How do you interpret and manage low Insulin-like Growth Factor 1 (IGF1) levels?

Interpretation and Management of Low IGF-1 Levels

Low IGF-1 levels require a systematic evaluation of underlying causes before initiating treatment, with priority given to addressing nutritional status and energy availability as first-line interventions. 1

Causes of Low IGF-1

Low IGF-1 levels can result from various conditions:

• Primary causes:

  • Growth hormone deficiency
  • Growth hormone resistance
  • Genetic disorders affecting IGF-1 production 2
  • ALS (acid-labile subunit) deficiency 2

• Secondary causes:

  • Malnutrition or low energy availability 1, 3
  • Severe hypothyroidism 1
  • Oral estrogen therapy 1
  • Liver disease 4
  • Uncontrolled diabetes 4
  • Inflammatory conditions

Diagnostic Approach

1. Verify low IGF-1 using age-specific and sex-specific reference ranges 1

   • IGF-1 levels naturally decline with age
   • Compare to appropriate normative data

2. Rule out non-GH deficiency causes:

   • Assess nutritional status and energy availability 3, 5
   • Check thyroid function (TSH, free T4) 3, 1
   • Evaluate liver and kidney function 1
   • Review medications (especially oral estrogens) 1

3. Evaluate for GH deficiency:

   • GH stimulation testing (insulin tolerance test or GHRH-arginine test) 1
   • Pituitary MRI to evaluate for structural abnormalities 1
   • Complete pituitary hormone assessment (TSH, ACTH, FSH, LH, prolactin) 1

Management Algorithm

Step 1: Address Underlying Causes

• If nutritional deficiency/low energy availability:

  • Increase caloric intake by 20-30% over baseline energy needs 3
  • Target energy availability ≥45 kcal/kg of fat-free mass 3
  • Consider nutritional consultation 3
  • Monitor weight with goal of 0.5 kg gain every 7-10 days if underweight 3

• If hypothyroidism:

  • Initiate thyroid hormone replacement 3

• If pituitary adenoma or other structural abnormality:

  • Refer to neurosurgery for evaluation 1
  • Consider medical therapy based on adenoma type 3

Step 2: Monitor Response

• Recheck IGF-1 levels after addressing underlying causes
• For nutritional interventions, improvement in IGF-1 can be seen within days to weeks 3, 5
• IGF-1 is more sensitive to nutritional changes than albumin or transferrin 5

Step 3: Consider GH Replacement Therapy

• If confirmed GH deficiency and no improvement with addressing underlying causes:
  • Initiate GH replacement therapy 1
  • Titrate dose based on IGF-1 levels 1
  • Monitor for side effects (fluid retention, joint pain, carpal tunnel syndrome)

Special Considerations

• Female athletes with low energy availability:

  • Low IGF-1 is part of the Female Athlete Triad 3
  • Recovery of energy status precedes recovery of menstrual status and bone mineral density 3
  • Increasing energy availability is the primary intervention 3

• Acromegaly/GH excess:

  • Paradoxically, some patients with acromegaly may have low IGF-1 due to GH receptor antagonism 3
  • Requires different management approach with somatostatin analogues, dopamine agonists, or pegvisomant 3

• Genetic causes:

  • Patients with genetic defects in IGF-1 production may have more modest growth failure than expected 2
  • May require lifelong IGF-1 replacement

Monitoring and Follow-up

• Regular IGF-1 measurements to assess treatment efficacy
• Bone density assessment due to increased osteoporosis risk 1
• Regular follow-up imaging if structural pituitary abnormality is identified 1
• Monitor for development of other pituitary hormone deficiencies 1

Remember that IGF-1 is a sensitive marker of nutritional status, and nutritional interventions should be the first-line approach before considering hormone replacement therapy in most cases of low IGF-1.