Growth Hormone Deficiency in Children

Growth Hormone Deficiency (GHD) is characterized by insufficient production of growth hormone (GH) from the anterior pituitary gland, leading to impaired growth and metabolic dysfunction.

Key Points

• Incidence: 1:4,000 to 1:10,000 live births
• Can be congenital or acquired
• May present as isolated GHD or as part of multiple pituitary hormone deficiencies
• Early diagnosis and treatment are crucial for optimal growth outcomes

Etiology and Classification

Congenital Causes

• Genetic mutations affecting GH synthesis or secretion (GH1, GHRHR, PROP1, POU1F1)
• Developmental defects: septo-optic dysplasia, holoprosencephaly
• Midline defects associated with hypothalamic-pituitary dysfunction

Acquired Causes

• Central nervous system tumors (craniopharyngioma, germinoma)
• Post-treatment effects: cranial radiation, surgery
• Infiltrative diseases: histiocytosis, sarcoidosis
• Trauma, infections, autoimmune conditions

Clinical Features

Growth Patterns

• Decreased growth velocity (< 25th percentile for age)
• Height below genetic potential
• Delayed bone age compared to chronological age

Physical Characteristics

• Proportionate short stature
• Central adiposity with decreased lean muscle mass
• Delayed dentition
• Frontal bossing and immature facial features
• High-pitched voice
• Delayed puberty in adolescents

Associated Features

• Hypoglycemia (especially in infants)
• Micropenis in males with congenital forms
• Fatigue and decreased exercise tolerance
• Poor nail and hair growth

Diagnosis and Evaluation

Initial Assessment

• Detailed growth charts and growth velocity calculations
• Family history and parental heights
• Medical history including birth history and previous treatments

Laboratory Evaluation

• IGF-1 and IGFBP-3 levels
• GH stimulation tests (two different stimuli):
  • Insulin tolerance test
  • Glucagon stimulation
  • Clonidine stimulation
  • Arginine stimulation
• Other pituitary hormone evaluation (TSH, ACTH, FSH, LH)

Imaging Studies

• Bone age x-ray (left hand and wrist)
• MRI of hypothalamic-pituitary region

Management

Growth Hormone Replacement

• Recombinant human GH (rhGH) administered subcutaneously daily
• Starting dose: 0.16-0.24 mg/kg/week divided into daily doses
• Dose adjustments based on growth response and IGF-1 levels

Additional Management

• Treatment of other pituitary hormone deficiencies if present
• Regular monitoring of growth velocity
• Psychosocial support and counseling
• Transition planning for adolescents

Monitoring and Complications

Regular Monitoring

• Height, weight, and BMI every 3-6 months
• IGF-1 levels every 6-12 months
• Bone age annually
• Thyroid function if on GH therapy

Potential Complications

• Slipped capital femoral epiphysis
• Intracranial hypertension
• Glucose intolerance
• Scoliosis progression

Prognosis and Outcomes

• Early diagnosis and treatment initiation correlate with better height outcomes
• Final height potential influenced by:
  • Age at diagnosis
  • Severity of GHD
  • Adherence to treatment
  • Genetic potential
• Quality of life improvements with treatment
• Need for lifelong GH replacement in severe cases