Biochemical predictors of outcome of pituitary surgery for Cushing's disease.
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 > or =600 nmol/l predicted early failure in 78% (NPV 100%). All relapses recorded CRH-stimulated peak cortisol >or =485 nmol/l. Metyrapone test: 11-deoxycortisol >or =345 nmol/l predicted an early failure in 86% of cases (NPV 94%).


CONCLUSIONS
Predictive factors of surgical failure are morning cortisol >or =200 nmol/l, 11-deoxycortisol >or =345 nmol/l after metyrapone and CRH-stimulated cortisol >or =600 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.
Alwani
R A
RA
Department of Internal Medicine, Division of Endocrinology, Erasmus Medical Centre, Rotterdam, The Netherlands.
de Herder
W W
WW
van Aken
M O
MO
van den Berge
J H
JH
Delwel
E J
EJ
Dallenga
A H G
AH
De Jong
F H
FH
Lamberts
S W J
SW
van der Lely
A J
AJ
Feelders
R A
RA
D000328:Adult; D003346:Corticotropin-Releasing Hormone; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000652:urine; D053208:Kaplan-Meier Estimate; D008297:Male; D008797:Metyrapone; D047748:Pituitary ACTH Hypersecretion / Q000175:diagnosis* / Q000401:mortality / Q000601:surgery*; D010901:Pituitary Function Tests; D010902:Pituitary Gland / Q000601:surgery*; D011183:Postoperative Complications; D011237:Predictive Value of Tests; D011300:Preoperative Care; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
D003346:Corticotropin-Releasing Hormone; D006854:Hydrocortisone; D008797:Metyrapone