What is the evaluation and treatment approach for pediatric short stature?

Evaluation and Treatment of Pediatric Short Stature

A comprehensive diagnostic evaluation followed by targeted treatment is essential for managing pediatric short stature, with genetic testing playing an increasingly important role in identifying underlying causes.

Definition and Initial Assessment

Short stature is defined as height more than two standard deviations below the mean for age (below the 3rd percentile) 1. The evaluation should begin with:

• Growth velocity measurement: Compare serial measurements over 4-6 months; crossing multiple centile lines after age 3 suggests pathology 2
• Midparental height calculation: To determine genetic growth potential
• Bone age determination: To assess growth potential and expected final height

Diagnostic Algorithm

Step 1: Differentiate between isolated short stature and short stature with other abnormalities

• Isolated short stature: Consider:

  • Constitutional delay of growth and puberty
  • Familial short stature
  • Idiopathic short stature
  • Primary endocrinopathies
  • Turner syndrome or variants (in girls)
  • SHOX gene mutations 2

• Short stature with physical/developmental abnormalities: Proceed to assess body proportions

Step 2: Evaluate body proportions

• Proportionate short stature: Consider chromosomal abnormalities, recognizable syndromes

  • Perform chromosome analysis to rule out Turner syndrome and other chromosomal disorders
  • If negative, consider genomic array studies 2

• Disproportionate short stature: Perform skeletal survey to evaluate for skeletal dysplasia 2

  • AP and lateral skull views
  • AP and lateral spine views
  • AP chest with rib views
  • AP pelvis
  • AP long bones
  • AP hands and feet
  • Lateral ankle and knee 2

Step 3: Laboratory Evaluation

For children with height SDS < -2:

• Complete blood count
• Comprehensive metabolic panel
• Thyroid function tests
• IGF-1 and IGFBP-3 levels
• Celiac disease screening
• Inflammatory markers
• Karyotype in girls to rule out Turner syndrome 3

For children with height SDS < -3:

• More extensive workup including growth hormone stimulation testing 3

Genetic Testing Considerations

• SHOX gene testing: For children with subtle skeletal changes or significant short stature (>3 SD) without other diagnosis 2
• Chromosomal analysis: For girls with short stature to rule out Turner syndrome 2
• Genomic array studies: When chromosome analysis is negative 2
• Targeted gene panels or whole exome sequencing: Consider for children with persistent unexplained short stature 4

Treatment Approaches

Growth Hormone Therapy

FDA-approved indications for growth hormone therapy in pediatric short stature include:

1. Growth Hormone Deficiency: Weekly dosage up to 0.3 mg/kg divided into daily subcutaneous injections; up to 0.7 mg/kg for pubertal patients 5

2. Chronic Kidney Disease: Weekly dosage up to 0.35 mg/kg divided into daily subcutaneous injections until renal transplantation 5

3. Idiopathic Short Stature: Weekly dosage up to 0.3 mg/kg divided into daily subcutaneous injections 5

4. Turner Syndrome: Weekly dosage up to 0.375 mg/kg divided into 3-7 doses per week 5

Treatment Monitoring

• Regular height measurements every 3-6 months
• Annual bone age assessment
• IGF-1 monitoring for safety and dosage adjustment
• Treatment should be discontinued when epiphyses are fused 5

Important Considerations

• Children more than 3 standard deviations below mean height are more likely to have underlying pathology 1
• Response to growth hormone therapy tends to decrease over time 5
• Failure to increase growth rate during the first year of therapy warrants assessment of compliance and evaluation for other causes 5
• Genetic diagnosis may allow for targeted therapy rather than empiric growth hormone treatment 4

Common Pitfalls to Avoid

• Overlooking subtle skeletal abnormalities that may indicate SHOX deficiency or mild skeletal dysplasia
• Failing to consider Turner syndrome in all girls with unexplained short stature
• Delaying treatment in children with pathologic short stature
• Missing non-endocrine causes such as celiac disease, inflammatory bowel disease, or chronic kidney disease 6
• Assuming all short stature is familial without proper evaluation 3