Immunotherapy-induced thyroid dysfunction and diabetes mellitus in gynecologic oncology patients: a retrospective cohort study.

OBJECTIVES

We sought to characterize immune-related endocrine toxicities (IETs) in gynecologic oncology patients receiving immunotherapy (IO), including risk factors, onset and resolution characteristics, and clinical outcomes.

METHODS

This IRB-approved retrospective cohort study included all gynecologic oncology patients who received IO at a single institution between January 1, 2017, to January 1, 2023. Clinical characteristics, IO regimen, endocrine toxicities, management strategies, time to onset, resolution, and oncologic outcomes were abstracted from electronic medical records.

RESULTS

Among 333 patients, 128 (38.4%) developed an IET (immune-related endocrine toxicities). The most common IETs were hypothyroidism (31.2%, n = 104), hyperthyroidism (11.7%, n = 39), and insulin-dependent diabetes mellitus (2.4%, n = 8). Most toxicities were grade 1 (44.5%, n = 57) or grade 2 (50.8%, n = 65), while 4.7% (n = 6) were grade 3 or 4. Median time from IO initiation to IET diagnosis was 9.0 weeks (IQR, 5.4-18.7). Overall, 62.5% of patients with an IET required endocrine-directed therapy, and 56.3% required subsequent dose adjustment. Most IETs did not resolve during the median follow-up period of 16.4 months (67.2%, n = 86). Among IETs that resolved, median time to resolution was 8.1 weeks (IQR, 3.4-16.3). Pre-existing endocrine disorders were present in 43.8% of patients, most commonly hypothyroidism and diabetes. Among patients receiving endocrine-directed therapy, 51.9% required medication dose escalation during IO.

CONCLUSIONS

IETs are common among patients with gynecologic cancers receiving immunotherapy. While mostly low-grade, these events are usually chronic and frequently require medications or dose adjustments. These findings highlight the need for routine endocrine monitoring and long-term management strategies.