Acromegaly
Epidemiology
Etiology
- Benign growth hormone-secreting pituitary adenoma (> 95% of cases)
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)
- Binding to IGF-1 and insulin receptors → stimulation of cell growth and proliferation, inhibiting programmed cell death
- 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
- Doughy skin texture, hyperhidrosis
- 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)