Acromegaly

  • Diagnosis
  • Algorithms
  • Monitoring
  • Background
  • Lab Tests
  • References
  • Related Topics

Indications for Testing

  • Adults
    • Chronic headaches or abnormal musculoskeletal growth (eg, increasing skull or chest size)
  • Children
    • Accelerated linear growth (gigantism)

Laboratory Testing

  • Concurrent fasting or random growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels
    • GH secretion is pulsatile and may or may not be elevated
      • Cannot be used as a single test in diagnosis
    • IGF-1 is usually elevated
      • Most important test – highly specific if elevated
    • GH <0.25 ng/mL and normal IGF-1 excludes acromegaly
    • Consensus criteria – nadir GH >0.53 ng/mL with high IGF-1 levels is diagnostic
  • If above criteria are not fulfilled, perform oral glucose tolerance test (OGTT) 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

Histology

  • Immunohistochemistry staining for growth hormone
    • May need to stain for other anterior pituitary hormones

Imaging Studies

  • MRI – preferred modality to evaluate adenoma presence and size

Differential Diagnosis

  • Monitor growth hormone (GH) and insulin-like growth factor 1 (IGF-1) levels for effectiveness of therapy
    • Active disease
      • Random GH >1 ng/mL and nadir GH after oral glucose tolerance test (OGTT) ≥0.4 ng/mL
      • IGF-1 elevated
      • Also consider periodic MRI for active disease
    • Controlled disease
      • GH <1 ng/mL or nadir GH after OGTT <0.4 ng/mL
      • IGF-1 normal

Acromegaly is a rare chronic endocrine disorder resulting from hypersecretion of growth hormone (GH) by the pituitary gland.

Epidemiology

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

Etiology

  • Pituitary adenomas – most common cause
  • Tumors
  • Familial disorders
    • MEN1 (MEN1 gene)
    • McCune-Albright syndrome (GNAS gene)
    • Carney complex (PRKAR1A gene)
    • Familial isolated pituitary adenoma (AIP gene in 20%)
  • Extrapituitary causes
    • Growth hormone-releasing hormone (GHRH)-secreting hypothalamic tumor
    • Ectopic secretion of GHRH

Pathophysiology

  • Most acromegaly is caused by sporadic GH-secreting pituitary adenomas
  • GH is synthesized in the somatotroph cells of the anterior lobe of the 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
  • Pituitary mass expansion symptoms
    • Headaches
    • Visual-field defects
    • Cranial nerve palsies
    • Symptoms consistent with hypopituitarism due to compression of remaining pituitary gland by the expanding mass
  • GH excess symptoms
    • 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 – prognathism
        • Children with open epiphyses –  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

Tests generally appear in the order most useful for common clinical situations. Click on number for test-specific information in the ARUP Laboratory Test Directory.

IGF-1 (Insulin-Like Growth Factor 1) 0070125
Method: Quantitative Chemiluminescent Immunoassay

Limitations

Increased in pubertal and in pregnant patients

Growth Hormone 0070080
Method: Quantitative Chemiluminescent Immunoassay

Growth Hormone by Immunohistochemistry 2003929
Method: Immunohistochemistry

Related Tests

Guidelines

Chanson P, Bertherat J, Beckers A, Bihan H, Brue T, Caron P, Chabre O, Cogne M, Cortet-Rudelli C, Delemer B, Dufour H, Gaillard R, Gueydan M, Morange I, Souberbielle J, Tabarin A, Club Français De L'hypophyse (French Pituitary Club), Société Française Dendocrinologie (French Endocrinology Society). French consensus on the management of acromegaly. Ann Endocrinol (Paris). 2009; 70(2): 92-106. PubMed

Giustina A, Chanson P, Bronstein MD, Klibanski A, Lamberts S, Casanueva FF, Trainer P, Ghigo E, Ho K, Melmed S, Acromegaly Consensus Group. A consensus on criteria for cure of acromegaly. J Clin Endocrinol Metab. 2010; 95(7): 3141-8. PubMed

Kannan S, Kennedy L. Diagnosis of acromegaly: state of the art. Expert Opin Med Diagn. 2013; 7(5): 443-53. PubMed

Katznelson L, Laws ER, Melmed S, Molitch ME, Murad MHassan, Utz A, Wass JA H, Endocrine Society. Acromegaly: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014; 99(11): 3933-51. PubMed

Melmed S, Colao A, Barkan A, Molitch M, Grossman AB, Kleinberg D, Clemmons D, Chanson P, Laws E, Schlechte J, Vance ML, Ho K, Giustina A, Acromegaly Consensus Group. Guidelines for acromegaly management: an update. J Clin Endocrinol Metab. 2009; 94(5): 1509-17. PubMed

General References

Bidlingmaier M, Strasburger CJ. Growth hormone assays: current methodologies and their limitations. Pituitary. 2007; 10(2): 115-9. PubMed

Capatina C, Wass JA H. 60 Years of Neuroendocrinology: Acromegaly. J Endocrinol. 2015; 226(2): T141-60. PubMed

Chanson P, Salenave S, Kamenicky P, Cazabat L, Young J. Pituitary tumours: acromegaly. Best Pract Res Clin Endocrinol Metab. 2009; 23(5): 555-74. PubMed

Chanson P, Salenave S. Acromegaly. Orphanet J Rare Dis. 2008; 3: 17. PubMed

Cordero RA, Barkan AL. Current diagnosis of acromegaly. Rev Endocr Metab Disord. 2008; 9(1): 13-9. PubMed

Tzanela M. Dynamic tests and basal values for defining active acromegaly. Neuroendocrinology. 2006; 83(3-4): 200-4. PubMed

Medical Reviewers

Last Update: July 2016