A rare case of macro-TSH phenomenon development during treatment with immune checkpoint inhibitors in a patient with uveal melanoma

Immune checkpoint inhibitors (ICIs) are currently widely used in the treatment of malignant neoplasms of various localizations. Among the common complications associated with ICI therapy are immune-related adverse events (irAEs), particularly endocrinopathies. This article presents a clinical case of a 33-year-old patient who underwent enucleation of the left eye with prosthetic replacement due to uveal melanoma (choroidal melanoma). Three years later, disease progression was detected with the development of multiple liver metastases, which led to transarterial chemoembolization followed by initiation of ICI therapy (nivolumab + ipilimumab). During treatment, hypothyroidism developed as a consequence of immune-mediated thyroiditis. Levothyroxine sodium replacement therapy was initiated with gradual dose escalation up to the maximum (300 μg/day), without normalization of thyroid profile parameters. The use of a combination regimen including liothyronine also failed to achieve target reduction of thyroid-stimulating hormone (TSH), while clinical signs of thyrotoxicosis were absent. Subsequently, during follow-up laboratory monitoring, an inadequate level of TSH was recorded at the current dose of thyroid hormone replacement therapy, which prompted serum analysis before and after polyethylene glycol precipitation, confirming the presence of the macro-TSH phenomenon. After discontinuation of liothyronine and reduction of levothyroxine sodium dose to 225 μg/day, stable euthyroidism was achieved based on biologically active TSH measurements. The described case demonstrates that the macro-TSH phenomenon may represent one of the rare manifestations of endocrine immune-related adverse events associated with cancer immunotherapy. This condition substantially complicates the interpretation of thyroid function tests and the management of hypothyroidism during treatment with immune checkpoint inhibitors.