In normal subjects the main form of circulating insulin-like growth factor (IGF) is the 150-kDa complex. This complex is formed by the IGF peptide, the acid-stable IGF-binding protein-3 (IGFBP-3), and the acid-labile subunit (ALS). Experimental and clinical data have demonstrated that ALS is primarily under the control of GH and plays a critical role in maintaining constant levels of circulating IGF-I. In this study we evaluated ALS, IGF-I, and IGFBP-1, -2, and -3 in 45 acromegalic patients in basal conditions and, in 37 of these, twice after surgical therapy compared with 100 age-and sex-matched control subjects to estimate their value as parameter of GH secretory state.The results demonstrated that in acromegaly before treatment all parameters (ALS, 523 Ϯ 26; IGF-I, 129 Ϯ 6; IGFBP-1, 0.7 Ϯ 0.1; IGFBP-3, 234 Ϯ 21; nmol/L; mean Ϯ SEM) but IGFBP-2 were significantly different (P Ͻ 0.0001) from those in healthy subjects (ALS, 281 Ϯ 4; IGF-I, 22 Ϯ 1; IGFBP-1, 1.6 Ϯ 0.1; IGFBP-3, 91 Ϯ 3). IGF-I was more sensitive (100%) than ALS (89%), and both were more predictive of disease status than IGFBP-3, in that 27% of the patients had IGFBP-3 levels within the normal range. Considering the ALS/ IGFBP-3 molar ratio, almost 55% of ALS circulated in a free form in active acromegaly. Before treatment, the IGF-I/IGFBPs (Ϫ1 ϩ Ϫ2 ϩ Ϫ3) molar ratio, which can be regarded as free, biologically active, IGF-I, was greatly increased (0.77 Ϯ 0.06; P Ͻ 0.0001) compared with that in control subjects (0.23 Ϯ 0.01).After surgery, all 10 patients with controlled disease showed normalization of ALS (100% sensitivity), whereas 9 of them had normal IGFBP-3; reevaluation after varying lengths of time showed all these parameters within the normal range. In the 27 patients with active disease, IGF-I and ALS were more predictive of disease status (91% and 83% negative predictive values, respectively) than IGFBP-3 (53%).The basal ALS concentration correlated only with IGFBP-3 (r ϭ 0.70; P Ͻ 0.001). In postsurgery samples (first control) a statistically significant (P Ͻ 0.001) correlation was found between mean GH values as well as minimum GH after oral glucose tolerance test and ALS (r ϭ 0.72 and 0.83, respectively), IGF-I (r ϭ 0.69 and 0.77), IGFBP-3 (r ϭ 0.50 and 0.72), and IGFBP-2 (r ϭ Ϫ0.36 and Ϫ0.63). Similarly, IGF-I, IGFBP-3, and ALS were positively correlated among themselves and negatively correlated with IGFBP-2 (P Ͻ 0.001).In conclusion, in the diagnosis of acromegaly, the measurement of total IGF-I appears to be the most sensitive parameter among the subunits of the 150K complex, and IGFBP-3 the least sensitive. For ALS, this subunit is quite sensitive and appears to be a useful parameter in reassessment after surgical treatment. (J Clin Endocrinol
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