A Combined Dexamethasone Desmopressin Test as an Early Marker of Postsurgical Recurrence in Cushing’s Disease

• Published in: The journal of clinical endocrinology and metabolism Vol. 94; no. 6; pp. 1897 - 1903
• Main Authors: Castinetti, Frederic, Martinie, Monique, Morange, Isabelle, Dufour, Henry, Sturm, Nathalie, Passagia, Jean-Guy, Conte-Devolx, Bernard, Chabre, Olivier, Brue, Thierry
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Endocrine Society 01.06.2009; Copyright by The Endocrine Society
• Subjects: Adrenals. Adrenal axis. Renin-angiotensin system (diseases); Adrenocorticotropic Hormone - blood; Adult; Aged; Biological and medical sciences; Biomarkers - analysis; Biomarkers - blood; Deamino Arginine Vasopressin - administration & dosage; Dexamethasone - administration & dosage; Diagnostic Techniques, Endocrine; Early Diagnosis; Endocrinopathies; Feeding. Feeding behavior; Female; Follow-Up Studies; Fundamental and applied biological sciences. Psychology; Humans; Hydrocortisone - blood; Male; Medical sciences; Middle Aged; Non tumoral diseases. Target tissue resistance. Benign neoplasms; Pituitary ACTH Hypersecretion - blood; Pituitary ACTH Hypersecretion - diagnosis; Pituitary ACTH Hypersecretion - pathology; Pituitary ACTH Hypersecretion - surgery; Postoperative Complications - diagnosis; Prognosis; Recurrence; Sensitivity and Specificity; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vertebrates: endocrinology; Young Adult; Endocrinopathy; Postoperative; Desmopressin; Obesity; Relapse; Adrenal cortex diseases; Peptides; Nutrition; Nutrition disorder; Cushing syndrome; Biological marker; Metabolic diseases; Hyperadrenocorticism; Dexamethasone test; Antidiuretic; Neurohypophyseal hormone; Adrenal gland diseases; Early; Endocrinology; Nutritional status
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/jc.2008-2234

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. Combined dexamethasone desmopressin testing for postoperative follow-up of Cushing’s disease patients diagnoses persistent disease.