Serum lipoprotein changes following IGF-I normalization using a growth hormone receptor antagonist in acromegaly.

2.50
Hdl Handle:
http://hdl.handle.net/10541/79978
Title:
Serum lipoprotein changes following IGF-I normalization using a growth hormone receptor antagonist in acromegaly.
Authors:
Parkinson, Craig; Drake, William M; Wieringa, Gilbert E; Yates, A P; Besser, G M; Trainer, Peter J
Abstract:
OBJECTIVE: Active acromegaly is associated with altered lipid metabolism. The purpose of this study was to investigate the effect of serum IGF-I normalization on serum lipoproteins and insulin, in patients with acromegaly receiving the GH receptor antagonist pegvisomant. PATIENTS: Twenty patients (9 male, mean age 58.7 years, range 28-79) with active acromegaly (baseline serum IGF-I > 130% the age-related upper limit of normal) received pegvisomant and achieved a normal serum IGF-I [585.2 +/- 54.3 (mean +/- SEM) to 169.2 +/- 13.9 ng/ml, P < 0.0001]. MEASUREMENTS: Total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, triglyceride (TG), apolipoprotein B (apo B), apolipoprotein A1 (apo A1), lipoprotein a [Lp(a)] and insulin were measured in a single batch analysis on samples obtained at baseline and the first occasion of serum IGF-I normalization. Low-density lipoprotein (LDL) was calculated using the Friedewald formula. Paired analysis was performed using Student's paired t-test and the Wilcoxon signed rank test. RESULTS: Normalization of serum IGF-I resulted in an increase in TC (5.0 +/- 0.3 to 5.7 +/- 0.4 mmol/l, P = 0.0068), an increase in LDL (3.0 +/- 0.25 to 3.7 +/- 0.31 mmol/l, P = 0.0093) and an increase in apo B (110.6 +/- 7.76 to 127.1 +/- 8.86 mg/l, P = 0.014). TC and LDL increased in all but four patients. Despite a significant fall in fasting insulin levels (9.9 to 8.3 mU/l, range 8.85-19.8 to 6.33-11.6, P < 0.001) and insulin resistance (2.7 to 1.9, range 1.2-10.4 to 1-6.2, P < 0.001), mean serum TG and HDL levels were unaffected by IGF-I normalization. The protein component of HDL, apo A1, increased (153 +/- 4 to 166.4 +/- 5.43 mg/l, P = 0.026) and Lp(a) declined (median 342 to 235 mg/l, range 60-1013 to 74-671), P = 0.0035). Baseline serum TC and LDL were below the age- and sex-matched mean population value but after normalization of serum IGF-I the distribution of serum TC and LDL values was similar to that of the general population. CONCLUSIONS: Active acromegaly is associated with lowered mean serum TC and LDL. Successful management using pegvisomant increases lowered baseline serum TC and LDL levels, restoring the distribution of values to that of the general population, and improves insulin resistance. These findings are consistent with the reported lipoprotein changes following GH administration to normal and GH-deficient individuals.
Affiliation:
Departments of Endocrinology, Christie Hospital, Wilmslow Road, Manchester, UK.
Citation:
Serum lipoprotein changes following IGF-I normalization using a growth hormone receptor antagonist in acromegaly. 2002, 56 (3):303-11 Clin. Endocrinol.
Journal:
Clinical Endocrinology
Issue Date:
Mar-2002
URI:
http://hdl.handle.net/10541/79978
DOI:
10.1046/j.1365-2265.2002.01460.x
PubMed ID:
11940041
Type:
Article
Language:
en
ISSN:
0300-0664
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorParkinson, Craig-
dc.contributor.authorDrake, William M-
dc.contributor.authorWieringa, Gilbert E-
dc.contributor.authorYates, A P-
dc.contributor.authorBesser, G M-
dc.contributor.authorTrainer, Peter J-
dc.date.accessioned2009-09-07T10:42:10Z-
dc.date.available2009-09-07T10:42:10Z-
dc.date.issued2002-03-
dc.identifier.citationSerum lipoprotein changes following IGF-I normalization using a growth hormone receptor antagonist in acromegaly. 2002, 56 (3):303-11 Clin. Endocrinol.en
dc.identifier.issn0300-0664-
dc.identifier.pmid11940041-
dc.identifier.doi10.1046/j.1365-2265.2002.01460.x-
dc.identifier.urihttp://hdl.handle.net/10541/79978-
dc.description.abstractOBJECTIVE: Active acromegaly is associated with altered lipid metabolism. The purpose of this study was to investigate the effect of serum IGF-I normalization on serum lipoproteins and insulin, in patients with acromegaly receiving the GH receptor antagonist pegvisomant. PATIENTS: Twenty patients (9 male, mean age 58.7 years, range 28-79) with active acromegaly (baseline serum IGF-I > 130% the age-related upper limit of normal) received pegvisomant and achieved a normal serum IGF-I [585.2 +/- 54.3 (mean +/- SEM) to 169.2 +/- 13.9 ng/ml, P < 0.0001]. MEASUREMENTS: Total cholesterol (TC), high-density lipoprotein (HDL) cholesterol, triglyceride (TG), apolipoprotein B (apo B), apolipoprotein A1 (apo A1), lipoprotein a [Lp(a)] and insulin were measured in a single batch analysis on samples obtained at baseline and the first occasion of serum IGF-I normalization. Low-density lipoprotein (LDL) was calculated using the Friedewald formula. Paired analysis was performed using Student's paired t-test and the Wilcoxon signed rank test. RESULTS: Normalization of serum IGF-I resulted in an increase in TC (5.0 +/- 0.3 to 5.7 +/- 0.4 mmol/l, P = 0.0068), an increase in LDL (3.0 +/- 0.25 to 3.7 +/- 0.31 mmol/l, P = 0.0093) and an increase in apo B (110.6 +/- 7.76 to 127.1 +/- 8.86 mg/l, P = 0.014). TC and LDL increased in all but four patients. Despite a significant fall in fasting insulin levels (9.9 to 8.3 mU/l, range 8.85-19.8 to 6.33-11.6, P < 0.001) and insulin resistance (2.7 to 1.9, range 1.2-10.4 to 1-6.2, P < 0.001), mean serum TG and HDL levels were unaffected by IGF-I normalization. The protein component of HDL, apo A1, increased (153 +/- 4 to 166.4 +/- 5.43 mg/l, P = 0.026) and Lp(a) declined (median 342 to 235 mg/l, range 60-1013 to 74-671), P = 0.0035). Baseline serum TC and LDL were below the age- and sex-matched mean population value but after normalization of serum IGF-I the distribution of serum TC and LDL values was similar to that of the general population. CONCLUSIONS: Active acromegaly is associated with lowered mean serum TC and LDL. Successful management using pegvisomant increases lowered baseline serum TC and LDL levels, restoring the distribution of values to that of the general population, and improves insulin resistance. These findings are consistent with the reported lipoprotein changes following GH administration to normal and GH-deficient individuals.en
dc.language.isoenen
dc.subject.meshAcromegaly-
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshCholesterol-
dc.subject.meshFemale-
dc.subject.meshFollow-Up Studies-
dc.subject.meshHuman Growth Hormone-
dc.subject.meshHumans-
dc.subject.meshInsulin-
dc.subject.meshInsulin Resistance-
dc.subject.meshInsulin-Like Growth Factor I-
dc.subject.meshLipoproteins-
dc.subject.meshLipoproteins, LDL-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshReceptors, Somatotropin-
dc.titleSerum lipoprotein changes following IGF-I normalization using a growth hormone receptor antagonist in acromegaly.en
dc.typeArticleen
dc.contributor.departmentDepartments of Endocrinology, Christie Hospital, Wilmslow Road, Manchester, UK.en
dc.identifier.journalClinical Endocrinologyen

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