Endocrine Abstracts

Introduction: Transsphenoidal surgery (TSS) is the first-choice treatment in Cushing’s disease (CD) with an immediate success rate of 70-80%. Unfortunately, due to the high rate of post-operative recurrences, CD patients require life-long surveillance. However, there is no consensus on how to follow these patients after TSS to early diagnose relapses. The aim of the study was to find reliable predictors of recurrence after neurosurgery in CD.

Material and methods: Fifty-five CD patients (f/m=43/12, median age 39, IQR 32-49 years) in remission after TSS (median 100, range 36–146 months) were included. Remission was defined by the presence of at least 2 of the following criteria: i) low-undetectable postoperative serum cortisol; ii) prolonged glucocorticoid replacement therapy; iii) normal urinary free cortisol (UFC) and late-night salivary cortisol (LNSC) for at least 12 months after surgery; iv) serum cortisol <50 nmol/l after 1 mg-DST. All patients were submitted to desmopressin (DDAVP) test in the diagnostic phase and were re-tested, at least once, 6-12 month after surgery.

Results: Thirteen patients (24%) recurred after a median time of 43 months (IQR 18-65). There were no differences in age and disease severity at time of diagnosis between patients who recurred and those in long-term remission, whereas macroadenomas were more frequently found in recurrent patients (P=0.003). No differences in histological features were recorded. Early post-operative serum cortisol was markedly lower in patients who remained in remission [55.5 (32.3-97) vs 120 (57-250), P=0.024], even though there was some degree of overlap between groups. A threshold of 63 nmol/l for serum cortisol was able to identify patient at high risk of relapse with sensitivity (SE) of 77% and specificity (SP) of 69%. Patients with recurrence displayed a greater ACTH and cortisol response to DDAVP test compared to those in prolonged remission (P<0.0001). An absolute increase in ACTH>7.6 ng/l was identified (AUC=0.8796; 95%CI:75–100) as the best predictor of recurrence, with SE of 85% and SP of 83%. At 6 and 12 months from TSS, no differences in UFC and LNSC were observed between groups.

Conclusions: The presence of corticotroph macroadenoma is a risk factor for CD relapse. Early post-operative serum cortisol level is a reliable indicator of surgical outcome but DDAVP test is far more accurate to predict future recurrence. The re-appearance of a positive response to this test precedes the increase in LNSC and UFC by several months, thus patients displaying such alteration should be closely monitored.