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

Abstract

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 ≧600 nmol/l predicted early failure in 78% (NPV 100%). All relapses recorded CRH-stimulated peak cortisol ≧485 nmol/l. Metyrapone test: 11-deoxycortisol ≧345 nmol/l predicted an early failure in 86% of cases (NPV 94%). Conclusion: Predictive factors of surgical failure are morning cortisol ≧200 nmol/l, 11-deoxycortisol ≧345 nmol/l after metyrapone and CRH-stimulated cortisol ≧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.

THERAPY OF ENDOCRINE DISEASE: Outcomes in patients with Cushing's disease undergoing transsphenoidal surgery: systematic review assessing criteria used to define remission and recurrence

“…A variety of definitions of remission of Cushing's disease after initial microscopic TSS is used in the literature: symptoms of hypercortisolism remitted (25), a continuous need for corticosteroid replacement for O6 months after TSS (26), no need for additional treatment because of clinical remission of the disease (27), resolution of symptoms and signs of hypercortisolism (28) or of clinical features (16,19), clinical evidence of eucortisolemia (23), appearance of clinical signs of adrenal insufficiency (29), regression of the clinical signs (30), presence of clinical and laboratory signs of adrenal insufficiency (17,22), and reversal of the clinical stigmata (31). Clinical parameters were never used alone to define remission; clinical evaluation was always combined with serum cortisol, UFC, and/or LDDST biochemical tests ( Table 1).…”

Endoscopic transsphenoidal pituitary surgery: a good and safe primary treatment option for Cushing's disease, even in case of macroadenomas or invasive adenomas

“…These reports show that, in experienced hands, excellent remission rates of over 80% can be achieved if a microadenoma is visualized on preoperative imaging (5,6,7,8,9,10,11,12,13,14,15,16). However, if no adenoma is visualized on preoperative imaging (magnetic resonance imaging (MRI)-negative CD), or if a macroadenoma is the cause of CD, remission rates are substantially lower (5,6,7,8,9,10,13,14,15,16). Furthermore, CD relapses in up to 25% of the patients.…”

Cushing's disease: pathobiology, diagnosis, and management

“…Since 2010, surgical series generally show remission rates between 65% and 85% and recurrence rates of 10%-35% (Table 1). [1][2][3]5,8,20,24,25,27,41,44,53,86,97,99,101,107 Surgical success and recurrence rates depend on surgeon experience, as well as the criteria used to define cure and length of follow-up.…”