Growth Hormone Stimulation
Rationale: Growth hormone (GH) is secreted in a pulsatile manner and is cleared rapidly, resulting in dramatic fluctuations in GH levels.1-3 For this reason, random GH levels are generally not useful in establishing GH deficiency. A number of physiologic and pharmacologic stimuli can be used to provoke GH release. Several growth hormone stimulation protocols are described below. These tests are best performed in the morning after an overnight fast.3 Patients should be confirmed as euthyroid before these protocols are initiated.
GH Stimulation in Children
The exercise stimulation test is often used as an initial screen for GH deficiency, but combinations of other tests have been advocated by various institutions. A subnormal response from a single provocative test is not diagnostic for GH deficiency and should be confirmed with a second provocative test. These tests produce an increase in plasma GH to >7 ng/mL in individuals with appropriate GH production.1-3 Some institutions use 10 ng/mL as a cutoff for normal GH response.1,3
The insulin-induced hypoglycemia and the GHRH tests provide additional information beyond establishing GH deficiency. The insulin-induced hypoglycemia test allows the assessment of the entire hypothalamic-pituitary-adrenal (HPA) axis. A normal GH response (>7 ng/mL) to GHRH in a patient proven to be GH deficient by previous stimulation testing suggests that the GH deficiency is due to insufficient GHRH production by the hypothalamus.
Due to low baseline levels of GH, prepubertal children should be “primed” prior to performing the stimulation tests by one of the following:3
- 5 mg Premarin® PO the night before and the morning of the test, or
- 50−100 μg/day of ethinyl estradiol for three consecutive days prior to testing, or
- 100 mg/day depot testosterone for three consecutive days prior to testing
GH Stimulation in Adults
The insulin-induced hypoglycemia test is considered to be the test of choice for diagnosing GH deficiency in adults.4 Since this test involves some risk to the patient (see note below), the GHRH + arginine test has been proposed as an equally sensitive alternative.5 Most normal adults will produce a GH concentration >5 ng/mL after either of these stimulation protocols. Severe GH deficiency has been defined as the inability to produce GH levels >3 ng/mL during these tests.4,5
Arginine Stimulation Protocol
Arginine hydrochloride, 0.5 g/kg body weight, is infused IV over 30 minutes. Exercise (10 to 15 minutes) may be added to potentiate the response. Collect GH samples at baseline, 30, 60, 90, and 120 minutes.1
Note: Arginine should be administered with caution in patients with liver or renal disease. The patient can walk around during the test.
Orderable Tests: Growth Hormone, Five Specimens (038836) (baseline, 30-, 60-, 90-, and 120-minute)
Clonidine Stimulation Protocol
Clonidine is administered at a dose of 0.15 mg/m2. Collect GH samples at baseline, 30, 60, 90, and 120 minutes.2
Note: Patients can complain of tiredness and postural hypotension can occur.
Orderable Tests: Growth Hormone, Five Specimens (038836) (baseline, 30-, 60-, 90-, and 120-minute)
Exercise Stimulation Protocol
The subject is asked to exercise vigorously for 20 minutes (ie, calisthenics or running up and down stairs). Collect a sample for GH immediately after the exercise.1
Orderable Tests: See Comprehensive List of Procedures section for individual test information.
Growth Hormone Releasing Hormone (GHRH) Stimulation Protocol
GHRH at 1.0 μg/kg body weight is administered by IV bolus. Collect GH samples at baseline, 15, 30, 45, 60, 90, and 120 minutes.3
Note: Estrogen priming does not enhance GH response to GHRH.2 Patients may experience flushing and may describe a metallic taste in their mouth.
Orderable Tests: Growth Hormone, Seven Specimens (038869) (baseline, 15-, 30-, 45-, 60-, 90-, and 120-minute)
Insulin-induced Hypoglycemia Protocol
The patient should remain recumbent for 30 minutes prior to the initiation and during the test.1Regular insulin, 0.10 unit/kg body weight, is administered by IV injection. Collect samples at baseline, 30, 60, and 90 minutes for glucose, GH, and cortisol determination. Glucose levels should be followed using bedside glucose monitoring. Adequate pituitary stimulation is evident when the patient becomes symptomatic (sweating or tremor), and/or when the glucose level drops below 45 mg/dL within 30 minutes. Additional insulin can be administered at 30 minutes if these criteria are not met. In this case, an additional (120-minute) sample should be collected. Cortisol levels at peak >20 μg/dL suggest that the HPA axis is intact. GH and ACTH levels reflect hypothalamic and pituitary functionality respectively.
Orderable Tests:
Growth Hormone, Four Specimens (045997) (baseline, 30-, 60-, and 90-minute);
Growth Hormone, Five Specimens (038836) (baseline, 30-, 60-, 90-, and 120-minute);
Cortisol, Four Specimens (026948) (baseline, 30-, 60-, and 90-minute);
Cortisol, Five Specimens (039222) (baseline, 30-, 60-, 90-, and 120-minute)
Note: This test is not without risk and a physician should be present; IV glucose should be available in case of severe hypoglycemia. The test should not be performed in patients with seizure disorder or cardiovascular disease.
Levodopa Stimulation Protocol
Levodopa should be administered orally at a dose of 10 mg/kg in children or 500 mg in adults. Collect GH samples at 30, 60, 90, and 120 minutes.2
Note: Patients may be given water throughout the test but should remain recumbent. Nausea and vomiting may occur.
Orderable Tests: Growth Hormone, Five Specimens (038836) (baseline, 30-, 60-, 90-, and 120-minute)
References
1. Demers LM. Pituitary function. In: Burtis CA, Ashwood ER, eds.Tietz Textbook of Clinical Chemistry.3rd ed. Philadelphia, Pa: WB Saunders; 1999: 1470-1499.
2. Wass JAH, Besser GM. Tests of pituitary function. In: DeGroot LJ, Besser GM, Burger HG, et al, eds. Endocrinology. 3rd ed. Philadelphia, Pa: WB Saunders; 1994: 487-496.
3. Rosenfield RG. Disorders of growth hormone and insulin-like growth factor secretion and action. In: Sperling MA, ed. Pediatric Endocrinology. Philadelphia, Pa: WB Saunders; 1996: 117-169.
4. Consensus Guidelines for the Diagnosis and Treatment of Adults With Growth Hormone Deficiency: Summary Statement of the Growth Hormone Research Society Workshop on Adult Growth Hormone Deficiency. J Clin Endocrinol Metab. 1998; 83(2):379-381. PubMed 9467545
5. Aimarette G, Corneli G, Razzore P, et al. Comparison between insulin-induced hypoglycemia and growth hormone (GH)-releasing Hormone + arginine as provocative tests for the diagnosis of GH deficiency in adults. J Clin Endocrinol Metab. 1998; 83(5):1615-1618. PubMed 9589665