Alteraciones tiroideas asociadas con los inhibidores de los puntos de control inmunitario

Abstract

IntroductionImmune checkpoint inhibitors (IPCI) have improved progression-free survival in several solid tumors. Side effects are related to overstimulation of the immune system. Thyroid dysfunction (TD) is the most common endocrine immune-related adverse event of IPCI. ObjectiveTo describe the clinical presentation and the course of TD in cancer patients treated with IPCI referred to an endocrinology outpatient clinic. Material and methodsThis was a descriptive, retrospective and multicenter study of patients with TD associated with IPCI in six Spanish hospitals. Results120 patients (50.1% women), mean age 60 ± 12 years were included. The initial TD was hypothyroidism in 49% of patients and hyperthyroidism in 51%, with an average of 76 (41-140) and 43 (26-82) days respectively between the onset of IPCI and the analytical alteration. Significantly, the earlier the first analytical determination was, the greater the prevalence of hyperthyroidism. A turnover was observed in 80% of subjects during follow-up, mostly from hyperthyroidism to hypothyroidism. Twenty-one percent received double IPCI therapy. The most frequent form of presentation in monotherapy was hypothyroidism (57%), and in double therapy it was hyperthyroidism (77%) (p = 0.002). Patients under double therapy showed thyroid alterations earlier than those in the monotherapy group (p = 0.001). After a follow-up of 205 (112-360) days, half of the patients continued under levothyroxine treatment. ConclusionsHypothyroidism and hyperthyroidism present in a similar proportion in cancer patients undergoing ICPI therapy. Our results suggest that transitory hyperthyroidism may not be detected in a relevant number of cases. In addition, TD in double therapy presents earlier. This should be taken into account in the follow-up protocols of these patients.