Faculty Collaboration Database

Glucocorticoid Withdrawal Syndrome following treatment of endogenous Cushing Syndrome. Pituitary 2022 Jun;25(3):393-403

Date

04/27/2022

Pubmed ID

35471718

Pubmed Central ID

PMC9170649

DOI

10.1007/s11102-022-01218-y

Scopus ID

2-s2.0-85128810700 (requires institutional sign-in at Scopus site)   21 Citations

Abstract

PURPOSE: Literature regarding endogenous Cushing syndrome (CS) largely focuses on the challenges of diagnosis, subtyping, and treatment. The enigmatic phenomenon of glucocorticoid withdrawal syndrome (GWS), due to rapid reduction in cortisol exposure following treatment of CS, is less commonly discussed but also difficult to manage. We highlight the clinical approach to navigating patients from GWS and adrenal insufficiency to full hypothalamic-pituitary-adrenal (HPA) axis recovery.

METHODS: We review the literature on the pathogenesis of GWS and its clinical presentation. We provide strategies for glucocorticoid dosing and tapering, HPA axis testing, as well as pharmacotherapy and ancillary treatments for GWS symptom management.

RESULTS: GWS can be difficult to differentiate from adrenal insufficiency and CS recurrence, which complicates glucocorticoid dosing and tapering regimens. Monitoring for HPA axis recovery requires both clinical and biochemical assessments. The most important intervention is reassurance to patients that GWS symptoms portend a favorable prognosis of sustained remission from CS, and GWS typically resolves as the HPA axis recovers. GWS also occurs during medical management of CS, and gradual dose titration based primarily on symptoms is essential to maintain adherence and to eventually achieve disease control. Myopathy and neurocognitive dysfunction can be chronic complications of CS that do not completely recover.

CONCLUSIONS: Due to limited data, no guidelines have been developed for management of GWS. Nevertheless, this article provides overarching themes derived from published literature plus expert opinion and experience. Future studies are needed to better understand the pathophysiology of GWS to guide more targeted and optimal treatments.

Author List

He X, Findling JW, Auchus RJ

Author

James W. Findling MD Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adrenal Insufficiency
Cushing Syndrome
Glucocorticoids
Humans
Hydrocortisone
Hypothalamo-Hypophyseal System
Pituitary-Adrenal System