From Nelson’s Syndrome to Corticotroph Tumor Progression Speed: An Update

Abstract

Since the first description 60 years ago of Nelson syndrome, the way to consider corticotroph pituitary neuroendocrine tumors (PitNETs) after bilateral adrenalectomy has evolved. Today, it is globally acknowledged that only a subset of corticotroph PitNETs is aggressive. After adrenalectomy, corticotroph tumor progression (CTP) occurs in about 30 to 40% of patients during a median follow-up of 10 years. When CTP occurs, various CTP (CTPS) speeds can be obsersed. Using a simple metrics in patients with CTP, CTPS was reported to vary from few millimeters per year to up to 40 mm per year. Rapid CTPS/Nelson’s syndrome was associated with more severe Cushing, higher ACTH in the year following adrenalectomy and higher Ki67 on pituitary pathology. Complications such as apoplexy, cavernous syndrome and visual defects were associated with higher CTPS. During follow-up, early morning ACTH absolute variations properly reflected CTPS. Finally, CTPS was not higher after than before adrenalectomy, suggesting that cortisol deprivation after adrenalectomy does not impact CTPS in a majority of patients. Taken together, rapid CTPS/Nelson’s syndrome probably reflects the intrinsic aggressiveness of some corticotroph PitNETs. The precise molecular mechanisms related to corticotroph PitNET aggressiveness remain to be deciphered. Regular MRIs combined to intermediate morning ACTH measurements probably provide a reliable way to detect early and manage fast growing tumors, and therefore to limit the complications.