Endocrine Abstracts

Introduction: Nivolumab, an anti–programmed cell death-1 (PD-1) monoclonal antibody, is a promising treatment of variety advanced malignancies. Immune checkpoint inhibitors can cause immune-related adverse events, including endocrine pathology. Destructive thyroiditis is one of the most frequently observed nivolumab-induced endocrine irAEs which associated with the presence of anti–thyroid peroxidase antibodies (TPO-Abs) and anti-thyroglobulin antibodies (Tg-Abs) prior to treatment. In this case we have described occurrence frank hypothyroidism during nivolumab treatment in young male without antithyroid autoimmunity at baseline.

Case: A 19-year-old male patient has presented with history of refractory classic Hodgkin lymphoma (stage III). It was decided to conduct nivolumab treatment after failure of several polychemotherapy courses (ABVD, BEACOPP). There was no history of endocrine diseases. Thyroid-stimulating hormone (TSH) levels was 2.4 mIU/l (reference range 0.4–4.0 IU/l) and TPO-Abs/Tg-Abs was absent at the time of therapy initiation. ¹⁸F-FDG PET/CT scan performed after four cycles of nivolumab (3 mg/kg once every two weeks) was revealed positive response to treatment and signs of increased ¹⁸F-FDG uptake in thyroid. Moreover, the patient developed symptoms of progressive fatigue and dizziness. Thyroid tests were performed: TSH level was 56.4 mIU/l (reference range 0.4–4.0 mIU/l), free T4 – 5.2 pmol/l (reference range 9.0–19.0 pmol/l), free T3 – 1.5 pmol/l (reference range 2.6–5.7 pmol/l), TPOAbs – 1.0 IU/l (reference range 0.0–5.6 IU/l), TgAbs – 0.4 IU/l (reference range 0.0–4.0 IU/l). Thyroid colour flow Doppler sonography demonstrated markedly decreased parenchymal blood flow within thyroid. Thus, the diagnosis of nivolumab-induced primary hypothyroidism was established due to destructive thyroiditis. The patient was commenced on gradually increasing doses of levothyroxine up to total dose 1.6 μg/kg without discontinuation of nivolumab therapy. Two weeks later, patient noted relief of symptoms and free T4 level was 14.4 pmol/l (reference range 9.0–19.0 pmol/l). Six weeks later, TSH level was 14.3 mIU/l (reference range 0.4–4.0 mIU/l) and subsequent values were within normal range.

Conclusion: Our observation implies that treatment with anti-PD-1 antibody could lead to frank primary hypothyroidism even in patients without prior antithyroid autoimmunity and emphasizes the importance of thyroid function monitoring during nivolumab treatment.