Endocrine Abstracts

Introduction

Current rise in use of monoclonal antibodies to Immune Check Point inhibitors (ICPIs) has led to the appearance of a great variety of immune-related adverse effects (irAEs), mainly affecting gastrointestinal tract, skin, liver and endocrinological system. With a variable prevalence (4–21%), thyroid dysfunction (TD) is the most common immune-mediated endocrinopathy. However, in the literature, it occurs in different patterns and levels of severity and its etiology is still unknown. Nivolumab is a monoclonal antibody, ICPI, indicated in advanced melanoma which acts by binding to the PD-1 receptor (programmed cell death protein 1), enhancing the immune response against tumor cells. We report a case of Nivolumab-induced thyroiditis in a woman with non-mutated BRAF cutaneous melanoma.

Case

An 82-year-old woman with non-mutated BRAF cutaneous melanoma (T3N0M1c) begins treatment with Nivolumab. The patient has no history of thyroid disease. After first cycle of Nivolumab, it is observed: TSH 0.008 uU/ml (0.50–4.00), FT4 1.80 ng/dl (0.80–2.00) and FT3 2.290 pg/ml (1.70–4.00). In following cycles, laboratory analysis revealed hypothyroidism: TSH 62.229 uU/ml, FT4 <0.400 ng/dl and FT3 <1.070 pg/ml. Due to sudden elevation of thyrotropin, antithyroid antibodies are requested: anti-peroxidase IgG (TPO) 27.56 IU/ml (0.00–5.61) and anti-thyroglobulin IgG (ATG) 518.59 IU/ml (0.00-4.11). At this time, replacement therapy with levothyroxine 50 micrograms is prescribed. Hypothyroidism continues in next cycle (TSH 66.638 uU/ml) and it is decided to increase the dose of Levothyroxine to 175 micrograms. Subsequently, TSH decreases to 3.143 uU/ml and the patient is currently continuing her anticancer treatment (Nivolumab) and thyroid replacement, remaining euthyroid.

Conclusion

Thyroiditis induced by amiodarone, lithium or interferon-alpha are well known. However, ICPI immune-mediated thyroiditis constitute a pathology whose characteristics, patterns and prevalence have yet to be determined. We present a case of thyroiditis with a sudden suppression of TSH, prior to its extraordinary elevation, which later normalizes with administration of levothyroxine, which reflects the importance of early diagnosis to avoid suspending antitumor treatment. Thyroid function monitoring is crucial to allow optimization of causal treatment since it may be necessary to modify anti-PD-1 dose or proceed to withdrawal in severe thyroid disfunction. Recent studies associate ICPI immune-mediated thyroiditis and increase of antithyroid antibodies with an improved overall survival and progression-free survival. So, in the future these irAEs could be considered a new prognostic marker in cancer patients with Anti-PD-1 immunotherapy and should be diagnosed correctly.