The effects of somatostatin analogue therapy on pituitary tumor volume in patients with acromegaly

Abstract

Introduction: In nearly all cases, acromegaly is caused by excess GH from a pituitary adenoma, resulting in elevated circulating levels of GH and, subsequently, IGF-1. Treatment goals are to eliminate morbidity and restore the increased mortality to normal rates. Therapeutic strategies aim to minimize tumor mass and normalize GH and IGF-1 levels. Somatostatin analogues are the medical treatment of choice in acromegaly, as first-line or post-surgical therapy, and have proven efficacy in pituitary tumor volume reduction (TVR).

Methods: Here we review the effects of somatostatin analogue therapy on pituitary tumor volume in patients with acromegaly.

Results: TVR with somatostatin analogues may be mediated by direct anti-proliferative effects via activation of somatostatin receptors, or by indirect effects, such as angiogenesis inhibition, and is more pronounced when they are administered as first-line therapy. Various studies of first-line treatment with octreotide LAR have shown significant TVR in ≥73% of patients. First-line treatment with lanreotide Autogel has shown evidence of TVR, although more studies are needed. In a recent randomized, double-blind, 12-month trial in 358 medical-treatment-naïve acromegaly patients, significant TVR was achieved by 81% of patients administered pasireotide LAR and 77% administered octreotide LAR. Pre-operative somatostatin analogue therapy may also induce TVR and improve post-operative disease control compared with surgery alone. TVR is progressive with prolonged treatment, and decreased IGF-1 levels may be its best predictor, followed by age and degree of GH decrease. However, TVR does not always correlate with degree of biochemical control.

Conclusion: Somatostatin analogues (first- or second-line treatment) are the mainstay of medical therapy and, as first-line medical therapy, are associated with significant pituitary TVR in most patients.

Keywords: Acromegaly; Lanreotide; Octreotide; Pasireotide; Somatostatin analogue; Tumor volume.

Fig. 1

Tumor size before and during first-line octreotide LAR treatment, evaluated in the whole series and according to tumor type [50]. Republished with permission of The Endocrine Society, from Cozzi et al. [50]; permission conveyed through Copyright Clearance Center, Inc. *P < 0.05

Fig. 2

Progressive tumor volume changes with octreotide LAR in a women and b men. The inset graphs indicate percentage tumor volume reduction on a yearly basis and total volume change after 5 years [55]. Republished with permission of The Endocrine Society, from Colao et al. [55]; permission conveyed through Copyright Clearance Center, Inc.