Hormonal and metabolic effects of radiotherapy in acromegaly: Long-term results in 128 patients followed in a single center

Conventional radiotherapy is usually indicated in acromegaly when surgery f ails to normalize GH secretion. However, the benefits of radiotherapy are d elayed. This has raised questions about the potency of this treatment for r eaching the safe GH level of 2.5 mu g/L and for normalizing insulin-like gr owth factor I (IGF-I) levels, both of which are currently recommended as th e 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 preradia tion 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 mu g/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 mu g/L was associated with suppression of GH below 2 mu g/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 mu g/L (P = 0.008). At the last follow-up, IGF-I levels were normalized in 79% of the patients (37 of 47; m ean follow-up, 15.0 +/- 11.3 yr). In the 32 patients presenting with diabetes mellitus, improvement of glucos e tolerance was associated with lower GH levels after treatment (35 +/- 78 mu g/L in the group of 13 patients still presenting diabetes; 9 +/- 12 mu g /L in the group of 4 patients with glucose intolerance; 5 +/- 8 mu g/L in t he 14 patients with normal glucose tolerance; P = 0.04). Ten years after te rmination of radiotherapy gonadotroph, thyreotroph and corticotroph deficie ncies were observed in 80%, 78%, and 82% of the patients, respectively. In conclusion, conventional radiotherapy can reduce GH levels below the opt imal level of 2.5 mu g/L and normalize IGF-I levels in acromegaly. However, the incidence of late hypopituitarism is high, and the delay to obtain thi s safe GH secretory status can be long, depending on the preradiation GH le vel. These parameters should be considered when adjuvant therapy is needed after surgery.