Nivolumab
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Thyrotoxicosis and interference in thyroid function tests: case report An 85-year-old man developed thyrotoxicosis and subsequent interference in thyroid function tests (TFTs) during treatment with nivolumab for metastatic melanoma. The man, who had melanoma of the right knee with lung and liver metastases, presented to the hospital due to severe thyrotoxicosis. He had been receiving chemotherapy with nivolumab 240mg every 2 weeks [route not stated]. Prior to the initiation of nivolumab, his TFTs were normal. A few days after receiving the second dose of nivolumab, he developed signs and symptoms including tachycardia, mild palpitations, tremor and anxiety, indicative of mild thyrotoxicosis. Five days after the initiation of nivolumab, TFTs were repeated, which showed severe thyrotoxicosis. His anti-TSH receptor autoantibodies test was negative, and ultrasonography of thyroid demonstrated a widely inhomogeneous echoic pattern normal vascularisation and no nodules. According to suggestions in evidence-based medicine, the man’s nivolumab treatment was continued with addition of unspecified β-blocker and careful monitoring of TFTs. Over the next few weeks, his TSH normalised and then rapidly increased, which was indicative of classical evolution of painless thyroiditis into hypothyroidism. However, his free thyroxine (fT4) levels were noted to be inappropriately elevated, which did not decrease as expected. An analytical interference was suspected based on the biochemical trend. All the samples were processed in the same laboratory using Siemens ADVIA Centaur immunoassay. The samples were reanalysed at another laboratory using a different immunoassay method (Roche Elecsys ECL), which demonstrated increased TSH levels with inappropriately increased fT4. Based on these results, severe hypothyroidism with low fT4 levels was confirmed. To exclude the possible analytical interference associated with heterophilic antibodies, the same sample was processed (with Siemens Centaur immunoassay following treatment with heterophilic blocking tubes. However, fT4 and free triiodothyronine (fT3) levels were comparable with previous detected levels. Hence, the presence of heterophilic antibodies was excluded. Considering his normal TFTs prior to the initiation of nivolumab, pre-existing interference on fT4 levels because of other endogenous factors was also excluded. Based on the findings, a possible nivolumab-related interference on the fT4 assay was suspected. To verify this assumptions, the same sample was subjected to polyethylene glycol (PEG) 6000 precipitation prior Siemens Centaur immunoassay for fT4 levels, which showed low fT4 levels. Hypothyroidism was confirmed. He was treated with levothyroxine sodium [levothyroxine], and monthly TFT monitoring using the Roche immunoassay (unaffected by nivolumab) was performed. Nine months after the initiation of nivolumab, nivolumab was discontinued. One month later, TFTs using Siemens immunoassay were performed, which showed appropriate levels of fT4 in accordance with normal TSH le
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