Growth hormone and analogs

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GH Physiology - The Body's Blueprint

  • Source & Regulation: Secreted in pulses by anterior pituitary somatotrophs, peaking during deep sleep.
    • Stimulated by: GHRH, ghrelin, hypoglycemia, exercise.
    • Inhibited by: Somatostatin, IGF-1 (negative feedback), hyperglycemia.
  • Mechanism & Effects:
    • Direct: ↑ Lipolysis, ↑ insulin resistance (diabetogenic effect).
    • Indirect: Primarily via IGF-1 (Somatomedin C) from the liver, promoting linear bone growth and protein synthesis.

Hypothalamic-pituitary-GH-IGF-1 axis with feedback loops

⭐ GH has a diabetogenic effect; it decreases glucose uptake and utilization, which can unmask latent Type 2 diabetes in adults with GH-secreting tumors (acromegaly).

GH Agonists - Boosting the Build

  • Somatropin (Recombinant hGH)

    • MoA: Activates GH receptors, stimulating linear growth, protein synthesis, and ↑ insulin-like growth factor-1 (IGF-1).
    • Uses: GH deficiency (pediatric/adult), Turner syndrome, Prader-Willi syndrome, idiopathic short stature.
    • AEs: Hyperglycemia, edema, arthralgia, myalgia, slipped capital femoral epiphysis (SCFE) in children.
  • Mecasermin (Recombinant IGF-1)

    • MoA: IGF-1 receptor agonist; bypasses the GH receptor.
    • AEs: Hypoglycemia (must administer with food), injection site reactions.

⭐ Use Mecasermin for Laron syndrome (GH insensitivity), where GH levels are high but IGF-1 is low, rendering Somatropin ineffective.

GH Antagonists - Hitting the Brakes

  • Somatostatin Analogs (e.g., Octreotide, Lanreotide)

    • Mechanism: Mimic natural somatostatin, inhibiting GH secretion from pituitary adenomas.
    • Use: First-line for acromegaly; also for carcinoid syndrome, gastrinomas.
    • Adverse Effects: GI upset, cholelithiasis (gallstones), bradycardia, vitamin B12 deficiency (long-term).
    • 📌 Mnemonic: "OCTO-"pus grabs the pituitary to stop GH.
  • GH Receptor Antagonist (Pegvisomant)

    • Mechanism: Binds to GH receptors, preventing downstream signaling and ↓ IGF-1 production.
    • Use: Acromegaly refractory to somatostatin analogs.
    • Adverse Effects: Elevated liver function tests (LFTs) - requires monitoring.

Exam Favorite: Pegvisomant blocks the GH receptor, leading to decreased IGF-1. This drop in IGF-1 removes negative feedback on the pituitary, paradoxically causing an increase in circulating GH levels.

  • Somatropin (recombinant GH) treats GH deficiency and Turner syndrome by stimulating hepatic IGF-1 production via JAK-STAT signaling.
  • Key side effects include hyperglycemia, scoliosis, and edema.
  • Mecasermin (recombinant IGF-1) is used for Laron syndrome (GH insensitivity).
  • Octreotide, a somatostatin analog, treats acromegaly and carcinoid tumors.
  • Pegvisomant, a GH receptor antagonist, is reserved for refractory acromegaly.

Practice Questions: Growth hormone and analogs

Test your understanding with these related questions

An investigator is studying a drug that acts on a G protein-coupled receptor in the pituitary gland. Binding of the drug to this receptor leads to increased production of inositol triphosphate (IP3) in the basophilic cells of the anterior pituitary. Administration of this drug every 90 minutes is most likely to be beneficial in the treatment of which of the following conditions?

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Flashcards: Growth hormone and analogs

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Octreotide may cause _____ side effects

TAP TO REVEAL ANSWER

Octreotide may cause _____ side effects

GI

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