What are the guidelines for using Sermorelin peptide (growth hormone-releasing hormone (GHRH) analogue)?

Sermorelin Peptide: Clinical Guidelines and Evidence

No Established Guidelines for General Clinical Use

Sermorelin (GHRH 1-29 analogue) lacks established clinical practice guidelines for routine therapeutic use, and the available evidence is limited to historical research from the 1990s with no recent high-quality studies supporting its widespread clinical application.

Diagnostic Applications

Growth Hormone Deficiency Testing

• Intravenous sermorelin 1 mcg/kg bodyweight serves as a rapid and relatively specific provocative test for diagnosing growth hormone deficiency in children 1
• Sermorelin produces fewer false-positive GH responses compared to other provocative tests in children without true GH deficiency 1
• Critical limitation: Normal GH response to sermorelin cannot exclude hypothalamic GH deficiency, requiring confirmation with subnormal responses to other provocative tests 1
• The combination of intravenous sermorelin with arginine may provide more specific testing, though pediatric data remain limited 1

Historical Therapeutic Use (Not Current Standard of Care)

Idiopathic Growth Hormone Deficiency in Children

• Historical studies used subcutaneous sermorelin 30 mcg/kg bodyweight given once daily at bedtime for treating prepubertal children with idiopathic GH deficiency 1
• Treatment produced significant increases in height velocity sustained through 12 months, with limited data suggesting effects maintained for 36 months 1
• Catch-up growth occurred primarily in slower-growing, shorter children with delayed bone and height age 1

Comparative Efficacy Concerns

• Sermorelin at 30 mcg/kg/day (given as continuous infusion or 3 divided doses) produced smaller increases in height velocity compared to once-daily somatropin 30 mcg/kg/day 1
• This inferior efficacy likely explains why sermorelin never became standard therapy despite initial promise

Alternative Dosing Regimens (Experimental)

• Low-dose sermorelin 1-2 mcg/kg given subcutaneously every 3 hours by pump promoted growth in 5 of 7 patients after 1 year, with growth velocities of 4.5-8.2 cm/year maintained for 2-4 years using 3 mcg/kg/pulse 2
• Twice-daily subcutaneous injections of 20 mcg/kg increased height velocity from 4.8 cm/year to 7.2 cm/year after 12 months in children with idiopathic short stature 3
• Cessation of therapy resulted in catch-down growth during the first 3 months, with return to pretreatment velocity by 12 months off therapy 3

Safety Profile

• Transient facial flushing and injection site pain are the most commonly reported adverse events 1
• Both intravenous single-dose and repeated subcutaneous daily dosing are well tolerated 1
• Fasting blood glucose and insulin levels increased during therapy in some studies 3

Current Clinical Context

Why Sermorelin Is Not Standard Therapy

• Recombinant human growth hormone (somatropin) remains the established first-line treatment for GH deficiency, as evidenced by modern guidelines focusing on somatropin rather than GHRH analogues 4, 5
• The lack of recent research (no studies after 1999 in provided evidence) and absence from current endocrine society guidelines indicates sermorelin has been superseded by more effective therapies
• Effect on final adult height remains undetermined 1

Populations That May Have Responded

• Therapy appeared more effective in patients with mild GH insufficiency than severe insufficiency 3
• Children with idiopathic short stature (height <3rd percentile, peak GH >20 mU/L on provocative testing) showed growth acceleration 3
• Limited data suggest potential benefit in chronic renal failure patients, though results were inconsistent (5 of 9 patients responded) 6

Critical Pitfalls

• Do not use sermorelin as replacement for established GH therapy with somatropin - the evidence base is outdated and efficacy is inferior 1
• Do not rely solely on sermorelin testing to exclude GH deficiency - hypothalamic defects may show normal responses 1
• Recognize that growth acceleration is temporary - cessation leads to catch-down growth 3
• The attenuation of GH response after repeated GHRH exposure reflects short-term negative feedback rather than true desensitization 2