Reversibility of immune checkpoint inhibitor-induced hypothyroidism

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment but can induce immune-related adverse events, most commonly hypothyroidism. The reversibility of ICI-induced hypothyroidism and the potential for discontinuing levothyroxine (LT4) treatment remain unclear. This retrospective study analyzed patients who developed hypothyroidism due to ICI treatment and were prescribed LT4 at a tertiary referral hospital from January 2016 to March 2024. Among 3,753 patients treated with ICIs, 254 (6.8%) developed hypothyroidism requiring LT4 treatment. Of the 184 patients who discontinued ICI, only 10 (5.4%) discontinued LT4 during a median follow-up of 13.2 months, while none did among those continuing ICIs. Multivariable Cox regression analysis revealed that the use of ICIs in early-stage cancer (HR 13.40, 95% CI: 1.99-90.06, P = 0.008) and TSH <20 μIU/mL before starting LT4 (HR 15.16, 95% CI: 2.17-105.85, P = 0.006) significantly increased the likelihood of discontinuing LT4. These findings suggest that while recovery from ICI-induced hypothyroidism is uncommon, patients treated for early-stage cancer and those with lower TSH levels before starting LT4 may have a greater likelihood of recovery.