MON-567 Clinical Significance of Thyroid-stimulating Hormone Receptor Mutation on Fine Needle Aspiration

Abstract E. Skutnik: None. W. Kamran: None. S. Koshy: None. S. Shaik: None. Introduction: Patients with primary toxic goiters have decreased TSH levels and are less likely to foster malignancy in the thyroid due to inhibition of related oncogenes. Therefore, hyperfunctioning thyroid disorders were thought to be protective against thyroid malignancy. However, recent data has shown an increased incidence of thyroid malignancy in toxic goiter patients, 12-18%2. Thyroid-stimulating hormone receptor (TSHR) is a G protein coupled receptor that is expressed primarily in follicular cells. This receptor plays a critical role in thyroid cell proliferation and function. Mutations of the TSHR gene are seen in hyperfunctioning nodules, hyperfunctioning follicular thyroid cancers (FTC), and papillary thyroid cancers (PTC). High allelic frequency of the TSHR gene is associated with a higher risk of cancer even when hyperfunctioning. In contrast, benign nodules are strongly associated with low allelic frequency of the TSHR gene3. Case: A 28-year-old female with mosaic turner syndrome and obesity presented with difficulty losing weight; thyroid lab work revealed TSH of 1.92 uIU/mL (0.45-5.33), free T4 of 0.82 ng/dL (0.61-1.12), and free T3 of 4.33 pg/mL (2.5-3.9). Thyroid ultrasound showed an enlarged mildly heterogeneous thyroid gland with multiple bilateral nodules, including a right lower hypoechoic solid nodule measuring 1.4 x 0.8 x 1.1 cm. She underwent fine needle aspiration (FNA) of this right lower nodule which resulted as Atypia of undetermined significance (AUS) . Afirma Xpression Atlas testing showed mutations of the TSHR p.M453T c.1358T>C (p.Met453Thr) genes with risk of malignancy estimated at 25%. No other mutations were identified. Nuclear medicine thyroid uptake scan showed a right lower lobe hyperfunctioning nodule without suppression of the rest of the thyroid gland. As the risk of malignancy in the hyperfunctioning nodule is low, the decision was made to monitor with thyroid labs and ultrasound without surgery. Discussion: TSHR mutations occur in about 5% of thyroid nodules that have intermediate cytology. Isolated TSHR mutations are rarely found in thyroid cancer. Twenty-two different TSHR mutations were identified and the most common one is M453T1. The inability to determine if a thyroid nodule is benign or malignant by cytology remains an obstacle in 20-30% of cases. Molecular markers have been developed to improve diagnostic yield and for prediction of thyroid cancer3. Although the clinical and diagnostic significance of TSHR mutation testing in FNA specimens remains unclear, in our patient finding a mutation with TSHR p.M453T on Afirma Xpression Atlas helped us determine further management. Monday, June 3, 2024