Objectives: Three major therapeutic modalities (transsphenoidal surgery, radiotherapy and medical therapy) are currently available for acromegaly. Although surgery is regarded as the primary option, 50--60% of macroadenomas require further treatment in the form of radiotherapy and/or medical therapy. Recent studies have suggested that radiotherapy might damage the normal hypothalamic-pituitary axis and also rarely leads to IGF-I normalization. The aims of this study were: (1) to examine the effect of different therapeutic modalities (transsphenoidal surgery, TSS; radiotherapy, RT; medical treatment with somatostatin analogues, SSA) on the daily spontaneous GH secretory pattern (day curve); and (2) to determine the relationship between the characteristics of the GH secretory pattern and the circulating concentration of IGF-I, acid-labile subunit (ALS) and IGFBP-3.
Design and measurements: Spontaneous GH secretion was evaluated at hourly intervals from 0800 to 1800 h. IGF-I, IGFBP-3 and ALS were measured in basal conditions. The mean and the minimum values obtained from the day curve profile and the coefficient of variation (CV) of single values, which are expressions of the magnitude of the spontaneous secretory pulses, were used for statistical analysis.
Patients: In a group of 45 acromegalic patients (28 women, mean age 51 years, range 26--83 years, and 17 men, mean age 57 years, range 37--78 years) treated with different protocols, including TSS, RT and SSA therapy, we evaluated GH secretion to determine the effect of single treatment options on the spontaneous secretory profile. Subjects were grouped on the basis of different therapeutic modalities: TSS+RT+SSA (group 1), TSS+SSA (group 2), SSA (group 3), TSS (group 4), TSS+RT (group 5). In patients treated with somatostatin analogues (SSA), tests were performed about midway between two injections.
Results: The number of deficiencies of the other pituitary functions (PD) was significantly higher in the groups that underwent RT (groups 1 and 5) than in the other groups; in both cases, P<0.01. No significant differences were observed with regard to the mean GH, IGF-I, ALS or IGFBP-3 among the different treatment groups. A significant difference in the GH nadir was found between groups 2 and 4 (P=0.042) and between groups 3 and 4 (P=0.015). GH CV showed lower values in subjects who underwent RT (groups 1 and 5) than in the other groups. The difference was statistically significant between group 5 and groups 2, 3 and 4 (P<0.05), between group 1 and groups 3 and 4 (P<0.05), and between groups 2 and 4 (P=0.007).
Conclusions: Our data confirm that radiation therapy decreases GH variability, and that this effect is probably due to hypothalamic damage, as already reported by others. In irradiated patients, a single random sample should therefore be sufficient to evaluate spontaneous GH secretion.