Endocrine Abstracts

Background: Nivolumab is a monoclonal antibody specific for human PD-1 (programmed cell death protein-1), a checkpoint molecule highly expressed in several cancers. Nivolumab is an immunotherapeutic strategy for human cancer, but it can interfere with endocrine system.

Case reports: We report four cases regarding nivolumab-associated endocrinopathies: (i) Male, 55-year-old, with previous normal cortisol and adrenocorticotropic hormone (ACTH) levels, treated with nivolumab for metastatic lung epidermoid carcinoma. After 14 cycles, he developed asthenia, anorexia, weight loss, hypotension and hyponatremia, resulting in hospital admission. Adrenal insufficiency was confirmed by morning cortisol <1.0 μg/dl; hydrocortisone treatment was started with clinical improvement. (ii) Male, 78-year-old, with previous normal cortisol and ACTH levels, treated with nivolumab for stage 3B lung epidermoid carcinoma. After 15 cycles, he developed adrenal insufficiency with morning cortisol<3.0 μg/dl and ACTH<5.0 ng/l. He had recent weight loss, but was hemodynamically stable, without electrolyte imbalance. He started hydrocortisone with clinical improvement. (iii) Male, 70-year-old, without previous thyroid disease, treated with nivolumab for metastatic clear cell renal carcinoma. After 2 cycles, he developed thyrotoxicosis with thyroid-stimulating hormone (TSH) 0.01 μUI/ml (ref:0.35–4.94), free thyroxine (FT₄) 1.82 ng/dl (ref:0.70–1.48), free triiodothyronine (FT₃) 3.68 pg/ml (ref:1.71–3.71), positive thyroglobulin antibody (TgAb), negative peroxidase (TPOAb) and TSH-receptor antibodies (TRAb). He was treated with methimazole for 3.5 months. He maintains normal thyroid function since antithyroid drug withdrawal. (iv) Male, 64-year-old, without previous thyroid disease, treated with nivolumab for metastatic lung adenocarcinoma. After 5 cycles, he developed thyrotoxicosis with TSH 0.003 μUI/ml and normal FT₄ and FT₃. He had spontaneous remission of thyrotoxicosis within 2 months and then developed hypothyroidism with TSH 7.78 μUI/ml, FT₄ 0.48 ng/dl, FT₃ 2.19 pg/ml and positive TPOAb and TgAb. Levothyroxine was initiated, compatible with the possible diagnosis of nivolumab-associated thyroiditis.

Conclusion: Health providers must be aware of endocrine disorders that may be associated with immunomodulatory therapies for a timely diagnosis and correct treatment.