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S. Wagle: None. D. Abraham: None. Introduction: Exogenous Cushing syndrome is prevalent due to prolonged exposure to glucocorticoid-containing medications, often found in over-the-counter (OTC) products imported from overseas. We report a patient who developed Cushing’s Syndrome after self-medicating with an agent from Mexico called Artri King. Case Description: A 39-year-old female with a history of non-alcoholic fatty liver disease and arthralgia presented to the emergency department with epigastric pain, melena, 60 lbs weight gain, and bilateral lower leg swelling for 4 months. Her medications included Artri King for arthralgia (2 tablets twice daily for the last four months) and Spironolactone, for leg swelling. Vital signs revealed an elevated blood pressure of 141/108 mmHg and a BMI of 31.28 kg/m². Clinical examination revealed purplish wide striae, bruising, proximal muscle weakness, and peripheral edema. Laboratory testing showed a white blood cell count of 26.73 k/μL, a blood glucose level of 132 mg/dL, HgbA1C 5.9%, a cortisol level of 0.3 µg/dL, and an ACTH level of < 1.5 pg/mL. Her TSH was 3.07 mU/L with a free T4 of 0.6 ng/dL. Imaging studies, including computed tomography and magnetic resonance imaging, revealed a normal adrenal gland. Gastroscopy was unremarkable. An exogenous source for corticosteroids was suspected with suppressed ACTH levels and normal adrenal glands on imaging. Therefore, mass spec testing for corticosteroids was performed. Her serum dexamethasone level of 1076 ng/dL confirmed the diagnosis. Upon inquiry, the patient recalled that her symptoms began after starting the Artri King supplement. Discontinuation of Arti King for two days resulted in a cortisol level of 6.8 µg/dL suggesting rapid recovery of adrenal function. Discussion: Artri King, an OTC supplement marketed for joint pain in Mexico, recommends a dosage of two tablets three times daily. On April 20, 2022, the FDA issued public warnings against its use, as laboratory testing detected undisclosed amounts of dexamethasone and diclofenac, which were not listed on the product label. The presence of surreptitious steroids in supplements should be suspected in patients presenting with exogenous Cushing syndrome. Physicians should review self-administered supplements closely and counsel patients on the risks. Monday, June 3, 2024

To determine the sensitivity and specificity of ultrasound (US)-guided fine-needle aspiration (FNA) and measurement of parathyroid hormone (PTH) in the aspirate (FNA/PTH) as a preoperative localization procedure. The study group consisted of 34 consecutive patients with primary hyperparathyroidism. The FNA/PTH estimations in these patients were compared with those from 13 proven thyroid nodules. All patients underwent US study of the neck, which suggested the presence of a solitary adenoma in 30 patients and of hyperplasia in 2; no adenoma or hyperplasia could be visualized in 2 patients. Thirty-two patients underwent FNA/PTH, which yielded a mean PTH level of 22,060.0 +/- 6,653.0 pg/mL. This result was significantly different (P<0.001) from the mean PTH level in 13 thyroid nodules (9.0 +/- 1.0 pg/mL). On the basis of the FNA/PTH results, 28 patients with suspected adenomas underwent minimally invasive parathyroidectomy (MIP), and 2 patients are awaiting a surgical procedure. Of these 28 patients, 27 had more than a 50% decline in intraoperative PTH level after removal of the suspected adenoma, confirming surgical success. In 1 patient, multigland hyperplasia was discovered during the operation. The 2 study subjects with US findings of suspected hyperplasia underwent 4-gland surgical procedures. All patients treated surgically continued to have normal serum calcium levels 6 to 18 months postoperatively. Primary hyperparathyroidism is caused most commonly by a solitary adenoma and less commonly by multigland hyperplasia of the parathyroid glands. Surgical resection is the only curative therapy. MIP has become a frequently used strategy, but there are limitations to current preoperative localization techniques. We conclude that US-guided FNA is a useful technique that facilitates MIP, with a high degree of specificity (95%) and sensitivity (91%).

Abstract Context Comprehensive genomic analysis of thyroid nodules for multiple classes of molecular alterations detected in a large series of fine needle aspiration (FNA) samples has not been reported. Objective To determine the prevalence of clinically relevant molecular alterations in Bethesda categories III-VI (BCIII-VI) thyroid nodules. Methods This retrospective analysis of FNA samples, tested by ThyroSeq v3 using Genomic Classifier and Cancer Risk Classifier at UPMC Molecular and Genomic Pathology laboratory, analyzed the prevalence of diagnostic, prognostic, and targetable genetic alterations in a total of 50 734 BCIII-VI nodules from 48 225 patients. Results Among 50 734 informative FNA samples, 65.3% were test-negative, 33.9% positive, 0.2% positive for medullary carcinoma, and 0.6% positive for parathyroid. The benign call rate in BCIII-IV nodules was 68%. Among test-positive samples, 73.3% had mutations, 11.3% gene fusions, and 10.8% isolated copy number alterations. Comparing BCIII-IV nodules with BCV-VI nodules revealed a shift from predominantly RAS-like alterations to BRAF V600E-like alterations and fusions involving receptor tyrosine kinases (RTK). Using ThyroSeq Cancer Risk Classifier, a high-risk profile, which typically included TERT or TP53 mutations, was found in 6% of samples, more frequently BCV-VI. RNA-Seq confirmed ThyroSeq detection of novel RTK fusions in 98.9% of cases. Conclusion In this series, 68% of BCIII-IV nodules were classified as negative by ThyroSeq, potentially preventing diagnostic surgery in this subset of patients. Specific genetic alterations were detected in most BCV-VI nodules, with a higher prevalence of BRAF and TERT mutations and targetable gene fusions compared to BCIII-IV nodules, offering prognostic and therapeutic information for patient management.

Abstract Disclosure: S. Wagle: None. L. Lomo: None. R.L. Dood: None. B. Chadwick: None. D. Abraham: None. Introduction: Struma ovarii is a mono-dermal teratoma of the ovary that is composed of more than >50% of mature thyroid tissue. It accounts for 5% of ovarian teratomas and 1% of ovarian tumors. Although rare, it is seen in women between 40-60 years of age. Most of these tumors are found incidentally. Malignant struma ovarii is even rarer and the mutational profile of these tumors is neither well studied nor understood. We present an uncommon case of malignant struma with NRAS p.Q61R mutation yet with papillary and solid histologic patterns. Case Description: A 53-year-old female with no significant medical or family history presented with acute worsening of chronic lower abdominal pain and irregular menstruation. Her symptoms developed gradually over 6 months. A pelvic and abdominal CT identified a 9.7 cm cystic left ovarian mass without evidence of ascites or peritoneal masses. She underwent laparoscopic left salpingo-oophorectomy. Histopathology examination of the ovarian tumor revealed classical type, well-differentiated papillary, and solid patterns of thyroid carcinoma. The cells revealed nuclear enlargement, irregular nuclei, finely dispersed chromatin, distinct nucleoli, and nuclear grooves. Due to the histologic pattern of classical papillary thyroid cancer, BRAF V600E pyrosequencing was conducted, which revealed wild-type BRAF. This was followed by NGS when NRAS p.Q61R pathogenic variant was identified. Her thyroid ultrasound did not reveal actionable nodules. A TSH (2.17mU/ml) and thyroglobulin (7.6 ng/ml, TG ab neg) levels are consistent with a normal functioning thyroid gland. This patient's tumor findings are unique in that papillary thyroid carcinoma (PTC) and solid growth patterns are typically associated with the BRAF V600E mutation but rarely seen in the context of an RAS mutation. Discussion: Typically, thyroid cancers with papillary and solid variant features are associated with the BRAF V600E mutation. RAS-type tumors have follicular histologic architecture. BRAF and RAS mutations are mutually exclusive in tumors. Our patient’s malignant struma is unique in that it contained a wild-type BRAF and was positive for NRAS p.Q61R mutation. However, the histology was that of papillary and solid patterns. NRAS mutation with papillary histology combination is rare and is seen in 12% of thyroid cancers. The mutational profile of malignant struma ovarii has not been fully understood or studied due to their rarity. Presentation: 6/3/2024

Abstract Medullary thyroid carcinoma (MTC) is rare and originates from parafollicular C cells and most cases present with a primary thyroid lesion. This report describes a 67-year-old woman with a left-sided neck mass and no evidence of intrathyroidal disease. Positron emission tomography–computed tomography (PET-CT) revealed paratracheal lymphadenopathy; other imaging and TSH were unremarkable. Fine-needle aspiration was inconclusive, and excisional biopsy suggested high-grade metastatic neuroendocrine carcinoma, initially suspected to be pulmonary due to thyroid transcription factor-1 (TTF-1) positivity. Pathology review raised concern for MTC. Endocrine evaluation showed elevated calcitonin (25.4 pg/ml) and carcinoembryonic antigen (CEA) (20.1 ng/ml). She denied personal or family history of thyroid disease or multiple endocrine neoplasia syndromes. Total thyroidectomy with central neck dissection was performed. All thyroid sections stained negative for calcitonin, excluding C cell hyperplasia or intrathyroidal MTC. Lymph node morphology and immunoprofile supported metastatic MTC arising from a thyroid rest. This is a rare entity, with only two other cases documented in the literature.

Abstract #1003 Objective: To review the clinical, histological and mutation characteristics of thyroid cancer (TC) manifesting as skeletal metastasis. Methods: TC presenting with pathological bone fracture or as spinal cord compression is rare. Case Presentation: Seven pts, 4 men and 3 women presented with bony metastasis from unknown primary cancer. 3 of them manifested acute pathological fracture of long bones. Whole body MRI or PET scans are used for risk assessment and treatment planning in...

Differentiated thyroid cancer patients uncommonly present with bone metastasis as the initial manifestation. Their molecular profile is largely unknown. The aim of this study was to evaluate the histopathology, molecular profiles, and response to radioactive iodine therapy in these patients. Eight patients presented with symptomatic bone metastasis from an unknown primary tumor. We identified these patients by performing a retrospective chart review. Pathology slides were reviewed and the molecular analysis of 112 thyroid cancer-related genes was performed on bone metastasis specimens using targeted next-generation sequencing. These patients presented with long bone fractures, spinal cord compression, or intractable bone pain. Histopathologic analysis of the bone and thyroid tumor specimens revealed follicular variant of papillary carcinoma in 7 patients and tall cell variant papillary carcinoma in 1 patient. Primary tumor size ranged from 0.4 to 7.5 cm. All patients received high dose radioiodine therapy following thyroidectomy. Molecular analysis revealed telomerase reverse transcriptase ( ) mutations in 7 (88%) tumors, 4 (50%) contained co-occurring and RAS GTPase gene ( ) mutations, 2 had isolated mutations, and 1 had and proto-oncogene B-Raf ( ) V600E mutations, respectively. Tumors carrying , , or a combination of these mutations were radioiodine-avid, with predictable tumor response and reduction in serum thyroglobulin levels. One patient with radioiodine-refractory disease harbored and mutations. These results demonstrate that differentiated thyroid cancers presenting with bone metastasis independent of the primary tumor size have a high prevalence of mutations, frequently coexisting with mutations. This molecular signature may predict a favorable response to radioiodine therapy. = proto-oncogene B-Raf; = deoxyribonucleic acid; = differentiated thyroid cancer; = follicular variant; = papillary thyroid carcinoma; = radioactive iodine; = Ras GTPase gene; = telomerase reverse transcriptase; = thyroglobulin.