Can a child experience excessive growth due to elevated growth hormone (GH) levels?

Can Children Experience Excessive Growth Due to Elevated Growth Hormone Levels?

Yes, children can grow too much too fast due to elevated growth hormone (GH) levels, leading to pituitary gigantism when it occurs before epiphyseal fusion, which can cause significant health complications and requires prompt medical intervention. 1

Clinical Presentation of Excessive Growth

Children with GH excess typically present with:

• Accelerated growth velocity >+2 standard deviation score (SDS) 1
• Abnormally tall stature defined as +2 or +3 SDS above age-appropriate and sex-appropriate mean height or +2 SDS above mid-parental height 1
• Persistently elevated growth velocity (>2 SDS) 1

Additional clinical features that may develop include:

• Acral enlargement (disproportionately enlarged hands and feet)
• Coarsened facial features
• Prognathism (protruding jaw)
• Dental malocclusion and teeth separation
• Frontal bossing
• Excessive sweating
• Headache and visual field defects
• Delayed puberty
• Joint pain and hypermobility

Diagnostic Approach

Testing for GH excess should be offered to children with:

1. Excess height (more than 2 SDS) OR
2. Consistently elevated height velocity AND
3. Acromegalic features, with or without delayed puberty or family history of pituitary adenoma 1

Key diagnostic tests include:

• Serum insulin-like growth factor 1 (IGF1) level in relation to age-adjusted, sex-adjusted, and Tanner stage-matched normal range 1
• Oral glucose tolerance test to assess GH suppression (GH levels should suppress below 1 μg/l in response to glucose load) 1

Etiology

The most common causes of GH excess in children include:

1. Somatotroph pituitary adenoma (somatotrophinoma) - most common cause 1
2. Genetic conditions:
   • X-linked acrogigantism (typically presents before age 5, usually before 2 years) 1
   • McCune-Albright syndrome (early onset from 3 years onwards) 1
   • Carney complex 1
   • MEN1 syndrome 1

Health Implications

Excessive growth due to elevated GH levels can lead to significant health complications:

• Insulin resistance and occasionally secondary diabetes mellitus 1
• Hypertension 1
• Sleep disturbance and sleep apnea 1
• Left ventricular hypertrophy and diastolic dysfunction 1
• Carpal tunnel syndrome 1
• Kyphosis 1
• Long-term risk of obesity and non-communicable diseases 2

Special Considerations

Differential Diagnosis

It's important to distinguish pathological growth acceleration from:

1. Normal pubertal growth spurt - GH suppression can be difficult to achieve in normal adolescence, particularly during mid-puberty (Tanner stage 2-3) 1

2. Appropriate catch-up growth - which may be beneficial in certain populations:

   • Preterm infants 2
   • Children with chronic kidney disease who have growth failure 1

Pitfalls in Diagnosis

Several factors can confound the diagnosis:

• IGF1 values might be falsely normal or low in children with concurrent severe hypothyroidism, malnutrition, or severe infection 1
• IGF1 values might be falsely elevated in children without GH-secreting adenoma in poorly controlled diabetes mellitus, hepatic and/or renal failure 1
• Oral estrogens can reduce IGF1 generation by the liver 1
• Approximately 30% of children with tall stature may lack normal GH suppression after glucose load 1

Management Approach

For confirmed cases of pathological GH excess:

1. Referral to pediatric endocrinology is essential
2. Imaging studies (contrast-enhanced pituitary MRI) to identify potential adenomas
3. Genetic testing - particularly important as gigantism has an identifiable genetic basis in almost 50% of patients 1
4. Treatment options - typically involve addressing the underlying cause (e.g., surgical removal of adenoma)

Only FDA-approved recombinant human growth hormone (rhGH) should be used when GH therapy is indicated for conditions such as GH deficiency or growth failure in chronic kidney disease 3, 4.