Endocrine Abstracts

Introduction: The occurrence of autoimmune adverse events is a frequent complication of oncoimmunotherapy with antibody drugs to PD-1.

Clinical Case: At the age of 33, the patient was diagnosed with melanoma, which was surgically removed. After 3 years, there was a progression with the appearance of liver metastases which were embolized with further initiation of oncoimmunotherapy with nivolumab. As a complication of this treatment the patient developed autoimmune thyroiditis with primary hypothyroidism, and levothyroxine therapy was initiated with gradual dose escalation over several months up to 300 mg per day (2.6 mg per kg of body weight), but without normalization of the thyroid profile: thyroid stimulating hormone (TSH) – 24.68 mU/l (0.35 - 4.94), free T3 – 2.98 pmol/l (2.63-5.9), free T4 – 9.18 pmol/l (10-19). No factors that could potentially alter the bioavailability of levothyroxine were detected. Subsequently, liothyronine was added to levothyroxine therapy and gradually increased from dose of 25 mg in the morning to dose of 25 mg in the morning and 50 mg in the afternoon, which led to normalization of TSH levels while maintaining free thyroxine is in the low normal range. There were no clinical signs of hyperthyroidism in the patient. During the examination at our Centre an inadequate TSH levels were suspected for the given dose of thyroid hormones taken. To address this issue a blood serum test for TSH was performed initially and after precipitation with polyethylene glycol (it allows to remove a high-molecular fraction of immunoreactive TSH from the blood, presumably due to the binding of part of TSH molecules with anti-TSH IgG, by analogy with macroprolactin). The results of the analysis confirmed macro-TSH phenomenon: TSH – 12.8 mU/l (0.25-3.5), bioactive TSH – 2.8 mU/l (0.25-3.5), free T4 – 13.24 mmol/l (9-19), free T3 – 3.04 (2.6-5.7). Thyroid hormone therapy was adjusted as follows: liothyronine was canceled, the dose of levothyroxine was reduced to 225 mg per day.

Conclusion: The phenomenon of macro-TSH may be one of the manifestations of autoimmune complications of oncoimmunotherapy with immune endpoint inhibitors, complicating the interpretation of laboratory tests