Glucagon Stimulation Testing in Adult Growth Hormone Deficiency— A 2014 Update

Abstract

Growth hormone deficiency (GHD) in adults is characterized by alterations in body composition, carbohydrate and lipid metabolism, bone mineral density, cardiovascular risk profile, and quality of life.1 Treatment with GH replacement has been shown to improve many, but not all, of these abnormalities. 2 By contrast, untreated GHD is associated with increased mortality and morbidity that was previously observed in adults with hypopituitarism. 3,4 These findings were substantiated in two large surveys based on national Danish registries, 5,6 where the morbidity of adults with GHD was found to be approximately threefold higher than that of a healthy population. This result was independent of gender and applied to patients with childhood-onset and adult-onset GHD, with mortality of childhoodonset GHD far exceeding that of adult-onset GH deficient patients. 6Current published consensus guidelines recommend the evaluation of adult GHD to be based on clinical findings, medical history and using the appropriate GH stimulation test for biochemical confirmation, 7-9 with the exception of patients with three or more pituitary hormone deficiencies and low serum insulin-like growth factor 1 (IGF-1) levels. 10 Serum IGF-1 levels should not be used alone to diagnose adult GHD and the maximum or peak GH secretion following GH stimulation testing is used as a surrogate of the capacity of the pituitary to release GH. The insulin tolerance test (ITT) is widely considered as the gold standard test for evaluation of GH deficiency and has been endorsed by several consensus guidelines. [7][8][9]11 However, this test is labor intensive, may be unpleasant for some patients, has potential risks, and is contraindicated in elderly patients and in patients with seizure disorders and ischemic heart disease. AbstractGrowth hormone deficiency (GHD) is a well-recognized clinical syndrome in adults, and its diagnosis is established through one or more GH stimulation tests. The decision to perform GH stimulation testing should be based on medical history and clinical findings, and using appropriate GH stimulation test/s for biochemical confirmation. The insulin tolerance test (ITT) remains the diagnostic test of choice; however, this test is labor intensive, contraindicated in the elderly and in adults with seizure disorders and ischemic heart disease, can be unpleasant for the patient, and is potentially hazardous. With the discontinuation of the growth hormone releasing hormone (GHRH) analog (Geref ® ) in the US in 2008, the glucagon stimulation test (GST) has gained increasing popularity as the alternative test to the ITT because of its availability, reproducibility, safety, lack of influence by gender and hypothalamic cause of GH deficiency (GHD), and relatively few contraindications. In this article, recommendations for performing this test, the potential drawbacks in conducting and caveats in interpreting this test, and its future perspectives are discussed.

GH Replacement in the Elderly: Is It Worth It?

“…The latest guidelines do not provide suggestions on the most appropriate test to diagnose EGHD and no dedicated studies have been performed to define it. Moreover, two of the most widely used tests for the diagnosis of GHD -the insulin tolerance test (ITT) and the glucagon stimulation test (GST) -are generally avoided in the elderly, due to their potential detrimental effect on patients with multiple comorbidities (23,24). The GHrh plus arginine test seems to have the best accuracy/safety ratio in the elderly.…”

Continuous Glucose Monitoring: A Possible Aid for Detecting Hypoglycemic Events during Insulin Tolerance Tests

“…Furthermore, an adult GH deficiency is a heterogeneous disorder involving dyslipidemia, low bone mass, and increased resistance and fat mass; GH replacement in adulthood has been associated with an improved lipid profile [ 2 , 3 , 4 ]. Although various stimulation tests are available, the insulin tolerance test remains the gold-standard method for diagnosing GH deficiencies [ 1 , 5 ].…”