What is the treatment for low Insulin-like Growth Factor 1 (IGF-1) levels?

Treatment for Low Insulin-like Growth Factor 1 (IGF-1) Levels

The primary treatment for low IGF-1 levels is recombinant human growth hormone (rhGH) therapy, which stimulates IGF-1 synthesis, normalizes somatomedin bioactivity, and promotes growth and metabolic function. 1

Diagnostic Evaluation Before Treatment

Before initiating treatment, a thorough evaluation should be conducted:

• Verify low IGF-1 using age-specific and sex-specific reference ranges
• Complete pituitary hormone assessment to identify potential causes 2
• Evaluate for growth hormone deficiency using GH stimulation testing if indicated
• Obtain pituitary MRI to evaluate for structural abnormalities
• Check thyroid function (TSH, free T4) to rule out non-GH deficiency causes
• Assess nutritional status and energy availability

Treatment Algorithm

First-Line Treatment: Growth Hormone Therapy

• Dosing: 0.045-0.05 mg/kg/day by daily subcutaneous injections 1
• Administration: Given as daily subcutaneous injections
• Duration: Until final height is reached in children or continued long-term in adults with documented deficiency

Special Populations:

1. Children with CKD (Chronic Kidney Disease):

   • GH insensitivity is common in advanced CKD
   • Recommended GH dosage: 0.045-0.05 mg/kg/day 1
   • Monitor for potential side effects including adenotonsillar hypertrophy and obstructive sleep apnea

2. Post-Renal Transplantation:

   • Consider initiating GH therapy 1 year after transplantation if spontaneous catch-up growth does not occur 1
   • Ensure steroid doses are minimized if possible

3. Prader-Willi Syndrome:

   • GH treatment can begin as early as 2-3 months of age 1
   • Requires polysomnography before and 6-10 weeks after beginning treatment
   • Monitor for potential respiratory complications

Monitoring During Treatment

• IGF-1 levels at least twice yearly, dosing GH to keep IGF-1 in physiologic range 1
• Polysomnography 6-10 weeks after initiation of therapy in children with risk factors for sleep apnea
• Regular monitoring of head circumference in children, especially if fontanelles are open when GH is started
• Glucose metabolism assessment due to potential insulin resistance
• Bone density assessment due to increased osteoporosis risk

Potential Drug Interactions

• Glucocorticoids: May attenuate growth-promoting effects of somatropin; adjust doses carefully 3
• Oral Estrogens: May reduce IGF-1 response to somatropin; women receiving oral estrogen may require higher somatropin doses 3
• Insulin/Hypoglycemic Agents: Dose adjustments may be needed when somatropin therapy is initiated 3
• CYP450-Metabolized Drugs: Somatropin may alter clearance of compounds metabolized by CYP450 liver enzymes 3

Common Pitfalls and Considerations

• Unmasking Central Hypoadrenalism: GH therapy may inhibit 11βHSD-1 and reduce serum cortisol concentrations, potentially unmasking previously undiagnosed central hypoadrenalism 3
• Sleep Apnea Risk: Adenotonsillar hypertrophy and obstructive apnea may occur during GH therapy, particularly in children with PWS 1
• Elderly Patients: May be more sensitive to somatropin; consider lower starting doses and smaller increments 3
• Renal Impairment: Patients with chronic renal failure tend to have decreased somatropin clearance; adjust dosing accordingly 3

Alternative Treatments for Specific Causes of Low IGF-1

• Malnutrition: Increase caloric intake, target adequate energy availability
• Hypothyroidism: Initiate thyroid hormone replacement
• Pituitary Adenoma: Refer to neurosurgery for evaluation, consider medical therapy based on adenoma type
• Severe Primary IGF-1 Deficiency: Consider direct rhIGF-1 therapy at 120 μg/kg twice daily by SC injection 4

Growth hormone therapy remains the cornerstone of treatment for low IGF-1 levels, with demonstrated efficacy in improving growth, body composition, and metabolic parameters across various patient populations.