Immune checkpoint inhibitors (ICI) 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.
A 85 years-old patient, diagnosed with a metastatic melanoma treated with nivolumab, presented to our hospital with severe ICI-related thyrotoxicosis. The diagnosis was complicated by a biochemical interference on thyroid hormones assay, probably induced by nivolumab.
Baseline laboratory examination conducted before the onset of anticancer therapy showed normal thyroid function test (TFTs). A few days after receiving the second nivolumab administration, the patient developed a severe thyrotoxicosis. According to destructive thyroiditis, in a short period thyroid-stimulating hormone (TSH) levels normalized and rapidly increased, but free thyroxine (FT4) levels were inappropriately elevated and did not decrease as expected. The sample was processed by using a Siemens Centaur® immunoassay. We reanalyzed the same sample at another laboratory and with a different immunoassay method (Roche Elecsys®). The results obtained from this assay confirmed severe hypothyroidism with appropriately low FT4 levels. We suspected a possible nivolumab-associated interference on the FT4 assay. Therefore, we subjected the same sample a polyethylene glycol (PEG) 6000 precipitation, a simple method for the removal of macromolecules, before assaying for FT4 levels. The evaluation of the post-PEG-precipitation sample (Siemens Centaur® immunoassay) revealed appropriately low FT4 levels. The patient was started on levothyroxine therapy, with monthly TFT monitoring using the Roche immunoassay. Approximately 9 months after starting nivolumab therapy, the patient was advised treatment cessation. A month later, the TFTs were retested on a Siemens Centaur® immunoassay, and appropriate FT4 levels were observed in accordance with normal TSH levels on adequate levothyroxine replacement therapy.
We report a possible novel nivolumab-induced biochemical interference on assays of FT4 levels. The hypothesis of a biochemical drug-induced interference is further supported by the disappearance of the interference after the withdrawal of nivolumab. Further studies are needed to prove the biochemical mechanisms of this interference.
Related Posts
Advertisement
Meeting Coverage
- ACC 2020The American College of Cardiology decided to cancel ACC.20/WCC due to COVID-19, which was scheduled to take place March 28-30 in Chicago. However, ACC.20/WCC Virtual Meeting continues to release cutting edge science and practice changing updates for cardiovascular professionals on demand and free through June 2020.
- ENDO: 2020ENDO 2020 Annual Conference has been canceled due to COVID-19. Here are highlights of emerging data that has still been released. Keep an eye out for ENDO Online 2020, which will take place from June 8 to 22.