Endocrine Abstracts

Introduction: Immune checkpoint inhibitors are used as therapy for advanced malignancies. The therapy is based on immune enhancement, thus, autoimmune side effects referred to as immune-related adverse events may occur. Thyroid function abnormalities have been reported, but more evidence is needed to substantiate the main subtypes and course of thyroid disease associated with this treatment.

Case report: A 51-year-old woman with metastatic pancreatic cancer and no previous history of autoimmune disease was referred to the Endocrine Department 4 months following the initial combined therapy with Ipilimumab (anti-CTLA-4) and Nivolumab (anti-PD-1). At the time of referral, the patient had biochemical overt hyperthyroidism with fully suppressed TSH (< 0.01 mIU/l), elevated free T4 (fT4) > 100 pmol/l (reference interval (RI): 12-22 pmol/l), and elevated free T3 (fT3) of 34.6 pmol/l (RI: 3.9-6.8 pmol/l). Despite the markedly biochemical hyperthyroidism, the patients presented with sparse symptoms of hyperthyroidism. TSH-receptor antibodies (TRAb) were negative as were thyroid-peroxidase antibodies, whereas elevated levels of thyroglobulin antibodies were found (993 kU/l). Due to recent CT-scan with contrast, thyroid ultrasound was performed revealing an enlarged, heterogenous hypoechoic gland with increased vascularity. High dose Propylthiouracil (PTU) was initiated with a response in thyroid function parameters (after one week of treatment: fT4: 42.2 pmol/l, fT3: 8.0 pmol/l; after two weeks: fT4: 20.6 pmol/l, fT3: 3.2 pmol/l). After four weeks of PTU treatment, the patient developed biochemical hypothyroidism, thus, treatment with PTU was discontinued, and treatment with Levothyroxine was initiated.

Conclusion: This case report illustrates the onset of autoimmune thyroid disease after combined immune checkpoint inhibitor therapy. The thyroid ultrasound findings and the response with antithyroid drug treatment makes TRAb-negative Graves’ hyperthyroidism the most likely initial diagnosis which was followed by seroconversion to autoimmune hypothyroidism. Results highlight the importance of monitoring thyroid function in relation to immune checkpoint inhibitor therapy.