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

Abstract

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.

Repeated transsphenoidal pituitary surgery (TS) via the endoscopic technique: a good therapeutic option for recurrent or persistent Cushing's disease (CD)

“…[21][22][23] However, this strategy ignores the fact that some patients who do not have a low early postoperative basal plasma cortisol level do achieve remission, so by using this strategy some patients will unnecessarily undergo immediate repeated TS. 8 Overall, the remission rates reported after second TS in persistent or recurrent CD seem to be slightly lower than the remission rates reported after first TS which vary from 50% to 90%, but are mostly 70-85%. [3][4][5][6][7][8][9] Nevertheless, the majority of the patients with persistent or recurrent CD can still instantly be cured by repeated TS, and the remission rate we achieved via the endoscopic technique seems to be at least as good as the remission rate achieved by repeated TS via the conventional microscopic technique.…”

“…However, CD persists in the remaining patients, and 5-25% of the patients who are initially in remission develop a recurrence. [3][4][5][6][7][8] Treatment options for persistent or recurrent CD include radiation therapy, bilateral adrenalectomy, medical therapy and repeated TS. Thus far, no consensus exists on which therapy is preferable.…”

Malignant pituitary corticotroph adenomas: report of two cases and a comprehensive review of the literature

“…In the reported cases CD recurred at least one time in 55% of cases. However, recurrence of benign Cushing's disease after initial surgical cure also occurs in 5-36% of the patients during long-term follow-up [52][53][54][55][56][57]. Furthermore, growth of the pituitary tumor occurred in 67% of the reported cases that were treated with bilateral adrenalectomy as primary treatment.…”

Criteria of cure and remission in Cushing's disease: an update

“…Less strict criteria could result in higher rates of cure. Even adopting more stringent criteria, recurrence occurs in 5 to 15% of cases (1,25,(33)(34)(35)(38)(39)(40). In cured patients, glucocorticoid replacement therapy is mandatory during HPA recover.…”