Endocrine Abstracts (2002) 3 P200

Disease activity in acromegaly may be assessed four weeks after discontinuation of pegvisomant

WM Drake1, RA Loureiro1, C Parkinson2, M Roberts2, SA Akker1, JP Monson1, GM Besser1 & PJ Trainer2


1Department of Endocrinology, St Bartholomew's Hospital, W Smithfield, London, UK; 2Department of Endocrinology, Christie Hospital, Manchester, UK.


Patients with acromegaly treated with medical therapy intermittently discontinue therapy to allow assessment of underlying disease activity. This is particularly so in patients treated with pituitary irradiation. Typical 'washout' times include 5 weeks for bromocriptine and 2 weeks for short-acting sc octreotide; longer periods are required for cabergoline and slow-release somatostatin analogues. Pegvisomant is a novel medical therapy for acromegaly that functions as a GH receptor antagonist. Hence, serum GH cannot be used as a marker of disease activity in patients taking pegvisomant; GH levels rise on pegvisomant and the drug cross-reacts with most GH assays. This study assessed the time for which it is necessary to discontinue pegvisomant prior to biochemical assessment of acromegaly in patients treated with this drug. The 15 patients (8 male, median age 60, range 43-77) were involved in two separate open-label studies of the efficacy of pegvisomant in the treatment of acromegaly. All had been taking a stable dose of pegvisomant (median dose 15mg daily, range 10-30) as monotherapy for >3 months prior to discontinuing the drug. Following discontinuation of pegvisomant, serum IGF-I and GH (single sample) were measured by RIA at 0, 2, 4, 6 and 8 weeks. Mean serum IGF-I rose from 177+/-102 ng/ml (SD) at baseline to 360+/-175 ng/ml two weeks after discontinuation (Student's t test p<0.0001). Although there was no statistically significant change in between 2 and 4 weeks (331+/-179 vs 360+/-175, p=0.26) serum IGF-I rose in 9 of the 15 patients. Serum IGF-I levels were virtually identical at 4, 6 and 8 weeks (360+/-175 vs 340+/-151 vs 341+/-147 ng/ml). In the six patients for whom GH data were available, mean serum GH fell slightly from a mean of 19.5+/-17.8 mU/L (SD) to 14.8+/-10 mU/L (p=NS); No change in mean serum GH was noted thereafter. These results indicate that the activity of acromegaly using serum IGF-I levels may be assessed four weeks after discontinuation of pegvisomant.

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