What are the indications for growth hormone (GH) replacement in adults?

Indications for Growth Hormone Replacement in Adults

Growth hormone replacement therapy in adults is indicated for patients with confirmed growth hormone deficiency (GHD) who have either adult-onset or childhood-onset GHD.

Diagnostic Criteria for Adult GHD

GHD in adults can be diagnosed in patients who meet either of the following criteria:

1. Adult-onset GHD: Patients who have developed GHD as adults, either alone or with multiple hormone deficiencies (hypopituitarism), resulting from:

   • Pituitary disease
   • Hypothalamic disease
   • Surgery
   • Radiation therapy
   • Trauma 1

2. Childhood-onset GHD: Patients who were GH deficient during childhood due to:

   • Congenital causes
   • Genetic causes
   • Acquired conditions
   • Idiopathic causes 1

Confirmation of Diagnosis

According to current standards, confirmation of adult GHD diagnosis requires:

• An appropriate GH provocative test (stimulation test) with two exceptions:
  1. Patients with multiple pituitary hormone deficiencies due to organic disease
  2. Patients with congenital/genetic GHD 1

Specific Clinical Indications

1. Post-Cushing's Disease

• GH deficiency is common in patients with Cushing's disease, with prevalence ranging from 50-60% when tested within 2 years after surgery to 8-13% when tested more than 2 years after surgery 2
• Testing for GHD is recommended at least 6-12 months after successful treatment of Cushing's disease when HPA axis recovery is expected 2
• For children and young people in remission from Cushing's disease who have not completed linear growth, dynamic testing for GH deficiency should be considered soon after definitive therapy 2

2. Other Pituitary Conditions

• Testing for GHD is indicated in patients with dilated cardiomyopathy who have other signs and symptoms of GH disorders 2
• Patients with 3 or more pituitary hormone deficiencies are more likely to have GHD and do not need dynamic testing 2

3. Post-Radiation or Surgery

• GHD is common after pituitary surgery and radiation therapy
• After radiotherapy, additional anterior pituitary deficiencies can develop over time 2

Clinical Features of Adult GHD

Adults with untreated GHD typically present with:

• Abnormal body composition (increased visceral fat, reduced muscle mass)
• Reduced bone mineral density and increased fracture risk
• Adverse cardiovascular risk profile
• Impaired quality of life
• Reduced exercise capacity
• Elevated total and LDL cholesterol
• Increased cardiovascular mortality 3, 4, 5

Treatment Approach

Dosing

• Initial dosing should be low with gradual increases to minimize side effects
• For adults with GHD, the FDA-approved product Nutropin AQ is administered as a subcutaneous injection 1
• Dosing should be individualized based on:
  • Age (dose requirement decreases with age)
  • Sex (women typically require higher doses, especially those on oral estrogen)
  • Time of GHD onset (childhood vs. adult onset) 5, 6

Monitoring

• Serum IGF-1 is the most commonly used biomarker for GH dose titration 5
• Monitor for side effects including fluid retention and insulin resistance 7
• In patients with pre-existing glucose intolerance, GH treatment may worsen glucose metabolism 2

Special Considerations

Patients with History of Cushing's Disease

• GH replacement therapy should be offered promptly to children and young people in remission from Cushing's disease who are proven GH deficient or fail to show catch-up growth 2
• For adults with persistent GHD after Cushing's disease treatment, GH replacement can improve body composition, bone mineral density, and quality of life 2

Patients with Cardiovascular Disease

• GH replacement may improve cardiovascular parameters in GH-deficient patients with dilated cardiomyopathy 2
• Appropriate therapy of GH deficiency should be performed in all patients with coexisting dilated cardiomyopathy 2

Contraindications and Cautions

• Active malignancy (due to potential mitogenic effects of GH)
• Critical illness
• Diabetic retinopathy
• Intracranial hypertension

Expected Benefits of Treatment

• Improved body composition (decreased fat mass, increased lean body mass)
• Increased bone mineral density
• Improved lipid profile
• Enhanced quality of life
• Increased exercise capacity
• Potential reduction in cardiovascular risk 4, 5, 7

GH replacement therapy has been shown to be generally well-tolerated with appropriate dosing and monitoring, with evidence suggesting it may reduce the excess mortality observed in untreated GH-deficient adults.