The role of somatostatin receptors in the medical treatment of acromegaly.
Somatostatin is a hypothalamic inhibitor of pituitary growth hormone secretion and cell proliferation, binding to five distinct receptor subtypes (sstr1-5). Since native somatostatin has a short half-life, somatostatin analogues with a longer half-life have been developed for therapeutic purposes. Octreotide and lanreotide are currently available for treatment of acromegaly, binding with high-affinity sstr2 and sstr5. Octreotide, the first somatostatin analogue used in the medical therapy of acromegaly, was initially given subcutaneously at doses of 100-500 microg three times daily. The introduction of new depot formulations, such as octreotide long-acting release, slow-release lanreotide and lanreotide-autogel, improved patients compliance of long-term therapy, overcoming the inconvenience of multiple daily administration. The treatment with somatostatin analogues induces biochemical control and tumour shrinkage in about 50-70% and 30-60% of patients with acromegaly, respectively. However, the efficacy of this therapy lies on an adequate expression of sstr2 and sstr5 on tumor cells. In the past, somatostatin receptor expression was tested in vivo by (111)In-diethylenetriaminepentaacetate-D-Phe-octreotide scintigraphy: this method has been abandoned since normal pituitary tissue can be visualised by (111)In-diethylenetriaminepentaacetate-D-Phe-octreotide scintigraphy. Currently, the somatostatin receptorial profile can be characterised by autoradiography, molecular biology techniques and immunohistochemistry on surgically removed tumor tissue. These methods may offer an individualised approach sparing patients from unnecessary treatment.
Vitale
G
G
Department of Molecular and Clinical Endocrinology, Federico II University of Naples, Via S. Pansini 5, 80131 Naples, Italy.
Pivonello
R
R
Ferone
D
D
De Martino
M C
MC
Auriemma
R S
RS
Caraglia
M
M
Abbruzzese
A
A
Lombardi
G
G
Colao
A
A
D000172:Acromegaly / Q000188:drug therapy*; D006801:Humans; D015282:Octreotide / Q000627:therapeutic use; D010456:Peptides, Cyclic / Q000627:therapeutic use; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000627:therapeutic use*
D010456:Peptides, Cyclic; C060347:lanreotide; D013004:Somatostatin; D015282:Octreotide