Endocrine Abstracts

The use of immune checkpoint inhibitors (ICPI) for treatment of different advanced cancers has opened a new therapeutic window. Thyroid dysfunction is an often side effect described for these drugs.

Objectives: To describe the thyroid alterations found in oncologic patients undergoing treatment with ICPI.

Materials and methods: A descriptive, retrospective study of oncologic patients receiving treatment with ICPI referred to the Endocrinology Clinic of our Center for thyroid disorders from October 2013 to January 2018.

Results: Thirty-four patients were detected, mean age 59.9 years old (from 34 to 79), 64.7% were women. Neoplasm treated were mainly breast (17.6%), lung (17.6%) and melanoma (14.7%), among others. The immunotherapy received was in monotherapy regimen in the majority of cases (73.5%), using a combination of ICPI in the remaining cases (Pembrolizumab 35.3%, Atezolizumab 20.6%, Nivolumab + Ipilimumab 14.7%, Nivolumab 11.8%, Nivolumab + Anti-LAG3 8.8%, Tremelimumab + Durvalumab 2.9%, Tremelimumab 2.9%, PDR001 2.9%). Before starting immunotherapy, 74% of patients were euthyroid, 18% had clinical or subclinical hypothyroidism, in two cases the previous thyroid status was unknown, and only one patient initiated immunotherapy with subclinical hyperthyroidism. Patients had a mean follow-up of 42.1±36.4 weeks, 61.8% of patients presented asymptomatic transient hyperthyroidism as first alteration 8.7±8.8 weeks after initiating the ICPI, the remaining developed asymptomatic hypothyroidism as first thyroid function alteration, on average 15.7±13.2 weeks after initiating immunotherapy. During follow-up, all patients with hyperthyroidism developed hypothyroidism 6.7±4.2 weeks later. When analyzed separated, those who received ICPI in monotherapy or combination, the combined therapy group presented hyperthyroidism earlier than the monotherapy group (3.4±1.0 weeks vs 12.6±9.1 weeks). No specific treatment was reported for patients with hypertiroidism, however substitutive Levothyroxine was iniciated when hypothyroidism was found. At the end of the follow-up 64.7% continued on Levothyroxine, althought only 48.6% of patients continued on treatment with ICPI. In 31.4% of patients immunotherapy was stopped due to progression of the neoplastic disease and in 5.7% due to immunotherapy related toxicity, but none because of the thyroid function alterations.

Conclusions: In our series, more than half of the patients initially presented with transient hyperthyroidism with subsequent hypothyroidism and the rest with hypothyroidism as first dysfunction, requiring replacement therapy with levothyroxine in most cases. These alterations did not merit the suspension of ICPI. Patients treated with combination of ICPI develop hyperthyroidism earlier compared with patients receiving ICPI as monotherapy.