Glucocorticoid withdrawal syndrome following surgical remission of endogenous hypercortisolism: a longitudinal observational study
Open accessAbstract
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.
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In patients following curative surgery for endogenous hypercortisolism, baseline clinical severity score was associated with the severity of glucocorticoid withdrawal, and symptoms worsened once total daily glucocorticoid dose reached below 30 to 35 mg of hydrocortisone equivalent (eg, 7.5 prednisone).
“In patients following a curative surgery for endogenous hypercortisolism (71) baseline clinical severity score was associated with the severity of glucocorticoid withdrawal, and symptoms worsened once total daily glucocorticoid dose reached below 30 to 35 mg of hydrocortisone equivalent (eg, 7.5 prednisone).”
From European Society of Endocrinology and Endocrine Society Joint Clinical Guideline: Diagnosis and Therapy of Glucocorticoid-induced Adrenal Insufficiency (2024) · cites this paper as [71]
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
Experimental — accuracy not yet measuredGlucocorticoid withdrawal syndrome results from tapering or abrupt cessation of excessive endogenous or exogenous glucocorticoids.
“Glucocorticoid withdrawal syndrome results from the tapering or abrupt cessation of excessive endogenous or exogenous sources of glucocorticoids (138, 139).”
From Measuring cortisol in Cushing syndrome: diagnosis, monitoring, and cortisol circadian rhythm improvement. (2026) · cites this paper as [139]
The Introduction defines glucocorticoid withdrawal syndrome as a reaction to a rapid reduction in glucocorticoid concentrations after supraphysiologic exposure, including after surgery for endogenous Cushing syndrome. The Discussion also describes symptoms flaring during a postoperative glucocorticoid taper. Our copy does not explicitly address abrupt cessation or establish the claim for excessive exogenous glucocorticoid use. (LLM, conf=0.84)
Experimental — accuracy not yet measuredGlucocorticoid withdrawal syndrome occurs due to dependence on supraphysiologic glucocorticoids while decreasing the dose of glucocorticoids.
“Glucocorticoid withdrawal syndrome occurs due to dependence on supraphysiologic glucocorticoids while decreasing the dose of glucocorticoids (70-72).”
From European Society of Endocrinology and Endocrine Society Joint Clinical Guideline: Diagnosis and Therapy of Glucocorticoid-induced Adrenal Insufficiency (2024) · cites this paper as [71]
In a recent study investigating glucocorticoid withdrawal syndrome in patients following curative surgery for endogenous hypercortisolism, symptoms included arthralgias, myalgias, weakness, fatigue, sleep disturbances, and mood changes in up to 50% of patients.
“In a recent study investigating glucocorticoid withdrawal syndrome in patients following curative surgery for endogenous hypercortisolism, symptoms of glucocorticoid withdrawal syndrome included arthralgias, myalgias, weakness, fatigue, sleep disturbances, and mood changes in up to 50% of patients (71).”
From European Society of Endocrinology and Endocrine Society Joint Clinical Guideline: Diagnosis and Therapy of Glucocorticoid-induced Adrenal Insufficiency (2024) · cites this paper as [71]
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- Authors
- Zhang, C. D., Li, D., Singh, S., Suresh, M., Thangamuthu, K., Nathani, R., Achenbach, S. J., Atkinson, E. J., Van Gompel, J. J., Young, W. F., & Bancos, I.
- Affiliations
- Mayo Clinic (US)
- Cleveland Clinic (US)
- Department of Neurosurgery, Mayo Clinic , Rochester, MN 55905 , USA
- Corresponding author
- Bancos, Irina
- ORCID
- Venue
- European Journal of Endocrinology
- Publisher
- Oxford University Press (OUP)
- Published
- 2023-07
- Volume
- 189
- Issue
- 1
- Pages
- 29-39
- ISSN
- 0804-4643 (ISSN-L)
- 1479-683X
- PMC
- PMC10376560
- OpenAlex
- W4382918011
- Cited by
- 29
- References
- 20
- Citations by year
- 2026: 5 · 2025: 12 · 2024: 10 · 2023: 2
- FWCI
- 5.95
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- European Journal of Endocrinology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Recordati Rare Diseases
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Institutes of Health (K23DK121888, R03DK132121)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Pituitary Gland Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Health Sciences › Medicine › Surgery › Adrenal and Paraganglionic Tumors
- Keywords
- Cushing's syndrome, hypercortisolism, adrenalectomy, surgical remission, postoperative recovery, quality of life, muscle function, grip strength, sit-to-stand test, clinical severity, fatigue
- MeSH terms
- Cushing Syndrome, Glucocorticoids, Humans, Muscular Diseases, Quality of Life, Substance Withdrawal Syndrome, Hand Strength
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