Endocrine Abstracts

JOINT2257

Background: Nivolumab is a monoclonal antibody directed against programmed cell death-1 (PD-1) and has become an effective treatment for metastatic melanoma. It enhances the cell-mediated killing of cancer cells however, it inadvertently increases the risk of autoimmune attack, which leads to various endocrinopathies, including hypothyroidism.

Case Presentation: A 48-year-old male with metastatic melanoma to the brain, who is currently undergoing monthly Nivolumab infusion, presented to the clinic with a 3-week history of fatigue, cold intolerance, and constipation. Vital signs were normal. Physical examination showed an intact sensorium, a symmetrically enlarged and nontender thyroid, and no skin changes. Laboratory tests were remarkable for a TSH of 27.1mIU/l (ref 0.3-4mIU/l), free T4 of 0.7 ng/dl (ref 0.9-1.7 ng/dl), negative thyroid receptor and thyroid peroxidase antibodies, and thyroid ultrasound showed a diffusely enlarged thyroid with low iodine uptake on the thyroid scan. No other hormonal abnormalities were detected. The endocrinology team was consulted, and the patient was started on Levothyroxine, which improved her symptoms, and the oncology team suggested temporarily discontinuing Nivolumab with frequent thyroid function monitoring and strict endocrinology and oncology follow-up.

Discussion: The incidence of Nivolumab-induced hypothyroidism is as high as 6.5%. It develops within 3-4 weeks of treatment. Smoking, hypertension, and other autoimmune diseases are risk factors. Thyroid autoantibodies are most often normal but can be elevated in some patients and a low TSH may indicate hypophysitis. Spontaneous thyroid recovery can occur. However, thyroid hormone replacement with serial measurements of thyroid function is often required. Because PD-1 inhibitors remain central in managing advanced melanoma, discontinuation may not be feasible, and continuation can be considered with close monitoring. Interestingly, according to Basak et al, the development of overt thyroid symptoms with higher antithyroid antibody levels during anti-PD-1 treatment of melanoma was associated with a significant improvement in overall and progression-free survival rates likely because of better malignancy response from treatment.

Conclusion: Immune checkpoint inhibitors such as Nivolumab remain central in managing different malignancies. However, all physicians should be aware of their potential endocrine adverse effects. In patients who develop Nivolumab-induced hypothyroidism, hormonal replacement with Levothyroxine is often needed. A multidisciplinary approach should be pursued for close monitoring and for patients to have a guided decision regarding possible Nivolumab continuation.

Reference: Basak EA et al. 2020 Overt thyroid dysfunction and antithyroid antibodies predict response to anti-PD-1 immunotherapy in cancer patients. Thyroid. Epub 2020 Mar 10. PMID: 32151195.