TY - JOUR
T1 - Paradoxical elevations in serum IGF-11 and IGF-11 and IGF binding protein-2 in acromegaly: insights into the regulation of these peptides
AU - Renehan, AG
AU - Toogood, Andrew
AU - Ryder, WD
AU - Jones, J
AU - Potten, CS
AU - O'Dwyer, ST
AU - Shalet, SM
PY - 2001/10/1
Y1 - 2001/10/1
N2 - OBJECTIVE: Circulating insulin-like growth factor (IGF)-II and IGF binding protein-2 (IGFBP-2) are frequently altered, often in parallel, in numerous pathologies including neoplastic disease but little is known about their normal regulation. This study compared serum IGF-II and IGFBP-2 distributions between acromegalics and a large normal adult population to explore possible determinants. PATIENTS: Sixty acromegalic patients undergoing screening colonoscopy (age range 25-81 years); normative data from 306 healthy adults (age range 20-89 years). MEASUREMENTS: Serum IGF-I, IGF-II, IGFBP-2 and IGFBP-3 were measured in healthy adults and acromegalics. Mean growth hormone (GH) levels were obtained for acromegalic patients. Differences were compared using t-tests (unadjusted) and multiple regression models (adjusted for age and gender). Correlations were expressed as Pearson's coefficient (r). RESULTS: For acromegalic patients, GH was significantly correlated with IGF-I (r = 0.50; P <0.001) and IGFBP-3 (r = 0.29; P = 0.03) but not IGF-II or IGFBP-2. Contrary to expectations, mean IGF-II and IGFBP-2 levels were significantly raised in the acromegalics compared with normals [adjusted mean difference (95% CI) = 226 (181, 271) microg/l and 305 (200, 410) microg/l, respectively]. Ten acromegalic patients had colorectal neoplasia but their presence did not contribute to the elevations in serum IGF-II and IGFBP-2. The (IGF-I + IGF-II)/IGFBP-3 molar ratios were remarkably constant in both healthy adults and acromegalics, but the relationships of the ligands individually with IGFBP-3 were not linear: as IGFBP-3 increased, IGF-I also increased whereas IGF-II initially increased but then decreased. IGFBP-2 did not correlate with IGF-II, but molar concentration significantly correlated with the IGF-II/IGFBP-3 molar ratio (r = 0.40; P = 0.001). CONCLUSIONS: Serum IGF-II and IGFBP-2 levels were paradoxically elevated in acromegalics, independent of the presence of colorectal neoplasia. The (IGF-I + IGF-II)/IGFBP-3 molar ratio appears to be pivotal in determining IGF-II values, which, in turn, expressed as a ratio of IGFBP-3, is related to IGFBP-2. These observations offer new insights into the regulation of these peptides.
AB - OBJECTIVE: Circulating insulin-like growth factor (IGF)-II and IGF binding protein-2 (IGFBP-2) are frequently altered, often in parallel, in numerous pathologies including neoplastic disease but little is known about their normal regulation. This study compared serum IGF-II and IGFBP-2 distributions between acromegalics and a large normal adult population to explore possible determinants. PATIENTS: Sixty acromegalic patients undergoing screening colonoscopy (age range 25-81 years); normative data from 306 healthy adults (age range 20-89 years). MEASUREMENTS: Serum IGF-I, IGF-II, IGFBP-2 and IGFBP-3 were measured in healthy adults and acromegalics. Mean growth hormone (GH) levels were obtained for acromegalic patients. Differences were compared using t-tests (unadjusted) and multiple regression models (adjusted for age and gender). Correlations were expressed as Pearson's coefficient (r). RESULTS: For acromegalic patients, GH was significantly correlated with IGF-I (r = 0.50; P <0.001) and IGFBP-3 (r = 0.29; P = 0.03) but not IGF-II or IGFBP-2. Contrary to expectations, mean IGF-II and IGFBP-2 levels were significantly raised in the acromegalics compared with normals [adjusted mean difference (95% CI) = 226 (181, 271) microg/l and 305 (200, 410) microg/l, respectively]. Ten acromegalic patients had colorectal neoplasia but their presence did not contribute to the elevations in serum IGF-II and IGFBP-2. The (IGF-I + IGF-II)/IGFBP-3 molar ratios were remarkably constant in both healthy adults and acromegalics, but the relationships of the ligands individually with IGFBP-3 were not linear: as IGFBP-3 increased, IGF-I also increased whereas IGF-II initially increased but then decreased. IGFBP-2 did not correlate with IGF-II, but molar concentration significantly correlated with the IGF-II/IGFBP-3 molar ratio (r = 0.40; P = 0.001). CONCLUSIONS: Serum IGF-II and IGFBP-2 levels were paradoxically elevated in acromegalics, independent of the presence of colorectal neoplasia. The (IGF-I + IGF-II)/IGFBP-3 molar ratio appears to be pivotal in determining IGF-II values, which, in turn, expressed as a ratio of IGFBP-3, is related to IGFBP-2. These observations offer new insights into the regulation of these peptides.
UR - http://www.scopus.com/inward/record.url?scp=0034797758&partnerID=8YFLogxK
U2 - 10.1046/j.1365-2265.2001.01380.x
DO - 10.1046/j.1365-2265.2001.01380.x
M3 - Article
C2 - 11678829
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
SN - 1365-2265
VL - 55
SP - 469
EP - 475
JO - Clinical Endocrinology
JF - Clinical Endocrinology
IS - 4
ER -