What laboratory tests should be ordered for a patient with idiopathic short stature?

Laboratory Tests for Idiopathic Short Stature Evaluation

For patients with idiopathic short stature, a comprehensive laboratory evaluation should include endocrine testing, chromosomal analysis, and genetic testing to rule out pathologic causes of growth failure. 1

Initial Laboratory Evaluation

• Complete blood count (CBC) to rule out chronic anemia or other hematologic abnormalities that may affect growth 1
• Comprehensive metabolic panel including liver and kidney function tests to identify systemic diseases affecting growth 1
• Erythrocyte sedimentation rate (ESR) to screen for inflammatory conditions 1
• Thyroid function tests (TSH, free T4) to rule out hypothyroidism as a cause of growth failure 1
• IGF-1 and IGFBP-3 levels to screen for growth hormone deficiency or resistance 1
• Celiac disease screening (tissue transglutaminase antibodies) 1
• Bone age assessment (radiographic evaluation) to determine skeletal maturation 1

Genetic Testing

• Karyotype analysis for all girls with unexplained short stature to rule out Turner syndrome or its variants 1
• SHOX gene testing should be considered, especially in cases with familial short stature or subtle skeletal changes, as mutations occur in 1.1% to 12.5% of idiopathic short stature cases 1
• Genomic array studies if chromosome analysis is negative, to evaluate for changes in genome copy number 1
• Targeted gene panels or whole exome sequencing may be considered when other evaluations are negative 2

Additional Tests Based on Clinical Findings

• Skeletal survey should be performed if:

  • Physical examination reveals disproportionate short stature 1
  • Significant short stature is present (≥3 standard deviations below mean) with no apparent diagnosis 1
  • Subtle skeletal changes suggesting dyschondrosteosis are present 1

• Growth hormone stimulation testing if IGF-1 and IGFBP-3 levels suggest growth hormone deficiency 1

Special Considerations

• For infants with intrauterine onset of short stature (SGA), compare birth weight, birth length, and birth head circumference to assess growth pattern 1

• In cases with significant short stature but normal initial laboratory evaluation, periodic reassessment is indicated as phenotypes may evolve over time 1

• When laboratory evaluations are negative, consider more advanced genetic testing, as new testing paradigms are reducing the pool of patients labeled as idiopathic 2

Pitfalls to Avoid

• Failing to consider SHOX gene mutations in cases of apparent familial short stature, as skeletal changes may not be apparent until late childhood or puberty 1

• Overlooking the need for skeletal surveys in cases of significant short stature (≥3 SD below mean), even without obvious skeletal abnormalities 1

• Neglecting to perform chromosomal analysis in girls with unexplained short stature, as Turner syndrome may present with minimal physical features 1

• Assuming idiopathic short stature without completing a thorough evaluation to rule out pathologic causes, as early identification of abnormal growth patterns offers the greatest chance for appropriate diagnosis and treatment 3