What is the proper usage and administration of Sermorelin (Growth Hormone-Releasing Hormone)?

Sermorelin: Proper Usage and Administration

Primary Indication and Mechanism

Sermorelin is a 29-amino acid analogue of growth hormone-releasing hormone (GHRH) that specifically stimulates growth hormone secretion from the anterior pituitary, but its clinical utility is limited primarily to diagnostic testing rather than routine treatment of growth hormone deficiency. 1

Diagnostic Use

Intravenous Administration for GH Deficiency Testing

• Administer 1 mcg/kg body weight as a single intravenous bolus for diagnostic evaluation of growth hormone deficiency 1
• This dose provides a rapid and relatively specific test with fewer false positives compared to other provocative tests 1
• Maximal GH release (mean peaks of approximately 90 mU/L) occurs with doses of 1-2 mcg/kg intravenously 2
• Important caveat: 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

Therapeutic Use (Limited Role)

Subcutaneous Administration for Growth Promotion

• Dosage: 30 mcg/kg body weight given subcutaneously once daily at bedtime 1
• Alternative regimen studied: 4-6 mcg/kg twice daily subcutaneously 3

Expected Outcomes and Limitations

• Sermorelin is NOT recommended for routine therapy of children with growth hormone deficiency because recombinant human growth hormone (rhGH) produces superior catch-up growth that sermorelin therapy does not consistently achieve 3
• In comparative studies, only 2 of 7 children with hypothalamic GH deficiency showed improved growth rates with sermorelin (4-6 mcg/kg twice daily), while all patients improved when switched to rhGH 2 U/m² daily 3
• When effective, sermorelin at 30 mcg/kg daily can sustain significant increases in height velocity for up to 12 months, with limited data suggesting effects may persist for 36 months 1
• Slow-growing, shorter children with delayed bone and height age appear to have the best response 1

Predictive Factors for Response

• A pretreatment peak serum GH response above 30 mU/L during an intravenous GHRH test predicts a good growth response to sermorelin therapy, though lower peaks do not preclude response 4
• Children previously responsive to human GH tend to show correlation between their hGH response and GHRH response 4

Intranasal Administration (Investigational)

• Intranasal bioavailability is only 3-5% 2
• Approximately 50 mcg/kg intranasally produces effects comparable to 1 mcg/kg intravenously 2
• Repeated intranasal administration (three times daily) maintains sustained GH response without suppression of nocturnal GH secretion 2
• This route remains investigational and is not standard practice 2

Safety Profile

Common Adverse Events

• Transient facial flushing (most common) 1
• Pain at injection site 1
• Development of anti-GHRH antibodies in approximately 78% of patients (14 of 18), though these do not appear to adversely affect growth or GH responses 4

Contraindications (Based on Related GHRH Analogue Data)

• Disruption of hypothalamic-pituitary axis due to hypophysectomy, hypopituitarism, pituitary tumor/surgery, head irradiation, or head trauma 5
• Active malignancy (GHRH induces release of endogenous GH, a known growth factor) 5
• Pregnancy 5
• Known hypersensitivity to sermorelin or excipients 5

Malignancy Concerns

• Critical safety consideration: Pharmacological dosing of growth-promoting agents raises concerns about future malignancy risk, particularly in children without classic severe GH deficiency 6
• For patients with history of malignancy, therapy should only be initiated after careful evaluation of benefit versus risk of reactivation 5

Clinical Algorithm for Use

1. For diagnostic purposes: Use IV sermorelin 1 mcg/kg as provocative test in conjunction with conventional tests 1

2. For therapeutic consideration:

   • First verify true GH deficiency with multiple provocative tests 1
   • Prioritize recombinant human GH over sermorelin for treatment, as rhGH demonstrates superior efficacy 3
   • Consider sermorelin only in select cases where rhGH is unavailable or contraindicated, using 30 mcg/kg subcutaneously at bedtime 1
   • Monitor growth velocity at 6-month intervals 4

3. If inadequate response after 6 months: Switch to recombinant human GH therapy 3

Key Clinical Pitfalls

• Do not assume sermorelin will produce equivalent growth outcomes to recombinant GH - direct comparisons show inferior results with sermorelin 3
• Do not rely solely on sermorelin testing to exclude GH deficiency - hypothalamic defects may show normal sermorelin responses but still require treatment 1
• Do not treat children close to puberty without careful consideration, as benefits on final adult height become increasingly unlikely 6
• The effect of long-term sermorelin treatment on final adult height remains undetermined 1