TSH-Free Thyroxine Discordance in an Athyreotic Patient During Ipiluminab and Nivoluminab Therapy

ABSTRACT Objective: The objective of this case report is to illustrate the clinical confusion resulting from discordance between serum thyrotropin and free thyroxine measurements in an athyreotic patient receiving immunotherapy with ipiluminab and nivoluminab. Methods: The case of a 50-year-old athyreotic man with metastatic melanoma is described. The patient was discontinued from his levothyroxine replacement by his primary care physician based on an elevated free thyroxine concentration of 3.87 ng/dL. Shortly afterwards, the patient was started on immunotherapy with ipiluminab and nivoluminab. After a subtherapeutic levothyroxine dose of 0.68 μg/kg/day was initiated concurrently with his immunotherapy, the patient continued to have a high free thyroxine level but additionally developed an elevated serum thyrotropin value of 33 mIU/L. He also became symptomatically hypothyroid over a period of 4 months. Resumption of a full weight-based dose resulted in normalization of the patient's thyrotropin and free triiodothyronine, but there was persistence of the free thyroxine elevation. Results: The patient's immunotherapy was associated with development of marked discordance between his free thyroxine values measured using a luminescent oxygen channeling immunoassay and his serum thyrotropin. This discordance resulted in clinical confusion that lead to the patient's levothyroxine being severely underdosed for his athyreotic state. It subsequently became clear, based on mass spectrometry methods and use of an alternate electrochemiluminescent assay to measure free thyroxine concentrations, that the patient's serum thyrotropin concentration accurately indicated his clinical situation and that he required an increase in his levothyroxine dose. Conclusion: Heightened awareness of the potential for multiple situations to cause inaccurate assessment of free thyroid hormone concentrations using different immunoassays will allow for interpretation of anomalous thyroid function results with such confounding factors in mind. With this knowledge, prevention of this patient's prolonged period of iatrogenic hypothyroidism would have been possible. Abbreviations: BMI = body mass index; BW = body weight; FT3 = free triiodothyronine; FT4 = free thyroxine; LT4 = levothyroxine; T4 = tetraiodothyronine; T3 = triiodothyronine; TSH = thyrotropin