Epidemiology

Etiology

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

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!

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)