Growth hormone (GH) exerts both direct and indirect effects. The indirect effects are mediated by IGF-1, which is produced primarily in the liver. A patient with Laron syndrome has elevated GH but low IGF-1 and short stature. The defect in Laron syndrome is:

• A Deficiency of GH-releasing hormone receptor causing failure of pituitary GH secretion
• B Activating mutation in SOCS proteins that constitutively suppress JAK-STAT signaling
• C Defect in IGF-1 receptor on target tissues causing resistance to IGF-1 effects
• D Loss-of-function mutation in the GH receptor, preventing JAK2-STAT5 signaling and IGF-1 transcription in hepatocytes ✓

Explanation

Laron syndrome (GH insensitivity syndrome) is caused by loss-of-function mutations in the GH receptor gene. GH cannot bind or signal through its receptor; in normal physiology, GH binding dimerizes the GH receptor and activates JAK2, which phosphorylates STAT5b, driving IGF-1 gene transcription in the liver. Without this signaling, IGF-1 synthesis is severely reduced despite high GH levels (due to lack of negative feedback). The clinical picture mimics GH deficiency (dwarfism, high fat-to-lean ratio) but is distinguished by elevated GH and failure to respond to exogenous GH injections.

Reference: Guyton & Hall, Textbook of Medical Physiology, 14th ed.

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Written and medically reviewed by the StethoPrep medical team.