Friday, December 18, 2009

Tumor Volume of Growth Hormone-Secreting Pituitary Adenomas during Treatment with Pegvisomant: A Prospective Multicenter Study

Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2009-1239
Jan-Hendrik Buhk*, Sabine Jung, Marios Nikos Psychogios, Sophia Göricke, Sabine Hartz, Susanne Schulz-Heise, Randolf Klingebiel, Michael Forsting, Hartmut Brückmann, Arnd Dörfler, Martina Jordan, Michael Buchfelder,  and Michael Knauth
Department of Neuroradiology (J.-H.B., S.J., M.N.P., M.K.), University of Goettingen, D-37075 Goettingen, Germany; Department of Diagnostic and Interventional Radiology (J.-H.B.), University of Hamburg, D-20246 Hamburg, Germany; Department of Diagnostic and Interventional Radiology (S.G., M.F.), University of Essen, D-45147 Essen, Germany; Department of Neuroradiology (S.H., H.B.), University of Munich, D-81377 Munich, Germany; Departments of Neuroradiology (S.S.-H., A.D.) and Neurosurgery (M.B.), University of Erlangen-Nuremberg, D-91054 Erlangen Germany; Department of Neuroradiology (R.K.), Charité, Free University of Berlin, D-10117 Berlin, Germany; and ClinSupport, Clinical Trials and Marketing Support (M.J.), Erlangen, Germany
* To whom correspondence should be addressed. E-mail:

Context: Clinical and biochemical remission in acromegaly can frequently be achieved with the recombinant GH receptor antagonist pegvisomant, even when other treatments fail. However, increases in tumor volume have been reported.
Objective: Because previous studies suffer from inhomogenous magnetic resonance imaging (MRI) protocols, this prospective study examined the long-term course of adenoma volume during pegvisomant therapy by standardized MRI.

Design: Five centers in Germany participated. High-resolution MRI was performed at baseline and 6, 12, and 24 months after enrollment.

Setting/Patients: Patients were outpatients, and pegvisomant is third-line therapy in most of the cases.

Main Outcome Measures: The primary end point was tumor volume at 24 month follow-up, measured by a single, double-blinded rater.

Results: Forty-five of 61 patients completed 24 months' follow-up (73.8%). Tumor volume increase greater than 25% during the study was observed in three of 61 patients (4.9%), all during the first year of enrollment. All three patients had had octreotide treatment before initiation of pegvisomant; none of them had had radiotherapy. All volumetric findings were comparable with clinical radiological interpretations. ANOVA revealed no significant change in tumor volume after 24 months (n = 45).

Conclusions: This study shows that pegvisomant therapy infrequently coincides with tumor growth during long-term treatment of acromegaly. Because all significant tumor volume increases occurred during the first year, these changes might correlate to the change of medication and thus be the result of a rebound from somatostatin-induced shrinkage.