Endocrine Abstracts

Introduction: Immune checkpoint inhibitors (ICI) are a new drug generation used for advanced neoplasias. They are monoclonal antibodies which enhance the immune system to combat cancer cells. As a result, immunologic tolerance can be altered and autoimmunity triggered. Toxicities associated to ICIs have been named immune-related adverse events (irAE). ‘Time to resolution’ of endocrine irAEs have not been well described as this term has not been defined in clinical trials. The aim of this study was to describe the frequency and characteristics of endocrine irAEs in the patients treated with ICIs at our centre.

Methods: Between 2010 and 2015, 91 patients have been treated with anti CTLA-4, PD1 and PD-L1mAbs for advanced neoplasias (melanoma, lung cancer and Hodgkin’s Lymphoma). This report is based on the retrospective review of the records of 81 patients considered suitable for inclusion. For thyroidopathies, we defined “time to resolution” as the time it took to normalize TSH levels.

RESULTS: Seven patients (8.6%) presented endocrine irAEs. Five patients (6.2%) developed painless thyroiditis, 1 (1.2%) Hashimoto’s thyroiditis and 1 (1.2%) hypophisitis. Endocrinopathies presented after a median of 9 weeks (2–11) once treatment started, and the patients received a median number of doses of 4.5. Thyroiditis where all secondary to antiPD1mAbs. All patients presented with the classic triphasic presentation with a median of 7 weeks of hyperfunction and a mean time to resolution of 20 weeks. Three of five patients developed permanent hypothyroidism. The patient with hypophysitis presented with asthenia, intense headache and blurred vision 11 weeks after starting treatment with an antiCTLA4mAb. Corticotroph and thyrotroph axes where affected and have not recovered 6 months after the event. Five more patients (6.2%) showed a transitory decrease in TSH with normal T₄ and T₃ levels which could correspond to Sick Euthyroid Syndromes or short, subclinical thyroiditis.

Conclusions: Endocrinopathies due to the use of ICIs are common and generally mild. In our series, thyroiditis was the most frequent irAE. Clinical presentation and duration of ICIs-induced thyroiditis is similar to sporadic cases, although there could possibly a higher tendency to develop permanent hypothyroidism. Hypophisitis is an unfrequent but serious irAE. Endocrinologists must be aware of this emerging cause of autoimmune endocrinopathies.