Affiliation:
1. Department of Endocrinology and National Reference Center for Rare
Adrenal Disorders, AP-HP, Hôpital Cochin, F-75014 Paris, France
2. Department of Neurosurgery, Pitié Salpétrière, AP-HP, Hôpital
Pitié-Salpétrière, F-75013 Paris, France
Abstract
AbstractSince the first description of Nelson syndrome 60 years ago, 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 speeds (CTPS) can be observed. Using simple metrics in patients with CTP,
CTPS was reported to vary from a few millimeters to up to 40 mm per year. Rapid
CTPS/ Nelson’s syndrome was associated with more severe Cushing’s disease,
higher adrenocorticotropic hormone (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 with intermediate morning ACTH measurements probably provide a
reliable way to detect early and manage fast-growing tumors and, therefore,
limit the complications.