MON-444 Defining Remission In Cushing Syndrome After Tumor Resection In Cases Of Non-suppressed Postoperative Serum Cortisol Levels

Abstract

Background: Remission of Cushings syndrome (CS) is generally defined as morning serum cortisol (F) values <5mcg/dL or Urine Free Cortisol < 28 - 56 nmol/d (<10-20/ μg/d) after tumor resection, as normal pituitary corticotropes are suppressed by sustained hypercortisolism (1). In cases where eucortisolemia is achieved by pharmacologic therapy preoperatively, the corticotrope cells can recover their function leading to detectable postoperative cortisol levels not always indicative of unsuccessful tumor resection. Here we describe the use of the 1mg dexamethasone suppression test (DST) and night time serum cortisol as tools to establish criteria for remission in patients where normal pituitary corticotrophs may not have been suppressed. Methods: We retrospectively reviewed 19 patients (pts) with biochemical evidence of ACTH dependent CS who underwent tumor resection. All had measurable serum F measurements within post op day 7 and underwent a 1mg DST to determine if surgery was successful. Remission was defined as serum F value of <1.8 mcg/dl after DST. Recognizing that DST results can be affected by various factors such as concurrent medications or dexamethasone metabolism, in cases where post DST serum F was > 1.8mcg/dl, late night serum F levels were collected at 2330 and 2359. Definition of remission was established as late night F level < 7.5mcg/dl.Results: Of 19 pts, 11 had Ectopic ACTH Syndrome (EAS) and 8 had Cushing’s disease (CD). The median age was 54, 12/19 were female. 15 were deemed to be in surgical remission, 10 having passed the DST with F value <1.8 (range <1 - 5.4mcg/dl). The remaining 5 had night serum F values <7.5mcg/dl (range <1-5.9). 3/10 pts had DST results >2mcg/dl; one had a 2cm adrenal nodule secondary to CD, one had bilateral adrenal hyperplasia, and in the 3rd case a dexamethasone level was not measured. These 3 cases underwent 24 hour urine cortisol measurements, all found within the lower end of the reference range; 5mcg/24hr, 8mcg/24h and 5.2ug/24hr respectively. 12/15 had documented or reported history of cyclic CS and/or were treated with steroidogenesis inhibitors prior to surgery. 21% (4/19) pts were concluded to have persistent hypercortisolemia based on abnormal DST results (F range 4.7-10.8mcg/dl) with 2 also having abnormal night serum F (>20mcg/d). All had CD, and of these 2 had no tumor identified on pathology, one had persistent disease requiring a repeat pituitary surgery with subsequent cure and positive adenoma on pathology, and the 4th had residual disease. Conclusion: In cases of cyclic CS, or where medical management was used prior to surgical resection, normal corticotrophs may not be suppressed, resulting in measurable or normal serum cortisol values post operatively. We suggest the use of the 1 mg DST and/or night time serum cortisol samples to differentiate between persistent hypercortisolism and remission after successful tumor resection.