pegvisomant
Meaning of pegvisomant: It blocks the receptor rather than the hormone, so the hormone level in blood rises even as its effects on the body fall away.
Definition of pegvisomant
Pegvisomant is an injected drug for acromegaly, the disease of excess growth hormone in adults. It is a laboratory-altered copy of the hormone that latches onto the hormone's receptor without switching it on, and keeps the real hormone from doing so. Insulin-like growth factor 1, the messenger through which growth hormone acts on tissue, then falls toward normal.
How does a copy of a hormone block it?
The receptor only works in pairs. A molecule of growth hormone has two separate binding faces: it grips one receptor with the first, then reaches out and catches a second receptor with the other, and only when the two are drawn together does a signal travel inside the cell. Pegvisomant has been altered at both faces. Changes to the first make it grip harder than the natural hormone does, so it wins the site. A single change at the second face makes that face useless, so no partner receptor is recruited and the pair never forms. The receptor is occupied and silent, which is what makes the drug an antagonist rather than a substitute.
What is measured to judge it?
| Feature | Growth hormone | Pegvisomant |
|---|---|---|
| First binding face | Binds the receptor | Binds it more tightly |
| Second binding face | Recruits a partner receptor | Cannot, so no pair forms |
| Signal into the cell | Sent | Blocked |
| Effect on growth factor levels | Raises them | Lowers them |
Because nothing is done to the gland producing the hormone, output continues and measured hormone levels commonly rise during treatment. They also cannot be trusted, since the drug resembles the hormone closely enough to be picked up by some laboratory tests. Response is therefore followed by measuring insulin-like growth factor 1 instead, which reflects what the tissues are actually receiving.
What does it leave untouched?
The tumor. Acromegaly almost always arises from a benign pituitary growth, and this drug acts far downstream of it, at receptors all over the body, so the growth itself is unaffected and continues to be watched on scans. Attaching strands of polyethylene glycol to the protein is what makes a daily injection workable, since the bare molecule would be cleared within minutes. Rises in liver enzymes occur and are tracked. Blood sugar tends to fall, because growth hormone normally opposes insulin, so control of diabetes often shifts once treatment begins.
Also known as
Used in a sentence
Pegvisomant was started after surgery failed to normalize the growth factor level.
Good to know
The drug blocks the receptor rather than hormone production, so growth hormone measurements rise and are further distorted by the assay, and response is judged by insulin-like growth factor 1 while the pituitary tumor is followed separately.