Low-dose, not low-risk: potential adrenal suppression identified by a risk-based approach to ACTH testing

This study aimed to investigate the frequency and associated factors of impaired adrenal response on Synacthen test in patients with rheumatic diseases undergoing low-dose maintenance GC therapy.

This single-center, retrospective, observational study included 48 patients with autoimmune rheumatic diseases on maintenance GC therapy (prednisolone ≤ 5 mg/day) who had previously received ≥ 5 mg/day for ≥ 3 months and underwent adrenal function testing between January 2021 and May 2023. Impaired adrenal response was defined by both low baseline cortisol and inadequate response to the standard-dose (250 μg) Synacthen test in this study. Daily dose, treatment duration, cumulative dose, and history of methylprednisolone pulse therapy were evaluated. Statistical comparisons were performed using Mann-Whitney U, Fisher's exact, and receiver operating characteristic (ROC) analyses.

Impaired adrenal response on Synacthen test meeting the study-defined criteria was identified in 30 of 48 patients (62.5%). Compared with the normal adrenal response group, affected patients had significantly higher cumulative GC doses, lower baseline cortisol levels, and more frequent histories of methylprednisolone pulse therapy. Exploratory ROC analysis identified an optimal cumulative glucocorticoid dose cutoff of 10,371.5 mg associated with impaired adrenal response on Synacthen test (prednisolone equivalent).

Impaired adrenal response on Synacthen test was frequently observed among patients selected for adrenal function testing during maintenance GC therapy at ≤ 5 mg/day. Higher cumulative GC exposure and prior pulse therapy were associated with impaired adrenal response on Synacthen test, suggesting that a targeted, risk-based approach to adrenal evaluation may be useful even during low-dose treatment. Key Points • Impaired adrenal response on Synacthen test was detected in 62.5% of patients selected for adrenal function testing during maintenance glucocorticoid therapy at ≤ 5 mg/day. • A cumulative glucocorticoid dose ≥ 10,371.5 mg was associated with impaired adrenal response on Synacthen test. • Exploratory ROC analysis identified basal cortisol ≤ 6.1 μg/dL and daily glucocorticoid dose ≥ 3.5 mg as potential thresholds associated with impaired adrenal response on Synacthen test. • Adrenal suppression may occur even in clinically stable patients receiving low-dose therapy.