Disease activity in acromegaly may be assessed 6 weeks after discontinuation of pegvisomant.
AffiliationDepartment of Endocrinology, St Bartholomew's Hospital, London EC1A 7BE, UK. firstname.lastname@example.org
MetadataShow full item record
AbstractOBJECTIVE: Pegvisomant, a modified growth hormone (GH) molecule, is a novel medical therapy for acromegaly that functions as a GH receptor antagonist. Serum GH cannot be used as a marker of disease activity in patients taking this form of therapy, partly because GH levels rise on pegvisomant and partly because the drug cross-reacts with many routine GH assays. The purpose of this study was to assess the time for which it is necessary to discontinue pegvisomant prior to biochemical reassessment of acromegaly. DESIGN AND METHODS: This was a retrospective study of 13 patients (seven male, median age 61 years, range 43-77) enrolled in two separate, open-label studies of the efficacy and tolerability of pegvisomant in the treatment of acromegaly. All had been taking a stable dose of pegvisomant (median dose 15 mg daily, range 10-30) as monotherapy for at least 3 months before discontinuing the drug. After discontinuation of pegvisomant, serum IGF-I was measured at 0, 2, 4, 6 and 8 weeks in all patients. Serum GH (single sample) was measured in nine patients at 2, 4, 6 and 8 weeks, but not at baseline on account of the cross-reactivity of pegvisomant with the GH assay. RESULTS: Mean serum IGF-I rose from 210+/-105 ng/ml (S.D.) at baseline to 392+/-175 ng/ml at 2 weeks after discontinuation of pegvisomant (P < 0.0001). Although there was no statistically significant change in mean serum IGF-I beyond 2 weeks (412+/-181, 392+/-152 and 399+/-150ng/ml at 4, 6 and 8 weeks respectively; P = 0.13 (2 vs 4 weeks), 0.31 (4 vs 6 weeks) and 0.46 (6 vs 8 weeks), serum IGF-I rose by more than twice the interassay coefficient of variation (CV) in two of the 13 patients between weeks 2 and 4. The standard deviation of the difference in serum IGF-I between time points was calculated. The values declined from 118% (weeks 0-2) 17%, 19.7% and 10% (weeks 2-4, 4-6 and 6-8 respectively). The expected measure if there was no systematic change in base would be 15% (1.4 x interassay CV). Mean serum GH was virtually unchanged at 2-8 weeks after cessation of pegvisomant therapy. CONCLUSIONS: These results suggest that the activity of acromegaly may be assessed by serum IGF-I levels 6 weeks after the discontinuation of pegvisomant.
CitationDisease activity in acromegaly may be assessed 6 weeks after discontinuation of pegvisomant. 2005, 152 (1):47-51 Eur. J. Endocrinol.
JournalEuropean Journal of Endocrinology
- The effect of pegvisomant-induced serum IGF-I normalization on serum leptin levels in patients with acromegaly.
- Authors: Parkinson C, Whatmore AJ, Yates AP, Drake WM, Brabant G, Clayton PE, Trainer PJ
- Issue date: 2003 Aug
- Cardiovascular risk factors in acromegaly before and after normalization of serum IGF-I levels with the GH antagonist pegvisomant.
- Authors: Sesmilo G, Fairfield WP, Katznelson L, Pulaski K, Freda PU, Bonert V, Dimaraki E, Stavrou S, Vance ML, Hayden D, Klibanski A
- Issue date: 2002 Apr
- Additional metabolic effects of adding GH receptor antagonist to long-acting somatostatin analog in patients with active acromegaly.
- Authors: Jawiarczyk A, Kałuzny M, Bolanowski M, Bednarek-Tupikowska G
- Issue date: 2008 Aug
- Effective combination treatment with cabergoline and low-dose pegvisomant in active acromegaly: a prospective clinical trial.
- Authors: Higham CE, Atkinson AB, Aylwin S, Bidlingmaier M, Drake WM, Lewis A, Martin NM, Moyes V, Newell-Price J, Trainer PJ
- Issue date: 2012 Apr
- Efficacy of 12-month treatment with the GH receptor antagonist pegvisomant in patients with acromegaly resistant to long-term, high-dose somatostatin analog treatment: effect on IGF-I levels, tumor mass, hypertension and glucose tolerance.
- Authors: Colao A, Pivonello R, Auriemma RS, De Martino MC, Bidlingmaier M, Briganti F, Tortora F, Burman P, Kourides IA, Strasburger CJ, Lombardi G
- Issue date: 2006 Mar