What is the most likely diagnosis for a 9-year-old boy with short stature, delayed bone age, and low Insulin-like Growth Factor-1 (IGF-1) level?

Growth Hormone Deficiency

This 9-year-old boy most likely has Growth Hormone Deficiency (GHD), as evidenced by the markedly low IGF-1 level (18 ng/mL, well below the normal range of 67-405 ng/mL) combined with delayed bone age (6 years in a 9-year-old child) and short stature. 1

Key Diagnostic Features Supporting GHD

The constellation of findings strongly points toward GHD rather than the other options:

• Severely low IGF-1: At 18 ng/mL, this is dramatically below the age-appropriate range (67-405 ng/mL), which is the most reliable marker for GH axis dysfunction 1
• Delayed bone age: A 3-year delay (bone age of 6 years in a 9-year-old) is characteristic of GHD and distinguishes it from familial short stature 2, 3
• Normal GH level: The random GH of 4.9 pg/L (within normal range 2-10 pg/L) does not exclude GHD, as GH is secreted in pulses and random levels are unreliable 3
• Proportionate short stature: Height of 120 cm at age 9 with normal physical examination suggests an endocrine rather than skeletal dysplasia cause 1

Why Not the Other Diagnoses?

Failure to Thrive (Option A) is excluded because:

• This term applies to infants and young children with inadequate weight gain and poor caloric intake 1
• This 9-year-old has normal systemic review and physical examination without feeding difficulties 1
• Weight (25 kg) is proportionate to height, not suggesting nutritional deficiency 1

Familial Short Stature (Option B) is unlikely because:

• Familial short stature presents with normal bone age and normal growth velocity 1, 2
• This child has significantly delayed bone age (3 years behind chronologic age) 2
• IGF-1 levels are normal in familial short stature, not severely depressed 1, 2
• While the mother appears short, the dramatic IGF-1 deficiency and bone age delay indicate pathology beyond genetics 1

Diagnostic Algorithm for This Case

The evaluation follows established guidelines for short stature with endocrinopathy 1:

1. IGF-1 is the critical discriminator: Severely low IGF-1 (18 ng/mL vs normal 67-405 ng/mL) indicates GH axis dysfunction 1

2. Bone age assessment confirms pathology: The 3-year delay distinguishes GHD from familial short stature (which has normal bone age) 2, 3

3. Other pituitary hormones are normal: TSH, FSH, LH, and testosterone are all within normal ranges, suggesting isolated GHD rather than multiple pituitary hormone deficiency 1

4. Random GH level is misleading: The normal random GH (4.9 pg/L) does not exclude GHD because GH secretion is pulsatile; provocative testing would be needed for definitive diagnosis 3

Important Clinical Considerations

Common pitfall: Relying on random GH levels to exclude GHD. GH is secreted episodically, and random measurements have no diagnostic value 3. The severely low IGF-1 is far more informative as it reflects integrated GH action over time 1.

Hypertension concern: The blood pressure of 130/85 mmHg is elevated for a 9-year-old and should be monitored, though it does not change the primary diagnosis 1.

Next steps would include:

• GH stimulation testing (arginine or clonidine stimulation) to confirm GHD, with peak GH <10 μg/L being diagnostic 3
• MRI of the pituitary to evaluate for structural abnormalities 3
• Genetic testing if family history suggests hereditary GHD 1, 4

Treatment implications: If GHD is confirmed, recombinant human GH therapy at 0.045-0.05 mg/kg/day would be indicated, with the severely delayed bone age suggesting substantial remaining growth potential 1, 5.

The combination of severely low IGF-1, delayed bone age, and proportionate short stature makes GHD the most likely diagnosis, distinguishing it clearly from both failure to thrive and familial short stature 1, 2.