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 fulilled, perform oral glucose tolerance test (OGTT) and measure GH
    • Administer 75 g glucose and perform GH measurements over 120 minutes
      • Failure to suppress GH is diagnostic
      • GH <1 ng/mL excludes acromegaly
      • Clinical scenarios resulting in high GH levels and nonsuppression of GH with OGTT

        Clinical scenarios resulting in high growth hormone (GH) levels and nonsuppression of GH with oral glucose tolerance test (OGTT)

        High GH + low IGF-1

        High GH + normal/high IGF-1

        Exogenous estrogenPuberty
        Liver diseaseUncontrolled hyperthyroidism
        Renal insufficiency 
        Uncontrolled diabetes mellitus 


  • 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

Clinical Background

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


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


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


  • 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
    • Headaches
    • Visual-field defects
    • Cranial nerve palsies
    • Endocrine
      • Deficiency of pituitary hormones due to compression of remaining pituitary gland by the expanding mass
  • 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 – prognathism
        • Obstructive sleep apnea – due to soft tissue overgrowth
        • In children when epiphyses are open, linear bone growth causes gigantism
    • Cardiovascular
      • Hypertension – ~30-40% of patients
      • Cardiomyopathy – biventricular hypertrophy
      • Arrhythmias
    • Dermatologic
      • Acanthosis nigricans
    • Metabolic
    • Neoplastic
      • Development of premalignant colon polyps
  • 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
    • 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 than in sporadic tumors
        • Frequent presentation is gigantism
      • Higher growth rate than with sporadic tumors

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
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

Increased in pubertal and in pregnant patients

Growth Hormone 0070080
Method: Quantitative Chemiluminescent Immunoassay

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

Use in conjunction with IGF-1 testing

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
Growth Hormone, 120 Minutes 0070164
Method: Quantitative Chemiluminescent Immunoassay
IGF Binding Protein-3 0070060
Method: Quantitative Chemiluminescent Immunoassay

Use to evaluate short stature in children and for acromegaly

Use in conjunction with GH and IGF-1 testing