Growth Hormone Deficiency
The most likely diagnosis is Growth Hormone Deficiency (GHD), based on the severely low IGF-1 level (18 ng/mL, dramatically below the normal range of 67-405 ng/mL) combined with a 3-year delayed bone age, which are the critical discriminators distinguishing GHD from benign variants of short stature. 1
Why This is Growth Hormone Deficiency
The diagnosis of GHD should be considered in children with severely low IGF-1 levels, delayed bone age, and proportionate short stature 1. This patient demonstrates all three cardinal features:
IGF-1 is the critical diagnostic marker: The IGF-1 level of 18 ng/mL is profoundly suppressed (normal 67-405 ng/mL), representing a reliable marker for GH axis dysfunction 1. IGF-1 mediates the postnatal growth effects of growth hormone, and such severe suppression indicates pathologic disruption of the GH-IGF-1 axis 2
Delayed bone age confirms pathology: The 3-year delay in bone age (6 years in a 9-year-old) is characteristic of GHD and is the key feature that distinguishes it from familial short stature, where bone age would be normal 1, 3
Proportionate short stature: Height of 120 cm at age 9 represents proportionate growth failure, suggesting an endocrine rather than skeletal dysplasia cause 1
Isolated hormone deficiency pattern: All other pituitary hormones (TSH, FSH, LH) are normal, suggesting isolated GHD rather than multiple pituitary hormone deficiency 1
Why NOT the Other Diagnoses
Familial Short Stature is excluded because it presents with normal bone age, normal growth velocity, and normal IGF-1 levels 1, 3. This patient has a 3-year delayed bone age and severely suppressed IGF-1, which are incompatible with familial short stature 1
Failure to Thrive is excluded because this diagnosis typically applies to infants and young children with inadequate weight gain and poor caloric intake 1. This 9-year-old is asymptomatic with normal physical examination and appropriate weight for height (25 kg at 120 cm) 1
Critical Diagnostic Algorithm
The diagnostic approach follows this hierarchy 1, 3:
- IGF-1 measurement is the primary screening tool - severely low levels indicate GH axis dysfunction 1
- Bone age assessment distinguishes pathologic causes (delayed) from familial short stature (normal) 1, 3
- Growth velocity documentation over 6 months identifies pathologic deceleration (crossing centile lines) 2, 3
- Other pituitary hormones differentiate isolated GHD from multiple pituitary hormone deficiency 1
Important Caveats About GH Testing
A critical pitfall to recognize: The "normal" random GH level of 4.9 pg/L in this case is misleading 4. GH stimulation tests have low specificity for diagnosing GHD, and children diagnosed with GHD based on stimulation tests often form a heterogeneous group with growth disorders frequently independent of GH function 4. However, when IGF-1 is severely suppressed and bone age is significantly delayed, these findings supersede the limitations of GH testing 1
Recent genetic studies show that in children with vertically transmitted short stature diagnosed with GHD, only 13% actually had genetic variants affecting GH secretion or function, while 67% had primary growth plate disorders 4. However, this patient's mother being short does not exclude GHD - it simply means genetic testing may be warranted if GH therapy response is suboptimal 4
Treatment Implications
If GHD is confirmed, recombinant human GH therapy at 0.045-0.05 mg/kg/day would be indicated 1. The severely delayed bone age (3-year delay) suggests substantial remaining growth potential, making this an optimal time to initiate therapy 1. Treatment should continue until height velocity drops below 2 cm/year and/or epiphyseal growth plates close 1, 5
The hypertension (130/85 mmHg) noted in this patient requires separate evaluation and management, as it is not a typical feature of isolated GHD 1