Growth hormone insensitivity syndrome

Growth hormone insensitivity syndrome (GHIS), also known as Laron syndrome or primary growth hormone resistance, is a rare genetic disorder characterized by the body's inability to respond appropriately to growth hormone (GH) despite normal or elevated circulating GH levels. The condition was first described by Zvi Laron in 1966. It is most commonly caused by mutations in the growth hormone receptor (GHR) gene, leading to defective or absent GH receptors on target cells. This results in markedly reduced production of insulin-like growth factor 1 (IGF-1), the key mediator of GH's growth-promoting effects. The hallmark feature of GHIS is severe postnatal growth failure, resulting in proportionate short stature that is typically more pronounced than in classical growth hormone deficiency. Affected individuals often present with characteristic craniofacial features including a prominent forehead, depressed nasal bridge, and underdevelopment of the midface. Other clinical features may include delayed bone maturation, delayed puberty, truncal obesity, small genitalia in males, hypoglycemia (particularly in infancy and early childhood), thin hair, and a high-pitched voice. Serum GH levels are normal to elevated, while IGF-1 and IGF-binding protein 3 (IGFBP-3) levels are markedly low and fail to rise following exogenous GH administration, which is a key diagnostic criterion. Since patients with GHIS do not respond to exogenous growth hormone therapy, the primary treatment is recombinant human IGF-1 (rhIGF-1, mecasermin), which bypasses the defective GH receptor signaling pathway. Treatment with rhIGF-1 can improve linear growth velocity, although final adult height typically remains below normal. Careful monitoring for side effects of IGF-1 therapy, including hypoglycemia, tonsillar hypertrophy, and intracranial hypertension, is essential. Supportive management addressing metabolic complications and psychosocial support are also important components of care.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Growth hormone insensitivity syndrome