GH-receptor antagonist

GH-Receptor Antagonists

Key Points

Primary agent: Pegvisomant
Selective growth hormone receptor antagonist
Used in resistant cases of gigantism and early-onset acromegaly
Requires careful monitoring due to potent GH-blocking effects

Overview

Growth hormone receptor antagonists represent a specialized class of medications used in pediatric endocrinology for managing conditions of excessive growth hormone action. Pegvisomant is the primary medication in this class, offering a unique approach to blocking GH effects at the receptor level.

Mechanism of Action

Molecular Basis

Receptor Interaction
- Competitive binding to GH receptors
- Prevents functional dimerization
- Blocks intracellular signaling cascade
- Inhibits IGF-1 production
Pharmacological Properties
- PEGylated analog of human GH
- Enhanced receptor binding affinity
- Prolonged half-life due to PEGylation
- Reduced immunogenicity

Physiological Effects

Primary Actions
- Reduction in IGF-1 levels
- Decreased somatic growth
- Improved metabolic parameters
- Reduction in GH-dependent symptoms
Tissue-Specific Effects
- Decreased hepatic IGF-1 production
- Reduced soft tissue overgrowth
- Impact on bone metabolism
- Effects on glucose homeostasis

Clinical Indications

Primary Indications

Pediatric Gigantism
- Resistant to first-line treatments
- Post-surgical persistent disease
- Bridge therapy before definitive treatment
- Combined therapy with somatostatin analogs
Early-Onset Acromegaly
- Refractory cases
- Contraindications to surgery
- Adjuvant therapy
- Genetic forms of GH excess

Special Considerations

Patient Selection
- Failed previous therapies
- Genetic testing results
- Growth velocity assessment
- Quality of life impact
Treatment Goals
- IGF-1 normalization
- Growth rate control
- Symptom improvement
- Prevention of long-term complications

Administration & Dosing

Dosing Guidelines

Initial Dosing
- Loading dose: 40 mg subcutaneously
- Starting maintenance: 10 mg/day
- Age and weight considerations
- Individual response assessment
Dose Titration
- Adjust by 5-10 mg increments
- Based on IGF-1 levels
- Maximum: 30 mg/day in children
- Frequency: Weekly adjustments

Administration Technique

Injection Procedure
- Subcutaneous administration
- Rotation of injection sites
- Proper storage requirements
- Patient/caregiver training
Practical Considerations
- Daily administration timing
- Storage conditions
- Travel considerations
- Emergency supply planning

Monitoring & Safety

Initial Assessment

Baseline Evaluation
- IGF-1 levels
- Liver function tests
- Growth parameters
- Metabolic profile
- Tumor imaging if applicable

Ongoing Monitoring

Regular Assessments
- IGF-1 levels every 4-6 weeks initially
- Monthly liver function tests
- Growth velocity every 3-4 months
- Bone age annually
- Quality of life measures
Safety Monitoring
- Liver enzyme monitoring
- Tumor size assessment
- Glucose homeostasis
- Development of antibodies

Side Effects and Management

Common Side Effects
- Injection site reactions
- Liver function abnormalities
- Headache
- Fatigue
- Gastrointestinal symptoms
Management Strategies
- Proper injection technique
- Dose adjustments if needed
- Regular monitoring schedule
- Patient education
- Early intervention for side effects

Long-term Considerations

Growth pattern monitoring
Final height predictions
Transition planning to adult care
Fertility preservation discussions