SAT-491 Transient Thyrotoxicosis with Immune Checkpoint Inhibitors Therapy: The Importance of Endocrine Evaluation

Abstract

IntroductionThe immune checkpoint-blocking antibody nivolumab is recognized as having a crucial role in different malignancies by blocking programmed death-1 (PD-1) receptor immune cells. Besides its benefits, nivolumab may cause endocrine immuno-related adverse events (irAEs), including thyroid dysfunction (TD).Clinical caseA 71-year-old man, with an uneventful past medical history, was diagnosed with stage IIIB (T4N2M0), epithelial-growth-factor-receptor (EGFR) wild type, lung adenocarcinoma.The patient underwent 4 cycles of first line chemotherapy with cisplatin/vinorelbine and then radiotherapy, obtaining a partial response.After 4 months, tumor progression was identified, as assessed by whole-body 18-Fluorodeoxyglucose positron emission tomography (FDG-PET) scan, showing pleural and nodal metastasis. Nivolumab, 3 mg/kg every 2 weeks, was started at this point.While pre-nivolumab thyroid function was normal, 3 months after starting the therapy, a low serum TSH level of 0.04 mUI/mL (0.38-5.33) was found, associated with a normal level of FT4, of 10.8 pmol/L (7.9-14.4). Thyroid antibody (Ab) tests, including TSH-receptor Ab, were negative. At ultrasound examination, thyroid gland parenchyma was normo-echoic, demonstrating an isoechoic thyroid nodule in the right lobe, with regular margins, measuring 14mm diameter. Previous medical history was negative for thyroid disease.One week after the referred thyroid function tests, nivolumab was discontinued due to progressive disease as assessed by abdominal magnetic resonance, demonstrating right adrenal metastasis and patient started cisplatin/permetrexed chemotherapy. One month after nivolumab suspension, patient had already normalized thyroid tests, with TSH 2.27 mUI/mL and FT4 9.1 pmol/L. More recently (6 months after nivolumab discontinuation), thyroid function tests continued stable, with TSH 1.05 mUI/ml and T4L 9.4 mmol/l. At this point, patient was receiving permetrexed maintenance therapy.ConclusionsImmune checkpoint molecules as nivolumab, play a crucial role in anti-tumor immunity evasion. Besides its benefits, it may cause irAEs, including TD.We believe it’s essential to perform thyroid function tests at baseline and before the administration of each nivolumab dose, if possible. Additionally, large prospective studies are required in order to assess, the impact of autoimmunity on the development of TD induced by nivolumab, and its potential effect on overall survival and specific cancer survival data.