Endocrine Abstracts

Background: Immune checkpoint inhibitors, including anti-programmed cell death-1 (PD-1) antibodies, have become promising treatments for a variety of advanced malignancies. Nivolumab, an anti–PD-1 monoclonal Ab, is an effective treatment of unresectable metastatic melanoma, non–small cell lung cancer, renal cell carcinoma, head and neck cancer, Hodgkin lymphoma, and gastric cancer. These medicines can cause immune-related adverse events (irAEs), including endocrinopathies. Thyroid dysfunction (TD) is a common irAE induced by nivolumab. The TD includes hypothyroidism and thyrotoxicosis, which are generally mild to moderate. The most common endocrine adverse event with anti-PD-1 therapy is hypothyroidism (around 5.9% cases). Thyrotoxicosis is related to destructive thyroiditis in most of the cases. Patients with TgAbs or TPOAbs are prone to develop destructive thyroiditis after initiation of nivolumab treatment. The development of hyperthyroidism owing to Graves’ disease is virtually very rare, with only 4 cases reported so far. Here we aimed to present the 5th case of Graves’ disease after Nivolumab therapy.

Case presentation: A 75-year-old woman with primary malignant urethral melanoma received three courses of nivolumab at a dose of 240 mg every two weeks. Laboratory tests performed before the 4th course due to the patient’ palpitation. Thyroid-stimulating hormone (TSH), free triiodothyronine and free thyroxine level were < 0.015 (normal range [NR]: 0.55–4.78) mU/l, 7.44 (NR: 2.3–4.2) ng/l and 2.4 (NR: 0.89–1.76) ng/dl, respectively. Her thyroglobulin (Tg-Ab) and thyroid peroxidase antibody (TPO-Ab) were both positive, while TSH receptor antibody (TRAb) was negative. Thyroid ultrasonography showed enlargement of both thyroid lobes with low echogenicity and increased vascularity. Thyroid scintigram showed an increased and diffuse uptake.

She had been diagnosed with Graves’ disease approximately eight years ago and treated medically. Tg-Ab and TPO-Ab were both positive, and TRAb was negative like now. After medical treatment was over, the patient was euthyroid in follow-up and even before PD-1 treatment.

Conclusion: While antibody positivity often causes destructive thyroiditis, differently caused Graves’ disease in this case. Also, this is the first case-reported that nivolumab therapy induced a relapse of Graves’ Disease.