Management of Nelson's syndrome: observations in fifteen patients.

OBJECTIVE: To analyse the results of different treatment modalities for Nelson's syndrome, which was defined as radiological evidence of a pituitary macroadenoma, fasting plasma ACTH levels of more than 200 pmol/l after stopping glucocorticoid substitution for at least 24 h in a patient who had undergone bilateral adrenalectomy for Cushing's disease.

DESIGN: The medical reports of all Nelson's patients known in our hospital were studied with regard to treatment modalities and result of treatment. Clinical 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 than 200 pmol/l after stopping glucocorticoid substitution for at least 24 h.

PATIENTS: Fifteen women with Nelson's syndrome were studied. Bilateral adrenalectomy had been performed 1-29 years before Nelson's syndrome was diagnosed. Before adrenalectomy eight patients had undergone unsuccessful transsphenoidal pituitary surgery.

RESULTS: Eight patients were initially followed without surgical or radiotherapeutical intervention during 1-7 years. In seven of them, plasma ACTH levels and tumour volumes increased progressively during this rather short observation 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 pituitary 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 revealed no residual tumour mass but the postoperative plasma ACTH level was still elevated. In another patient a residual intrasellar macroadenoma and an increased plasma ACTH level remained stable for 22 years. The remaining four patients received postoperative radiotherapy because of residual tumour masses. Of these patients, one had a clinical remission. In two others relatively 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 correlation was stronger at the moment of decision of either pituitary surgery or radiotherapy (r = + 0.85, P < 0.001). At the end of the follow-up period the correlation between tumour volumes and plasma ACTH levels in the combined pituitary surgery and/or irradiation only group was + 0.77 (P < 0.001). In the pituitary surgery group tumour volumes before and after surgery were directly correlated (r = + 0.70, P < 0.05).

CONCLUSIONS: Our results demonstrate that pituitary surgery of Nelson's macroadenomas is more successful when Nelson's adenomas are relatively small. Pituitary surgery should be performed before extrasellar expansion of the tumour occurs in order to attain long lasting remissions. Pituitary irradiation 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 volume.