INTERRELATIONS BETWEEN GROWTH-HORMONE, INSULIN, INSULIN-LIKE GROWTH FACTOR-I (IGF-I), IGF-BINDING PROTEIN-1 (IGFBP-1) AND SEX HORMONE-BINDING GLOBULIN IN ACROMEGALY

Acromegaly is characterized by a hypersecretion of GH, which in turn results in an excess of IGF-I, an important mediator of its actions. IGF-I itself is intimately related to insulin both in structure and function. IGF-I circulates associated with specific binding proteins which appear to have important effects on its activity. We have examined the inter-relations between GH, prolactin, insulin, IGF-I and one of the binding proteins, IGFBP-1, in 62 patients with acromegaly of varying activity. Serum IGF-I levels were closely related to the logarithm of mean GH levels (r = 0.76; n = 62; P < 0.001) but multiple regression analysis suggested that, after accounting for the variation due to GH, insulin accounted for some of the additional variation of IGF-I. IGF-I concentrations were independent of prolactin. Fasting insulin levels were high and unrelated to mean GH levels but correlated with those of IGF-I (r = 0.542; n = 57; P < 0.001). This correlation coefficient was further improved by also accounting for variations in IGFBP-1 (r = 0.684; n = 57; P < 0.001). Even in subjects whose acromegaly was well controlled or cured, as indicated by GH level of < 1 mU/I or IGF-I levels of < 2 U/ml, fasting insulin levels remained significantly elevated in some individuals. The reason for this persistent abnormality is not clear. Fasting IGFBP-1 levels were low and unrelated to mean GH but were inversely related to fasting insulin levels (r = -0.593; n = 57; P < 0.001). We propose that a cascade of events occurs in acromegaly. GH hypersecretion causes chronic elevation of IGF-I levels which in turn could lead to increased pancreatic insulin production. This raised insulin could then have additional effects, raising IGF-I levels further and lowering IGFBP-1; the latter could then result in accentuated IGF-activity.