Management of Nelson's syndrome: observations in fifteen patients

OBJECTIVE To analyse the results of different treatment modalities for Nels on's syndrome, which was defined as radiological evidence of a pituitary ma croadenoma, fasting plasma ACTH levels of more than 200 pmol/l after stoppi ng glucocorticoid substitution for at least 24 h in a patient who had under gone bilateral adrenalectomy for Cushing's disease. DESIGN The medical reports of all Nelson's patients known in our hospital w ere studied with regard to treatment modalities and result of treatment. Cl inical remission of Nelson's syndrome was defined as a reduction of tumour size to a diameter of 10 mm or less and fasting plasma ACTH levels less tha n 200 pmol/l after stopping glucocorticoid substitution for at least 24 h. PATIENTS Fifteen women with Nelson's syndrome were studied. Bilateral adren alectomy had been performed 1-29 years before Nelson's syndrome was diagnos ed. Before adrenalectomy eight patients had undergone unsuccessful transsph enoidal pituitary surgery. RESULTS Eight patients were initially followed without surgical or radiothe rapeutical intervention during 1-7 years. In seven of them, plasma ACTH lev els and tumour volumes increased progressively during this rather short obs ervation period, with development of extrasellar extension in four patients . In one of these patients, who was planned for elective pituitary surgery, massive pituitary haemorrhage occurred which was fatal despite emergency p ituitary surgery. Elective pituitary surgery was performed in 11 patients, of whom three were operated twice. Clinical remission was documented in five patients in the first year after operation. In one patient postoperative MR-imaging reveale d no residual tumour mass but the postoperative plasma ACTH level was still elevated. In another patient a residual intrasellar macroadenoma and an in creased plasma ACTH level remained stable for 22 years. The remaining four patients received postoperative radiotherapy because of residual tumour mas ses. Of these patients, one had a clinical remission. In two others relativ ely small residual intrasellar tumour masses remain, with a fasting plasma ACTH level of more than 200 pmol/l in one of them. The fourth patient died of the consequences of progressive tumour growth. Radiotherapy was the only treatment in two patients and did not result in clinical remission. Tumour volumes and plasma ACTH levels at the time of diagnosis of Nelson's syndrome were positively correlated (r = + 0.61, P < 0.05). This correlatio n was stronger at the moment of decision of either pituitary surgery or rad iotherapy (r = + 0.85, P < 0.001). At the end of the follow-up period the c orrelation between tumour volumes and plasma ACTH levels in the combined pi tuitary surgery and/or irradiation only group was + 0.77 (P < 0.001). In th e pituitary surgery group tumour volumes before and after surgery were dire ctly correlated (r = + 0.70, P < 0.05). CONCLUSIONS Our results demonstrate that pituitary surgery of Nelson's macr oadenomas is more successful when Nelson's adenomas are relatively small. P ituitary surgery should be performed before extrasellar expansion of the tu mour occurs in order to attain long lasting remissions. Pituitary irradiati on should be performed postoperatively in all patients with residual tumour . Our data also illustrate that in patients with Nelson's syndrome, plasma ACTH levels can reliably be used as an indirect approximation for tumour vo lume.