Nelson syndrome is an important complication of treatment with total bilateral
adrenalectomy (TBA) for patients with refractory
Cushing's disease. Although early cases of
Nelson syndrome often presented with the clinical features of large sellar masses, the modern face of
Nelson syndrome has changed primarily due to earlier detection (with highly resolved magnetic resonance imaging (MRI) and sensitive
ACTH assays) and greater awareness of the condition, resulting in reduced morbidity and mortality. Although lack of administration of neoadjuvant pituitary
radiotherapy post-TBA surgery may predict future development of
Nelson syndrome, other predictive factors remain controversial. Therefore,
Nelson syndrome should be screened for closely and long-term in all patients with a history of
Cushing's disease and TBA. The diagnosis of
Nelson syndrome remains controversial, and the pathogenesis of this condition is incompletely understood. Current hypotheses include the "released negative feedback" mechansism (residual pituitary corticotropinoma cells are "released" from the negative feedback effects of
cortisol following TBA), and the "aggressive corticotropinoma" mechanism (
Nelson syndrome is most likely to develop in those patients with refractory treatments - including TBA - for an underlying aggressive corticotropinoma). Effective management of
Nelson syndrome with pituitary surgery and
radiotherapy is often a challenge. Other
therapies (such as Gamma Knife surgery and
temozolomide) play an important role and merit further research into their efficacy and placement in the management pathway of
Nelson syndrome.