1. Overview
The Glucagon Stimulation Test (GST) is a dynamic endocrine function test used to evaluate the integrity of the hypothalamic–pituitary–adrenal (HPA) axis and growth hormone (GH) reserve. By administering glucagon intramuscularly, the test induces hyperglycemia, which stimulates insulin release and indirectly triggers the secretion of growth hormone (GH) and adrenocorticotropic hormone (ACTH) through the hypothalamic–pituitary axis.
GST is particularly valuable as an alternative to the Insulin Tolerance Test (ITT) when ITT is contraindicated. It is commonly used in both pediatric and adult populations to assess pituitary function, GH deficiency, and secondary or tertiary adrenal insufficiency.
2. Symptoms / Clinical Context
GST itself does not diagnose symptoms directly but is indicated in patients presenting with clinical features suggestive of hormonal deficiencies. These may include short stature or growth failure in children, features of GH deficiency or acromegaly, unexplained hypoglycemia, fatigue, weakness, weight loss, or symptoms of cortisol deficiency.
It is also used in the evaluation of suspected pituitary dysfunction, adrenal insufficiency, and disorders of glucose metabolism.
3. Causes / Physiological Basis
Glucagon increases blood glucose by stimulating hepatic glycogenolysis. This metabolic stress activates counter-regulatory hormonal responses, including the release of GH and ACTH, followed by cortisol secretion from the adrenal glands.
An inadequate hormonal response during the test suggests dysfunction of the pituitary gland or impaired hypothalamic signaling. Poor glucose response may indicate impaired glycogenolysis or hepatic dysfunction.
4. Risk Factors and Contraindications
GST should not be performed in certain high-risk conditions due to the potential for severe adverse reactions. Contraindications include:
- Pheochromocytoma, where glucagon may precipitate a hypertensive crisis
- Insulinoma, due to the risk of severe hypoglycemia
- Prolonged starvation (>48 hours)
- Glycogen storage diseases
- Severe hypocortisolaemia
- Malnourished patients
- Severe fasting hyperglycemia (>180 mg/dL)
Careful patient selection and clinical evaluation are essential before performing the test.
5. Prevention, Procedure, and Clinical Management
Preparation before the test includes stopping estrogen therapy at least six weeks prior, discontinuing growth hormone therapy 4–6 weeks before testing, overnight fasting from midnight (water allowed), recording body weight, obtaining a baseline ECG, and reviewing current medications with a physician.
Test protocol requires strict one-to-one nursing supervision. An intravenous cannula is placed for serial blood sampling. Glucagon is administered intramuscularly at a dose of 1.0 mg for patients ≤90 kg and 1.5 mg for patients >90 kg.
Blood samples are collected for growth hormone, cortisol, and blood glucose at baseline (0 minutes) and at 30, 60, 90, 120, 150, 180, 210, and 240 minutes. Patients are monitored throughout the test and observed for at least one hour afterward. Blood glucose must be above 72 mg/dL before discharge, and patients should eat before leaving the test area.
Interpretation of results:
- Growth Hormone: A peak value >8.3 ng/mL indicates an adequate response. Peak levels <7 ng/mL suggest GH deficiency, while values between 7.0–8.3 ng/mL indicate partial deficiency.
- Cortisol: An adequate response is defined as a peak >18–20 µg/dL. Lower values suggest secondary or tertiary adrenal insufficiency.
- Blood Glucose: A rise of ≥20–30 mg/dL from baseline is expected; a poor rise suggests impaired glycogenolysis or liver dysfunction.
Clinical utility of GST includes diagnosis of GH deficiency in children, confirmation of adult GH deficiency, assessment of adrenal function, differentiation of Cushing syndrome from pseudo-Cushing states, investigation of hypoglycemia, and comprehensive pituitary function testing.
The test offers several advantages: it is safer than ITT, does not induce hypoglycemia, is widely available, and relatively inexpensive.
Limitations include common side effects such as nausea, vomiting, and headache, lower sensitivity compared to ITT, long test duration (3–4 hours), need for trained personnel, and contraindications in certain endocrine tumors.
