Short Stature in Pediatric Age: Diagnostic Evaluation Tool

Clinical History Assessment

Systematic approach to history taking for a child presenting with short stature

Physical Examination Guide

Systematic approach to examining a child with short stature

Diagnostic Approach

Initial Assessment

For a child presenting with short stature, the initial assessment should include:

• Detailed growth history with accurate height measurements plotted on appropriate growth charts
• Family growth history including parental heights and growth patterns
• Complete physical examination to identify dysmorphic features or systemic disease
• Assessment of growth velocity over time (minimum 6-12 months observation preferred)
• Evaluation of pubertal status and bone age

Definitions and Clinical Significance

Understanding key definitions in growth assessment:

Term	Definition	Clinical Significance
Short Stature	Height below -2 SD (3rd percentile) for age, sex, and population	Statistical definition that warrants evaluation
Growth Velocity	Rate of growth over time (cm/year)	More sensitive indicator than single height measurement
Growth Deceleration	Decreasing growth velocity or crossing percentile lines downward	Suggests pathological growth even if absolute height is normal
Target Height	Midparental height ±6.5 cm (boy/girl) or (father+mother+13)/2 ±6.5 cm for boys and (father+mother-13)/2 ±6.5 cm for girls	Genetic potential for height; values outside this range suggest pathology
Bone Age	Radiological assessment of skeletal maturity	Helps predict adult height and identify etiology of short stature

Differential Diagnosis

Category	Conditions	Clinical Features
Normal Variants	- Familial (genetic) short stature - Constitutional growth delay - Combination of both	- Family history of short stature - Normal growth velocity - Delayed bone age in constitutional delay - Pubertal delay in constitutional delay - Normal body proportions
Endocrine Causes	- Growth hormone deficiency - Hypothyroidism - Cushing syndrome - Growth hormone resistance - Hypopituitarism	- Growth deceleration - Central obesity with GH deficiency - Delayed bone age - Delayed puberty - Neonatal hypoglycemia, micropenis in congenital GH deficiency
Chromosomal Disorders	- Turner syndrome - Down syndrome - Prader-Willi syndrome - Noonan syndrome	- Dysmorphic features - Associated congenital anomalies - Developmental delay (variable) - Other system involvement - Typical phenotypic features
Chronic Diseases	- Inflammatory bowel disease - Chronic kidney disease - Cystic fibrosis - Cardiac disease - Celiac disease - Rheumatologic disorders	- System-specific symptoms - Poor weight gain often precedes height deceleration - Delayed bone age - Delayed puberty - Signs of specific underlying disease
Skeletal Dysplasias	- Achondroplasia - Hypochondroplasia - Osteogenesis imperfecta - Mucopolysaccharidoses	- Disproportionate short stature - Abnormal body proportions - Radiographic skeletal abnormalities - Often present at birth - Family history in some cases
Psychosocial	- Psychosocial dwarfism - Neglect - Malnutrition - Emotional deprivation	- Growth failure with catch-up in new environment - Abnormal behavior - Developmental delay - Signs of neglect - Disordered eating patterns
Intrauterine Growth Restriction	- Small for gestational age (SGA) - Fetal alcohol syndrome - Congenital infections	- Birth weight and/or length <-2 SD - Specific dysmorphic features in syndromes - May have catch-up growth in first 2 years - Lack of catch-up by age 2-3 years suggests permanent short stature

Laboratory Studies

First-line investigations for short stature:

Investigation	Clinical Utility	When to Consider
Complete Blood Count	Screen for chronic inflammation, anemia	All patients as part of initial screening
Chemistry Panel (electrolytes, renal function, liver function)	Screen for chronic kidney disease, liver disease	All patients as part of initial screening
Thyroid Function Tests (TSH, Free T4)	Screen for hypothyroidism	All patients as part of initial screening
IGF-1, IGFBP-3	Screen for GH deficiency/resistance	Severe short stature, growth deceleration, or delayed bone age
Celiac Antibody Panel	Screen for celiac disease	All patients, especially those with GI symptoms or family history
Karyotype	Screen for Turner syndrome, other chromosomal disorders	All girls with unexplained short stature, boys with genital abnormalities
Erythrocyte Sedimentation Rate, C-Reactive Protein	Screen for inflammatory conditions	Suspected chronic inflammatory disease
Bone Age X-ray (left wrist and hand)	Assess skeletal maturity	All patients with significant short stature

Advanced Studies

Consider when initial evaluation suggests specific diagnoses:

Investigation	Clinical Utility	When to Consider
Growth Hormone Stimulation Tests	Diagnose GH deficiency	Low IGF-1, IGFBP-3, significant growth deceleration, suggestive clinical features
Genetic Testing (e.g., SHOX gene, syndromic gene panels)	Identify genetic causes of short stature	Dysmorphic features, skeletal abnormalities, family history of genetic disorders
MRI of Brain (pituitary focus)	Evaluate pituitary abnormalities	Confirmed or strongly suspected GH deficiency, multiple pituitary hormone deficiencies
Skeletal Survey	Diagnose skeletal dysplasias	Disproportionate short stature, suspected skeletal dysplasia
Chromosomal Microarray	Identify microdeletions or duplications	Developmental delay, dysmorphic features, normal karyotype
GHRH-R Gene Testing	Diagnose isolated GH deficiency	Severe GH deficiency with family history

Diagnostic Algorithm

A stepwise approach to diagnosing short stature:

1. Accurate height measurement plotted on appropriate growth chart
2. Calculate growth velocity over minimum 6-month period
3. Calculate target height based on parental heights
4. Detailed history and physical examination including body proportions
5. Obtain bone age X-ray and compare with chronological age
6. First-line laboratory testing (CBC, chemistry, thyroid, celiac, karyotype in girls)
7. Categorize based on findings:
   • Normal variant (familial short stature or constitutional delay) if appropriate family history, normal body proportions, normal labs, appropriate bone age delay
   • Pathological short stature requiring further investigation if red flags present
8. Second-line investigations guided by clinical suspicion (GH testing, genetic studies, etc.)
9. Referral to pediatric endocrinologist for pathological short stature or unclear diagnosis

Management Strategies

General Approach to Management

Key principles in managing short stature in children:

• Establish correct diagnosis: Treatment depends on accurate identification of etiology
• Treat underlying condition: When specific cause is identified (e.g., hypothyroidism, celiac disease)
• Growth monitoring: Regular height and weight measurements with accurate plotting
• Psychosocial support: Address psychological impact of short stature
• Growth-promoting therapy: Consider in specific indications
• Multidisciplinary approach: Involve relevant specialists based on etiology

Management of Normal Variants

Condition	Management Approach	Prognosis and Follow-up
Familial Short Stature	- Reassurance about normal variant - Regular growth monitoring - Psychosocial support if needed - Growth hormone therapy generally not indicated	- Adult height likely within target height range - Follow-up every 6-12 months until final height achieved - Normal timing of puberty expected - Normal growth velocity maintained
Constitutional Growth Delay	- Reassurance about eventual catch-up - Regular growth monitoring - Psychological support for delayed puberty - Consider brief testosterone in boys with significant pubertal delay and psychological impact	- Normal adult height usually achieved, but later than peers - Follow-up every 6 months through puberty - Delayed but normal puberty expected - Family history often positive

Specific Treatment for Pathological Short Stature

Condition	Treatment Approach	Expected Outcomes
Growth Hormone Deficiency	- Recombinant human GH (rhGH) - Typical dose: 0.16-0.24 mg/kg/week - Daily subcutaneous injections - Monitor IGF-1 levels, growth response	- First-year growth velocity often doubles - Height gain of 8-12 cm in first year - Height normalization in most cases - Adult height within target range possible with early treatment
Turner Syndrome	- High-dose rhGH (up to 0.375 mg/kg/week) - Consider estrogen therapy for pubertal induction - Comprehensive care for associated conditions - Early initiation improves outcomes	- Average height gain of 5-12 cm - Best results with early initiation - Adult height remains below population average - Timing of estrogen initiation impacts final height
Chronic Kidney Disease	- Optimize nutrition and renal management - rhGH if growth failure persists - Dose: 0.05 mg/kg/day - Consider renal transplantation	- Variable response depending on CKD stage - Catch-up growth possible with early treatment - Pubertal delay common - Improved growth after transplantation
Small for Gestational Age without Catch-up	- rhGH after age 2-4 years if no catch-up - Dose: 0.035-0.07 mg/kg/day - Early initiation preferred - Long-term treatment required	- First-year height velocity increase of 3-4 cm - Final height improvement of 7-10 cm - Better results with earlier initiation - Monitor for insulin resistance
SHOX Deficiency	- rhGH (0.35 mg/kg/week) - Address associated skeletal abnormalities - Early initiation recommended	- Response similar to Turner syndrome - Height gain of 7-10 cm possible - Treatment most effective before puberty - Monitor for skeletal complications
Prader-Willi Syndrome	- rhGH from diagnosis (0.24 mg/kg/week) - Strict weight management - Sleep study before initiation - Multidisciplinary approach	- Improved body composition - Increased height velocity - Enhanced physical performance - Monitor for scoliosis and glucose intolerance
Hypothyroidism	- Levothyroxine replacement - Dose based on weight and age - Regular monitoring of thyroid function - Adjust dose as needed	- Rapid catch-up growth with treatment - Normal adult height possible with early diagnosis - Monitoring of bone age advancement - Lifelong therapy often needed

Growth Hormone Therapy: FDA-Approved Indications

Indication	Diagnostic Criteria	Treatment Considerations
Growth Hormone Deficiency	- Height <-2.25 SD - Growth velocity <-1 SD - Failed GH stimulation tests - Low IGF-1 and IGFBP-3	- Generally most responsive to treatment - Monitor for recombinant GH antibodies - Long-term therapy until final height - May need retesting after completion of growth
Turner Syndrome	- Karyotype confirmation - Typical height deficit	- Earlier initiation improves outcome - Higher doses than GHD - Combined with estrogen replacement (delayed timing) - Long-term treatment required
Small for Gestational Age without Catch-up	- Birth weight/length <-2 SD - Height at age 2-4 years <-2 SD - No catch-up growth	- Initiate after age 2 years - Monitor metabolic parameters - Potential for insulin resistance - Consider genetic testing
Chronic Renal Insufficiency	- Documented CKD - Growth failure despite optimal management	- Continue through transplantation - Adjust dosing with renal function - Monitor fluid retention - Coordinate with nephrology
Prader-Willi Syndrome	- Genetic confirmation - Growth failure	- Screen for sleep apnea before starting - Monitor glucose homeostasis - Benefits beyond height improvement - Address scoliosis risk
SHOX Deficiency	- Genetic confirmation - Height <-2 SD	- Similar protocol to Turner syndrome - Monitor for skeletal disproportions - Long-term treatment - Early initiation recommended
Noonan Syndrome	- Clinical/genetic diagnosis - Height <-2 SD	- Monitor cardiac function - Moderate height gains expected - Long-term treatment - Regular ophthalmology follow-up
Idiopathic Short Stature	- Height <-2.25 SD - Normal GH stimulation tests - No other identified cause	- Modest expected height gain (4-7 cm) - Cost-benefit considerations - Limited insurance coverage - Treatment until near-final height

Growth Hormone Therapy: Monitoring and Safety

• Pre-treatment evaluation:
  • Baseline IGF-1, thyroid function, glucose metabolism
  • Bone age determination
  • Ophthalmologic evaluation if risk factors present
  • Sleep study for PWS or significant obesity
• Ongoing monitoring:
  • Height, weight, BMI every 3-6 months
  • Annual bone age after age 5-6 years
  • IGF-1 levels (maintain between 0 and +2 SD)
  • Thyroid function annually
  • Glucose metabolism annually
  • Spinal examination annually (scoliosis risk)
• Potential adverse effects:
  • Injection site reactions (common)
  • Intracranial hypertension (rare)
  • Slipped capital femoral epiphysis (rare)
  • Glucose intolerance (monitoring needed)
  • Scoliosis progression (monitoring needed)
• Contraindications:
  • Active malignancy
  • Severe respiratory compromise (for PWS)
  • Active proliferative diabetic retinopathy
  • Severe obesity in PWS

Psychosocial Management

• Psychological support: Address bullying, self-image concerns, and social challenges
• Family education: Realistic expectations about treatment outcomes
• School involvement: Ensure supportive school environment
• Age-appropriate discussion: Include child in decision-making as appropriate
• Support groups: Connect with other families facing similar challenges

When to Refer

• Pediatric Endocrinologist:
  • Height <-2.5 SD at any age
  • Height <-2 SD with growth velocity <-1 SD
  • Height >2 SD below target height
  • Height crossing percentiles downward
  • Severe short stature with dysmorphic features
• Medical Genetics:
  • Disproportionate short stature
  • Multiple congenital anomalies
  • Syndromic features
  • Family history of genetic disorders
• Other Specialists: Based on suspected etiology (gastroenterology, nephrology, etc.)
• Psychology/Psychiatry: Significant psychosocial impact of short stature