What is the proper protocol for Sermorelin (growth hormone-releasing hormone (GHRH) analogue) treatment?

Sermorelin Treatment Protocol

Sermorelin should be administered subcutaneously at a dose of 30 micrograms/kg body weight once daily at bedtime for children with growth hormone deficiency, with treatment sustained for at least 12 months to achieve significant increases in height velocity. 1, 2

Indications for Sermorelin Therapy

• Diagnostic use: Intravenous sermorelin at 1 microgram/kg body weight serves as a rapid and specific provocative test for growth hormone deficiency, producing fewer false-positive responses compared to other stimulation tests 1
• Therapeutic use: Prepubertal children with idiopathic growth hormone deficiency who demonstrate subnormal growth hormone responses to provocative testing are candidates for treatment 1, 2
• Special populations: Children with chronic kidney disease (CKD stages 3-5) may benefit from sermorelin therapy, with 5 out of 9 patients showing improved growth velocity in one study 3

Important caveat: Normal growth hormone responses to intravenous sermorelin cannot exclude hypothalamic growth hormone deficiency—subnormal responses to other provocative tests are needed to confirm disease in these patients 1

Treatment Protocol

Dosing Regimen

• Standard dose: 30 micrograms/kg body weight administered subcutaneously once daily at bedtime 1, 2
• Alternative regimen: For more intensive therapy, 1-2 micrograms/kg every 3 hours via subcutaneous pump has shown efficacy, though this is less practical 4
• Twice-daily dosing: 26 micrograms/kg/day divided into two subcutaneous injections has been used in CKD patients 3

Expected Response

• Initial response: Mean height velocity increases from baseline 4.1 cm/year to 8.0 cm/year at 6 months and 7.2 cm/year at 12 months of therapy 2
• Response rate: Approximately 74% of growth hormone-deficient children demonstrate a good response at 6 months 2
• Sustained effect: Growth acceleration is maintained through 12 months of continued treatment, with limited data suggesting effects persist up to 36 months 1
• Best responders: Slower growing, shorter children with delayed bone age and height age demonstrate the most favorable responses 1

Monitoring Requirements

Baseline Assessment

• Growth hormone response to acute GHRH test (1 microgram/kg IV) 3
• Height standard deviation score (SDS) and baseline growth velocity 3, 2
• Bone age radiography 2
• Fasting glucose and insulin-like growth factor I (IGF-I) levels 2

Follow-up Monitoring (Every 3-6 Months)

• Growth parameters: Height velocity, height SDS, and bone age progression 2
• Metabolic parameters: Fasting glucose concentration and IGF-I generation 2
• Renal function (if applicable): Serum urea and creatinine in CKD patients 3
• Safety monitoring: General biochemical and hormonal analyses 2

Critical monitoring point: The ratio of change in bone age to height age should remain approximately 1.0, indicating proportional skeletal maturation without excessive bone age advancement 2

Safety Profile and Adverse Events

• Common side effects: Transient facial flushing and pain at injection site are the most frequently reported adverse events 1
• Metabolic effects: No adverse changes in fasting glucose or excessive IGF-I generation occur with recommended dosing 2
• Renal considerations: In CKD patients, mean serum urea and creatinine remain stable, though 2 of 9 patients on conservative treatment showed moderate creatinine increases 3
• Overall tolerability: Sermorelin is well tolerated with both single intravenous doses and repeated daily subcutaneous administration 1, 2

Special Populations

Chronic Kidney Disease Patients

• Sermorelin may serve as an alternative therapy to increase growth velocity in CKD patients on conservative treatment, dialysis, or post-transplantation 3
• Response predictor: Patients with lower peak GH response to acute GHRH testing demonstrate better growth responses to chronic therapy 3
• No consistent adverse effects on renal function have been detected 3

Elderly Adults (Age-Advanced Populations)

• Dosing: 10 micrograms/kg administered subcutaneously nightly at 2100h for age-advanced men and women (ages 55-71 years) 5
• Effects: Activates the somatotropic axis, increasing IGF-I and IGFBP-3 levels within 2 weeks, with effects sustained for 12 weeks 5
• Gender differences: Men show greater anabolic effects including increased lean body mass, insulin sensitivity, general well-being, and libido compared to women 5
• Adverse effects: Transient hyperlipidemia may occur but typically resolves by end of treatment 5

Comparison to Growth Hormone Therapy

Sermorelin produces smaller increases in height velocity compared to recombinant growth hormone: Subcutaneous sermorelin 30 micrograms/kg/day (whether as continuous infusion or divided doses) results in less height velocity increase than once-daily subcutaneous somatropin 30 micrograms/kg body weight 1

However, sermorelin offers the theoretical advantage of preserving physiologic pulsatile GH secretion patterns rather than providing continuous exogenous hormone exposure 4

Duration of Therapy

• Minimum duration: At least 12 months of treatment is necessary to assess efficacy and achieve sustained growth acceleration 1, 2
• Extended therapy: Treatment can be continued for 2-4 years with maintained growth velocities ranging from 4.5 to 8.2 cm/year using 3 micrograms/kg/pulse dosing 4
• Long-term outcomes: The effect of long-term treatment on final adult height remains to be determined 1