Acromegaly

Acromegaly

 

Acromegaly is a chronic endocrine disorder caused by hypersecretion of growth hormone (GH).

Epidemiology

  • Incidence – 3-5/100,000
  • Age – mean age of onset is 40 years
  • Gender – affects both genders equally

Etiology

  • Most cases are secondary to pituitary adenomas
  • Rare causes – growth hormone secretion from tumors (carcinoid or small cell lung cancer)

Pathophysiology

  • GH is synthesized and secreted by the somatotroph cells of the anterior lobe of the pituitary gland
  • GH secretion is regulated by the hypothalamus with stimulation by growth hormone releasing hormone (GHRH) and inhibition by somatostatin
  • Circulating GH stimulates production of insulin-like growth factor 1 (IGF-1) from the liver
  • IGF-1 inhibits GH secretion at the level of the pituitary and hypothalamus as a negative feedback loop
  • Tumor defect mimics stimulation of adenylyl cyclase by GH releasing hormone receptor activation causing autonomous GH secretion

Clinical Presentation

  • Related to both excess GH & IGF-1 secretion and to the expanding pituitary mass
  • Indolent course
  • Pituitary mass expansion symptoms
    • Headaches
    • Visual field defects
    • Cranial nerve palsies
  • GH excess symptoms
  • Musculoskeletal
    • Hypertrophic arthropathy – both axial and peripheral skeleton
    • Carpal tunnel syndrome
    • Coarse facial features
    • Spade-shaped hands
    • Enlarged feet
    • Growth of mandible – prognathism
    • If epiphyses are open – linear bone growth causes gigantism
  • Cardiovascular
    • Hypertension – about 30% of patients
    • Cardiomyopathy
    • Arrhythmias
  • Dermatologic
    • Acanthosis nigricans
  • Metabolic
    • Diabetes mellitus
    • Dyslipidemia
  • Neoplastic
    • Increased risk for developing colon cancer due to increased risk of premalignant colon polyps
  • Carney complex – rare syndrome associated with acromegaly
    • Pigmented skin, myxoma, cardiac myxoma, thyroid nodules or carcinoma, primary pigmented nodular adrenocortical disease

Diagnosis

  • Laboratory testing
    • Fasting or random GH (may be elevated, but since growth hormone secretion is pulsatile, it may not be elevated) and insulin-like growth factor 1 (IGF-1) level (usually elevated)
      • GH <0.3 μg/L and IGF-1 normal excludes acromegaly
    • If either test does not meet the criteria above, perform oral glucose tolerance test and measure GH
      • GH <0.3 μg/L excludes acromegaly
  • Imaging studies
    • MRI to evaluate adenoma

Treatment

  • Three goals – control hypersecretion of GH, decrease morbidity/mortality related to hypersecretion, reduce mass effects of tumor
  • Surgical removal – usually initial therapy
  • Radiotherapy
  • Medical therapy
    • Dopamine agonists
    • Somatostatin analogues
    • GH receptor antagonists

See Also