bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract
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

Abstract
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

Abstract
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 &lt;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&gt; 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

Abstract
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

Abstract
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 &lt; 10 pg/mL), low calcium levels (corrected calcium [Ca] &lt; 8.5 mg/dL or ionized Ca [iCa] &lt; 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

Abstract
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

Abstract
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

Abstract
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