Glucocorticoid withdrawal syndrome is a challenging clinical phenomenon that can complicate the postsurgical recovery of Cushing syndrome. It is characterized by physical tolerance and dependence to supraphysiologic glucocorticoid exposure during active Cushing syndrome followed by the abrupt decline in cortisol levels after surgical treatment. The symptoms of glucocorticoid withdrawal often overlap with those of postoperative adrenal insufficiency and can be difficult for patients to cope with and for clinicians to treat. This mini review will discuss the clinical characteristics, pathophysiology, and management of glucocorticoid withdrawal syndrome while highlighting recent data in the field.

OBJECTIVE: 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.

OBJECTIVE: An increased prevalence of thyroid autoimmunity has been observed after successful treatment of Cushing\'s syndrome. On the other hand, De Quervain\'s thyroiditis (DQT), in which autoimmunity is not a pathogenetic contributor, has not been reported during recovery from Cushing\'s syndrome. We describe 2 female patients with DQT coinciding with the resolution of hypercortisolism after treatment of Cushing\'s syndrome/disease.
METHODS: The first patient had been diagnosed with Cushing\'s disease due to a corticotroph pituitary microadenoma, declined neurosurgery, and was receiving pharmacological treatment with pasireotide. Her hypercortisolism was optimally controlled with a minimum dose. The second patient had undergone unilateral adrenalectomy due to a cortisol-secreting adenoma and was on tapering doses of hydrocortisone due to a suppressed corticotroph axis. Both patients presented with clinical, functional, and imaging features of DQT at a time when their endogenous glucocorticoid levels were very low.
RESULTS: Oral glucocorticoid treatment was administered in both cases, resulting in prompt recovery.
CONCLUSIONS: The incidence of DQT following the resolution of hypercortisolism, either medical or surgical, has not been previously described. The exact pathogenetic mechanism can only be speculated on. Perhaps the relative or absolute glucocorticoid deficiency after effective treatment of hypercortisolism alters immunologic responses and renders patients more vulnerable to thyrolytic processes.