Although immune-related thyroiditis (irT) with immune checkpoint inhibitors (ICI) is a common consequence, its natural course and management recommendations are not well characterized in existing guidelines. We sought to study the evolution of irT and describe its course and sequelae.
Retrospective study of cancer patients treated with ICI between 11/2014 and 07/2016 at MD Anderson Cancer Center and referred for endocrinology evaluation for suspected irT. Patients included had normal baseline thyroid function tests (TFTs) prior to starting ICI and developed thyrotoxicosis due to irT.
Of 657 patients treated with ICI during study period, 43(6.5%) met inclusion criteria. ICI included: Ipilimumab + nivolumab (40%), nivolumab (33%), pembrolizumab (21%), other (7%). Cancer diagnoses observed were melanoma (23%), renal cell carcinoma (21%), lung cancer (19%), bladder cancer (12%), colon cancer (9%) and other cancers (15%). Median time from ICI start to thyrotoxicosis was 5.3 weeks (range 0.6-19.6). Clinically, patients presented with painless thyroiditis and 67% were asymptomatic during thyrotoxicosis phase. Thyrotoxicosis lasted a median of 6 weeks (range 2.6- 39.7). Hypothyroidism developed in 37 patients (84%) at a median of 10.4 weeks (range 3.4 - 48.7) after starting ICI. These patients remained on levothyroxine and ICI at a median follow up of 57.4 weeks (range 1- 156.7) from hypothyroidism onset. Four patients recovered without initiating levothyroxine and remain euthyroid at a median follow up of 11.35 months (range 4.43 -14.43). Subgroup analysis of ipilimumab plus nivolumab vs. nivolumab alone showed a median time to thyrotoxicosis of 2 weeks (95% CI 3.5, 8.4) vs. 6 weeks (95% CI 1.2, 2.8); p = 0.26 and time to hypothyroidism of 10 weeks (95% CI 8.1, 11.9) vs. 17 weeks (95% CI 8.8-25.2); p=0.029 after starting ICI. Thyroid peroxidase and thyroglobulin antibodies were present in 45% and 33% at the time of irT diagnosis.
IrT manifests as an early onset of thyrotoxicosis, which is largely asymptomatic followed by rapid transition to hypothyroidism requiring long-term levothyroxine. The evolution of irT is more rapid with combination ICI. Frequent monitoring of TFTs during ICI is warranted. Future guidelines need to recognize this entity and incorporate their management.
Thyroid : official journal of the American Thyroid Association. 2018 Aug 22 [Epub ahead of print]
Priyanka C Iyer, Maria Cabanillas, Steven G Waguespack, Mimi I Hu, Sonali N Thosani, Victor R Lavis, Naifa Busaidy, Sumit K Subudhi, Adi Diab, Ramona Dadu
University of Texas MD Anderson Cancer Center, 4002, Endocrine Neoplasia and Hormonal Disorders , 1515 Holcombe Blvd , Houston , Houston, Texas, United States , 77030-4000., University of Texas M.D. Anderson Cancer Center, Endocrine Neoplasia and Hormonal Disorders , 1515 Holcombe Blvd, unit 1461 , Houston, Texas, United States , 77030 ; ., University of Texas M. D. Anderson Cancer Center, Endocrine Neoplasia and Hormonal Disorders , PO Box 301402 , Unit 1461 , Houston, United States , 77230-1402 ; ., University of Texas M. D. Anderson Cancer Center, Endocrine Neoplasia and Hormonal Disorders , 1500 Holcombe Blvd. , Unit 1461 , Houston, Texas, United States , 77230-1402 ; ., University of Texas MD Anderson Cancer Center, Endocrine Neoplasia and Hormonal Disorders , 1400 Pressler Street , Unit 1461 , Houston, Texas, United States , 77030 ; ., University of Texas MD Anderson Cancer Center, 4002, Endocrine Neoplasia and Hormonal Disorders, Houston, Texas, United States ; ., MD Anderson Hospital, Endocrine Neoplasia & Hormonal Disorders , 1515 Holcombe blvd, , unit 1461 , houston, Texas, United States , 77030 ; ., University of Texas MD Anderson Cancer Center, 4002, Department of Genitourinary Medical Oncology, Division of Cancer Medicine, Houston, Texas, United States ; ., University of Texas MD Anderson Cancer Center, 4002, Department of Melanoma Medical Oncology, Division of Cancer Medicine, Houston, Texas, United States ; ., University of Texas M. D. Anderson Cancer Center, Department of Endocrine Neoplasia and Hormonal Disorders , 3 Hermann Museum Circle Drive , Apt 4117 , Houston, Texas, United States , 77004 ; .