Reevaluation of the 4 mg intravenous dexamethasone suppression test for differentiation of Cushings disease from pseudo-Cushings syndrome
M. Nouvel1, M. Rabilloud2, V. Raverot2, C. Pignard2, J. Vouillarmet2, C. Thivolet2, E. Jouanneau2, F Borson Chazot1, M. Pugeat1 & G. Raverot1,3
Context: Differentiating Cushings disease (CD) from pseudo-Cushings syndrome (PCS) is one of the most challenging problems since no biological test is yet perfect. Almost 30 years ago our group demonstrated the interest of 4 mg i.v. dexamethasone suppressing test (DST) to differentiate obese patients to CD.
Objective: To reevaluate the diagnostic accuracy of the 4 mg i.v. DST in carefully selected patients with PCS and CD.
Design: Patients recruited from November 2008 to July 2011 were retrospectively studied.
The criteria for PCS were: presence of clinical and biochemical (Urinary Free Cortisol and/or 1 mg DST) features compatible with CS, normal pituitary MRI and at least one year of clinical and biochemical follow-up.
Diagnosis of CD has been confirmed by pathology in 29 patients operated, three patients with abnormal MRI were medically treated.
Patients underwent 4 mg dexamethasone infusion according to Abou-Samra et al (JCEM 1985). The diagnosis of CD is based on absence of ACTH and cortisol suppression at 8 am on day 2.
Results: 68 patients (54F/14M), 32 with CD and 36 with PCS were included. Age and BMI were similar between groups but hirsutism, proximal amyotrophy, and vascular weakness were significantly more frequent in the CD group (P<0.001).
Midnight plasma cortisol, 8 am cortisol and ACTH after 4 mg DST were respectively associated with a 95.4% (86.599), 90.5% (81.896.7) and 98.4% (92.199.6) diagnostic accuracy. Cortisol and ACTH threshold used in our endocrine units to affirm the CD (respectively 100 nmol/l and 5 ng/l) yielded more accurate sensibility (93.8%) and specifity (86.1%) than midnight plasma cortisol cut-off of 207 nmol/l retained by the Endocrine and European Societies which was associated with a 96.8% of sensibility and 58.1% of specificity.
Conclusion: 4 mg i.v. DST is a very easy and accurate test to distinguish CD from PCS and deserve a place in the CD diagnosis assessment.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.