagnosis. J Clin Diagn Res. 2013 Apr;7(4):715-7. 2. Kristen Kobaly, Susan J. Mandel, Jill E. Langer, Clinical Review: Thyroid Cancer Mimics on Surveillance Neck Sonography, The Journal of Clinical Endocrinology & Metabolism, Volume 100, Issue 2, 1 February 2015, Pages 371-375 3. Ryan Alghanemi, Thomas Steinmüller, Abrupt onset of suture granuloma 27 years after hemithyroidectomy, Journal of Surgical Case Reports, Volume 2023, Issue 6, June 2023, rjad284.

Presentation: 6/2/2024
7147 A Retrospective Evaluation of Biochemical and Clinical Criteria of Permanent Hypoparathyroidism After Total Thyroidectomy and Their Associated Outcomes
Authors: Su David G , Tsou Sarah , Shen Wen , Duh Quan-Yang , Graves Claire , Suh Insoo
Published: October 2024

Disclosure: D.G. Su: None. S. Tsou: None. W. Shen: None. Q. Duh: None. C. Graves: None. I. Suh: None.

Background: Postoperative hypoparathyroidism (hypoPT) is the most common complication of total thyroidectomy and carries long-term morbidity. However, reported incidences vary widely due to nonstandardized measurement practices and absence of a universally accepted definition. This study aims to evaluate various definitions of hypoPT and to identify influencing factors such as diagnosis and operative duration. Methods: We performed a retrospective analysis of patients with a diagnosis of hypoPT (ICD-9: E20, E20.0, E20.8, E20.9, E89.2) between January 2012 and January 2019 at a single large academic institution, and only included those who had underwent a total thyroidectomy six months prior. Definitions based on low parathyroid hormone (PTH) values (PTH < 10 pg/mL), low calcium levels (corrected calcium [Ca] < 8.5 mg/dL or ionized Ca [iCa] < 1.1 mmol/L), and postoperative supplementation (elemental calcium or vitamin D) were evaluated at 6 and 12 months postoperatively. Postoperative hypocalcemic symptoms were graded by disease severity (based on the presence of numbness/paresthesia, muscle spasms/aches, and Chvostek/Trousseau signs). Patient demographics, operative and pathological characteristics, and use of parathyroid autotransplantation were recorded. Results: Of 879 patients with hypoPT ICD-9 diagnoses, 124 (14%) underwent a total thyroidectomy and were included. Our cohort was 64% female with a median age of 52.9 years. Fifty-one patients (41%) had low PTH levels, 49 (39%) had low calcium levels, and only 26 (21%) had both low PTH and calcium. Of 94 patients (76%) with hypocalcemic symptoms, 68 (73%) required long-term calcium or vitamin D supplementation. Twenty-eight (22.6%) patients had either an ED visit or readmission for hypocalcemia postoperatively. One hundred seven patients (86%) had a pathologic diagnosis of malignancy, of which 37% had extrathyroidal extension, 25% vascular invasion, and 36% positive margins. Those who underwent parathyroid autotransplantation (33%) were less likely to meet biochemical definition of hypoPT (p = 0.0312). Dosage of calcium/vitamin D supplementation did not correlate with symptom grade. Conclusions: Postoperative hypocalcemic symptoms and long-term calcium/vitamin D supplementation were the most common characteristics found in our permanent hypoPT cohort. However, substantial heterogeneity in defining postoperative hypoPT exists, with no definition capturing the full spectrum of affected patients. Further research is necessary to develop reliable diagnostic criteria or biomarkers for hypoPT prediction and management.

Presentation: 6/2/2024
6651 A Traceable Clinical Free Thyroxine Assay Based on Equilibrium Dialysis ID-LC/MS/MS
Authors: Spector David , Zhang Li , Ribera Ashley , Doty Alex , Tse Chui Ying , Sugahara Otoe , Vazquez Norma , Danilenko Uliana , Vesper Hubert W
Published: October 2024

Disclosure: D. Spector: None. L. Zhang: None. A. Ribera: None. A. Doty: None. C. Tse: None. O. Sugahara: None. N. Vazquez: None. U. Danilenko: None. H.W. Vesper: None.

Accurate diagnosis and effective treatment of thyroid diseases rely on reliable thyroid function tests. Serum free thyroxine (FT4) immunoassays (IAs) are most commonly used for FT4 measurements in clinical practice. However, FT4 IAs have not been standardized with large variations between different assay platforms. A reference measurement procedure (RMP) for FT4 based on well-defined equilibrium dialysis (ED) of serum has been established for CDC standardization program to support the standardization of clinical assays for patient care. In the current study, we aim to develop a routine clinical FT4 assay based on ED-LC/MS/MS that is traceable to the RMP. ED-LC/MS/MS analysis was performed using a commercially available micro-ED plate. FT4 in dialysate was extracted with a 96-well C18 SPE plate. FT4 in the samples was quantitated by using LC/MS/MS in positive ion mode. The assay was calibrated with the certified primary reference material. By using RMP as a reference, we compared the analysis of 40 single donor sera between the ED-LC/MS/MS assay and FT4 IA on Roche e401platform. ED-LC/MS/MS assay could resolve T4, T3, reverse triiodothyronine (rT3), and other interferences in the samples with C18 chromatography in 4 min. The linear range of the routine FT4 assay was from 0.5-100 pg/mL covering clinically relevant FT4 concentrations including hypo-, hyperthyroid patient samples. The intra and inter-run CV% of the assay in 20 days was 3.72 and 5.25%, respectively. The effect of minor changes to the method conditions was studied. It was determined that serum/buffer ratios from 1:1 to 1:2 in the ED inserts, speeds of shaker for ED, and ED incubation time, did not influence the FT4 measurement. However, elevated ED temperature at 38°C could result in a more than 10% increase in FT4 values. A microplate format for the procedures of ED and SPE is amiable to the application of an automation system which significantly improves the throughput of the procedure. Method comparison showed good agreement between ED-LC/MS/MS assay and RMP in Deming regression analysis with a slope close to 1, while there was significant bias of IA from RMP. ED-LC/MS/MS assay was also applied for pregnancy serum samples with minimal difference on the FT4 measurement from RMP. We have developed a routine clinical FT4 assay that is traceable to RMP. The accuracy, precision, and sensitivity of the assay are suitable for high-throughput FT4 measurements in clinical laboratories and large epidemiologic studies. We demonstrate that the developed method can provide accurate FT4 measurements in patients including pregnant women.

Presentation: 6/3/2024
12203 FDXR Variants Cause Adrenal Insufficiency And Atypical Sexual Development
Authors: Pignatti E , Slone J , Gomez-Cano M , Campbell T M , Vu J , Sauter K S , Pandey A V , Alonso-Riaño M , Martínez-Azorín F , Neilson D , Longo N , Toit T Du , Voegel C D , Huang T , Flueck C E
Published: October 2024

Disclosure: E. Pignatti: None. J. Slone: None. M. Gomez-Cano: None. T.M. Campbell: None. J. Vu: None. K. Sauter: None. A.V. Pandey: None. M. Alonso-Riaño: None. F. Martínez-Azorín: None. D. Neilson: None. N. Longo: None. T. Du Toit: None. C.D. Voegel: None. T. Huang: None. C.E. Flueck: Consulting Fee; Self; Novo Nordisk. Grant Recipient; Self; Novo Nordisk, Sandoz, Pfizer, Inc., Merck. Speaker; Self; Sandoz.

Background. Biallelic variants in the mitochondrial flavoprotein ferredoxin—NADP(+)-reductase (FDXR) have been associated with a progressive neuropathic mitochondriopathy named FDXR-Related Mitochondriopathy (FRM). FRM patients often experience worsening or demise following stress, but the cause is unclear. Ambiguous genitalia at birth have now been observed in some FRM patients. As FDXR is an essential partner for several steroid enzymes, we explored the impact of FDXR variants on steroid biosynthesis. Methods. To investigate whether the abnormal stress response of many FRM patients is caused by glucocorticoid deficiency, and whether observed ambiguous genitalia is related to androgen excess, we investigated the impact of FDXR variants on adrenal steroidogenesis. Clinical, genetic, biochemical, and functional studies were performed in index patients, steroidogenic cell lines reprogrammed from patient fibroblasts, and a novel disease mouse model. Results. Two paradigmatic female FRM patients carrying novel homozygous FDXR mutation p.G437R with ambiguous genitalia at birth and sudden death in the first year of life had cortisol deficiency and androgen excess compatible with 11-hydroxylase deficiency. Steroidogenic FDXR-variant cells lines reprogrammed from three patients’ fibroblasts also displayed deficient mineralocorticoid and glucocorticoid production. Likewise, Fdxr-variant mice allelic to the severe p.R386W human variant, showed reduced progesterone and corticosterone production. Conclusions. Our comprehensive studies show that FDXR variants in FRM patients may cause compensated, but possibly life-threatening adrenocortical insufficiency in stress by affecting adrenal glucocorticoid and mineralocorticoid synthesis through direct enzyme inhibition, most likely in combination with disturbed mitochondrial redox balance.

Presentation: 6/1/2024
9327 Abnormal Presentation of Myoedema and Pseudohypertrophy in Hypothyroidism
Authors: Sperry Bailey , Horani Mohamad Hosam
Published: October 2024

Disclosure: B. Sperry: None. M.H. Horani: None.

Atypical presentations of hypothyroidism are dramatically under researched and studied in the male population. Signs and symptoms of myoedema and pseudohypertrophy, which can be classified as overt signs of hypothyroidism, should be in the differential for hypothyroidism to decrease the delay in diagnosis and patient care. Hypothyroidism is a common pathological process that has been well studied in the endocrinology society. By definition, it is the abnormally low production of the thyroid gland, resulting in slowing of growth and mental development in children and metabolic changes in adults (1). However, in a community survey, only 0.1-2 percent of patients present with overt signs of hypothyroidism; of that, only 1/1000 males presented with overt signs whereas females were at a range of 14/1000 to 19/1000 when including all scenarios and cases [1]. It should be made apparent that although autoimmune disorders are more common in females, the male population has been dramatically overlooked which poses a risk to patient care and proper diagnosis and treatment. Although it may be difficult to diagnose hypothyroidism with only physical signs and symptoms of myoedema and pseudo-hypertrophy, these are key clinical features of Hoffman’s syndrome; which is well-known to be associated with hypothyroidism. Rhabdomyolysis can be a complication secondary to myoedema and further diagnostic studies should be obtained to ensure the diagnosis of hypothyroidism is not missed. I present a case of a 32-year-old male who was not properly diagnosed with hypothyroidism until after the third hospitalization, despite showing overt signs and symptoms of hypothyroidism which put him at risk of end-organ damage.

Presentation: 6/3/2024
6525 Alternating Hypothyroidism and Hyperthyroidism Complicated by Thyroid Eye Disease
Authors: Chen A M , Barnett B G
Published: October 2024

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 <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

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 <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

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 <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) (<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

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 < 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

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< 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

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