Thyroid dysfunction in patients treated with the immune checkpoint inhibitor nivolumab: different clinical features

Abstract

Rationale. Immune Checkpoint Inhibitors (ICIs) are approved for some advanced neoplasms, increasing survival. ICIs block inhibitor receptors cytotoxic T lymphocyte antigen 4 (CTLA4) and programmed death-1 (PD-1) and trigger T cell-mediated immunity against tumor. Their action is accompanied by several immunity-related adverse events (IRAEs), also involving the endocrine system (pituitary, thyroid, adrenals). We report two different cases of thyrotoxicosis following administration of the anti-PD-1 nivolumab. Patients. Patient 1, M, 75 years-old, treated for non-small cell lung carcinoma (NSCLC) since September 2016, with euthyroid multinodular goiter. In January 2017 (12 weeks from baseline), he developed frank hyperthyroidism, with positive TSH-receptor antibodies (TRAb) and thyroperoxidase antibodies (TPOAb). A Tc99m thyroid scintiscan showed diffuse uptake and “cold” areas. After nivolumab withdrawal, treatment with metimazole (MMI) 5 mg per day was started and euthyroidism was resumed, so to restart the drug in May 2017. Patient 2, M, 80 years-old, treated for a left-eye choroid melanoma since January 2017, with euthyroid nodular goiter. In April 2017 (6 weeks from baseline), thyrotoxicosis was detected, with positive thyroglobulin antibodies (Tg-Ab, 244 IU/ml, nv <4) and no scintiscan uptake, as in destructive thyroiditis. Scalar-dose prednisone was initiated, and after 3 months TSH was >4.5 µIU/ml (subclinical hypothyroidism). Patient was treated with replacement doses of levothyroxine (LT-4), and continued nivolumab infusions. Conclusions. Two forms of thyrotoxicosis were reported: the first with thyroid hyperfunction and positive TRAb, the latter as a destructive thyroiditis. In both cases (mean onset after 9 weeks), the moderate severity and the appropriate management of endocrine IRAEs allowed treatment continuation.