Pathophysiology of GH Hypersecretion and IGF-1 Mediation

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Acromegaly is a chronic, progressive metabolic disorder primarily caused by the hypersecretion of Growth Hormone (GH) from the anterior pituitary gland. In over 95% of cases, this is due to a benign monoclonal pituitary adenoma—specifically a somatotroph adenoma. Unlike gigantism, which occurs before the closure of the epiphyseal plates in children, acromegaly occurs in adults and leads to the disproportionate growth of soft tissues and membranous bones.

The physiological hallmark of the disease is the dysregulation of the GH-IGF-1 axis. Under normal conditions, GH stimulates the liver to produce Insulin-like Growth Factor-1 (IGF-1), which mediates the majority of the growth-promoting effects of GH. In acromegaly, the negative feedback loop is disrupted, leading to tonically elevated IGF-1 levels. For a detailed analysis of the clinical and economic landscape of these hormonal therapies, the Acromegaly Market resource provides data on the prevalence and therapeutic trends within the somatostatin analog and GH-antagonist sectors. This chronic exposure results in multisystemic complications, including macroglossia (enlarged tongue), cardiomegaly, and skeletal changes like mandibular prognathism (protruding jaw).

Beyond skeletal growth, the excess GH induces significant metabolic changes, most notably insulin resistance. Approximately 50% of acromegalic patients develop impaired glucose tolerance or overt Type 2 diabetes. The disease is often insidious, with an average delay of 7 to 10 years between the onset of symptoms and formal diagnosis. This delay is dangerous, as untreated acromegaly is associated with a 2- to 3-fold increase in mortality, primarily from cardiovascular and respiratory failure.

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