Endocrine Abstracts

: Recent Phase 3 studies have demonstrated the clinical utility of immunotherapy with inhibitors of PD1 in cancers, including melanoma and non-small cell lung cancer. Autoimmune side effects are common. Both hypothyroidism and hyperthyroidism have been observed in up to 16% of patients. We report for the first time the endocrine evaluation of patients with anti-PD1 induced thyroid dysfunction.

Methods: All patients treated in published trials of anti-PD1 therapies for malignant melanoma in our institution were identified. Thyroid function at baseline and during treatment was recorded. Data about investigation and treatment of thyroid abnormalities was obtained from the electronic patient record.

Results: Sixty-four patients with melanoma were treated with nivolumab or pembrolizumab, either alone or in combination trials. one patient was excluded due to pre-existing hypopituitarism. five patients developed overt hypothyroidism during treatment requiring thyroxine replacement. Two had a symptomatic thyrotoxic phase preceding the hypothyroidism. Both of these patients had technetium uptake scans with markedly reduced uptake in keeping with a thyroiditis and one had thyroid antibodies tested which were positive. One required beta blockers but neither received anti-thyroid drugs. A further six patients developed a TSH of <0.3 mU/l but did not go on to develop hypothyroidism. Only one of these had an elevated T₄. Six patients had elevated TSH less than 2× ULN not requiring thyroxine. Mean time to first abnormal TSH was 38 days.

Conclusions: These results confirm the significant rate of thyroid abnormalities in patients treated with anti-PD1 agents and show that a thyrotoxic phase can occur before hypothyroidism develops. Uptake scans confirm this to be a thyroiditis; presumed autoimmune in origin. Sub-clinical hyperthyroidism is also common and can resolve without subsequent hypothyroidism. These results will inform endocrinologists managing the side effects of these important new cancer therapies.