Abstract

Background: 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. This study sought to investigate the evolution of irT and describe its course and sequelae.
Methods: This was a retrospective study of cancer patients treated with ICI between November 2014 and July 2016 at MD Anderson Cancer Center and referred for endocrinology evaluation for suspected irT. Patients included had normal baseline thyroid function tests prior to starting ICI and developed thyrotoxicosis due to irT.
Results: Of 657 patients treated with ICI during the study period, 43(6.5%) met the inclusion criteria. ICI included: ipilimumab + nivolumab (40%), nivolumab (33%), pembrolizumab (21%), and 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 weeks). Clinically, patients presented with painless thyroiditis, and 67% were asymptomatic during the thyrotoxicosis phase. Thyrotoxicosis lasted a median of six weeks (range 2.6–39.7 weeks). Hypothyroidism developed in 37 (84%) patients at a median of 10.4 weeks (range 3.4–48.7 weeks) after starting ICI. These patients remained on levothyroxine and ICI at a median follow-up of 57.4 weeks (range 1–156.7 weeks) from hypothyroidism onset. Four patients recovered without initiating levothyroxine and remained euthyroid at a median follow-up of 11.35 months (range 4.43–14.43 months). Subgroup analysis of ipilimumab + nivolumab versus nivolumab alone showed a median time to thyrotoxicosis of two weeks [confidence interval (CI) 3.5–8.4] versus six weeks ([CI 1.2–2.8]; p = 0.26) and time to hypothyroidism of 10 weeks [CI 8.1–11.9] versus 17 weeks ([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.
Conclusions: IrT manifests as an early onset of thyrotoxicosis, which is largely asymptomatic, followed by rapid transition to hypothyroidism requiring long-term levothyroxine substitution. The evolution of irT is more rapid with combination ICI. Frequent monitoring of thyroid function tests during ICI is warranted. Future guidelines need to recognize this entity and incorporate their management.

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cover image Thyroid®
Thyroid
Volume 28Issue Number 10October 2018
Pages: 1243 - 1251
PubMed: 30132401

History

Published in print: October 2018
Published online: 18 September 2018
Published ahead of production: 22 August 2018

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Priyanka C. Iyer
Department of Endocrine Neoplasia and Hormonal Disorders, Division of Internal Medicine; The University of Texas MD Anderson Cancer Center, Houston, Texas.
Department of Endocrinology, Diabetes and Metabolism, Baylor College of Medicine, Houston, Texas.
Maria E. Cabanillas
Department of Endocrine Neoplasia and Hormonal Disorders, Division of Internal Medicine; The University of Texas MD Anderson Cancer Center, Houston, Texas.
Steven G. Waguespack
Department of Endocrine Neoplasia and Hormonal Disorders, Division of Internal Medicine; The University of Texas MD Anderson Cancer Center, Houston, Texas.
Mimi I. Hu
Department of Endocrine Neoplasia and Hormonal Disorders, Division of Internal Medicine; The University of Texas MD Anderson Cancer Center, Houston, Texas.
Sonali Thosani
Department of Endocrine Neoplasia and Hormonal Disorders, Division of Internal Medicine; The University of Texas MD Anderson Cancer Center, Houston, Texas.
Victor R. Lavis
Department of Endocrine Neoplasia and Hormonal Disorders, Division of Internal Medicine; The University of Texas MD Anderson Cancer Center, Houston, Texas.
Naifa L. Busaidy
Department of Endocrine Neoplasia and Hormonal Disorders, Division of Internal Medicine; The University of Texas MD Anderson Cancer Center, Houston, Texas.
Sumit K. Subudhi
Department of Genitourinary Medical Oncology; The University of Texas MD Anderson Cancer Center, Houston, Texas.
Adi Diab
Melanoma Medical Oncology, Division of Cancer Medicine; The University of Texas MD Anderson Cancer Center, Houston, Texas.
Ramona Dadu [email protected]
Department of Endocrine Neoplasia and Hormonal Disorders, Division of Internal Medicine; The University of Texas MD Anderson Cancer Center, Houston, Texas.

Notes

Address correspondence to:Ramona Dadu, MDDepartment of Endocrine Neoplasia and Hormonal DisordersThe University of Texas MD Anderson Cancer Center1400 Pressler Street, Unit 1461Houston, TX 77230-1402 [email protected]

Author Disclosure Statement

R.D. is a member of the Bristol Myers Squibb advisory board. The remaining authors have nothing to disclose.

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