This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Arosio, M. Articles by Barreca, A. Search for Related Content PubMed PubMed Citation Articles by Arosio, M. Articles by Barreca, A.

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 -3¹

Institute of Endocrine Sciences, University of Milan, Ospedale Maggiore Istituto Ricovero e Cura a Carattere Scientifico (M.A., G.F.), I-20122 Milan; and Department of Endocrinology and Metabolism, University of Genova (S.G., A.C., F.M., A.B.), and Unit of Clinical Epidemiology and Trials, National Institute for Cancer Research (P.B.), I-16132 Genova, Italy

Address all correspondence and requests for reprints to: Dr. A. Barreca, Department of Endocrinology and Metabolism, University of Genova, Viale Benedetto XV, no 6. I-16132 Genova, Italy. E-mail: barreca{at}unige.it

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 ± 26; IGF-I, 129 ± 6; IGFBP-1, 0.7 ± 0.1; IGFBP-3, 234 ± 21; nmol/L; mean ± SEM) but IGFBP-2 were significantly different (P < 0.0001) from those in healthy subjects (ALS, 281 ± 4; IGF-I, 22 ± 1; IGFBP-1, 1.6 ± 0.1; IGFBP-3, 91 ± 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 (-1 + -2 + -3) molar ratio, which can be regarded as free, biologically active, IGF-I, was greatly increased (0.77 ± 0.06; P < 0.0001) compared with that in control subjects (0.23 ± 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 = 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 = 0.72 and 0.83, respectively), IGF-I (r = 0.69 and 0.77), IGFBP-3 (r = 0.50 and 0.72), and IGFBP-2 (r = -0.36 and -0.63). 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.

This article has been cited by other articles:

				K. M Morrison, M. Bidlingmaier, S. Stadler, Z. Wu, L. Skriver, and C. J Strasburger Sample pre-treatment determines the clinical usefulness of acid-labile subunit immunoassays in the diagnosis of growth hormone deficiency and acromegaly Eur. J. Endocrinol., March 1, 2007; 156(3): 331 - 339. [Abstract] [Full Text] [PDF]

				R. A. Feelders, M. Bidlingmaier, C. J. Strasburger, J. A. M. J. L. Janssen, P. Uitterlinden, L. J. Hofland, S. W. J. Lamberts, A. J. van der Lely, and W. W. de Herder Postoperative Evaluation of Patients with Acromegaly: Clinical Significance and Timing of Oral Glucose Tolerance Testing and Measurement of (Free) Insulin-Like Growth Factor I, Acid-Labile Subunit, and Growth Hormone-Binding Protein Levels J. Clin. Endocrinol. Metab., December 1, 2005; 90(12): 6480 - 6489. [Abstract] [Full Text] [PDF]

				A. Colao, D. Ferone, P. Marzullo, and G. Lombardi Systemic Complications of Acromegaly: Epidemiology, Pathogenesis, and Management Endocr. Rev., February 1, 2004; 25(1): 102 - 152. [Abstract] [Full Text] [PDF]

				D. R. Clemmons, K. Chihara, P. U. Freda, K. K. Y. Ho, A. Klibanski, S. Melmed, S. M. Shalet, C. J. Strasburger, P. J. Trainer, and M. O. Thorner Optimizing Control of Acromegaly: Integrating a Growth Hormone Receptor Antagonist into the Treatment Algorithm J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 4759 - 4767. [Abstract] [Full Text] [PDF]

				T.-J. Wu, E. H. Yu, L. Song, R. L. Taylor, and P. C. Kao Filter Paper Collection of Plasma for IGF-I Test in Patients with Acromegaly Ann. Clin. Lab. Sci., July 1, 2002; 32(3): 287 - 291. [Abstract] [Full Text] [PDF]

				P. Marzullo, C. Di Somma, K. L. Pratt, J. Khosravi, A. Diamandis, G. Lombardi, A. Colao, and R. G. Rosenfeld Usefulness of Different Biochemical Markers of the Insulin-Like Growth Factor (IGF) Family in Diagnosing Growth Hormone Excess and Deficiency in Adults J. Clin. Endocrinol. Metab., July 1, 2001; 86(7): 3001 - 3008. [Abstract] [Full Text] [PDF]