Thursday, November 12, 2009

Biochemical Predictors of Outcome of Pituitary Surgery for Cushing's Disease

R.A. Alwania, W.W. de Herdera, M.O. van Akena, J.H. van den Bergeb, E.J. Delwelb, A.H.G. Dallengab, F.H. De Jonga, S.W.J. Lambertsa, A.J. van der Lelya, R.A. Feeldersa
aDepartment of Internal Medicine, Division of Endocrinology, and
bDepartment of Neurosurgery, Erasmus Medical Centre, Rotterdam, The Netherlands

Address of Corresponding Author

Neuroendocrinology (DOI: 10.1159/000258677)

Key Words

  • Cushing's disease
  • Pituitary adenoma
  • Pituitary surgery
  • Cortisol
  • Metyrapone
  • Corticotropin-releasing hormone


Objective: Transsphenoidal surgery (TS) is the primary therapy for Cushing's disease (CD). The aims of this retrospective study were twofold: (i) investigate early and late results of TS for CD, and (ii) evaluate various postoperative tests in order to predict the outcome of TS.

Methods: We reviewed the long-term outcome in 79 patients with CD who underwent TS (median follow-up 84 months, range 6-197). Within 2 weeks after surgery, morning serum cortisol concentrations were obtained (n = 78) and corticotropin-releasing hormone (CRH) (n = 53) and metyrapone tests (n = 72) were performed. Three groups of outcome were identified: sustained remission, early failure (persistent CD), and late relapse.

Results: Immediate postoperative remission was achieved in 51 patients (65%), whereas 28 patients (35%) had persistent CD after TS. Ten patients developed recurrent CD after initial remission (20%). Morning cortisol: all relapses but one recorded serum cortisol >50 nmol/l. A cortisol threshold value of 200 nmol/l has a positive predictive value of 79% for immediate surgical failure (negative predictive failure [NPV] 97%). CRH test: CRH-stimulated peak cortisol ge600 nmol/l predicted early failure in 78% (NPV 100%). All relapses recorded CRH-stimulated peak cortisol ge485 nmol/l. Metyrapone test: 11-deoxycortisol ge345 nmol/l predicted an early failure in 86% of cases (NPV 94%).

Conclusion: Predictive factors of surgical failure are morning cortisol ge200 nmol/l, 11-deoxycortisol ge345 nmol/l after metyrapone and CRH-stimulated cortisol ge600 nmol/l. CRH and/or metyrapone testing are not superior to morning cortisol concentration in the prediction of outcome of TS. Careful long-term follow-up remains necessary independent of the outcome of biochemical testing.

Copyright © 2009 S. Karger AG, Basel

Author Contacts

Rehmat A. Alwani, MD
Department of Internal Medicine, Division of Endocrinology
Erasmus Medical Centre, Room H555, PO Box 2040
NL-3000 CA Rotterdam (The Netherlands)
Tel. +31 107 040 704, Fax +31 104 63639, E-Mail

Article Information

Received: April 2, 2009
Accepted after revision: June 18, 2009
Published online: November 12, 2009
Number of Print Pages : 10
Number of Figures : 5, Number of Tables : 2, Number of References : 39


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