Endocrine Abstracts

Background and Aim: Bilateral Macronodular Adrenal Hyperplasia (BMAH) is a rare form of adrenal Cushing’s syndrome (CS). The treatment of choice in patients with BMAH and overt CS is bilateral adrenalectomy (B-Adx), which however implies lifelong glucocorticoid and mineralocorticoid replacement therapy. Unilateral adrenalectomy (U-Adx) has been proposed as an alternative to B-Adx, especially in case of clearly asymmetric adrenal size. Our aim was to determine predictive factors (e.g. gender, age, mutation status, response to dynamic tests) for remission after U-Adx in BMAH patients.

Patients and Methods: BMAH patients undergoing U-Adx for overt CS were considered eligible. Overt CS was defined as urinary free cortisol (UFC) ≥2 times the upper limit of normality (ULN) and unsuppressed serum cortisol after overnight 1-mg dexamethasone (DST). After U-Adx, BMAHremission was defined as UFC<ULN without additional therapy. BMAHactive were patients with UFC>ULN who required medical therapy or additional surgery for B-Adx. 9 patients were mutated in ARMC5 gene,12 were wild-type, while 2 have not been studied. We compared patients considering therapeutic outcome (BMAHremission vs BMAHactive), gender, ARMC-5 mutational status, baseline UFC (≥2 or >3 times the ULN), overnight 1-mg DST (50-138 or >138 nmol/l), and the delta ACTH increase to CRH (positive test response: >50%).

Results: Twenty-three patients with U-Adx for overt CS were enrolled (69% females, mean age 55 years). According to genetic workup, 9 patients were ARMC5 mutated (wild type, n=12; no genetic workup, n=2). After U-Adx, 17 patients (74%) had remission for at least 18 months. BMAHremission and BMAHactive groups were comparably distributed regarding gender (P=0.621), UFC (P=1.000), overnight 1-mg DST (P=1.000), and ARMC5 status (P=0.611). The CRH test was performed in 15 patients (65%). Absence in ACTH response to CRH was observed in 6 patients (BMAHactive after U-Adx, n= 3; recurrence after initial remission, n=2; CS in remission, n=1. The other 9 patients showed a positive test response, (BMAHremission after U-Adx at last follow-up, n=8; recurrence after initial remission, n=1). A significant correlation between ACTH response to CRH and positive outcome after U-Adx was found (P=0.011).

Conclusions: Remission rate from overt CS after U-Adx was higher in patients with a positive ACTH response during the CRH test (8/9 (89%) vs 1/6 (17%) in non-responders). We therefore suggest to perform the CRH test during the preoperative diagnostic workup for estimating the therapeutic outcome of U-Adx