Growth Hormone Deficiency in Children

Background

• Growth hormone deficiency (GHD) is the result of impaired production of growth hormone (GH) by the pituitary gland.
• Failure of the pituitary gland to secrete sufficient or functional GH leads to reduced GH-dependent protein insulin-like growth factor 1, which may result in poor skeletal and muscle growth, impaired glucose metabolism, and central nervous system abnormalities.
  • It often presents as short stature or growth failure.
  • In neonates, GHD may present with hypoglycemia, prolonged jaundice, microphallus, or craniofacial midline abnormalities.
• It can occur as an isolated hormone deficit, or in conjunction with other pituitary hormone deficits.
• GHD may be congenital (for example due to genetic defects, intracranial malformations, or prenatal infection) or acquired (for example due to radiation, trauma, central nervous system infection, or other insults to the hypothalamic-pituitary axis).

Evaluation

• Evaluate for growth hormone deficiency (GHD) in children with any of the following:
  • height > 3 standard deviations (SD) below mean for age or > 1.5 SD below mid-parental height
  • height > 2 SD below mean for age and either height velocity > 1 SD below mean over past year or decrease in height SD > 0.5 over past year in children > 2 years old
  • height velocity > 2 SD below mean over past year or > 1.5 SD below mean over past 2 years
  • signs of an intracranial lesion or multiple pituitary hormone deficiency
  • neonatal signs or symptoms of GHD such as hypoglycemia, prolonged jaundice, microphallus, or craniofacial midline abnormalities
• Perform testing (including blood tests and bone age) to exclude alternative diagnoses.
• If initial testing excludes alternative diagnoses, measure insulin-like growth factor 1 (IGF-1) level and/or insulin-like growth factor binding protein 3 (IGFBP-3) level - low levels suggest GHD, but should be used in combination with other diagnostic measures.
• If IGF-1 or IGFBP-3 is low and/or bone age is significantly delayed, measure growth hormone (GH) levels in response to provocative testing.
  • In most children, diagnosis of GHD requires inadequate responses to 2 different GH provocative tests; however, do not rely upon GH provocative test results as the sole diagnostic criterion of GHD (Strong recommendation).
  • GHD may be diagnosed without provocative testing in children with auxological criteria for growth failure, hypothalamic-pituitary defect, and deficiency of ≥ 1 pituitary hormone in addition to growth hormone (Weak recommendation).
  • GHD due to congenital hypopituitarism may be diagnosed without provocative testing in neonates with hypoglycemia and low serum GH while hypoglycemic, plus deficiency of ≥ 1 other pituitary hormone and/or ectopic posterior pituitary, pituitary hypoplasia, and abnormal stalk on imaging (Weak recommendation).
• If provocative testing confirms GHD or an intracranial tumor or anomaly is suspected, obtain cranial magnetic resonance imaging to detect structural pituitary abnormalities.

Management

• Physicians with expertise in managing endocrine disorders in children should manage or provide consultation for treatment of growth hormone deficiency (GHD) (Weak recommendation).
• Recombinant human growth hormone is first-line treatment for GHD.
  • Use growth hormone (GH) to normalize adult height and avoid extreme shortness in children and adolescents with GHD (Strong recommendation).
  • Start GH therapy as soon as possible after diagnosis.
  • Dosing
    • Use initial GH dose of 0.16-0.24 mg/kg/week (22-35 mcg/kg/day), with individualization of subsequent dosing (Strong recommendation).
    • Consider dose adjustments based on insulin-like growth factor 1 (IGF-1) levels (Weak recommendation).
  • Follow-up
    • Monitor growth and IGF-1 levels.
    • Assess for other hormone deficiencies in children at risk, as well as for adverse effects of GH therapy.
    • Discontinue GH treatment at pediatric doses once growth velocity is < 2-2.5 cm/year (Strong recommendation).
    • Provide transitional care, which may include reevaluation of somatotropic axis to determine need for continued GH therapy into adulthood.
• Other medications to consider may include aromatase inhibitors in boys.