Which of the following best describes the mechanism of action of pegvisomant in acromegaly?
- A GH receptor antagonist that blocks GH signal transduction ✓
- B Somatostatin analogue that inhibits GH secretion from somatotrophs
- C Dopamine agonist that reduces GH release
- D IGF-1 receptor antibody reducing peripheral effect of GH
Correct answer: A. GH receptor antagonist that blocks GH signal transduction
Explanation
Pegvisomant is a genetically engineered GH receptor antagonist — it binds the GH receptor but does not activate it, thus blocking dimerization and JAK2/STAT5 signal transduction, preventing IGF-1 production. Unlike somatostatin analogues (octreotide, lanreotide) which reduce GH secretion, pegvisomant acts peripherally and can normalize IGF-1 in >90% of patients resistant to somatostatin analogues. Serum GH levels paradoxically rise due to loss of IGF-1 feedback, so IGF-1 (not GH) is used for monitoring.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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