Glucocorticoid withdrawal syndrome following surgical remission of endogenous hypercortisolism: a longitudinal observational study.

Objective: Glucocorticoid withdrawal syndrome (GWS) is a scarcely studied phenomenon that complicates the recovery following surgical remission of hypercortisolism. We aimed to characterize the presence and trajectory of glucocorticoid withdrawal symptoms in the postoperative period and to determine presurgical predictors of GWS severity.
Design: Longitudinal observational study.
Methods: Glucocorticoid withdrawal symptoms were prospectively evaluated weekly for the first 12 weeks following surgical remission of hypercortisolism. Quality of life (CushingQoL and Short-Form-36) and muscle function (hand grip strength and sit-to-stand test) were assessed at the baseline and at 12 weeks after surgery.
Results: Prevalent symptoms were myalgias and arthralgias (50%), fatigue (45%), weakness (34%), sleep disturbance (29%), and mood changes (19%). Most symptoms persisted, while myalgias, arthralgias, and weakness worsened during weeks 5-12 postoperatively. At 12 weeks after surgery, normative hand grip strength was weaker than at baseline (mean Z-score delta -0.37, P = .009), while normative sit-to-stand test performance improved (mean Z-score delta 0.50, P = .013). Short-Form-36 Physical Component Summary score worsened (mean delta -2.6, P = .015), but CushingQoL score improved (mean delta 7.8, P < .001) at 12 weeks compared to baseline. Cushing syndrome (CS) clinical severity was predictive of postoperative GWS symptomology.
Conclusion: Glucocorticoid withdrawal symptoms are prevalent and persistent following surgical remission of hypercortisolism with baseline CS clinical severity predictive of postoperative GWS symptom burden. Differential changes observed in muscle function and quality of life in the early postoperative period may reflect the competing influences of GWS and recovery from hypercortisolism.
Competing Interests: Conflicts of interest: I.B. serves on the editorial board of the European Journal of Endocrinology. She was not involved in the review or editorial process for this paper, for which she is listed as an author. I.B. also reports advisory board participation/consulting (fees to institution) with HRA Pharma, Corcept, Recordati, Sparrow Pharmaceutics, Neurocrine, Spruce, and Diurnal outside the submitted work, and data monitoring and safety board participation for Adrenas. W.F.Y. reports consulting fees and drug safety monitoring board participation for Bayer AG and scientific advisory board participation for Crinetics Pharma. C.D.Z. reports advisory board participation/consulting (fees to institution) with Corcept. D.L. is currently an employee of BridgeBio, which is unrelated to the submitted work. The remaining authors have nothing to disclose.
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