Epidemiology

---

Etiology

---

• Benign growth hormone-secreting pituitary adenoma (> 95% of cases)

Pathophysiology

---

Question

• 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)
• Effects of a pituitary adenoma
  • Overproduction of GH → abnormally high serum IGF-1 levels → overstimulation of cell growth and proliferation → symptoms of acromegaly
  • Impaired secretion of other pituitary hormones, especially gonadotropins → ↓ LH and FSH → ↓ estrogen and testosterone

Clinical features

---

• Tumor mass effects
  • Headache, vision loss (bitemporal hemianopsia), cranial nerve palsies
  • ♂: Erectile dysfunction, decreased libido
• Soft tissue effects
  • Doughy skin texture, hyperhidrosis
    • Caused by enlarged sweat glands
  • Deepening of the voice, macroglossia with fissures, obstructive sleep apnea
    • Caused by enlargement of larynx and pharynx in addition to macroglossia
• Skeletal effects
  • Coarsening of facial features slowly progressing with age: enlarged nose, forehead, and jaw (macrognathia) with diastema
  • Widened hands, fingers, and feet

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)