ABSTRACT 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 ofGHand 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 6 26; IGF-I, 129 6 6; IGFBP-1, 0.7 6 0.1; IGFBP-3, 234 6 21; nmol/L; mean 6 SEM) but IGFBP-2 were significantly different (P , 0.0001) from those in healthy subjects (ALS, 281 6 4; IGF-I, 22 6 1; IGFBP-1, 1.6 6 0.1; IGFBP-3, 91 6 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 (21122 1 23) molar ratio, which can be regarded as free, biologically active, IGF-I, was greatly increased (0.77 6 0.06; P , 0.0001) compared with that in control subjects (0.23 6 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 5 0.70; P , 0.001). In postsurgery samples (first control) a statistically significant (P , 0.001) correlation was found between mean GH values as well as minimum GH after oral glucose tolerance test and ALS (r 5 0.72 and 0.83, respectively), IGF-I (r 5 0.69 and 0.77), IGFBP-3 (r 5 0.50 and 0.72), and IGFBP-2 (r 5 20.36 and 20.63). Similarly, IGF-I, IGFBP-3, and ALS were positively correlated among themselves and negatively correlated with IGFBP-2 (P , 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.
Diagnostic Value of the Acid-Labile Subunit in Acromegaly: Evaluation in Comparison with Insulin-Like Growth Factor (IGF) I, and IGF-Binding Protein-1, -2, and -3 / M. AROSIO, S. GARRONE, P. BRUZZI, G. FAGLIA, F. MINUTO, AND A. BARRECA. - In: THE JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM. - ISSN 0021-972X. - 86:3(2001 Mar), pp. 1091-1098.
|Titolo:||Diagnostic Value of the Acid-Labile Subunit in Acromegaly: Evaluation in Comparison with Insulin-Like Growth Factor (IGF) I, and IGF-Binding Protein-1, -2, and -3|
AROSIO, MAURA (Primo)
|Parole Chiave:||ACROMEGALY; ACID-LABILE SUBUNIT; INSULIN-LIKE GROWTH FACTOR BINDING PROTEIN-3; INSULIN-LIKE GROWTH FACTOR-I|
|Settore Scientifico Disciplinare:||Settore MED/13 - Endocrinologia|
|Data di pubblicazione:||mar-2001|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1210/jc.86.3.1091|
|Appare nelle tipologie:||01 - Articolo su periodico|