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Long-Term Predictive Value of Postsurgical Cortisol Concentrations for Cure and Risk of Recurrence in Cushing’s Disease

Departments of Endocrinology and Metabolism (A.M.P., M.O.v.A., N.R.B., J.W.A.S., F.R., J.A.R.) and Neurosurgery (H.v.D., P.J.S.), Leiden University Medical Center, 2300 RC Leiden, The Netherlands

Address all correspondence and requests for reprints to: Alberto M. Pereira, M.D., Ph.D., Department of Endocrinology and Metabolism, C4-R, Leiden University Medical Center, Albinusdreef 2, P.O. Box 9600, 2300 RC Leiden, The Netherlands. E-mail: a.m.pereira{at}lumc.nl.

We assessed the value of postoperative plasma cortisol concentrations to predict cure and recurrence of Cushing’s disease after transsphenoidal surgery (TS). Seventy-eight of 80 consecutive patients treated by TS for Cushing’s disease were evaluated. TS cured 72% (n = 56) of the patients. Two weeks after surgery, patients with plasma cortisol levels below 138 nmol/liter (n = 50; three macroadenomas) and eight (27%) of 30 patients (nine macroadenomas) with cortisol greater than 138 nmol/liter were cured. Six (five with a macroadenoma) of these eight patients had cortisol values less than 50 nmol/liter 3 months after surgery. Therefore, the optimal cut-off value of cortisol predicting remission was 138 nmol/liter, measured 3 months after surgery (positive and negative predictive values 87 and 90%, respectively).

Five patients (9%) had recurrent Cushing’s disease during a median follow-up of 7 yr. Recurrence occurred in four of 24 (17%) patients with a follow-up of more than 10 yr. Therefore, cortisol levels above 138 nmol/liter, obtained 2 wk after TS, should be repeated, because they do not predict persistent Cushing’s disease in 27% of those patients. Postoperative cortisol levels do not positively predict recurrence of disease during long-term follow-up of initially cured patients.

Abbreviations: AUC, Area under the curve; ROC, receiver operating characteristic; TS, transsphenoidal surgery; UFC, urinary free cortisol.

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