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 complete the cure of unsuccessfully operated acromegalic patients. Several studies 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.


METHODS
Retrospective study.


METHODS
Sixty-seven acromegalic patients (20 males and 47 females, aged 40 +/- 6 years) who underwent postoperative RT (in fractionated doses for a total of 40-75 Gy) were followed-up for 11 +/- 6 years (range: 1-26 years, median: 10 years). Serum GH and IGF-I levels off medical therapy were measured in all patients; ALS and IGFBP-3 were measured in 11 patients with normalization of IGF-I concentrations. Computed tomography or nuclear magnetic resonance imaging periodically assessed possible development of pituitary deficiency along with imaging of the hypothalamic-pituitary region.


RESULTS
Forty-one out of 67 patients (58%) achieved GH levels < 2.5 microg/l by 1-15 years after RT (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 of both parameters being seen in 37 patients. GH < 2.5 microg/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 patients studied. With respect to secondary pituitary insufficiency, acquired ACTH deficiency was found in 25 patients, TSH deficiency in 20, gonadotropin deficiency in 23 and GH deficiency in seven. In total, two cases of meningioma and one pineal tumour, possibly related to RT, were seen 9-22 years after RT.


CONCLUSIONS
RT is an effective, although slow-acting, therapeutic tool for acromegaly, with 'safe' GH levels and normal IGF-I concentrations being achieved 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 pituitary function and appearance of second brain tumours must be carried out life-long.
Epaminonda
P
P
Institute of Endocrine Sciences, University of Milano, Ospedale Maggiore IRCCS, Milano, Italy.
Porretti
S
S
Cappiello
V
V
Beck-Peccoz
P
P
Faglia
G
G
Arosio
M
M
D000172:Acromegaly / Q000378:metabolism / Q000532:radiotherapy*; D000324:Adrenocorticotropic Hormone / Q000172:deficiency; D000328:Adult; D002352:Carrier Proteins / Q000032:analysis*; D005260:Female; D006023:Glycoproteins / Q000032:analysis*; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000097:blood / Q000528:radiation effects*; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000528:radiation effects*; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008577:Meningeal Neoplasms / Q000175:diagnosis / Q000209:etiology; D008579:Meningioma / Q000175:diagnosis / Q000209:etiology; D016609:Neoplasms, Second Primary / Q000175:diagnosis / Q000209:etiology; D012189:Retrospective Studies
D002352:Carrier Proteins; D006023:Glycoproteins; D018972:Insulin-Like Growth Factor Binding Protein 3; C075944:insulin-like growth factor binding protein, acid labile subunit; D007334:Insulin-Like Growth Factor I; D000324:Adrenocorticotropic Hormone