Growth hormone and analogs

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.

⭐ 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.