Harvey's Garden

Acromegaly

2 min read

Epidemiology

Etiology

Pathophysiology

Question

  • IGF-1 is produced primarily by the liver in response to Growth Hormone (GH) stimulation and mediates most of GH’s anabolic and growth-promoting effects.
  • Insulin-like growth factor is just a growth hormone, except
    • It binds to insulin receptor, but not metabolizing glucose, thus contributing to glucose intolerance?

  • Physiology of GH and IGF-1
    • GH secretion induced by stress, sport, and hypoglycemia; inhibited especially by hyperglycemia or food intake
    • Hypothalamus secretes GHRH → ↑ secretion of GH → GH induces IGF-1 synthesis → ↑ serum IGF-1 via liver synthesis which leads to the following effects:
      • Binding to IGF-1 and insulin receptors → stimulation of cell growth and proliferation, inhibiting programmed cell death
        • Proliferative effects especially on bone, cartilage, skeletal muscle, skin, soft tissue, and organs
        • Impaired glucose tolerance caused by binding to insulin receptors
      • ↑ Secretion of somatostatin from the hypothalamus → ↓ serum GH and IGF-1 (negative feedback)
  • Core Pathophysiology: A GH-secreting pituitary adenoma leads to ↑ Growth Hormone (GH), which stimulates the liver to produce excess IGF-1. This occurs after epiphyseal plate fusion.
  • Key Systemic Effects (Mediated by IGF-1):
    • Skeletal: Overgrowth of acral areas (hands, feet), prominent jaw (prognathism), and frontal bossing.
    • Metabolic: GH antagonizes insulin → insulin resistance, leading to hyperglycemia and secondary diabetes.
    • Cardiovascular: Cardiomyopathy and hypertension (HTN) are the leading causes of death.
    • Soft Tissue: Macroglossia (→ obstructive sleep apnea), carpal tunnel syndrome, and arthralgias.
  • Mass Effect of Adenoma:
    • Compression of the optic chiasm causes bitemporal hemianopsia.
    • Headaches and hypopituitarism are also common.

Clinical features

  • General Appearance:
    • Coarse facial features, frontal bossing.
    • Macrognathia (protruding jaw), malocclusion.
    • Macroglossia (enlarged tongue) → can cause obstructive sleep apnea.
    • Large hands and feet (pt reports ↑ ring or shoe size).
  • Skin & Soft Tissue:
    • Hyperhidrosis (excessive sweating).
    • Thick, oily skin; skin tags.
    • Carpal tunnel syndrome (due to soft tissue overgrowth).
  • Musculoskeletal:
    • Arthralgias and arthritis.
    • Proximal muscle weakness.
  • Cardiovascular (Most common cause of death):
    • Concentric hypertrophic cardiomyopathy.
    • Hypertension, heart failure.
  • Metabolic:
    • Insulin resistance → glucose intolerance or overt Diabetes Mellitus (GH is a counter-regulatory hormone).
  • Local Tumor Effects:
    • Headaches.
    • Bitemporal hemianopsia (compression of the optic chiasm).

Tip

Consider acromegaly in patients who report having had to increase hat, shoe, glove, and ring sizes in the past!

Diagnostics

Treatment

  • Surgery
    • Transsphenoidal adenomectomy (preferred method)
  • Medication
    • Somatostatin analogs (e.g., octreotide, lanreotide)
    • Dopamine agonists (e.g., cabergoline): reduce tumor size and GH secretion
    • GH receptor antagonists (e.g., pegvisomant)

Graph View

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