Endocrine Abstracts

Introduction

Immunological side effects related with use of immune checkpoint inhibitors (ICIs) are named as immune-related adverse events (irAEs). irAEs include clinical pictures such as autoimmune thyroiditis, hypophysitis, primary adrenal insufficiency and autoimmune diabetes mellitus. Nivolumab is an anti-PD-1 (anti-programmed cell death-1) monoclonal antibody approved for the treatment of malignant melanoma, advanced non-small cell lung cancer and advanced renal cell carcinoma. In the literature, Nivolumab was reported for causing thyroid dysfunction in some patients treated for cancer. The incidence of Nivolumab-induced grade 3 hypothyroidism is reported as 0.12%. Here, we present two cases of overt hypothyroidism after nivolumab treatment.

Case-1

A 49-year-old male patient with a diagnosis of metastatic malignant melanoma has a treatment history for 9 cycles of nivolumab. The patient has no known thyroid disease and no history of thyroidectomy or longitudinal radiotherapy. TSH (Thyroid stimulating hormone) and FT4 levels were checked 3 months before Nivolumab therapy and were measured as 1.43 mIU/l (normal range) and 1.21 ng/dl (normal range), respectively. Overt hypothyroidism was detected in the workup performed due to the headache complaint of patient 2.5 months after the last nivolumab treatment. Result of biochemical workup was as follows: TSH>47.9 mIU/l (high), FT4:0.27 ng/dl (low), FT3: 2.71 ng/dl (low), anti-TPO(Anti-thyroid peroxidase): 0.6 IU/ml (negative), anti-TG (Anti-thyroglobulin):1651 IU/ml (positive). Performed neck ultrasound was compatible with chronic thyroiditis. Patient started receiving levothyroxine treatment and was followed up.

Case-2

A 65-year-old female patient with a diagnosis of metastatic breast cancer received 11 cycles of nivolumab treatment, and the last cure was 1 month ago. The patient has no known thyroid disease and no history of thyroid surgery or longitudinal radiotherapy. TSH measured 2 years ago was.6 mIU/l and patient was euthyroid. Overt hypothyroidism was detected in the patient’s workup: (TSH> 47.9 mIU/l (high) FT4: 0.2 ng/dl (low) FT3: 1.07 ng/l (low) anti-TPO: 0.5 IU/ml (negative), anti-TG: 680 IU/ml (positive)). Patient was started on levothyroxine treatment.

Conclusion

Although there was no known history of thyroid disease; anti-TPO was negative and anti-thyroglobulin was positive at high titer and overt hypothyroidism was identified in both patients who received Nivolumab. Since there are no thyroid autoantibody tests before the treatment, it is not known whether the anti-thyroglobulin positivity alone is due to the treatment. Performing thyroid autoantibody and thyroid ultrasound before treatment would guide the follow-up of patient’s thyroid function tests.