Endocrine Abstracts

Objective: Immune checkpoint inhibitors (ICPI) have become an effective therapeutic option for certain advanced malignant tumours. Immune-related adverse events affecting thyroid function are among the most frequent toxicities. The aim of our study is to determine the prevalence of thyroid disorders in patients undergoing treatment with ICPI.

Methods: Retrospective study including all patients treated with ICPI in our centre, from 07/2015 to 12/2017. Patients were divided into three groups, according to the drug received: Nivolumab, Pembrolizumab or Atezolizumab. Those patients treated with levothyroxine before ICPI therapy were excluded. We used the SPSS program, version 20.

Results: A total of 79 patients were treated with ICPI in our centre; seven of them being treated previously with levothyroxine were excluded. We studied 72 patients, 70.8% men (51/72) with a mean age of 64±8.6 years. 44 patients (61.1%) were treated with nivolumab, 14 patients (19.4%) with atezolizumab and 14 (19.4%) with pembrolizumab. The 54.2% (n=39) had lung cancer, followed by melanoma 19.4% (n=14), bladder 11.1% (n=8), kidney 8.3% (n=6), colon 4.2% (n=3) and ovarian cancer 2.8% (n=2). In 16 patients (22.2%), thyroid side-effects were detected. Two of 16 patients (12.5%) had autoimmune thyroid disease prior to treatment. Mean thyrotropin (TSH) before ICPI therapy was 1.47 (0.39–4.18) mU/l. The most frequent thyroid disorder was subclinical hyperthyroidism in 12/16 patients (75%); the median onset was 5 weeks (range, 1–52). Out of these, 8/12 patients presented transient thyrotoxicosis, 3/12 continued with subclinical hyperthyroidism and 1/12 evolved to hypothyroidism. None of them received antithyroid drugs. 4/16 patients (25%) developed hypothyroidism, without a previous hyperthyroid phase; the median onset was 9 weeks (range, 8-22). 60% hypothyroid patients needed treatment with levothyroxine. No patient needed interruption of ICPI treatment because of thyroid dysfunction. 35.7% of patients treated with atezolizumab developed thyroid disorders, 28.6% of pembrolizumab and 15.9% of nivolumab (P=0.16). Indeed, in terms of age, sex and type of tumour, no significant differences were found between those who developed thyroid disorder or not.

Conclusions: In our study, 22.2% of patients with IPCI treatment developed thyroid side-effects. Of these patients, 50% presented transient thyrotoxicosis, 31.3% developed hypothyroidism and 18.7% developed persistent subclinical hyperthyroidism. The median onset was 5 weeks for hyperthyroidism and 9 weeks for hypothyroidism.