Introduction Successful first-line treatment of Cushing’s syndrome (CS) by resection of the underlying tumor is usually followed by adrenal insufficiency (AI) due to suppression of the hypothalamic-pituitary-adrenal axis after prolonged exposure to high cortisol concentrations. The aims of this study are to determine the recovery rate and time to recovery of adrenal function after treatment of CS and to identify factors associated with recovery.

Methods In this retrospective study, in 174 patients with CS (135 Cushing’s disease (CD), 35 adrenal CS, 4 ectopic CS) the recovery rate and time to recovery of adrenal function after surgery was determined.

Results The 1-, 2- and 5-year recovery rate of patients with CD was 37.8%, 70,1% and 81,1% respectively. For patients with adrenal CS, the 1-, 2- and 5-year recovery rates were: 49,3%, 86,9% and 91,3% respectively (p=0.05). For CD, the median recovery time was 12,6 months (IQR: 9.4-17,6) and for adrenal CS 10.3 months (IQR: 8,2-15,7). Higher age was associated with a lower probability of recovery: HR 0.84 per decade of age (95% CI 0.71-0.99). The median time to recovery in CD patients who developed a recurrence during follow up was shorter than in those without a recurrence: 9.8 months vs. 13.3 months respectively. In CD patients with pituitary hormonal deficiencies (other than AI) after surgery, had a lower chance of recovery than those with intact pituitary function (p = 0.05).

Conclusion The recovery rate of adrenal function after successful surgery as first-line treatment in patients with CS is high. The recovery rate is higher in patients with adrenal CS versus CD, in younger patients and in CD patients with preserved pituitary function. However, it may take months to years before adrenal function recovers. These results could help motivate patients who suffer from glucocorticoid withdrawal syndrome during lowering the glucocorticoid replacement therapy after surgery, to follow through with their attempts to taper off the glucocorticoids.