What is the approach to diagnosing and managing growth hormone (GH) deficiency in a short individual?

Diagnostic Approach to Growth Hormone Deficiency in Short Individuals

The diagnostic workup for growth hormone deficiency (GHD) in short individuals should begin with a thorough evaluation of growth patterns, family history, and physical examination, followed by targeted laboratory testing including growth hormone stimulation tests if indicated. 1

Initial Assessment

• Determine if short stature is isolated or associated with other physical/developmental abnormalities, and whether it is proportionate or disproportionate 2
• Document height (or supine length for patients <2 years) and calculate height velocity over at least 6 months, comparing to standardized growth charts 2
• Assess growth potential through calculation of genetic target height based on parental heights and evaluation of epiphyseal closure via left wrist radiography 2
• Review birth measurements (weight, length, head circumference) to identify any intrauterine growth restriction 2
• Evaluate for dysmorphic features that might suggest a syndrome or chromosomal abnormality 2

Differentiating Non-Pathologic from Pathologic Short Stature

• Constitutional delay of growth: characterized by deceleration of growth in first 3 years, normal velocity during childhood (4-7 cm/year), delayed bone age and puberty, with final adult height within normal range 2
• Familial short stature: early deceleration in linear growth, normal growth velocity, normal bone age and pubertal development, with final height appropriate for genetic target 2
• Pathologic short stature: crossing of several centile lines between 3 years and late childhood/early adolescence 2

Laboratory Evaluation for GHD

• Initial screening tests should include:

  • Complete blood count, comprehensive metabolic panel, thyroid function tests 1
  • IGF-1 and IGFBP-3 levels (low levels suggest GHD) 3
  • Bone age assessment via left wrist radiography 2

• Growth hormone stimulation testing is required for diagnosis of GHD:

  • Indicated when clinical suspicion exists after ruling out other causes 3
  • Random GH measurements are not recommended as GH secretion is pulsatile 3
  • Two stimulation tests showing peak GH levels <10 μg/L are typically required to confirm diagnosis 4
  • Common stimulation agents include clonidine, arginine, glucagon, and insulin 3

Imaging Studies

• MRI of the pituitary gland should be performed in confirmed GHD to identify structural abnormalities 4
• Fundoscopic examination to rule out papilledema before initiating GH therapy 2
• For disproportionate short stature, skeletal survey should be performed to evaluate for skeletal dysplasia 2

Special Considerations

• For girls with short stature, chromosomal analysis should be performed to rule out Turner syndrome, which is the most common pathologic diagnosis in genetic evaluations of short stature 1
• SHOX gene testing should be considered in cases of familial short stature with subtle skeletal changes or findings suggestive of dyschondrosteosis 2
• For children with chronic kidney disease, additional evaluation of renal function, metabolic status, and mineral dysregulation is necessary 2

Management After Diagnosis

• For confirmed GHD, recombinant human growth hormone therapy is recommended at a dosage of 0.16 to 0.24 mg/kg body weight/week divided over 6-7 days of subcutaneous injections 5
• Treatment should be supervised by a physician experienced in diagnosing and managing pediatric patients with short stature 5
• Treatment should be discontinued when height velocity drops below 2 cm/year and/or when epiphyseal growth plates close 6

Common Pitfalls to Avoid

• Failing to distinguish between normal variants (constitutional delay, familial short stature) and pathologic causes can lead to delayed or inappropriate treatment 1
• Missing Turner syndrome in girls with short stature 1
• Interpreting a single growth hormone stimulation test as definitive; two tests are typically required 4
• Not accounting for factors that can affect GH stimulation test results, such as obesity, puberty status, and concurrent medications 3
• Overlooking the need for regular monitoring of growth velocity during treatment 2

By following this systematic approach, clinicians can effectively diagnose and manage growth hormone deficiency in short individuals, improving outcomes related to final adult height, quality of life, and metabolic health.