Impact of postoperative hydrocortisone replacement dose on health-related quality of life and metabolic parameters in patients with cured Cushing's syndrome: randomized, open-label, controlled trial.
In cured Cushing's syndrome, 15 mg/day hydrocortisone does not worsen HRQoL and had a better metabolic profile, with HRQoL improving over time irrespective of dose, suggesting no benefit from supraphysiological hydrocortisone replacement after curative surgery.
Key Findings
Results
No significant between-group differences in health-related quality of life were observed during the three-month postoperative period between the 15 mg/day and 30 mg/day hydrocortisone groups.
HRQoL was assessed using EQ-5D and SF-36 questionnaires at baseline, 1 month, 3 months, and final follow-up
42 adults with CS and postoperative hypocortisolism were randomized to either 15 mg/day or 30 mg/day hydrocortisone for the first three postoperative months
EQ-5D visual analogue scale scores improved significantly at the final follow-up in both groups
SF-36 domain scores showed overall improvement over time in both groups
Results
Patients receiving 15 mg/day hydrocortisone had lower triglycerides, total cholesterol, and HbA1c levels at three months compared to those receiving 30 mg/day.
Metabolic parameters were evaluated at baseline and 3 months
Dose effects on metabolic parameters were evaluated using ANCOVA
After adjustment for baseline values, hydrocortisone dose independently affected triglycerides and total cholesterol
HbA1c levels were lower in the 15 mg/day group at three months, though independent dose effect on HbA1c after adjustment was not specifically noted as significant in the abstract
Results
No adrenal crises occurred in the lower-dose (15 mg/day) hydrocortisone group, and there was no excess of acute intercurrent illness or hospitalization compared to the higher-dose group.
Safety outcomes were monitored across both groups during the three-month treatment period
The absence of adrenal crises in the lower-dose group suggests that 15 mg/day was sufficient for adrenal safety in this population
No excess of acute intercurrent illness or hospitalization was recorded in the lower-dose group
Results
HPA axis recovery occurred in 71% of patients and was not associated with hydrocortisone replacement dose.
HPA axis recovery was assessed using Kaplan-Meier and Cox regression analyses
71% of patients overall achieved HPA axis recovery during follow-up
Cox regression analysis showed no significant association between hydrocortisone dose (15 mg/day vs. 30 mg/day) and the rate or timing of HPA axis recovery
Methods
This was a single-centre, randomized, open-label trial enrolling 42 adults with Cushing's syndrome and postoperative hypocortisolism.
Participants were randomized to 15 mg/day or 30 mg/day hydrocortisone during the first three postoperative months
The trial design was open-label and controlled
HRQoL was assessed at four time points: baseline, 1 month, 3 months, and final follow-up
The study was conducted at a single centre
What This Means
This research suggests that after surgery to cure Cushing's syndrome (a condition caused by excess cortisol), patients do not need high doses of hydrocortisone replacement therapy to feel better or recover well. In this randomized trial, 42 patients were given either a lower dose (15 mg/day) or a higher dose (30 mg/day) of hydrocortisone for the first three months after surgery. Both groups showed similar improvements in quality of life over time, and the lower-dose group had no increased risk of adrenal crises, serious illness, or hospitalization.
This research also suggests that the lower hydrocortisone dose was associated with better metabolic outcomes, including lower levels of triglycerides, total cholesterol, and blood sugar control (HbA1c) at three months. The dose of hydrocortisone did not affect whether or how quickly patients' own adrenal glands recovered their normal function, with about 71% of all patients recovering HPA axis function regardless of which dose they received.
These findings matter because Cushing's syndrome patients already have a history of metabolic problems from excess cortisol, and using unnecessarily high replacement doses after surgery may worsen those problems without providing any quality-of-life benefit. This research suggests that a lower, more physiological dose of hydrocortisone is sufficient and potentially preferable in the postoperative management of cured Cushing's syndrome.
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Nekic A, Kastelan D, Solak M, Polovina T, Balasko A, Kraljevic I. (2026). Impact of postoperative hydrocortisone replacement dose on health-related quality of life and metabolic parameters in patients with cured Cushing's syndrome: randomized, open-label, controlled trial.. Endocrine. https://doi.org/10.1007/s12020-026-04666-9