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Midnight Salivary Cortisol Determination for Assessing the Outcome of Transsphenoidal Surgery in Cushing’s Disease

Service des Maladies Endocriniennes et Métaboliques, Centre de Référence de Maladies Rares des surrénales (C.A.C., L.Gu., L.Gr., X.B., J.B.), Service de Biostatistique (J.C.), and Service d’Hormonologie (M.A.D.), Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, 75014 Paris, France; Institut National de la Santé et de la Recherche Médicale Unit 567, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8104, (C.A.C., L.Gr., X.B., J.B.), Institut Cochin, 75014 Paris, France; Université Paris Descrates (J.C., M.A.D., L.Gr., X.B., J.B.), 75270 Paris, France; and Service de Neurochirurgie (S.G.), Hôpital Foch, 92150 Suresnes, France

Address all correspondence and requests for reprints to: Prof. Jérôme Bertherat, Service des Maladies Endocriniennes et Métaboliques, Hôpital Cochin, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France. E-mail: jerome.bertherat{at}cch.aphp.fr.

Context: Midnight salivary cortisol (MSC) is now recognized as a reliable index for Cushing’s syndrome diagnosis but has to be validated for the follow-up of treated patients.

Objective: Our objective was to evaluate MSC for assessing the outcome of transsphenoidal surgery (TSS) in patients with Cushing’s disease (CD).

Design: We conducted a retrospective cohort study in a single center.

Patients and Methods: Sixty-eight patients treated by TSS between 1996 and 2006 and followed for at least 6 months with postoperative MSC were included. Mean follow-up (± SD) was 45 ± 31 months. Morning plasma cortisol was determined 5 d after TSS, and MSC and urinary cortisol (UC) were determined 6–12 months after surgery. The remission group included hypocortisolic (morning plasma cortisol < 50 ng/ml and/or insufficient response to cosyntropin) and eucortisolic (midnight plasma cortisol < 75 ng/ml and normal UC) patients. Patients in the treatment failure group had high midnight plasma cortisol and UC concentrations.

Results: Fifty patients (74%) were in remission. Mean MSC was 0.7 ± 0.4 ng/ml (range, 0.4–2.1 ng/ml) and 6.5 ± 6.5 ng/ml (range, 2.1–27.2 ng/ml) for the remission and treatment failure groups, respectively (P = 0.001). A cutoff of 2 ng/ml for MSC gave a sensitivity of 100% and a specificity of 98% for treatment failure diagnosis, whereas UC less than 90 µg/d had a sensitivity of 71% and specificity of 98%. Postsurgical morning plasma cortisol less than or equal to 18 ng/ml had a sensitivity of 93% and specificity of 74%.

Conclusions: MSC is a simple, robust marker of remission after TSS for CD.

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