Thyroid disorders associated with immune control point inhibitors

Abstract

Introduction: Immune checkpoint inhibitors (ICPI) 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 ICPI.

Objective: To describe the clinical presentation and the course of TD in cancer patients treated with ICPI referred to an endocrinology outpatient clinic.

Material and methods: This was a descriptive, retrospective and multicenter study of patients with TD associated with ICPI in six Spanish hospitals.

Results: 120 patients (50.8% 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 ICPI 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 ICPI 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.

Conclusions: Hypothyroidism 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.

Keywords: Disfunción tiroidea; Hipertiroidismo; Hipotiroidismo; Hyperthyroidism; Hypothyroidism; Immune checkpoint inhibitors; Inhibidores de puntos de control inmunitario; Ipilimumab; Nivolumab; Pembrolizumab; Thyroid dysfunction.