What are the available treatments for pediatric short stature?

Available Treatments for Pediatric Short Stature

Growth hormone therapy is the primary treatment for pediatric short stature, with specific indications including growth hormone deficiency, chronic kidney disease, Turner syndrome, and idiopathic short stature, administered at condition-specific dosages via daily subcutaneous injections. 1

Diagnostic Evaluation Before Treatment

Before initiating treatment, proper diagnosis is essential:

1. Height Assessment:

   • Short stature defined as height below the 3rd percentile or below -2 standard deviations for age and sex 2
   • Monitor height velocity (growth rate) over 4-6 months 2
   • Calculate midparental height to assess genetic potential 2

2. Laboratory Evaluation:

   • Chromosomal analysis (especially for girls to rule out Turner syndrome) 2
   • Thyroid function tests 2
   • IGF-1 levels 1
   • Growth hormone stimulation testing (for suspected GH deficiency) 1

3. Radiographic Assessment:

   • Bone age determination to assess growth potential 2
   • Skeletal survey for disproportionate short stature to evaluate for skeletal dysplasia 2

Treatment Options

1. Growth Hormone Therapy

FDA-approved indications and dosages 1:

• Growth Hormone Deficiency (GHD):

  • Weekly dosage: Up to 0.3 mg/kg divided into daily subcutaneous injections
  • For pubertal patients: Up to 0.7 mg/kg weekly

• Chronic Kidney Disease (CKD):

  • Weekly dosage: Up to 0.35 mg/kg divided into daily subcutaneous injections
  • Continue until renal transplantation
  • Mean first-year growth rate: 10.8 cm/yr (vs. 6.5 cm/yr in controls)

• Idiopathic Short Stature (ISS):

  • Weekly dosage: Up to 0.3 mg/kg divided into daily subcutaneous injections
  • Defined as height SDS ≤ -2.25 with no other identifiable cause

• Turner Syndrome:

  • Weekly dosage: Up to 0.375 mg/kg divided into 3-7 doses per week
  • Adult height gain: 5.0-8.3 cm depending on treatment timing

2. Treatment for Specific Conditions

• For CKD patients 3:

  • GH therapy should be initiated when height is below the 3rd percentile and height velocity is below the 25th percentile for 3 months in infants or 6 months in children
  • Optimize other factors first: nutrition, metabolic acidosis, renal osteodystrophy, electrolyte abnormalities
  • Special injection timing for dialysis patients:
    • Hemodialysis: Inject at night before sleep or 3-4 hours after dialysis
    • CCPD: Inject in morning after dialysis
    • CAPD: Inject in evening during overnight exchange

• For Genetic Syndromes 3, 2:

  • SHOX gene-related disorders may benefit from GH therapy
  • Cardio-facio-cutaneous syndrome: GH therapy only approved for documented GH deficiency

Monitoring During Treatment

1. Growth Response:

   • Height measurements every 3-6 months 2
   • Successful first-year response: Increase in height SDS >0.3-0.5 4

2. Safety Monitoring:

   • Annual bone age assessment 2
   • IGF-1 monitoring for safety and dosage adjustment 2, 1
   • Fundoscopic examination before starting therapy to rule out papilledema 3

3. Duration of Treatment:

   • Continue until epiphyseal fusion occurs 1
   • Mean increase in adult height: 3.5-7.5 cm for ISS 4

Important Considerations and Caveats

• Response Variability: Individual responses to GH therapy vary significantly 4

• Timing Matters: Earlier treatment initiation generally yields better height outcomes, especially in conditions like Turner syndrome 1

• Contraindications:

  • Active malignancy
  • Uncontrolled diabetes mellitus
  • Pre-existing papilledema
  • Known hypersensitivity to growth hormone 3

• Emerging Approaches:

  • Genetic testing is increasingly important for identifying specific causes of short stature that may respond to targeted therapies 5
  • For children with skeletal dysplasia, early orthopedic consultation is recommended 6

Growth hormone therapy should be discontinued when epiphyses are fused, indicating the end of growth potential 1. The decision to treat should prioritize patients with the most severe height deficits and those with documented conditions known to respond to GH therapy.