Efficacy of radiotherapy in normalizing serum IGF-I, acid-labile subunit (ALS) and IGFBP-3 levels in acromegaly

OBJECTIVE Radiotherapy (RT) has been used for many years in order to comple te the cure of unsuccessfully operated acromegalic patients. Several studie s have shown its efficacy in normalizing GH levels, while reports about IGF -I normalization are conflicting. Moreover, data regarding other markers of disease activity, such as IGFBP-3 and acid-labile subunit (ALS), i.e. the other two components of the circulating 150 kDa complex, are lacking. DESIG N Retrospective study. PATIENTS AND MEASUREMENTS Sixty-seven acromegalic patients (20 males and 47 females, aged 40 +/- 6 years) who underwent postoperative FIT (in fraction ated doses for a total of 40-75 Gy) were followed-up for 11 +/- 6 years (ra nge: 1-26 years, median: 10 years). Serum GH and IGF-I levels off medical t herapy were measured in all patients; ALS and IGFBP-3 were measured in 11 p atients with normalization of IGF-I concentrations. Computed tomography or nuclear magnetic resonance imaging periodically assessed possible developme nt of pituitary deficiency along with imaging of the hypothalamic-pituitary region. RESULTS Forty-one out of 67 patients (58%) achieved GH levels <2.5 <mu>g/l by 1-15 years after FIT (mean 8 +/- 6) and 37/67 patients (55%) had normal or low IGF-I levels 1-26 years after RT (mean: 12 +/- 6), a normalization o f both parameters being seen in 37 patients. GH <2.5 <mu>g/l and normal IGF -I levels were achieved in 17/26 (65%) patients followed-up for at least 15 years. ALS and IGFBP-3 concentrations paralleled IGF-I levels in all patie nts studied. With respect to secondary pituitary insufficiency, acquired AC TH deficiency was found in 25 patients, TSH deficiency in 20, gonadotropin deficiency in 23 and GH deficiency in seven. In total, two cases of meningi oma and one pineal tumour, possibly related to FIT, were seen 9-22 years af ter RT. CONCLUSIONS RT is an effective, although slow-acting, therapeutic tool for acromegaly, with 'safe' GH levels and normal IGF-I concentrations being ach ieved in 65% of patients after 15 years. IGF-I levels normalize more slowly than GH levels. Radiotherapy is able to normalize the concentration of all three components of the circulating 150 kDa complex. Checks for loss of pi tuitary function and appearance of second brain tumours must be carried out life-long.