Is the use of glucagon and ondansetron medically indicated for growth hormone stimulation testing in a patient with short stature and low growth velocity?

Medical Necessity Determination: Glucagon and Ondansetron for Growth Hormone Stimulation Testing

The use of glucagon (J1611) and ondansetron (Q0162) is medically indicated for growth hormone stimulation testing in this 8-year-old male with documented short stature (<1st percentile, Z-score -2.7 SD) and low-normal growth velocity (4.77 cm/year). 1

Rationale for Growth Hormone Stimulation Testing

Growth hormone stimulation testing is the appropriate diagnostic step for this patient based on established clinical criteria:

• The patient meets diagnostic thresholds with height below the 3rd percentile (Z-score -2.7 SD) and growth velocity at the lower end of normal (4.77 cm/year), which falls below the 25th percentile threshold that indicates progressive growth failure 2
• The patient has a complex medical history including global cerebral hypomyelination, developmental delay, and previous GJ tube dependence, all of which can be associated with growth hormone deficiency 3
• Mid-parental height is 5'9" (father 5'8", mother 5'5"), indicating significant deviation from genetic potential 2
• Bone age radiograph was appropriately obtained to assess remaining growth potential before proceeding with stimulation testing 3, 2

Medical Necessity of Glucagon Administration

Glucagon is an FDA-approved and guideline-supported agent for growth hormone stimulation testing:

• The FDA label explicitly indicates R-Gene® 10 (arginine hydrochloride) combined with glucagon as a diagnostic stimulant to assess pituitary reserve for human growth hormone in conditions including pituitary dwarfism and problems of growth and stature 1
• The glucagon test has demonstrated effective GH-releasing activity in young children with short stature, with studies showing median GH peak response of 13.5 mcg/liter in children under 6 years 4
• Combined arginine-glucagon testing is a standard protocol, as documented in the clinical notes where 0.618 mg glucagon was administered intramuscularly along with 10.3 g arginine intravenously 1
• The test successfully ruled out growth hormone deficiency in this patient, providing critical diagnostic information that will guide management decisions 5

Medical Necessity of Ondansetron Administration

Ondansetron administration was medically necessary to manage an expected adverse effect of the diagnostic procedure:

• The patient experienced two episodes of emesis at the 150-minute mark during the stimulation test, which is a known complication of glucagon administration 1
• Nausea and vomiting during growth hormone stimulation testing can compromise test completion and patient safety, particularly in a child with history of feeding difficulties and recent G-tube removal 3
• Ondansetron was appropriately ordered by the on-call provider and administered by nursing staff to control symptoms, allowing the patient to tolerate food and drink and complete the test safely 3
• The patient also experienced hypoglycemia at the 90-minute mark (requiring orange juice), demonstrating the metabolic stress of the test and justifying antiemetic prophylaxis for patient comfort and safety 3

Clinical Context Supporting Medical Necessity

The testing was performed according to appropriate clinical algorithms:

• Initial evaluation included bone age radiograph and consideration of nutritional factors (patient drinking Pediasure, G-tube recently removed, BMI normal) before proceeding to hormonal testing 3, 2
• The endocrinologist appropriately discussed additional evaluation with the family and documented the plan for growth hormone stimulation testing given the patient's height <1st percentile 3
• Testing confirmed the patient does NOT have growth hormone deficiency, which is critical information that prevents unnecessary and potentially harmful growth hormone therapy 3
• The test results will guide appropriate follow-up focused on growth trends, nutritional optimization, and management of underlying neurological conditions rather than hormonal replacement 3, 2

Important Clinical Caveats

Several factors support the appropriateness of this testing approach:

• Growth hormone deficiency is rare but when present in children with complex medical histories, responds well to therapy; therefore, definitive testing is warranted 3
• The false positive rate for arginine-glucagon testing is approximately 32% and false negative rate is approximately 27%, making confirmation of results important 1
• Random GH measurements are not recommended for screening (except in neonates) due to episodic and pulsatile secretion patterns, necessitating provocative testing 5
• The patient's complex medical history (cerebral hypomyelination, developmental delay, history of VSD, undescended testes) increases the likelihood of pituitary abnormalities that could affect growth hormone secretion 3, 6

The testing was performed safely with appropriate monitoring and management of complications, including hypoglycemia management with orange juice and antiemetic therapy with ondansetron when emesis occurred. 3