Unusual Dosing of Long-Acting Hydrocortisone in a Rapid Hydrocortisone Metabolizer With Addison's Disease: A Case Report.

While the management of primary adrenal insufficiency often follows a structured approach with standard glucocorticoid replacement, not all patients fit into this regimen. We present the case of a woman in her 40s with Addison's disease whose symptoms persisted despite escalating doses of immediate-release hydrocortisone (HC) and a trial of prednisolone. Cortisol day curves revealed an unusual pattern: rapid hydrocortisone clearance, with sharp declines just hours after dosing. A trial of once-daily modified-release hydrocortisone (HCMR) (Plenadren®) yielded only modest improvement. However, further personalisation of her regimen, that is, splitting the dose into 25 mg in the morning and 5 mg in the late afternoon, led to remarkable improvement. Her symptoms stabilised, cortisol levels smoothed out, and no evidence of biochemical over-replacement was observed. In patients with Addison's disease and rapid hydrocortisone metabolism, standard once-daily HCMR may be insufficient. A divided dosing strategy can offer improved clinical outcomes without overtreatment. This case supports an individualised approach to steroid replacement in adrenal insufficiency.