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 et al., 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, J CLIN END, 86(3), 2001, pp. 1091-1098
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, th
e acid-stable IGF-binding protein-3 (IGFBP-3), and the acid-labile subunit
(ALS). Experimental and clinical data have demonstrated that ALS is primari
ly under the control of GH and plays a critical role in maintaining constan
t levels of circulating IGF-I. In this study we evaluated ALS, IGF-I, and I
GFBP-1, -2, and -3 in 45 acromegalic patients in basal conditions and, in 3
7 of these, twice after surgical therapy compared with 100 age- and sex-mat
ched 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; IGFB
P-1, 1.6 +/-: 0.1; IGFBP-3, 91 +/-: 3). IGF-I was more sensitive (100%) tha
n 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. Con
sidering the ALS/IGFBP-3 molar ratio, almost 55% of ALS circulated in a fre
e 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 co
ntrol 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; reevaluat
ion after varying lengths of time showed all these parameters within the no
rmal range. In the 27 patients with active disease, IGF-I and ALS were more
predictive of disease status (91% and 83% negative predictive values, resp
ectively) than IGFBP-3 (53%).
The basal ALS concentration correlated only with IGFBP-3 (r = 0.70; P < 0.0
01). 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 corre
lated 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 150
K complex, and IGFBP-3 the least sensitive. For ALS, this subunit is quite
sensitive and appears to be a useful parameter in reassessment after surgic
al treatment.