INSULIN-LIKE GROWTH-FACTORS (IGF)-I AND (IGF)-II AND IGF BINDING PROTEIN-1, PROTEIN-2, AND PROTEIN-3 IN PATIENTS WITH ACROMEGALY BEFORE AND AFTER ADENOMECTOMY

The interrelationship between insulin-like growth factors (IGFs) and their major binding proteins (IGFBPs) as a function of disease activity in acromegaly has not previously been prospectively evaluated. We studied basal and insulin-stimulated serum levels of IGF-I and -II and IGFBP-1, -2, and -3 in six acromegalic patients before and 2 months after successful adenomectomy compared with a group of sex- and age-matched healthy, untreated subjects. All were studied postabsorptively (11 am) and at the end of a 2-hour euglycemic glucose clamp (0.4 mU insulin/kg × min). Serum IGF-I levels (mean ± SE) were elevated in acromegaly but were normalized following therapy (basal state IGF-I [μg/L], 857 ± 119 [active] v 255 ± 65 [postoperative] v 190 ± 20 [control]). Serum IGF-II levels did not change following therapy and were similar to those of the control group. IGF levels did not change during the clamp. Serum IGFBP-3 levels were elevated in active acromegaly, but were normalized after therapy (basal state IGFBP-3 [μg/L] 6,983 ± 612 [active] v 3,939 ± 504 [postop] v 3,358 ± 125 [control]). The molar ratio of (IGF-I + IGF-II):IGFBP-3 was similar in all studies. Serum IGFBP-1 interacted significantly with time in all studies, exhibiting a gradual decrease in the basal state and ensued by further suppression during the clamp. Insulin and IGFBP-1 correlated inversely in the pooled data and in the acromegalic patients. Serum IGFBP-2 was significantly decreased in active acromegaly, but became normalized following therapy (basal state IGFBP-2 [μg/L], 275 ± 11 [active] v 396 ± 16 [postop] v 345 ± 19 [control]). Both IGFBP-2 and IGFBP-3 were unchanged during the clamp. Multiple stepwise regression analysis showed IGFBP-2 to correlate inversely with IGF-I, whereas IGF-I and IGFBP-3 intercorrelated positively. In summary, (1) IGF-I but not IGF-II is elevated in active acromegaly, (2) the molar ratios of (IGF-I + IGF-II):IGFBP-3 were similar in all studies, (3) IGFBP-2 levels are decreased in active acromegaly and do not seem to be regulated by insulin, and (4) Successful adenomectomy results in normalization of circulating IGF-I and IGFBPs. We speculate that the increased IGF-I activity in active acromegaly may be accentuated by the decreased IGFBP-2 and -1 levels. © 1994.