Medical therapy of acromegaly: efficacy and safety of somatostatin analogues.
Acromegaly is a chronic disease with signs and symptoms due to growth hormone (GH) excess. The most frequent cause of acromegaly is a GH-producing pituitary adenoma. Chronic GH excess is accompanied by long-term complications of the locomotor (arthrosis) and cardiovascular (atherosclerosis, cardiomyopathy) systems and is, when untreated, associated with an increased mortality. The aim of treatment of acromegaly is to improve symptoms, to achieve local tumour mass control, and to decrease morbidity and mortality. Treatment options include surgery, medical therapy and radiotherapy. Transsphenoidal surgery is the first choice of treatment when a definitive cure can be achieved, particularly in the case of microadenomas and when decompression of surrounding structures (optic chiasm, ophthalmic motor nerves) is indicated. Primary medical therapy has been increasingly applied in recent years, especially when a priori chances of surgical cure are low (because of adenoma size and localization) and in patients with advanced age and/or serious co-morbidity. In addition, preoperative primary medical therapy may result in tumour shrinkage, facilitating tumour resection, and may reduce perioperative complications due to GH excess. Within the spectrum of medical therapy, long-acting somatostatin analogues (somatostatins) are considered as first-line treatment. Treatment with somatostatin analogues results in GH control in approximately 60% of patients. In addition, somatostatin analogues induce tumour shrinkage in 30-50% of patients, particularly when applied as primary therapy. Prolonged treatment with somatostatin analogues appears to be safe and is usually well tolerated. The currently available somatostatin analogues, octreotide and lanreotide, seem to be equally effective; however, this should still be evaluated in prospective, randomized trials evaluating efficacy with respect to GH control and tumour shrinkage. In patients with an insufficient clinical and biochemical response to somatostatin analogues, combination therapy with dopamine receptor agonists or the GH receptor antagonist pegvisomant usually leads to disease control. New developments in the medical therapy of acromegaly include the universal somatostatin receptor agonist pasireotide, which has a broader affinity for all somatostatin receptor (sst) subtypes compared with the currently available somatostatin analogues with preferential affinity for the sst2 receptor, and chimeric compounds that interact with both somatostatin and dopamine receptors with synergizing effects on GH secretion.
Department of Internal Medicine, Section of Endocrinology, Erasmus Medical Center, Rotterdam, The Netherlands. r.feelders@erasmusmc.nl
Richard A
RA
Feelders
Leo J
LJ
Hofland
Maarten O
MO
van Aken
Sebastian J
SJ
Neggers
Steven W J
SW
Lamberts
Wouter W
WW
de Herder
Aart-Jan
AJ
van der Lely
D000172:Acromegaly / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D000236:Adenoma / Q000150:complications; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000150:complications; D019382:Human Growth Hormone / Q000378:metabolism; D006801:Humans; D008297:Male; D015282:Octreotide / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D010456:Peptides, Cyclic / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D017481:Receptors, Somatostatin / Q000187:drug effects* / Q000378:metabolism; D013004:Somatostatin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
D000970:Antineoplastic Agents; D010456:Peptides, Cyclic; D017481:Receptors, Somatostatin; C060347:lanreotide; D019382:Human Growth Hormone; D013004:Somatostatin; D015282:Octreotide