title: The Recovery of Hypothalamic-Pituitary-Adrenal Axis Is Rapid in Subclinical Cushing Syndrome.
abstract: BACKGROUND
  In subclinical Cushing syndrome (SC), it is assumed that glucocorticoid production is insufficient to cause a clinically recognizable syndrome. Differences in hormonal levels or recovery time of the hypothalamic-pituitary-adrenocortical (HPA) axis after adrenalectomy between patients with overt Cushing syndrome (OC) and SC remain unknown.
  
  
  METHODS
  Thirty-six patients (10 with OC and 26 with SC) with adrenal Cushing syndrome who underwent adrenalectomy from 2004 to 2014 were reviewed retrospectively. Patients were treated with glucocorticoid after adrenalectomy and were reevaluated every 1 to 6 months using a rapid adrenocorticotropic hormone (ACTH) stimulation test.
  
  
  RESULTS
  Levels of basal 24-hour urine free cortisol (UFC), serum cortisol after an overnight dexamethasone suppression test (DST), and serum cortisol and 24-hour UFC after low-dose DST and high-dose DST were all significantly lower in patients with SC compared with OC. Basal ACTH levels showed significantly higher in patients with SC compared with OC. The probability of recovering adrenal function during follow-up differed significantly between patients with OC and SC (P=0.001), with significant correlations with the degree of preoperative cortisol excess. Patients with OC required a longer duration of glucocorticoid replacement to recover a normal ACTH stimulation test compared with patients with SC (median 17.0 months vs. 4.0 months, P<0.001).
  
  
  CONCLUSIONS
  The HPA axis recovery time after adrenalectomy in patients with SC is rapid and is dependent on the degree of cortisol excess. More precise definition of SC is necessary to achieve a better management of patients and to avoid the risk of under- or over-treatment of SC patients.
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Hee Kyung
authors.identifier: http://orcid.org/0000-0002-1617-3171
authors.initials: HK
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Jee Hee
authors.identifier: http://orcid.org/0000-0002-5919-6162
authors.initials: JH
authors.lastname: Yoon
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea.
authors.forename: Yun Ah
authors.identifier: http://orcid.org/0000-0002-3417-707X
authors.initials: YA
authors.lastname: Jeong
authors.affiliation: Department of Internal Medicine, Chonnam National University Medical School, Gwangju, Korea. drkang@chonnam.ac.kr.
authors.forename: Ho Cheol
authors.identifier: http://orcid.org/0000-0002-0448-1345
authors.initials: HC
authors.lastname: Kang
keywords: Adrenal incidentaloma; Hydrocortisone; Hypothalamic-pituitary-adrenocortical axis recovery; Overt Cushing syndrome; Subclinical Cushing syndrome