Clinical presentation, predictive factors and management of patients with Nelson syndrome: a retrospective study

Background: Nelson syndrome (NS), or corticotroph tumor progression after bilateral adrenalectomy (CTP-BADX/NS), is a serious complication in patients with Cushing disease (CD) following BADX. Surgical tumor removal is the recommended treatment, though adjuvant therapies may be necessary. Aim of the study: To evaluate clinical, radiological, and hormonal features of CD patients after BADX, identify risk factors for CTP-BADX/NS and assessed treatment outcome and cardio-metabolic complications. Methods: Retrospective study of 30 patients (male/female: 9/21; median age at CD diagnosis: 33 years, IQR 27-42) who underwent BADX and had a minimum follow-up of 18 months. Data were collected at diagnosis and during follow-up (6, 24 months and last visit). Results: Over a median follow-up of 135 months, 9/30 patients (30%) developed NS, median 60 months after BADX. NS patients had earlier CD diagnosis and higher ACTH levels two years post-BADX [458 ng/L (IQR 245-723) vs. 146 ng/L (61-247), p = 0.020]. They also took lower fludrocortisone [0.05 mg/day vs. 0.1 mg/day, p = 0.001] and tended to use less hydrocortisone [20 mg/day [20-25] vs. 30 [25-30], p = 0.06]. Pre-BADX stereotactic radiosurgery (SRS) was more frequent in non-NS patients (52% vs. 22%, p = 0.11). Hypertension was more common in NS patients (78% vs 43%), but diabetes less so (33% vs 48%). In the CTP-BADX group, 6/9 required pituitary surgery and/or radiotherapy; medical therapy was used in 5 patients with varied results. Conclusion: CTP-BADX/NS occurred in 30% of cases in our cohort. Higher ACTH post-BADX and younger age at CD onset may predict NS. No hormonal or radiological markers reliably predicted tumor progression. SRS before BADX and higher hydrocortisone doses might offer protection. Tumor control often needed a multimodal approach, with limited success from medical therapy alone.