What is Sermorelin (growth hormone-releasing hormone (GHRH) analogue) used for?

Sermorelin: A Growth Hormone-Releasing Hormone Analogue

Sermorelin is a synthetic 29-amino acid analogue of growth hormone-releasing hormone (GHRH) that stimulates endogenous growth hormone (GH) secretion from the anterior pituitary, primarily used as a diagnostic test for GH deficiency in children and, less commonly, as a therapeutic agent for select cases of idiopathic GH deficiency of hypothalamic origin. 1

Mechanism of Action

• Sermorelin acts through G-protein coupled receptors (GPCR) on pituitary somatotrophs, activating adenylyl cyclase, cyclic AMP, and protein kinase A pathways to stimulate GH release 2
• It represents the shortest synthetic peptide with full biological activity of GHRH, retaining complete functionality despite being shorter than the native 44-amino acid hormone 1
• The peptide specifically targets the anterior pituitary to trigger endogenous GH secretion rather than providing exogenous hormone replacement 1

Diagnostic Applications

Intravenous sermorelin at 1 mcg/kg bodyweight provides a rapid and relatively specific provocative test for diagnosing GH deficiency, with fewer false-positive responses compared to other stimulation tests. 1

• The test produces rapid GH responses that help differentiate true GH deficiency from normal variants 1
• However, normal GH responses to sermorelin cannot exclude GH deficiency due to hypothalamic deficits; subnormal responses to other provocative tests are needed to confirm disease in these patients 1
• Adult data suggest combining intravenous sermorelin with arginine provides more specific testing, though this requires further evaluation in pediatric populations 1

Therapeutic Use in Children

Indications and Patient Selection

• Sermorelin therapy should only be considered after documenting persistent growth failure (height below 3rd percentile AND height velocity below 25th percentile for ≥6 months in older children) 3
• GH deficiency must be established through appropriate GH-stimulation tests using validated cut-points before initiating any GH-related therapy 3
• Slow-growing, shorter children with delayed bone age and height age appear to have the best response to sermorelin treatment 1

Dosing and Administration

• The standard therapeutic regimen is subcutaneous sermorelin 30 mcg/kg bodyweight given once daily at bedtime 1
• This dosing schedule takes advantage of the physiologic nocturnal GH surge 1

Efficacy Limitations

Sermorelin demonstrates inferior efficacy compared to recombinant human growth hormone (rhGH) for treating GH deficiency, with inconsistent growth responses that limit its clinical utility. 4

• In comparative studies, subcutaneous sermorelin 30 mcg/kg/day (whether as continuous infusion or divided doses) produced smaller increases in height velocity than once-daily subcutaneous somatropin 30 mcg/kg 1
• One study of seven children with hypothalamic GH deficiency showed that continuous subcutaneous GHRH at 4-6 mcg/kg twice daily failed to improve growth rate in five patients over 6 months; when switched to rhGH 2 U/m² daily, all patients achieved mean growth rates of 8.5 cm/year 4
• Limited data suggest significant height velocity increases can be sustained for 12 months in some prepubertal children with idiopathic GH deficiency, with effects potentially maintained for 36 months in a few cases 1
• The effect of long-term sermorelin treatment on final adult height remains undetermined 1

Pharmacokinetics

• After intravenous injection, sermorelin is rapidly eliminated, yet GH levels remain elevated for approximately 3 hours 5
• Intranasal absorption through nasal mucosa is poor, with bioavailability only 3-5% 5
• Maximal GH release (mean peaks ~90 mU/L) occurs with intravenous doses of 1-2 mcg/kg 5
• Intranasal administration requires approximately 50 mcg/kg to achieve potency equivalent to 1 mcg/kg intravenous dose 5

Safety Profile

Sermorelin is well tolerated with minimal adverse effects at both diagnostic and therapeutic doses. 1

• Transient facial flushing is the most commonly reported adverse event 1
• Pain at injection site occurs with subcutaneous administration 1
• Repeated intranasal administration does not suppress nocturnal GH secretion, suggesting no negative feedback on endogenous GH production 5

Clinical Context and Current Role

• Sermorelin cannot be recommended for routine therapy of children with GH deficiency since single daily doses of rhGH produce catch-up growth that sermorelin therapy does not consistently achieve 4
• The availability of large quantities of recombinant hGH has made direct GH replacement the preferred therapeutic approach 2
• Sermorelin remains primarily a diagnostic tool rather than a first-line therapeutic agent 1
• The peptide is prohibited by the World Anti-Doping Agency (WADA), though detection in anti-doping samples has been limited due to small urinary concentrations and complex metabolism 6

Key Clinical Pitfalls

• Do not assume sermorelin will produce equivalent growth outcomes to rhGH therapy; direct comparative data show inferior efficacy 4
• Do not interpret normal sermorelin stimulation test results as definitively excluding GH deficiency, particularly in hypothalamic disorders where other provocative testing is required 1
• Do not initiate any GH-related therapy without first documenting true growth failure through objective measurements over appropriate time periods (≥6 months in older children) 3