Endocrine Abstracts

Background: Nelson syndrome is a rare complication of Cushing disease (CD), which occurs either in patients with very aggressive CD or as a result of misdiagnosis. Clinical characterization of patients with Nelson syndrome could provide important insights in management of the disorder.

Methods: We analyzed medical records of patients with CD between 2015 and 2021 to identify those who developed Nelson syndrome.

Results: Nine patients developed Nelson syndrome: 2 males and 7 females. Median age of CD onset 27.0 years [20.8;29;8]. Prior to adrenalectomy, 3 patients presented with macroadenomas, 5 – microadenomas, in 1 patient adenoma was not visualized. Seven patients received CD treatment before adrenalectomy: 5 patients underwent multiple transsphenoid neurosurgeries and radiation therapy, 2 were treated only surgically. Mean duration of CS before adrenalectomy was 62 months [48;89]. Mean duration between adrenalectomy and confirmation of Nelson syndrome was 25.5 months [18.5;36.3]. All nine patients developed Nelson syndrome: all had elevated morning ACTH levels – 1176 pg/ml [434;1713], pituitary tumor regrowth or visualization was seen in 6 patients, 4 patients presented with darkened skin tone, 3 – with severe headaches. Median follow-up duration after Nelson diagnosis was 28 months [17;75]. All patients received glucocorticoid replacement therapy – median dose 35 mg/day [25;35]. Three patients received medical therapy, either with cabergoline, long-acting octreotide or lanreotide. Combination of neurosurgery an pituitary radiation was used to treat 3 patients, 2 patients underwent only surgery and 2 received only radiation therapy. At last follow-up visit, 7 patients had pituitary adenoma remnant (5 macro-, 2 microadenoma): without further progression in 6 cases, 1 patient with tumor progression was referred for pituitary irradiation. In 2 patients no signs of regrowth was found on pituitary MRI. Median ACTH during last follow-up was 715.5 pg/ml [453.4;1173].

Conclusion: Nelson syndrome is a severe complication of CD which requires a strict long-term follow-up and all the treatment options to increase the chances of stabilization. In our cohort, combination of treatment modalities led to stabilization of tumor growth in 8 cases, however, ACT remained elevated in all patients. Further reports on this complication could help to identify optimal management strategies and improve the outcomes for Nelson syndrome.