Thyroid Dysfunction Induced by Pembrolizumab: Five Case Reports

Although pembrolizumab, as a programmed cell death receptor-1 (PD-1) inhibitor, has revolutionized cancer therapy, it is frequently accompanied by immune-related adverse events. Thyroid dysfunction represents a common irAE, yet its clinical trajectory, optimal management approaches, and long-term outcomes remain incompletely characterized.

We conducted a retrospective analysis of 5 cancer patients who developed thyroid dysfunction following pembrolizumab therapy. All patients ultimately progressed to hypothyroidism, manifesting heterogeneous patterns: biphasic thyroid dysfunction, persistent hypothyroidism, and delayed presentation after treatment cessation. Patients with baseline positivity for thyroid antibodies (thyroglobulin/thyroid peroxidase antibodies) and elevated thyrotropin levels demonstrated higher susceptibility to severe hypothyroidism. Longitudinal follow-up revealed that thyroid function achieved stabilization following early initiation of hormone replacement therapy, whereas delayed intervention was associated with increased requirements for hormone dose titration.

Thyroid dysfunction induced by pembrolizumab is characterized by diverse clinical manifestations and heterogeneous timing of onset. Combination regimens and baseline thyroid status may be significantly associated with its course. Re-treatment risk assessment and dynamic monitoring during therapy should be strengthened in clinical practice as early intervention may improve patient outcomes.