Growth Hormone Stimulation Testing with Arginine and Glucagon: Fasting Requirements
Yes, the child must fast overnight before growth hormone stimulation testing using arginine and glucagon. This is explicitly stated in the FDA-approved testing protocol and is essential for accurate test results.
Fasting Protocol
The overnight fast is mandatory and must continue throughout the entire test period 1. According to the FDA drug label for arginine:
- The test should be scheduled in the morning following a normal night's sleep
- An overnight fast must continue through the test period
- The child should be placed at bed rest for at least 30 minutes before infusion begins
This fasting requirement applies to both arginine and glucagon stimulation tests, as both are used interchangeably as provocative tests for growth hormone deficiency (GHD) diagnosis 2, 3.
Why Fasting Matters
The fasting state is critical because:
- Baseline glucose levels affect test interpretation: Glucagon's mechanism involves secondary stimulation of endogenous insulin release, making glucose monitoring essential 2
- Food intake can interfere with GH secretion: Growth hormone is secreted episodically, and metabolic factors from recent meals can confound results
- Test standardization: Fasting ensures comparable conditions across all patients and reduces false-positive results
Test Administration Details
For Arginine Testing:
- Pediatric dose: 0.5 g/kg (5 mL/kg of R-Gene® 10) infused over 30 minutes, maximum 30 g 1
- Adult dose: 30 g infused over 30 minutes 1
- Blood samples drawn at: -30,0,30,60,90,120, and 150 minutes 1
For Glucagon Testing:
- GH release may be delayed compared to other secretagogues
- Monitoring over at least 3 hours is recommended 2
- Critical safety consideration: Monitor glucose carefully for possible delayed hypoglycemia due to glucagon's mechanism of action 2
Clinical Context and Test Selection
The Endocrine Society guidelines suggest that when GHRH is unavailable and ITT (insulin tolerance test) is contraindicated or impractical, the glucagon stimulation test can be used 2. Both ITT and glucagon testing evaluate the complete hypothalamic-somatotroph axis, which is particularly important after cranial radiation therapy 3.
Recent evidence suggests that glucagon as the first test may be superior to arginine, with a lower rate of discordant results (37.4% vs 50.7%) when two sequential tests are required 4. This potentially reduces the need for a second test, minimizing patient burden.
Important Caveats
Factors That Blunt GH Response:
- Obesity: May significantly reduce GH response to both tests 2, 5. BMI-SDS shows a negative association with peak GH levels (β = -1.10, p < 0.001) 5
- Hypothyroidism and hypogonadism: Must be adequately replaced before testing 2
- Sex steroid deficiency: In peripubertal children, consider sex steroid priming to improve test specificity 6
Test-Specific Considerations:
- Arginine alone has poorer diagnostic performance compared to GHRH-arginine combination or glucagon 2
- Glucagon produces higher mean GH values (9.65 ng/mL) compared to arginine (8.50 ng/mL) 5
- GH cut-off levels: 10 ng/mL in the United States, though some advocate for 7 ng/mL with newer assays 7
Safety Monitoring:
For glucagon specifically, monitor for delayed hypoglycemia throughout the 3-hour testing period, as this is a known risk due to its mechanism involving insulin release 2. Ensure IV access is maintained and glucose monitoring equipment is readily available.
Bottom line: The overnight fast is non-negotiable for both arginine and glucagon stimulation testing. Schedule the test in the morning, ensure the child has fasted overnight, maintain the fast throughout testing, and keep the child at bed rest for optimal results 1.