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

Giuseppe Giuffrida, Alfredo Campennì, Francesco Trimarchi, Rosaria M. Ruggeri

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.

Keywords


immune checkpoint inhibitors; autoimmunity; autoimmune thyroid diseases

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DOI: http://dx.doi.org/10.6092/1828-6550/APMB.105.2.2017.A2

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