Conventional radiotherapy is usually indicated in acromegaly when surgery fails to normalize GH secretion. However, the benefits of radiotherapy are delayed. This has raised questions about the potency of this treatment for reaching the safe GH level of 2.5 microg/L and for normalizing insulin-like growth factor I (IGF-I) levels, both of which are currently recommended as the therapeutic goal. To evaluate the long-term hormonal and metabolic effects of radiotherapy in acromegaly, a retrospective analysis was undertaken studying 128 patients followed for 11.5+/-8.5 yr (mean +/- SD) in a single center. The preradiation GH levels decreased as a function of time to 50% at 2 yr, 20% at 5 yr, and 10% at 10 yr. Basal GH levels below 2.5 microg/L were obtained in 7% of the patients at 2 yr, 35% at 5 yr, 53% at 10 yr, and 66% at 15 yr. A basal GH level below 2.5 microg/L was associated with suppression of GH below 2 microg/L during an oral glucose tolerance test and normalization of IGF-I levels in 9 of 10 patients. Preradiation GH levels was the sole factor that could predict the delay in GH fall to below 2.5 microg/L (P = 0.008). At the last follow-up, IGF-I levels were normalized in 79% of the patients (37 of 47; mean follow-up, 15.0+/-11.3 yr). In the 32 patients presenting with diabetes mellitus, improvement of glucose tolerance was associated with lower GH levels after treatment (35+/-78 microg/L in the group of 13 patients still presenting diabetes; 9+/-12 microg/L in the group of 4 patients with glucose intolerance; 5+/-8 microg/L in the 14 patients with normal glucose tolerance; P = 0.04). Ten years after termination of radiotherapy gonadotroph, thyreotroph and corticotroph deficiencies were observed in 80%, 78%, and 82% of the patients, respectively. In conclusion, conventional radiotherapy can reduce GH levels below the optimal level of 2.5 microg/L and normalize IGF-I levels in acromegaly. However, the incidence of late hypopituitarism is high, and the delay to obtain this safe GH secretory status can be long, depending on the preradiation GH level. These parameters should be considered when adjuvant therapy is needed after surgery.