Prof. S.M. Shalet, Department of Endocrinology, Christie Hospital NHS Trust, Wilmslow Road, Manchester M20 4BX, UK. Tel.: +161 4463667; Fax: +161 4463772;E-mail: [email protected]Andrew Renehan, Christopher Potten, Sarah O'Dwyer and Stephen Shalet initiated and designed the study. Andrew Renehan and Andrew Toogood were responsible for blood collection and generation of the normative reference data. The serum assays were performed by Jenny Jones. All investigators contributed to the writing of the paper.

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Abstract

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) µg/l and 305 (200, 410) µg/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.

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Volume55, Issue4

October 2001

Pages 469-475

Paradoxical elevations in serum IGF-II and IGF binding protein-2 in acromegaly: insights into the regulation of these peptides

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Paradoxical elevations in serum IGF-II and IGF binding protein-2 in acromegaly: insights into the regulation of these peptides

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