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

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

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