In this section, you will find information about:
Acromegaly Epidemiology
Acromegaly is a rare disease with a prevalence of 50 to 70 cases per million and an incidence of 3 to 4 new cases per million annually1. Diagnosis generally occurs 10 to 15 years after the onset of pathological growth hormone (GH) secretion1.
The Pathophysiology of Acromegaly
The somatic growth and metabolic dysfunction associated with acromegaly result from excess secretion of GH and subsequent elevation of circulating and locally produced insulin-like growth factor-1 (IGF-1). In healthy individuals, GH secretion is under the dual regulation of growth hormone-releasing hormone (GHRH) and somatostatin, with variations in the secretion of somatostatin being the primary mode of regulation2.
The interaction of GHRH and somatostatin, as well as fluctuations in levels of somatostatin, regulate GH secretion3. Hypersecretion of GH and IGF-1 may be caused by4:
- Primarily, GH-secreting adenoma(s) of the pituitary resulting from clonal expansion of a single mutated cell
- Rarely, GHRH- and GH-secreting neoplasms such as gangliocytomas of the hypothalamus and carcinoid tumors
GH-secreting tumors have a large number of receptors for somatostatin5 and, thus, are frequently responsive to therapy with analogues of somatostatin such as Sandostatin® LAR Depot (octreotide acetate for injectable suspension).
GH, growth hormone; GHRH, growth hormone-releasing hormone; IGF-1, insulin-like growth factor-1; SRIF, somatotropin-releasing inhibitory factor. Adapted with permission from Melmed2.
The Role of GH and IGF-1
Rather than stimulating growth directly, GH induces the release of IGF-1, which promotes DNA, RNA, and protein synthesis, as well as cell and tissue growth6. GH, or somatotropin, is responsible for the growth of almost all cells and tissues. GH activity encompasses both of the following:
Direct effects (anti-insulin effects) such as increased lipolysis and increased glucose mobilization. The direct growth promoting actions of GH include2,3,6:
- Induction of insulin resistance in peripheral tissues
- Hyperinsulinism
- Lipolysis
- Ketogenesis
- Hyperglycemia
- Sodium and water retention
Indirect effects (insulin-like effects) result from GH stimulation of IGF-1 production, causing effects such as growth of skeletal muscle, connective tissue, soft tissue, and bone-epiphyseal cartilage. Indirect growth-promoting actions of GH are mediated by the induction of growth factors, or somatomedins, the most important of which is somatomedin-C, or IGF-1. IGF-1 is produced by cells primarily in the liver, but also is present in the kidney, pituitary gland, GI tract, muscle, and cartilage2,6. Like insulin, the indirect IGF-1 dependent growth-promoting actions of GH include3,6:
- Induction of protein synthesis
- Amino acid transportation
- Muscle mass, cartilage, and bone growth
- DNA and RNA synthesis
- Cell proliferation
Clinical Aspects of Acromegaly
Structural Changes
The structural changes that occur with acromegaly cause chronic pain. These changes include1:
- Skeletal overgrowth deformities, particularly of the hands, feet, and face
- Cardiovascular disease (hypertension, enlarged heart)
- Arthropathy
- Neuropathy
- Respiratory obstruction
In addition to magnetic resonance imaging (MRI) or computed tomography (CT) imaging, somatostatin receptor scintigraphy (SRS) may be used to obtain images of pituitary adenomas. In this procedure, radiolabeled octreotide is injected into the systemic circulation. Since pituitary adenomas frequently contain elevated numbers of somatostatin receptors, the radioactive octreotide binds to these receptors and can be detected subsequently as bright spots in the resulting images7,8.
Physiologic and Morphologic Changes
Specific signs and symptoms of the disease can include6:
Changes in Appearance with Acromegaly
Cardiovascular System and Acromegaly
The cardiovascular system is particularly affected in acromegaly. Acromegalic cardiomyopathy seems to be correlated with the duration of disease, with a constellation of different abnormalities occurring9.
Acromegalic cardiomyopathy develops during the disease from the early to the advanced stage. The different abnormalities may be recognized using appropriate cardiological investigations.
Adapted from Lombardi et al.9
Important Safety Information
Carcinoid Syndrome:
Sandostatin® LAR Depot (octreotide acetate for injectable suspension) is indicated for long-term treatment of the severe diarrhea and flushing episodes associated with metastatic carcinoid tumors and for the long-term treatment of the profuse watery diarrhea associated with VIP-secreting tumors in patients in whom initial treatment with immediate release Sandostatin® (octreotide acetate) Injection has been shown to be effective and tolerated.
Important Safety Information:
As with immediate release Sandostatin® Injection, the most frequently reported drug-related adverse events were biliary disorders (62%), gastrointestinal disorders (14% to 38%), and injection-site pain (20% to 50%). Hypoglycemia (4%), hyperglycemia (27%), sinus bradycardia (19%), conduction abnormalities (9%), and arrhythmias (3%) have been reported.
The controlled clinical trials that support the marketing clearance for Sandostatin® LAR Depot did not include determination of effect on tumor size or rate of growth. Sandostatin® LAR Depot is not indicated for tumor shrinkage.
Acromegaly
Sandostatin® LAR Depot (octreotide acetate for injectable suspension) is indicated for long-term maintenance therapy in acromegalic patients who have had an inadequate response to surgery and/or radiotherapy, or for whom surgery and/or radiotherapy is not an option. The goal of treatment in acromegaly is to reduce GH and IGF-1 levels to normal.
Important Safety Information:
As with immediate release Sandostatin® Injection, the most frequently reported drug-related adverse events were biliary disorders (52%), gastrointestinal disorders (7% to 36%), and injection-site pain (2% to 11%). Hypoglycemia (2%), hyperglycemia (15%), and hypothyroidism (2%) have been reported. While not measured in acromegalic patients receiving Sandostatin® LAR Depot, ECG changes have been reported in patients receiving immediate release Sandostatin® Injection; the degree to which these abnormalities are related to octreotide acetate is not clear, as many acromegalics have cardiovascular disease. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.



