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

2.50
Hdl Handle:
http://hdl.handle.net/10541/84131
Title:
Paradoxical elevations in serum IGF-II and IGF binding protein-2 in acromegaly: insights into the regulation of these peptides.
Authors:
Renehan, Andrew G; Toogood, Andy; Ryder, W David J; Jones, Jenny; Potten, Christopher S; O'Dwyer, Sarah T; Shalet, Stephen M
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) 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.
Affiliation:
Department of Surgery, Christie Hospital NHS Trust, Manchester, UK. arenehan@picr.man.ac.uk
Citation:
Paradoxical elevations in serum IGF-II and IGF binding protein-2 in acromegaly: insights into the regulation of these peptides. 2001, 55 (4):469-75 Clin. Endocrinol. (Oxf)
Journal:
Clinical Endocrinology
Issue Date:
Oct-2001
URI:
http://hdl.handle.net/10541/84131
PubMed ID:
11678829
Type:
Article
Language:
en
ISSN:
0300-0664
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorRenehan, Andrew Gen
dc.contributor.authorToogood, Andyen
dc.contributor.authorRyder, W David Jen
dc.contributor.authorJones, Jennyen
dc.contributor.authorPotten, Christopher Sen
dc.contributor.authorO'Dwyer, Sarah Ten
dc.contributor.authorShalet, Stephen Men
dc.date.accessioned2009-10-13T10:02:50Z-
dc.date.available2009-10-13T10:02:50Z-
dc.date.issued2001-10-
dc.identifier.citationParadoxical elevations in serum IGF-II and IGF binding protein-2 in acromegaly: insights into the regulation of these peptides. 2001, 55 (4):469-75 Clin. Endocrinol. (Oxf)en
dc.identifier.issn0300-0664-
dc.identifier.pmid11678829-
dc.identifier.urihttp://hdl.handle.net/10541/84131-
dc.description.abstractOBJECTIVE: 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.en
dc.language.isoenen
dc.subjectColorectal Canceren
dc.subject.meshAcromegaly-
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAged, 80 and over-
dc.subject.meshAging-
dc.subject.meshCase-Control Studies-
dc.subject.meshColorectal Neoplasms-
dc.subject.meshHumans-
dc.subject.meshInsulin-Like Growth Factor Binding Protein 2-
dc.subject.meshInsulin-Like Growth Factor Binding Protein 3-
dc.subject.meshInsulin-Like Growth Factor I-
dc.subject.meshInsulin-Like Growth Factor II-
dc.subject.meshMiddle Aged-
dc.subject.meshRegression Analysis-
dc.titleParadoxical elevations in serum IGF-II and IGF binding protein-2 in acromegaly: insights into the regulation of these peptides.en
dc.typeArticleen
dc.contributor.departmentDepartment of Surgery, Christie Hospital NHS Trust, Manchester, UK. arenehan@picr.man.ac.uken
dc.identifier.journalClinical Endocrinologyen

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