Objective: It is still unknown whether prolonged treatment with somatostatin analogs (SSTa) may cause a long-lasting disease remission in GH-secreting adenomas after drug discontinuation. The aim of the present study was to investigate the evolution of GH/IGF-I secretion and tumor mass after SSTa withdrawal in patients affected by acromegaly. Patients and Design: A total of 27 patients with acromegaly (12 de novo and 15 previously operated) were treated with SSTa for a median period of 48 months and considered optimally controlled in hormonal and neuroradiological terms. None of them were previously irradiated. Methods: Basal GH, post-glucose GH nadir, IGF-I, clinical signs/symptoms, and metabolic parameters were evaluated after 12-16 weeks from drug withdrawal. Only patients who met the current criteria for disease remission remained in drug suspension being periodically re-evaluated for biochemical/-clinical data and neuroradiological imaging. Results: After 12-16 weeks withdrawal, 15 of the 27 patients had disease relapse and restarted SSTa, while 12 were considered 'in disease remission' (44% of total). Glucose metabolism improved in both euglycemic and diabetic patients after short-term SSTa discontinuation. Only one of the ten patients who reached 24 weeks withdrawal showed biochemical disease recurrence. On the whole, five of the patients still in remission after 6 months have already prolonged the follow-up over 12 months (median: 24 months), without clinical and biochemical/neuroradiological evidence of disease recurrence. Conclusions: These preliminary data indicate a successful withdrawal of SSTa at least in a subset of wellresponsive patients with acromegaly and challenge the previously held concept that medical therapy is always a lifelong requirement.

The current GH nadir limit is still adequate to define both short- and long-lasting remission of acromegaly, independently of the type of definitive treatment. Patients with the lowest GH nadir should probably be monitored long-term for adequacy of their GH secretion.

The HPA axis function must be carefully monitored over the time by dynamic testing in all acromegalic patients, independently from the type of treatment.