FRI493 Immune Checkpoint Inhibitors: Effects On Thyroid Nodular Disease

Abstract

Abstract Disclosure: D.L. Bignoli: None. N. Kalara: None. A.J. Manzano: None. Introduction: Immune checkpoint inhibitors (ICI) are more recent pharmacologic agents used to treat malignancies, linked to immune related adverse events (irAEs) especially involving the thyroid. Classically, a transient silent thyroiditis occurs followed by hypothyroidism, however the effects on multinodular goiter are not fully recognized. We report a patient with poorly differentiated colon adenocarcinoma, treated with Pembrolizumab and Ipilimumab with significant improvement in the size of her thyroid nodules. Pembrolizumab is a monoclonal antibody directed against PD-1 receptors and Ipilimumab is an anti-CTLA-4 antibody; combination therapy has a higher incidence of irAEs compared with monotherapy (54% versus 24%). Clinical Case: 71-year-old female with a history of nontoxic benign multinodular goiter and Hashimoto’s hypothyroidism began ICI therapy as adjunctive treatment for poorly differentiated colon adenocarcinoma with MSH 2 mutation. She was euthyroid on same dose of levothyroxine for years however developed subclinical hyperthyroidism after starting immunotherapy; reporting anxiety, palpitations, tremors, and anterior neck fullness. TSH then was 0.02 mIU/mL (reference range 0.40-4.50 mIU/mL), free T4 1 ug/dl (reference range 0.9-1.7 ng/dl), and T3 122 ng/dl (reference range 100-200 ng/dl) with positive TPO antibodies. Levothyroxine was stopped and her symptoms subsequently self-resolved at follow-up 4 weeks later. Ultrasonography (US) performed in 2018 prior to starting ICI revealed: left lobe 1.3 x 2.5 x 4.66 cm, right lobe 1.3 x1.4 x 4.6 cm, isthmus 0.7 cm. There were multiple nodules: 0.4 x 0.9 x 0.7 cm, 0.3 x 0.3 x 0.4 cm nodule at right lobe, and 0.9 x 2 x 2.1 cm over right isthmus. The left lobe had four nodules: 0.4 x 0.5 x 0.8 cm, 0.4 x 0.5 x 0.9 cm, 0.8 x 0.8 x 1.36 cm, and 1 x 1.1 x 1.5 cm. Repeat ultrasonography after immunotherapy in October 2022 revealed substantial decrease in thyroid size, and the previously reported isthmus nodule was no longer visualized. The left thyroid lobe measured 0.5 x 1.1 x 3.3 cm, the right lobe 0.92 x 0.6 x 3.4 cm, and isthmus measured 0.2 cm. The right lobe nodule measured 0.40 x 0.33 x 0.86 cm and the left lobe nodule 0.34 x 0.24 x 0.50 cm. TSH was 1.150 mIU/mL, free T4 1.61 ug/dl, T3 96 ng/dl; evidencing a drastic improvement of her multinodular goiter due to ICI therapy. Conclusion: To the best of the author’s knowledge at this point in time, this is one of the few cases demonstrating effects of ICI therapy on nontoxic multinodular goiter. As described, there was a significant change in size and a previously biopsied isthmus nodule was not seen on her last ultrasound. Although irAEs are well established, there is limited literature regarding changes in anatomy and thyroid nodule architecture. Presentation: Friday, June 16, 2023