DETERMINANTS OF SERUM INSULIN-LIKE-GROWTH-FACTOR I IN GROWTH-HORMONE DEFICIENT ADULTS AS COMPARED TO HEALTHY-SUBJECTS

OBJECTIVE Growth hormone status is an important determinant of serum I GF-I but it is well known that hypopituitary adults with pronounced GH -deficiency (GHDA) may exhibit normal IGF-I levels. To elucidate possi ble causes of this apparent paradox we compared the significance of pu tative IGF-I predictors in GHDA and normal subjects. DESIGN A cross-se ctional study. SUBJECTS Twenty-seven GHDA (9 females, 18 males, mean /- SE age 44 +/- 1 years) and 27 healthy control subjects (9 females, 18 mates, mean +/- SE age 43 +/- 2 years). RESULTS Serum IGF-I and IGF BP-3 were significantly lower in GHDAs, but a considerable overlap exi sted (IGF-I (mu g/l) 87 +/- 12 (GHDA) vs 177 +/- 10 (Control) (P < 0.0 01)). In both Controls and GHDA, IGF-I was higher in males than female s (Control: 196 +/- 12 vs 138 +/- (P = 0.004); GHDA: 97 +/- 16 vs 56 /- 11 (P = 0.05)). In GHDA, males on testosterone substitution had the highest IGF-I concentrations. The molar IGF-I:IGFBP-3 ratio was signi ficantly lower in GHDAs (0.18 +/- 0.01 vs 0.23 +/- 0.02 (P = 0.002)). IGFBP-1 (mu g/l) was significantly elevated in GHDAs (6.28 +/- 1.11 vs 3.07 +/- 0.32 (P < 0.001)) despite comparable fasting insulin levels. Percentage total body fat (TBF, DEXA, waist/hip ratio, and intra-abdo minal fat (CT) were all elevated in GHDAs. IGF-I correlated positively with lean body mass (DEXA) and negatively with TBF and IGFBP-1 in bot h groups. IGF-I correlated negatively with age in CON but not in GHDAs , whereas IGF-I correlated positively with IGFBP-3 only in GHDAs. Mult iple regression analysis revealed that age and IGFBP-1 were the only s ignificant predictors of IGF-I in CON, whereas IGFBP-3 and, to a lesse r extent TBF, were the only independent predictors of IGF-I in GHDAs. Neither peak stimulated GH, nor physical fitness contributed in any eq uations in the two groups. CONCLUSIONS 1) IGF-I levels are regulated b y several variables in addition to GH status 2) age per se is an indep endent negative determinant in healthy subjects but not in GHDA 3) It is probable that some cases of paradoxically high IGF-I levels in GHDA are secondary to inappropriately elevated IGFBP-3 levels. 4) in mid-a dulthood males have higher IGF-I levels than females and it is likely that testosterone directly stimulates IGF-I. The influence of gender a nd sex steroids must therefore be accounted for when comparing IGF-I l evels between hypopituitary and healthy subjects.