Dua Al-Husni, MD: No financial relationships to disclose
Immune checkpoint inhibitors (ICIs) frequently induce endocrine immune-related adverse events (irAEs), most commonly hypothyroidism and adrenal insufficiency (AI) from hypophysitis. While these toxicities are often managed as permanent conditions, systematic data on long-term recovery and the success of hormone replacement weaning remains limited and conflicting. This study evaluates real-world hormone weaning practices and recovery rates clinical patterns following ICI-induced hypothyroidism and AI.
We performed retrospective cohort analyses of patients who developed ICI-related thyroid dysfunction requiring levothyroxine (n=237) and ICI-related AI (predominantly secondary AI/hypophysitis, n=23) between 2011-2023. Clinical variables included cancer type, ICI regimen utilized, hormone replacement dosing, and documentation of weaning attempts. For the thyroid cohort, levothyroxine dosing evaluated as absolute (µg/day) and weight-adjusted (µg/kg/day) doses. Descriptive statistics were used to characterize weaning success rates (successful discontinuation vs. unsuccessful attempts).
In the thyroid cohort (n=237), weaning was rarely attempted (n=10, 4.2%). Successful discontinuation occurred in only 3 patients (1.3% overall; 30% of attempts) and was associated with lower maximum levothyroxine doses (mean 33.3 µg/day [0.38 µg/kg/day] vs. 123.1 µg/day [1.50 µg/kg/day] in unsuccessful attempts). In the AI cohort (n=23), glucocorticoid weaning was attempted more frequently (n=12, 52.2%) over a mean follow-up of 27 months. However, successful discontinuation was achieved in only 1 patient (4.3% overall; 8.3% of wean attempts), with 91.7% of weaning attempts proving unsuccessful.
Long-term recovery of ICI-induced endocrine toxicities is uncommon. These findings support the prevailing clinical assumption that ICI-related hypothyroidism and adrenal insufficiency are frequently persistent. While thyroid hormone weaning is seldom attempted but potentially more successful in those on low doses, glucocorticoid weaning is attempted more often but rarely results in adrenal recovery. The low rates of successful de-escalation highlight a critical need for evidence-based strategies for evaluating who may most benefit from an attempt at hormone weaning. Improved collaboration between oncology and endocrinology is essential to guide safe hormone titration.
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