• Clinical science

Acromegaly

Abstract

Acromegaly is a condition in which benign pituitary adenomas lead to an excess secretion of growth hormone (GH) and insulin-like growth factor 1 (IGF-1). In adults, whose epiphyseal plates are closed, the disease causes enlarged hands and feet, coarsened facial features, and pathological growth of internal organs. If the condition occurs in children, before epiphyseal plate closure, it is known as gigantism, which is discussed in a separate learning card. The first step in diagnosing acromegaly is to measure IGF-1 levels. Further testing includes an oral glucose tolerance test (OGTT) with assessment of GH levels, and evaluation of pituitary tumors via cranial MRI. Management consists of transsphenoidal adenomectomy for operable tumors, or GH-inhibiting medication and radiotherapy if surgery is contraindicated or unsuccessful. Adequate treatment is vital to reduce the risk of complications, such as cardiovascular disease and cerebral aneurysms, as these may considerably increase mortality.

Epidemiology

  • Age of onset: 3rd decade of life (mean age at diagnosis usually 40–45 years) )

References:[1][2]

Epidemiological data refers to the US, unless otherwise specified.

Etiology

References:[3][2]

Pathophysiology

  • 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 :
      • → binds to IGF-1 and insulin receptors → stimulation of cell growth and proliferation, inhibits programmed cell death
        • Proliferative effects especially on bone, cartilage, skeletal muscle, skin, soft tissue, and organs
        • Pathological 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
    • Tumor mass compresses neighboring structures (e.g., optic nerve) → symptoms of mass effect
    • Impaired secretion of other pituitary hormones possible, especially gonadotropinsLH and FSHestrogen and testosterone

Excess GH secretion before the conclusion of longitudinal growth (i.e., prior to epiphyseal plate closure) leads to pituitary gigantism with a possible height of ≥ 2 m. After epiphyseal plate closure, GH excess causes acromegaly, but no change in height!
References:[1][4]

Clinical features

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

References:[1][5][6][2]

Diagnostics

  • Hormone analysis
    • ↑ Serum IGF-1 concentration
      • Normal IGF-1 levels rule out acromegaly
    • If IGF-1conduct OGTT with baseline GH → measure GH after 2 hours
      • → if GH suppressed → acromegaly ruled out
      • → if GH not suppressed: confirmed acromegaly → conduct pituitary MRI
  • Pituitary MRI
    • Usually shows a visible mass → confirmed GH-secreting pituitary adenoma
    • If normal → screen for an extrapituitary cause (e.g., CT scan of the chest and abdomen, measure GHRH)
  • Tumor DNA analysis
    • shows an activating mutation of adenylyl cyclase → overexpression of G-protein coupled receptor
    • found in 40% of patients

References:[3]

Treatment

Transsphenoidal adenomectomy is the method of choice for treating acromegaly. In patients with inoperable tumors or unsuccessful surgery, medication and radiotherapy are indicated to reduce tumor size and limit the effects of GH and IGF-1.

  • Surgery: transsphenoidal adenomectomy
  • Medication
  • Radiotherapy
    • Conventional fractionated radiotherapy
    • Stereotactic radiosurgery (e.g., Gamma Knife, Cyber Knife, proton beam)

Danger of hypopituitarism following surgery or radiotherapy!
References:[1][7][8]

Complications


References:[1][2][9]

We list the most important complications. The selection is not exhaustive.