4- ACROMEGALY & GIGANTISM

• GH secretion

  Secreted in a pulsatile fashion, regulated by GHRH, Somatostatin, Ghrelin
• GH action


  Induces metabolic changes directly on liver, muscle, fat and bone or indirectly by inducing IGF-1 secretion
• Acromegaly

  Results from excess secretion of pituitary GH after epiphyseal closure
• Gigantism

  Results from excess secretion of pituitary GH before epiphyseal closure
• Acromegaly & Gigantism


  • Soft tissue overgrowth throughout the body leading to broadening of the skeleton, abnormal growth of the hands, feet, and face
• Symptoms of Acromegaly & Gigantism

  1. Symptoms due to local mass effects of an intracranial tumor

  2. Symptoms due to excess of GH/IGF-I: soft tissue (cartilage & bone) enlargement
• Symptoms due to local mass effects

  • Headaches and visual field defects
  • Hyperprolactinemia
  • Deficiencies of glucocorticoids, sex steroids, and thyroid hormone
• Symptoms due to excess of GH/IGF-I

  • Enlargement of extremities (spade- like hands)
  • Increase in ring, hat and/or shoe size
  • Carpal tunnel syndrome
  • Hyperhidrosis (increased sweating from sweat gland hypertrophy) & body odor
  • Coarsening of facial features
  • Prominent supra-orbital ridges
  • Prognathism (protrusion of the jaw)
  • Macroglossia (enlargement of the tongue) & deep voice
  • Dental indentation (from jaw growth)
  • Arthralgias from joints growing out of alignment
  • Increased incidence of obstructive sleep apnea
  • Hyperglycemia & increased incidence of glucose intolerance or frank diabetes mellitus
  • Acanthosis nigricans & skin tags
  • Hypertension resistant to Tx for unclear reasons in 50%
  • Increased incidence of congestive heart failure
  • Hyperphosphatemia, hypercalciuria, and hypertriglyceridemia
  • Colonic polyps and increased risk of colon cancer
  • Erectile dysfunction (prolactin co-secreted w/ pituitary adenoma)
• Diagnosis of Acromegaly & Gigantism

  1. Serum IGF-1 (significantly elevated)

  2. Oral glucose suppression test (glucose load fails to suppress GH)

  3. MRI of the pituitary area

  4. Serum prolactin level

  5. Random GH level (not useful due to wide physiologic fluctuation, but normal GH excludes the diagnosis)

  6. Laboratory tests will show glucose intolerance & hyperlipidemia
• Treatment of Acromegaly & Gigantism

  1. Transsphenoidal resection of pituitary adenoma (treatment of choice, 70% respond)

  2. Medications: Cabergoline (DA inhibits GH release), Octreotide (somatostatin inhibits GH release), Pegvisomant (GH receptor antagonist, inhibits IGF release)

  3. Radiation therapy only in those who don't respond to surgery or medications