MON-342 Utilizing MicroRNA profiling in the Diagnosis of Medullary Thyroid Cancer

Abstract Disclosure: P. Phan: None. N. Meda: None. A. Barsegian: None. M. Kinaan: None. Introduction: Medullary thyroid cancer (MTC) is a rare condition with aggressive potential, therefore early diagnosis is important to achieve remission. While most cases of MTC are diagnosed on cytological examination of fine-needle aspiration (FNA) samples, a small fraction of cases may be missed or misdiagnosed, especially in cases with atypia of undetermined significance (AUS). Therefore, genetic classifier tests can be instrumental in improving MTC detection rates. We present a case of a patient who was diagnosed with MTC based on overexpression of microRNA 375 (miR-375) on FNA sample with AUS. Case Description A 33-year-old female presented to the endocrine clinic for ultrasound surveillance of a thyroid nodule. She was first diagnosed with a thyroid nodule 8 years prior to establishing care with us and reported having a previous benign FNA. Repeat thyroid ultrasound revealed evolution of the nodule from 4.2 x 2.9 x 3.0 cm with TIRADS 3 features to 4.2 x 3.4 x 3.4 cm with microcalcifications and TIRADS 5 features. Given these findings, a repeat FNA biopsy was performed revealing AUS. Molecular testing revealed overexpression of miR-375, consistent with medullary thyroid cancer. Biochemical testing showed calcitonin level 7300 pg/mL and CEA 947 ng/mL. Screening for multiple endocrine neoplasia (MEN) syndrome manifestations such as primary hyperparathyroidism and pheochromocytoma were negative. CT scan of the neck and Ga68 DOTATE PET scan showed no cervical or extra-cervical metastases. The patient underwent thyroidectomy with neck exploration and will be following up in endocrinology clinic for postoperatively. Discussion: Approximately 70% of MTC -positive FNA samples with AUS had at least one genomic alteration on genetic classifier. Studies have shown that miR-375 is overexpressed in MTC tissues and can be detected in both tissue and serum samples. A study showed circulating miR-375 levels were found to be 101 times higher in the serum of patients with MTC compared to controls, with a sensitivity of 92.6% and specificity of 97.6% for distinguishing MTC from other thyroid conditions. This high level of accuracy underscores the potential utility of miR-375 as a diagnostic marker. Additionally, miR-375 has been shown to be overexpressed in FNA samples diagnosed as MTC, with a sensitivity of 97.1% and specificity of 100% in distinguishing malignant from benign nodules. Conclusion: miR-375 can significantly enhance the diagnostic accuracy for MTC in AUS cases, providing a reliable molecular tool to support clinical decision-making and potentially reduce the need for diagnostic surgeries. Presentation: Monday, July 14, 2025