# Incidence of Hypothyroidism and Thyroid Function Monitoring After Immune Checkpoint Inhibitor Therapy Completion for Lung Cancer: A Nationwide Analysis of a Japanese Claims Database

## TL;DR

This study finds that 4% of lung cancer patients develop hypothyroidism after immune checkpoint inhibitor therapy, often beyond current monitoring practices.

## Contribution

The study reveals late-onset hypothyroidism after ICI therapy and identifies risk factors, suggesting extended monitoring is needed.

## Key findings

- 4% of patients developed hypothyroidism requiring hormone therapy after ICI discontinuation, with a median onset of 67 days.
- Thyroid function testing was most commonly performed 21 days post-discontinuation, missing many late-onset cases.
- ICI combined with bevacizumab and preexisting myasthenia gravis increased hypothyroidism risk, while long-term steroids reduced it.

## Abstract

Immune checkpoint inhibitors (ICIs) have significantly advanced lung cancer treatment but can lead to immune-related side effects, including thyroid dysfunction. While prior research has focused on thyroid issues during treatment, little is known about thyroid issues emerging post therapy. In this nationwide Japanese study, 4% of patients developed hypothyroidism requiring thyroid hormone therapy after ICI discontinuation, with a median onset of 67 days. Although 73.7% of patients underwent thyroid function testing after treatment, the most common (modal) timing of testing was just 21 days post-discontinuation—well before the typical onset of hypothyroidism. This suggests that current monitoring practices may not fully capture late-onset cases. ICI combined with bevacizumab and preexisting myasthenia gravis increased the risk, while long-term steroid use lowered the risk. These findings emphasize the need to extend thyroid monitoring beyond the initial few weeks after ICI therapy, potentially improving timely diagnosis and patient care in future clinical practice.

Immune checkpoint inhibitors (ICIs) improve lung cancer prognosis but are associated with immune-related adverse events, most commonly thyroid dysfunction. While prior studies and guidelines have focused on thyroid dysfunction during ICI therapy, data on hypothyroidism and its monitoring after ICI therapy remain limited. We aimed to investigate hypothyroidism incidence and implementation of thyroid function monitoring after ICI therapy completion in patients with lung cancer. We conducted a retrospective observational study using the DeSC claims database of approximately 12 million individuals in Japan. Patients with lung cancer who received ICI therapy between April 2014 and August 2023 were included; those with a history of thyroid hormone replacement or insufficient follow-up were excluded. Among 6883 eligible patients, 277 (4.0%) developed hypothyroidism requiring hormone replacement post-ICI therapy completion (median onset, 67.0 d). Risk factors included ICI plus bevacizumab therapy and a history of myasthenia gravis, while steroid use for ≥28 d during ICI therapy lowered the risk. Post-ICI therapy completion thyroid monitoring was performed in 73.7% of patients, with test date distribution showing a median of 126.0 d and mode of 21.0 d. Hypothyroidism was frequently found to develop within 2 months post-ICI therapy completion, highlighting the need for continued thyroid monitoring and prospective studies to establish optimal surveillance strategies.