Pegvisomant, known by its brand name Somavert, is a prescription medication designed for the treatment of acromegaly. It functions as a growth hormone receptor antagonist, a type of protein-based therapy for adults, aiming to normalize certain hormone levels in the body.
Medical Use for Acromegaly
Acromegaly is a rare medical condition characterized by elevated levels of growth hormone (GH) in the body. This excess GH typically originates from a non-cancerous tumor in the pituitary gland, located at the base of the brain.
In adults, prolonged high GH levels cause bones, cartilage, and other tissues to enlarge, leading to noticeable changes such as increased hand, foot, and facial features, including a more prominent jaw, brow, lips, and nose. These physical changes develop slowly, making early diagnosis challenging.
Growth hormone signals the liver to produce insulin-like growth factor 1 (IGF-1), which is the primary mediator of growth and tissue changes observed in acromegaly. Elevated IGF-1 levels also influence how the body processes blood glucose and fats, potentially leading to complications like type 2 diabetes and heart disease.
Pegvisomant is used to manage persistent acromegaly when other therapies, such as surgery, radiation, or somatostatin analogs, have not fully controlled the condition, or when IGF-1 levels remain high. It serves as an important option for patients whose condition is not adequately managed by initial treatments.
Mechanism of Action
Pegvisomant operates as a growth hormone (GH) receptor antagonist. Structurally, it is a modified version of human growth hormone, engineered to bind selectively to GH receptors found on cell surfaces. When pegvisomant occupies these receptor sites, it prevents the body’s own growth hormone from attaching and activating them. One way to understand this action is to imagine a lock (the GH receptor) that can be opened by a specific key (endogenous GH); pegvisomant acts like a key that fits into the lock but cannot turn it, thus preventing the actual key from entering and initiating a response.
This binding effectively interferes with the signal transduction pathways that normally occur when GH binds to its receptor, particularly blocking the dimerization of the growth hormone receptor. By doing so, pegvisomant prevents the liver from producing excessive amounts of Insulin-like Growth Factor 1 (IGF-1). Since IGF-1 is largely responsible for the symptoms of acromegaly, reducing its levels helps to control the disorder. Importantly, pegvisomant’s mechanism means it blocks the effects of GH, leading to decreased IGF-1, but it does not reduce the actual levels of growth hormone in the bloodstream; in fact, GH levels can sometimes increase while on this medication due to altered feedback mechanisms.
Administration and Monitoring
Pegvisomant is administered as a daily subcutaneous injection. Patients or their caregivers can be trained to perform these injections at home, typically in areas such as the thigh, buttocks, upper arm, or abdomen. It is important to rotate the injection site daily to help prevent skin reactions. The medication comes as a powder that must be mixed with a provided diluent before use, and the prepared solution should be injected within six hours of reconstitution.
Monitoring treatment with pegvisomant primarily focuses on blood tests for Insulin-like Growth Factor 1 (IGF-1) levels. The goal is to normalize IGF-1 concentrations to an age-adjusted normal range, as this indicates the drug is effectively blocking the effects of growth hormone.
Blood tests for IGF-1 are typically performed 4 to 6 weeks after starting treatment and after any dose adjustments, then every 3 to 6 months once levels are stable. Monitoring growth hormone (GH) levels is not useful for assessing pegvisomant’s effectiveness, because the drug’s action can cause GH levels to rise, making standard GH assays unreliable. Liver function enzymes (such as ALT and AST) are also regularly monitored due to potential liver-related side effects.
Potential Side Effects and Safety Considerations
Like all medications, pegvisomant can cause side effects. Common ones include injection site reactions like redness, pain, swelling, or itching. Other frequently reported side effects include pain, nausea, diarrhea, flu-like symptoms, headaches, and fatigue. Swelling in the face, arms, hands, lower legs, or feet has also been noted.
A significant safety consideration is the potential for liver enzyme elevations, which can indicate liver inflammation or damage. Regular liver function tests (including serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin) are performed before starting treatment and periodically throughout therapy. If liver enzyme levels become significantly elevated, especially if they are five times the upper limit of normal or associated with increased bilirubin, pegvisomant treatment may need to be discontinued.
There is also a theoretical concern that because pegvisomant blocks the effects of GH but does not reduce its secretion, the growth hormone-secreting pituitary tumor might increase in size. Therefore, periodic magnetic resonance imaging (MRI) scans of the pituitary gland are recommended to monitor the tumor for any growth.