Adrenal axis integrity after IV methylprednisolone therapy for thyroid eye disease: a retrospective cohort study

Only 5 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.

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-min post-ACTH. A peak cortisol level ≥18.1 μg/dL (≥500 nmol/L) was considered indicative of adrenal sufficiency.

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 min, 93% achieved adequate cortisol response, and at 60 min, 100% met the sufficiency threshold. All patients with baseline cortisol <5 μg/dL (150 nmol/L) demonstrated intact adrenal function on dynamic testing.

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.