Rationale: Octreotide is known to shrink acromegalic tumours in vivo. However, the mechanism for this is unclear. To investigate the mechanism of shrinkage we used dynamic contrast enhanced MR imaging (DCE-MRI) to visualise the vascular components within the somatotroph adenomas.
Subjects & Methods: Six patients with confirmed acromegaly comprising 4 microadenomas (all male) and 2 macroadenomas (1 male, 1 female) were recruited. All patients were treated with 3 times daily subcutaneous octreotide for a 24-week period. Then all but one microadenoma were treated with monthly Sandostatin LAR for a further 24 weeks. All patients underwent growth hormone day curves at the beginning, 24 weeks and at 48 weeks. DCE-MRI was performed at 0, 24 and 48 weeks. The data was analysed using a two compartment model, providing an estimate of vascular permeability and contrast distribution volume. Study was approved by local ethics committee.
Results: All but one macroadenoma achieved a medical cure with a mean growth hormone of less than 5 mU/l at 24 and 48 weeks. In the microadenomas, tumour size decreased by 55% (at 24 weeks for the microadenoma that stopped treatment), 59%, 70% and 83% at 48 weeks. In the macroadenomas, tumour size decreased by 2% and 80% at 48 weeks. Mean maximal enhancement and gadolinium exchange rate, a measure of tumour vascularity, did not differ before and after octreotide treatment (ME 96±36 vs 117±28 respectively; ExCH 662±352 vs 420±393, respectively; P<0.05). Distribution volume, which is a measure of extracellular volume, increased significantly by 62% before and after octreotide therapy (95±58 vs 154±81, respectively, P<0.028).
Conclusion: The shrinkage of acromegalic tumours by octreotide is either due to a direct reduction in cell volume or a reduction in cell number, but not due to a reduction in tumour vascularity.
01 - 05 Apr 2006
European Society of Endocrinology