How is sermorelin (a synthetic growth‑hormone‑releasing hormone analogue) used to treat confirmed growth‑hormone deficiency, including indications, dosing (adult and pediatric), administration route, adverse effects, contraindications, and required monitoring?

Sermorelin Overview

Sermorelin is a synthetic 29-amino acid analogue of growth hormone-releasing hormone (GHRH) used primarily as a diagnostic test for growth hormone deficiency in children, with limited therapeutic application compared to recombinant human growth hormone. 1

Mechanism of Action

Sermorelin specifically stimulates growth hormone (GH) secretion from the anterior pituitary by activating adenylyl cyclase, cyclic AMP, and protein kinase A pathways through G-protein coupled receptors. 2 This mechanism differs from direct GH replacement and relies on intact pituitary function to produce endogenous GH. 1

Primary Clinical Use: Diagnostic Testing

Diagnostic Protocol

• Administer 1 mcg/kg intravenously as a single dose for provocative testing of GH deficiency 1
• Sermorelin testing produces fewer false-positive GH responses compared to other provocative tests, making it more specific for diagnosing true GH deficiency 1
• Critical limitation: Normal GH response to sermorelin cannot exclude hypothalamic GH deficiency; subnormal responses to other provocative tests are needed to confirm disease in these patients 1

Therapeutic Use (Limited)

Pediatric Dosing for Treatment

• 30 mcg/kg subcutaneously once daily at bedtime for prepubertal children with idiopathic GH deficiency 1, 3
• Some protocols use twice-daily subcutaneous injections 3

Efficacy Considerations

Sermorelin is less effective than recombinant human GH for promoting growth. 1 Height velocity increases with sermorelin 30 mcg/kg/day (given as continuous infusion or 3 divided doses) were inferior to those achieved with once-daily subcutaneous somatropin 30 mcg/kg/day. 1

Patient Selection for Therapy

Children most likely to respond to sermorelin treatment include:

• Slow-growing, shorter children with delayed bone age and delayed height age 1
• Those with peak serum GH response above 30 mU/L during intravenous GHRH testing (though lower peaks don't preclude response) 3
• Prepubertal children with idiopathic GH deficiency 1

Treatment Duration and Response

• Significant increases in height velocity can be sustained for 12 months of treatment 1
• Limited data suggest effects may be maintained for 36 months of continued treatment 1
• Sermorelin induces catch-up growth in the majority of GH-deficient children 1
• The effect on final adult height remains undetermined 1

Administration Route

• Intravenous: For diagnostic testing (1 mcg/kg single dose) 1
• Subcutaneous: For therapeutic use (30 mcg/kg once daily at bedtime) 1, 3

Adverse Effects

Sermorelin is generally well tolerated with minimal adverse events:

• Transient facial flushing (most common) 1
• Pain at injection site (most common) 1
• Development of anti-GHRH antibodies in some patients (14 of 18 in one study), though these did not adversely affect growth or GH responses 3

Contraindications

While not explicitly detailed in the evidence for sermorelin specifically, standard contraindications for GH-related therapies apply:

• Closed epiphyses 4
• Known hypersensitivity to the active substance or excipients 4
• Active malignancy 4
• Acute critical illness 4

Monitoring Requirements

No specific monitoring protocols for sermorelin are provided in the evidence. However, if used therapeutically, monitoring should parallel GH therapy protocols:

• Height velocity and growth parameters every 3-6 months 4
• Skeletal maturation via wrist radiography 4
• IGF-I levels to assess adherence and response 4
• Thyroid function (TSH, free T4) 4
• Glucose metabolism 4

Clinical Context and Limitations

Sermorelin has been largely superseded by recombinant human GH for therapeutic purposes due to superior efficacy. 1 Its primary role remains as a diagnostic tool for GH deficiency, where it offers better specificity than traditional provocative tests. 1 The combination of sermorelin with arginine may provide even greater diagnostic specificity, though this requires further evaluation in pediatric populations. 1

The requirement for intact pituitary function limits sermorelin's therapeutic utility to hypothalamic causes of GH deficiency, whereas recombinant GH can treat both hypothalamic and pituitary causes. 1, 2