A combined dexamethasone desmopressin test as an early marker of postsurgical recurrence in Cushing's disease

J Clin Endocrinol Metab. 2009 Jun;94(6):1897-903. doi: 10.1210/jc.2008-2234. Epub 2009 Mar 10.

Abstract

Context: Recurrence of Cushing's disease (CD) after transsphenoidal surgery (TSS) occurs in about 25% of cases. Twenty percent of patients with immediate postsurgical corticotroph deficiency will present late recurrence.

Objective: The aim of the study was to evaluate a coupled dexamethasone desmopressin test (CDDT) as a predictor of recurrence of CD.

Design: We conducted a prospective bicenter study (Marseille and Grenoble, France).

Patients: We studied 38 patients treated by TSS for CD with a mean follow-up of 60 months.

Intervention(s): We evaluated 24-h urinary free cortisol, ACTH, and cortisol plasmatic levels and performed low-dose dexamethasone suppression test and CDDT 3 to 6 months after surgery and then yearly.

Main outcome measures: After CDDT, ACTH ratio (ACTHr) was defined as (PeakACTH - BaseACTH)/BaseACTH. Cortisol ratio (Cortisolr) was defined as (PeakCortisol - BaseCortisol)/BaseCortisol. Basal values were observed after low-dose dexamethasone suppression test. Receiver operator characteristics curve defined ACTHr and Cortisolr giving the best sensitivity and specificity associated with recurrence.

Results: Ten patients presented recurrence. ACTHr and Cortisolr were superior or equal to 0.5 in all patients with recurrence and in three of 28 patients in remission (100% sensitivity, 89% specificity). The test became positive in eight of 10 patients with recurrence 6-60 months before classical markers of hypercortisolism. Six patients with immediate postsurgical corticotroph deficiency presented recurrence. All of them presented CDDT positivity during the 3 yr after surgery, and recurrence 6 to 60 months after CDDT positivity.

Conclusions: CDDT is an early predictor of recurrence of CD and could be of particular interest in the first 3 yr after surgery, by selecting patients at high risk of recurrence despite falsely reassuring classical hormonal markers.

Publication types

  • Clinical Trial
  • Multicenter Study

MeSH terms

  • Adrenocorticotropic Hormone / blood
  • Adult
  • Aged
  • Biomarkers / analysis
  • Biomarkers / blood
  • Deamino Arginine Vasopressin / administration & dosage*
  • Dexamethasone / administration & dosage*
  • Diagnostic Techniques, Endocrine*
  • Early Diagnosis
  • Female
  • Follow-Up Studies
  • Humans
  • Hydrocortisone / blood
  • Male
  • Middle Aged
  • Pituitary ACTH Hypersecretion / blood
  • Pituitary ACTH Hypersecretion / diagnosis*
  • Pituitary ACTH Hypersecretion / pathology
  • Pituitary ACTH Hypersecretion / surgery*
  • Postoperative Complications / diagnosis
  • Prognosis
  • Recurrence
  • Sensitivity and Specificity
  • Young Adult

Substances

  • Biomarkers
  • Dexamethasone
  • Adrenocorticotropic Hormone
  • Deamino Arginine Vasopressin
  • Hydrocortisone