Pegvisomant interference in GH assays results in underestimation of GH levels.

2.50
Hdl Handle:
http://hdl.handle.net/10541/70196
Title:
Pegvisomant interference in GH assays results in underestimation of GH levels.
Authors:
Paisley, Angela N; Hayden, K; Ellis, A; Anderson, John; Wieringa, Gilbert E; Trainer, Peter J
Abstract:
INTRODUCTION: Pegvisomant use in acromegaly negates the use of GH levels to monitor disease activity. To achieve antagonism, plasma concentrations must be approximately 1000-fold greater than GH which with the high homology between the peptides makes GH measurement a challenge when pegvisomant is present. OBJECTIVE: We investigated the effect of pegvisomant on GH measured using commercially available assays. METHODS: Pooled serum samples with GH concentrations <0.38, 3.85 and 7.69 microg/l were spiked with increasing pegvisomant concentrations (9000-494 000 microg/l). Samples were analysed by the Nichols Advantage, DPC Immulite 2000, Diasorin IRMA, Beckman Access Dxl, Tosoh AIA and Wallac Delfia assays. RESULTS: With baseline GH <0.38 microg/l measured levels were <0.38 in all assays except Nichols, Diasorin and Beckman where GH peaked at 1.5, 9.6 and 17.7 micarog/l respectively at low pegvisomant concentrations, falling thereafter. With the other two samples, measured GH levels progressively fell with increasing pegvisomant concentrations, except the Beckman assay where an increase (30.8 microg/l) was seen at a pegvisomant concentration of 9000 microg/l; and Diasorin and Tosoh where smaller increases were seen at lower pegvisomant concentrations, levels gradually falling thereafter. CONCLUSION: The presence of pegvisomant resulted in artefactually low measured GH in most assays. We speculate this fall is due to assay antibody-binding pegvisomant, reducing the amount of available antibody to bind actual GH thereby producing less sandwich formation: the 'high-dose hook' effect. In most assays, this effect is modest and results in lower GH, but the level of interference makes them unsuitable for studies on the influence of pegvisomant on GH neuroregulation.
Affiliation:
Department of Endocrinology, Christie NHS Trust, Wilmslow Road, Withington, Manchester M20 4BX, UK.
Citation:
Pegvisomant interference in GH assays results in underestimation of GH levels. 2007, 156 (3):315-9 Eur. J. Endocrinol.
Journal:
European Journal of Endocrinology
Issue Date:
Mar-2007
URI:
http://hdl.handle.net/10541/70196
DOI:
10.1530/eje.1.02341
PubMed ID:
17322491
Type:
Article
Language:
en
ISSN:
0804-4643
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorPaisley, Angela N-
dc.contributor.authorHayden, K-
dc.contributor.authorEllis, A-
dc.contributor.authorAnderson, John-
dc.contributor.authorWieringa, Gilbert E-
dc.contributor.authorTrainer, Peter J-
dc.date.accessioned2009-06-11T13:21:03Z-
dc.date.available2009-06-11T13:21:03Z-
dc.date.issued2007-03-
dc.identifier.citationPegvisomant interference in GH assays results in underestimation of GH levels. 2007, 156 (3):315-9 Eur. J. Endocrinol.en
dc.identifier.issn0804-4643-
dc.identifier.pmid17322491-
dc.identifier.doi10.1530/eje.1.02341-
dc.identifier.urihttp://hdl.handle.net/10541/70196-
dc.description.abstractINTRODUCTION: Pegvisomant use in acromegaly negates the use of GH levels to monitor disease activity. To achieve antagonism, plasma concentrations must be approximately 1000-fold greater than GH which with the high homology between the peptides makes GH measurement a challenge when pegvisomant is present. OBJECTIVE: We investigated the effect of pegvisomant on GH measured using commercially available assays. METHODS: Pooled serum samples with GH concentrations <0.38, 3.85 and 7.69 microg/l were spiked with increasing pegvisomant concentrations (9000-494 000 microg/l). Samples were analysed by the Nichols Advantage, DPC Immulite 2000, Diasorin IRMA, Beckman Access Dxl, Tosoh AIA and Wallac Delfia assays. RESULTS: With baseline GH <0.38 microg/l measured levels were <0.38 in all assays except Nichols, Diasorin and Beckman where GH peaked at 1.5, 9.6 and 17.7 micarog/l respectively at low pegvisomant concentrations, falling thereafter. With the other two samples, measured GH levels progressively fell with increasing pegvisomant concentrations, except the Beckman assay where an increase (30.8 microg/l) was seen at a pegvisomant concentration of 9000 microg/l; and Diasorin and Tosoh where smaller increases were seen at lower pegvisomant concentrations, levels gradually falling thereafter. CONCLUSION: The presence of pegvisomant resulted in artefactually low measured GH in most assays. We speculate this fall is due to assay antibody-binding pegvisomant, reducing the amount of available antibody to bind actual GH thereby producing less sandwich formation: the 'high-dose hook' effect. In most assays, this effect is modest and results in lower GH, but the level of interference makes them unsuitable for studies on the influence of pegvisomant on GH neuroregulation.en
dc.language.isoenen
dc.subject.meshHuman Growth Hormone-
dc.subject.meshHumans-
dc.subject.meshImmunoassay-
dc.subject.meshReproducibility of Results-
dc.titlePegvisomant interference in GH assays results in underestimation of GH levels.en
dc.typeArticleen
dc.contributor.departmentDepartment of Endocrinology, Christie NHS Trust, Wilmslow Road, Withington, Manchester M20 4BX, UK.en
dc.identifier.journalEuropean Journal of Endocrinologyen

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