Endocrine Abstracts

Background: Immune checkpoint inhibitors (ICI), anticancer therapy blocking specific molecules expressed in tumor microenvironment, are associated to several endocrine side effects. In particular, the use of PD-1/PD-L1 inhibitors is related to a higher incidence of thyroid dysfunction. The most frequent form of thyrotoxicosis is a destructive thyroiditis, which can evolve into hypothyroidism.

Patient findings:We report the case of an 85 years-old patient, affected by metastatic melanoma and treated with Nivolumab, which experienced a severe ICI-related thyrotoxicosis. The diagnosis was complicated by a biochemical interference on thyroid hormones assay, probably induced by Nivolumab.

Summary: Laboratory examination performed before starting anticancer therapy showed normal thyroid function test. Few days after the second administration, the patient developed a severe thyrotoxicosis. According to destructive thyroiditis, in a short period TSH levels normalized and rapidly increased, but FT4 levels resulted inappropriately elevated. A possible analytical interference has been suspected: the sample has been analyzed with a different immunoassay, which confirmed a severe hypothyroidism with appropriately low FT4 levels. Furthermore, we processed the same blood sample after polyethylene glycol (PEG) 6000 precipitation to remove the macromolecules and after this evaluation, FT4 levels resulted appropriately low. Nine months after starting anticancer therapy, the patient stopped Nivolumab administration. Thyroid function tests performed one month later with the first immunoassay showed normal and appropriate FT4 levels.

Conclusions: The peculiarity of this case is represented by the possible biochemical interference of Nivolumab on FT4 immunoassay. In our hypothesis, Nivolumab should determinate interference on FT4 dosage by a mechanism similar to that reported for anti-FT4 autoantibodies. In our case, the interference detected with the one step immunoassay has not been confirmed using a two-step immunoassay. However, further studies will be necessary to prove the biochemical mechanisms which cause this interference.