Acromegaly

Diagnosis

Indications for Testing

  • Chronic headaches or musculoskeletal growth in an adult

Laboratory Testing

  • Fasting or random GH and IGF-1 levels
    • GH secretion is pulsatile and may or may not be elevated
    • IGF-1 usually elevated
    • GH <0.25 ng/mL and normal IGF-1 excludes acromegaly
    • Consensus criteria – nadir GH >1 ng/mL with high IGF-1 levels is diagnostic
  • If either test does not meet the criteria above, perform oral glucose tolerance test (OGTT) and measure GH
    • Administer 75g glucose and perform GH measurements over 120 minutes
      • Failure to suppress GH is diagnostic
      • GH <0.25 ng/mL excludes acromegaly
    • Usefulness limited in high catabolic states, patients on estrogen replacement, tall adolescents

Histology

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

Imaging Studies

  • MRI – preferred modality to evaluate adenoma
    • Can detect tumors as small as 2 mm

Differential Diagnosis   

Monitoring

  • Monitor GH and IGF-1 levels for effectiveness of therapy
    • Active disease
      • Random GH >1 ng/mL and nadir GH after 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

Clinical Background

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

Epidemiology

  • Incidence – 3-5/1,000,000
  • Age – mean onset is 40 years
  • Sex – M:F, equal

Etiology

  • Most cases are secondary to pituitary adenomas
  • Rare causes – growth hormone secretion from tumors (carcinoid or small cell lung cancer)
  • Genetic diseases associated with acromegaly – MEN1, McCune-Albright syndrome, Carney complex

Pathophysiology

  • GH is synthesized and has pulsatile secretion from the somatotroph cells of the anterior lobe of the pituitary gland
  • GH secretion is regulated by the hypothalamus
    • Stimulation by GH releasing hormone (GHRH)
    • Inhibition 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, causing autonomous GH secretion
    • Symptoms are related to both excess GH and IGF-1 secretion and to the expanding pituitary mass

Clinical Presentation

  • 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, macrognathia
      • 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
    • Endocrine
      • May cause deficiency of other pituitary hormones from mass effect
    • Dermatologic
      • Acanthosis nigricans
    • Metabolic
    • Neoplastic
      • Development of premalignant colon polyps increases risk of colon cancer
  • Carney complex – rare syndrome associated with acromegaly

Treatment

  • Three goals of treatment
    • Control hypersecretion of GH
    • Decrease morbidity/mortality related to hypersecretion
    • Reduce mass effects of tumor
  • Surgical removal of tumor – usually initial therapy
  • Radiotherapy
  • Medical therapy
    • Dopamine agonists
    • Somatostatin analogues
    • GH receptor antagonists

Indications for Laboratory Testing

  • 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
Test Name and Number Recommended Use Limitations Follow Up
Growth Hormone 0070080
Method: Quantitative Chemiluminescent Immunoassay

Use as initial test in the evaluation of suspected growth hormone excess

Use in conjunction with IGF-1 testing

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

Use as initial test in the evaluation of suspected growth hormone excess

Use in conjunction with growth hormone testing

Monitor adequacy of growth hormone therapy

Increased in pubertal and in pregnant patients

  
Growth Hormone by Immunohistochemistry 2003929
Method: Immunohistochemistry

Aid in histologic diagnosis of acromegaly

Stained and returned to client pathologist; consultation available if needed

    
Additional Tests Available
 
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Growth Hormone, 60 Minutes 0070083
Method: Quantitative Chemiluminescent Immunoassay
  Measure after glucose administration
Growth Hormone, 120 Minutes 0070164
Method: Quantitative Chemiluminescent Immunoassay
IGF Binding Protein-3 0070060
Method: Quantitative Chemiluminescent Immunoassay

Evaluate short stature in children and for acromegaly

Use in conjunction with GH and IGF-1 testing
Insulin, 30 Minutes 0070064
Method: Quantitative Chemiluminescent Immunoassay
Insulin, 60 Minutes 0070066
Method: Quantitative Chemiluminescent Immunoassay
Insulin, 120 Minutes 0070068
Method: Quantitative Chemiluminescent Immunoassay
Parathyroid Hormone (PTH) by Immunohistochemistry 2004118
Method: Immunohistochemistry
ACTH by Immunohistochemistry 2003427
Method: Immunohistochemistry

Diagnostic Algorithm