Abstract Background Only five prior studies, each involving 12 to 32 patients, have evaluated the impact of high-dose intravenous methylprednisolone (IVMP) on hypothalamic-pituitary-adrenal (HPA) axis function in patients with active moderate-to-severe thyroid eye disease (TED). Due to their small sample sizes and methodological limitations, uncertainty remains regarding the risk of adrenal suppression following this regimen. Methods We conducted a retrospective observational study of 127 adults with active moderate-to-severe TED treated with the standard IVMP protocol (cumulative dose: 4.5 g over 12 weeks) at the Department of Endocrinology and Metabolic Diseases, University General Hospital of Larissa, Greece. HPA axis integrity was assessed 7–10 days after the final IVMP dose using the 250-μg ACTH(1–24) stimulation test. Serum cortisol was measured at baseline, 30-, and 60-minutes post-ACTH. A peak cortisol level ≥18.1 μg/dL (≥500 nmol/L) was considered indicative of adrenal sufficiency. Results Twelve patients were excluded due to unavailability of testing or contraindications. Among the 115 patients tested, 15 (13%) had baseline cortisol ≥18.1 μg/dL. At 30 minutes, 93% achieved adequate cortisol response, and at 60 minutes, 100% met the sufficiency threshold. All patients with baseline cortisol 5 μg/dL (150 nmol/L) demonstrated intact adrenal function on dynamic testing. Conclusion In this cohort, adrenal responsiveness to the 250 μg ACTH test 7–10 days after completion of IVMP was preserved in all patients, suggesting that early post-treatment secondary adrenal insufficiency is uncommon. Although reassuring, these results should be interpreted cautiously, and clinicians should continue to rely on clinical judgment, supported by biochemical testing when indicated.
Effraimidis et al. (2026) studied this question.