MON-167 Use of a Morning Cortisol Level to Predict Recovery of the Hypothalamic-Pituitary-Adrenal (HPA) Axis in Secondary Adrenal Insufficiency Following Remission of Cushing’s Syndrome

BACKGROUND: Remission of Cushing’s syndrome (CS) is generally defined as morning serum cortisol values <5mcg/dL (<138 nmol/L) or Urine Free Cortisol <10-20ug/dL (< 28 – 56 nmol/d) after tumor resection, which reflects suppression of the hypothalamic-pituitary-adrenal (HPA) axis by sustained hypercortisolism. Endocrine Society guidelines recommend glucocorticoid replacement until the HPA axis is normal as assessed by a morning (AM) or post-ACTH stimulation test cortisol level of approximately 18 ug/dL (500 nmol/L) or greater (1). Patients with subnormal cortisol levels remain on glucocorticoid until retested in 3-6 months. The goal of this study was to determine whether a baseline cortisol value predicts a normal response to the ACTH stimulation test. Methods: We reviewed 235 ACTH stimulation (stim) tests conducted on 76 patients with secondary adrenal insufficiency following remission of CS. Patients had resection of a single adrenal gland (n=7), pituitary adenoma [with (n=3) or without (n = 47) subsequent radiation], 70% of pituitary tissue (n=5), or ACTH secreting intrathoracic tumor (n=13). One had an ectopic ACTH secreting tumor in spontaneous remission (n=1). ACTH stim tests were conducted between 0800h and 0900h, 24 hours after the last dose of glucocorticoid, using 250 mcg of cosyntropin intravenously. Cortisol levels were measured just before administration of cosyntropin, and 30 and 60 minutes afterwards. Patients were considered to have passed the test if baseline or peak cortisol values reached > 18mcg/dL. Baseline cortisol values were compared to the ‘pass’ rate. Results: Baseline F values (ug/dL) and passing rates (# pass/total) were: <4: 1/91; 4-4.9: 2/27; 5-5.9: 8/31; 6-6.9: 2/21; 7-7.9: 7/25; 8-8.9: 4/12; 9-9.9: 8/12; >10 - < 15: 6/11 15 – 19.5: 5/5 Thus, Am cortisol values >9 ug/dl were significantly more likely to predict a normal response to ACTH stim than lower values (p<0.0001). ACTH values (n=184) did not predict peak F levels. However, no patient with ACTH value <5 pg/ml passed the test; all had peak F values of 0-10.5. Conclusion: Baseline cortisol can be a guide as to whether the more costly stimulation test is needed. In the small cohort with baseline 0800h – 0900h cortisol >15 ug/dL, all passed the test, suggesting that it is not needed in such patients. We recommend use of an ACTH stimulation test to assess recovery of the HPA axis when a morning cortisol reaches 9 mcg/dL, with an expected pass rate of about 66%. Reference: 1. Nieman LK, Biller BM, Findling JW, Murad MH, Newell-Price J, Savage MO et al. Treatment of Cushing’s Syndrome: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 100:2807, 2015.