Growth hormone deficiency is a congenital or an acquired growth hormone axis disruption in the higher brain, hypothalamus or pituitary which results in short stature.
It may occur at any age.
Short stature is often the only feature present in patients with growth hormone deficiency and other causes of subnormal growth rate.
Etiology may be congenital conditions (eg defective pituitary development that leads to pituitary aplasia, empty sella, encephalocele, midline defects) or acquired conditions (eg tumors of the hypothalamic-pituitary region, cranial irradiation, infiltrative disease).


  • Short stature is often the only feature present in patients w/ growth hormone deficiency (GHD) & other causes of subnormal growth rate
    • Exclude other causes of growth failure using appropriate tests
      • Eg hypothyroidism, chronic systemic diseases, skeletal diseases & Turner syndrome
  • Diagnose GHD based on comprehensive clinical & auxological assessment together w/ laboratory tests [eg, GH-insulin-like growth factor (IGF-1) axis] & radiological evaluation


  • Family history of growth hormone deficiency (GHD)
  • Perinatal history (eg difficult labor, traumatic delivery)
  • History of cranial irradiation
  • History of head trauma
  • Growth chart & history of slow or no growth
  • Symptoms of GHD in neonates & children

Physical Examination

  • Height & weight evaluation
    • Plot weight & height measurements on growth charts which will graphically depict changes in growth & growth velocity
  • Short stature may suggest growth hormone deficiency (GHD) & immediate investigation should be conducted if any of the following criteria are present:
    • Severe short stature (defined as height >2-3 SD below population mean)
    • Height >2 SD below population mean w/ 1-year height velocity >1 SD below mean for chronological age or (in child age >2 years), a 1-year decrease of >0.5 SD in height
    • In the absence of short stature, a 1-year height velocity >2 SD below the mean or a 2-years height velocity >1.5 SD below the mean (especially growth hormone manifesting during infancy or in organic acquired GHD
    • Height >1.5 SD below midparental height (average of father’s & mother’s)
    • Signs indicative of an intracranial lesion
    • Signs of multiple pituitary hormone deficiencies (MPHD)
    • Neonatal signs & symptoms of GHD
  • Other manifestations of growth hormone deficiency (GHD) in children
    • Increased subcutaneous fat, especially around the trunk
    • Immature facie, w/ a prominent forehead & depressed midfacial development
    • Delayed dentition
    • Age of puberty may be delayed
    • In males, the phallus may be small

Laboratory Tests

Serum Growth Hormone (GH) Level

  • In newborns, serum GH level <20 mcg/L is highly suggestive of growth hormone deficiency (GHD)
    • GH level measured in neonates w/ hypoglycemia but no metabolic disorder
  • After the newborn period, random serum GH levels are not reliable indicators of GHD due to the pulsatile nature of GH secretion

Growth Hormone (GH) Stimulation (Provocative) Tests

  • At least 2 provocative tests are ideal to ascertain the diagnosis because of the high frequency of false-negative results
    • 2 provocative tests w/ low peak levels of GH, poor linear growth, & delayed skeletal age is highly indicative of chronic GHD
  • Provocative tests in children w/ peak GH concentration <10 mcg/L supports GHD diagnosis:
    • Insulin tolerance test (ITT)
      • GH level ≤5.0 mcg/L indicative of GHD
      • Contraindicated in patients w/ cardiovascular disease, cerebrovascular disease & seizure disorders
    • Growth hormone–releasing hormone (GHRH w/ or w/o arginine
      • GH level <4.1 mcg/L indicates GHD in a GHRH-arginine test
    • Clonidine
    • Levodopa
    • Glucagon w/ or w/o beta-blockers
      • Peak GH of ≤3.0 mcg/L indicative of GHD & possible initiation of treatment
    • Propranolol

Insulin-like Growth Factor 1 (IGF-1) or Somatomedin Test & IGF-binding Protein 3 (IGFBP-3) Test

  • Produced when the liver & other tissues are stimulated by GH
  • Values ≥2 SD below the mean for IGF-1 or IGFBP-3 strongly suggest an abnormality in the GH axis, if other causes of low IGF have been excluded
  • However, normal values for IGF-1 & IGFBP-3 can be found in children w/ GHD

Other Tests

  • Lipid profile
    • Patients w/ GHD may have increased total cholesterol, low-density lipoprotein-cholesterol (LDL-C), apolipoprotein B & triglyceride (TG) levels & decreased high-density lipoprotein-cholesterol (HDL-C)
  • Thyroxine & thyroid-stimulating hormone (TSH)
  • To rule out hypothyroidism
  • Evaluate for possible causes of GHD:
    Congenital, genetic or acquired causes
  • Karyotype
    • Perform to evaluate the presence of genetic syndromes (eg Turner syndrome in females)
  • Increased type-1 plasminogen activator inhibitor (PAI-1) activity
  • Increased fibrinogen levels



  • Assesses the bone age in children
  • Reveals delayed bone age in children w/ growth hormone deficiency (GHD)
  • Bone age is estimated from a radiograph of the:
    • Left wrist & hand for children 1 year of age or older
    • Knee & ankle for infants <1 year old
  • X-ray of the head may show intracranial calcification in craniopharyngoma

Magnetic Resonance Imaging (MRI) or Computed Tomography (CT) of the Central Nervous System (CNS)

  • Performed to define the anatomy of the hypothalamic-pituitary region & to identify intracranial tumors, optic nerve hypoplasia, septo-optic dysplasia or other structural or developmental anomalies
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