A middle-aged male patient presents with protrusion of the chin, excessive sweating, impaired glucose tolerance, and enlargement of hands and feet. Which of the following is a growth hormone receptor antagonist used to treat this condition?

Correct Answer: B. Pegvisomant

The clinical presentation—protrusion of chin (prognathism), excessive sweating, impaired glucose tolerance, and acromegaly (enlargement of hands and feet)—is pathognomonic for acromegaly, caused by excessive growth hormone (GH) secretion, typically from a pituitary adenoma. The question specifically asks for a GH receptor antagonist. Pegvisomant is a genetically engineered GH analog that binds competitively to GH receptors on target tissues (liver, muscle, adipose tissue) but does not activate them, thereby blocking the peripheral effects of GH. Unlike somatostatin analogs (octreotide, lanreotide) which suppress GH secretion at the pituitary level, pegvisomant works downstream at the receptor level. This mechanism makes it uniquely effective in patients with acromegaly who are resistant to or intolerant of somatostatin analogs or dopamine agonists. In Indian clinical practice, pegvisomant is reserved for refractory cases due to cost, but it remains the only true GH receptor antagonist available. The drug normalizes IGF-1 levels and improves symptoms without reducing GH levels themselves—a key discriminator from other agents.

Why the other options are wrong

A. Octreotide — Octreotide is a somatostatin analog that suppresses GH secretion at the pituitary level, not a GH receptor antagonist. While it is a first-line agent for acromegaly in India (per RNTCP guidelines and common practice), it works upstream by inhibiting GH release, not by blocking GH receptors. The question explicitly asks for a receptor antagonist, making this a common trap for students who confuse mechanism of action. C. Olcegepant — Olcegepant is a calcitonin gene-related peptide (CGRP) receptor antagonist used for acute migraine treatment, not acromegaly. This is an NBE distractor that exploits students' unfamiliarity with newer drug classes. It has no role in GH or acromegaly management and is unrelated to the endocrine axis. D. Cabergoline — Cabergoline is a dopamine D2 agonist used as a second-line agent in acromegaly (especially in prolactin-secreting adenomas with acromegaly), but it is not a GH receptor antagonist. It works by suppressing GH secretion indirectly through dopamine pathways, not by blocking GH receptors. This is a trap for students who know dopamine agonists are used in pituitary disorders but confuse their mechanism.

High-Yield Facts

Mnemonics

GH Receptor Antagonist = PEG PEGvisomant = Peripheral Effects GH blocker. Blocks GH receptors on target tissues (liver, muscle, fat), not pituitary GH release. Use this when you see 'receptor antagonist' in acromegaly questions. Acromegaly Drug Mechanisms (SODA) Somatostatin (suppress GH release) | Octreotide (suppress GH release) | Dopamine agonist (suppress GH indirectly) | Antagonist = Pegvisomant (block GH-R). Helps distinguish mechanism when multiple acromegaly drugs appear.

NBE Trap

NBE pairs pegvisomant with octreotide and cabergoline (all acromegaly drugs) to trap students who know these agents treat acromegaly but confuse their mechanisms—somatostatin analogs and dopamine agonists suppress GH secretion, while pegvisomant alone blocks GH receptor signaling.

Clinical Pearl

In Indian tertiary centers, pegvisomant is increasingly used in patients with acromegaly who fail surgery and are intolerant to somatostatin analogs (e.g., due to gallstones or GI side effects). Its unique advantage is that it normalizes IGF-1 and clinical symptoms without suppressing GH—a critical distinction when counseling patients about treatment goals.

_Reference: KD Tripathi Pharmacology Ch. 31 (Endocrine Pharmacology); Harrison Ch. 375 (Acromegaly and Growth Hormone Excess)_