Proper Usage and Dosage of Sermorelin for Growth Hormone Deficiency
Sermorelin (GHRH analogue) is not recommended as first-line therapy for growth hormone deficiency, as direct growth hormone replacement therapy has demonstrated superior efficacy in promoting catch-up growth and improving final height outcomes.
Mechanism and Indications
Sermorelin is a 29-amino acid analogue of human growth hormone-releasing hormone (GHRH) that stimulates the pituitary gland to release endogenous growth hormone. It represents the shortest synthetic peptide that maintains the full biological activity of GHRH 1.
Primary uses:
- Diagnostic testing: Sermorelin at 1 μg/kg bodyweight intravenously can be used as a provocative test for diagnosing growth hormone deficiency 1
- Treatment option: May be considered in select cases of growth hormone deficiency where the defect is at the hypothalamic level rather than the pituitary level
Dosing Recommendations
When used for treatment (though not first-line):
- Standard dosage: 30 μg/kg bodyweight subcutaneously once daily, administered at bedtime 1
- Alternative regimens: Some studies have explored twice-daily administration at 15 μg/kg per dose 2
- Duration: Treatment should continue until final height is reached or until transition to direct growth hormone therapy
Efficacy Considerations
Sermorelin has demonstrated limited efficacy compared to direct growth hormone replacement:
- Sermorelin produces significant increases in height velocity compared to pre-treatment (from 3.3 cm/year to 6.0 cm/year in one study) 2
- However, direct growth hormone therapy produces superior growth responses (7.5 cm/year in the same comparative study) 2
- Another study found that 5 out of 7 children with hypothalamic GH deficiency showed no improvement with GHRH administration, while all responded to direct GH therapy 3
Monitoring Parameters
For patients on sermorelin therapy:
- Height velocity every 3 months
- Bone age assessment every 6-12 months
- IGF-1 levels periodically to assess adequacy of response
- Glucose metabolism parameters (fasting glucose, insulin)
- Thyroid function tests
Adverse Effects
Sermorelin is generally well-tolerated with minimal side effects:
- Transient facial flushing (most common)
- Pain at injection site
- Potential for mild insulin resistance (though less pronounced than with direct GH therapy) 4
Special Considerations
Patient Selection
Sermorelin may be more appropriate for:
- Children with documented hypothalamic (rather than pituitary) cause of GH deficiency
- Patients with slow growth, shorter stature, and delayed bone age 1
- Cases where direct GH therapy is unavailable or contraindicated
Limitations
- Effect on final adult height remains undetermined 1
- Less effective than direct GH therapy in radiation-induced GH deficiency 2
- Requires functioning pituitary gland to be effective
Clinical Decision Algorithm
- Confirm growth hormone deficiency through standard provocative testing
- Determine if deficiency is of hypothalamic or pituitary origin
- Consider direct GH therapy as first-line treatment (0.025-0.05 mg/kg/day)
- Reserve sermorelin (30 μg/kg/day) for:
- Cases where the defect is primarily hypothalamic
- Situations where direct GH therapy is unavailable
- Patients who cannot tolerate direct GH therapy
Important Caveats
- The European Society for Paediatric Nephrology recommends direct GH therapy for growth failure in children with chronic conditions 5
- Growth hormone therapy should be initiated early to maximize catch-up growth potential and final height outcomes 5
- Careful monitoring for metabolic effects is necessary with any growth hormone-related therapy 4