Last Literature Review: January 2018 Last Update:

Acromegaly is a rare chronic endocrine disorder resulting from hypersecretion of growth hormone (GH), typically by a pituitary adenoma, which results in abnormal musculoskeletal growth that is most often noted in the face and distal extremities. Diagnosis is made on the basis of GH and insulin-like growth factor testing.


Indications for Testing

  • Adults
    • Enlarged facial or acral features, abnormal musculoskeletal growth
    • Combination of several of the following – chronic headaches, sleep apnea, bony arthritis, carpal tunnel syndrome, diabetes mellitus type 2, and hyperhidrosis (Katznelson, Endocrine Society, 2014)
  • Children
    • Accelerated linear growth (gigantism)

Laboratory Testing

  • Screening
    • Insulin-like growth factor 1 (IGF-1)
      • Most relevant test due to steady secretion
      • Highly specific if elevated
    • Growth hormone (GH)
      • Secretion is pulsatile; even morning levels may not be elevated
      • Should not be used alone to diagnose acromegaly (Katznelson, Endocrine Society, 2014)
  • Confirmation
    • Perform glucose tolerance test (GTT) and measure GH
      • Administer 75 g glucose and perform GH measurements over 120 minutes
        • Failure to suppress GH during hyperglycemia is diagnostic
        • GH <1 ng/mL excludes acromegaly
      • Clinical scenarios resulting in high GH levels and nonsuppression of GH with GTT
        High GH + Low IGF-1 High GH + Normal/High IGF-1
        Anorexia/fasting Pregnancy
        Exogenous estrogen Puberty
        Liver disease Uncontrolled hyperthyroidism
        Renal insufficiency  
        Uncontrolled diabetes mellitus  
        GH, growth hormone; GTT, glucose tolerance test; IGF-1, insulin-like growth factor 1


Imaging Studies and Procedures

  • Magnetic resonance imaging (MRI) – preferred modality to evaluate tumor presence and size
  • Computed tomography (CT) – if MRI unavailable
  • Visual field testing
    • Recommended in pregnant patients with macroadenomas (Katznelson, Endocrine Society, 2014)
    • Use if optic chiasm compression is suspected

Differential Diagnosis


  • Monitor growth hormone (GH) and/or insulin-like growth factor 1 (IGF-1) levels for effectiveness of therapy
    • Use the same test type for consistency, if possible
    • Target concentrations
      • GH <1 ng/mL or
      • Normal IGF-1 levels
  • GH and/or IGF-1 monitoring not recommended during pregnancy (Katznelson, Endocrine Society, 2014)



  • Incidence – 3-4/million (Kannan, 2013)
  • Age – mean onset 40 years
  • Sex – M:F, equal


  • Pituitary adenomas – most common cause
  • Tumors
  • Familial disorders
  • Extrapituitary causes
    • Growth hormone-releasing hormone (GHRH)-secreting hypothalamic tumor
    • Ectopic secretion of GHRH


  • Most acromegaly is caused by sporadic GH-secreting pituitary adenomas
  • GH is synthesized in somatotroph cells of the anterior lobe of pituitary gland
    • Pulsatile secretion
  • GH secretion is regulated by the hypothalamus
    • Stimulated by GHRH
    • Inhibited by somatostatin
  • Circulating GH stimulates synthesis and secretion of insulin-like growth factor 1 (IGF-1) from the liver
  • IGF-1 inhibits GH secretion at the pituitary and hypothalamus level, creating a negative feedback loop
  • Pituitary tumors mimic stimulation of adenylyl cyclase by GHRH receptor activation
    • Causes autonomous GH secretion
    • Symptoms are related to excess GH and IGF-1 secretion and to expansion of the pituitary mass

Clinical Presentation

  • Indolent course – delay in diagnosis of 4-10 years
  • Symptoms of pituitary mass expansion
    • Headaches
    • Visual field defects
    • Cranial nerve palsies
    • Symptoms consistent with hypopituitarism due to compression of remaining pituitary gland by expanding mass
  • Symptoms of GH excess
    • Musculoskeletal
      • Hypertrophic arthropathy – both axial and peripheral skeleton
      • Carpal tunnel syndrome
      • Bony overgrowth
        • Coarse facial features, macrognathia, frontal bossing
        • Spade-shaped hands
        • Enlarged feet
        • Mandibular overgrowth – prognathia
        • Open epiphyses in children – linear bone growth causes gigantism
      • Obstructive sleep apnea – due to soft tissue overgrowth (eg, macroglossia)
    • Cardiovascular
      • Hypertension
      • Cardiomyopathy – biventricular hypertrophy
      • Arrhythmias
    • Dermatologic
      • Acanthosis nigricans
      • Hyperhydrosis
    • Metabolic
    • Neoplastic
  • Familial acromegaly
    • MEN1
      • Autosomal dominant inheritance
      • ~10% incidence of GH-producing tumors
    • McCune-Albright syndrome
      • Rare
      • Triad of peripheral precocious puberty, café-au-lait spots, fibrous dysplasia of the bone
      • Thyrotoxicosis
    • Carney complex
      • Rare
      • Pigmented skin, myxoma, cardiac myxoma, thyroid nodules or carcinoma, primary pigmented nodular adrenocortical disease
      • ~10% incidence of GH-producing tumors
    • Familial isolated pituitary adenoma
      • More common for childhood onset – frequent presentation is gigantism
      • Higher growth rate than with sporadic tumors

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