Pituitary Disorders
Glucagon Testing in Adult Growth Hormone Deficiency – Current Status and Future Perspectives
Kevin C J Yuen Assistant Professor in Endocrinology, Division of Endocrinology, Diabetes and Clinical Nutrition, Oregon Health and Science University
Abstract
Growth hormone deficiency (GHD) in adults is a recognised clinical syndrome and its diagnosis is established through GH stimulation testing. The decision to perform GH stimulation testing should be based on clinical findings, medical history and using the appropriate GH stimulation test to obtain biochemical evidence. The insulin tolerance test (ITT) remains the diagnostic test of choice, but this test is labour intensive, contraindicated in the elderly and in adults with seizure disorders and ischaemic heart disease, can be unpleasant for the patient, and is potentially hazardous. The glucagon stimulation test (GST) in recent years has been increasingly used as the alternative test to the ITT in the US and Europe because of its availability, reproducibility, safety, lack of influence by gender and hypothalamic cause of GHD, and relatively few contraindications. In the article, we discuss our recommendations in performing this test, the potential drawbacks in conducting and caveats in interpreting this test, and its future perspectives.
Keywords
Growth hormone, glucagon, insulin tolerance test, growth hormone releasing hormone plus arginine, diagnosis, adult growth hormone deficiency
Disclosure: Kevin CJ Yuen has received research support from Pfizer, Genentech and Novo Nordisk. Received: 11 September 2010 Accepted: 5 January 2011 Citation: European Endocrinology, 2011;7(2):104–7 Correspondence: Kevin CJ Yuen, Division of Endocrinology, Diabetes and Clinical Nutrition, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Mailcode: L607, Portland, OR 97239-3098, US. E:
yuenk@ohsu.edu
Growth hormone deficiency (GHD) in adults is characterised 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 some, but not all, of these abnormalities.2
associated with increased morbidity and mortality that was previously observed in adults with hypopituitarism.3,4
These findings were
substantiated in two large surveys based on national Danish registries, where the morbidity of adults with GHD was found to be approximately threefold higher than that of a healthy population.5
This result was
independent of gender and applied to patients with childhood-onset and adult-onset GHD,5
with mortality of childhood-onset GHD far exceeding that of adult-onset GHD.6
Current published guidelines recommend evaluation of adult GHD to be based on clinical findings, medical history and using the appropriate GH stimulation test for biochemical confirmation,7,8
with
the exception of patients with three or more pituitary hormone deficiencies and low serum IGF-I levels.9
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 generally considered the gold standard test for evaluation of GH deficiency and has been endorsed by different consensus guidelines,7,8,10
but this test is labour intensive, may be unpleasant for some patients, has potential risks, and is contraindicated in elderly patients and in patients with seizure disorders and ischaemic heart disease. Thus, there remains a real unmet medical need for an
104
In contrast, untreated GHD is
alternative test to the ITT that is safe yet reliable. For this reason, other dynamic tests have been proposed such as arginine (ARG), combined GH releasing hormone plus ARG (GHRH-ARG), levodopa (L-DOPA) in spite of data indicating poor performance of some of these tests for evaluation of adult GHD.9,11
A potential alternative to the
ITT is the glucagon stimulation test (GST) that has been used extensively in the UK,12
Update on the Glucagon Stimulation Test in Diagnosing Adult Growth Hormone Deficiency Following the publication of several validation studies11,14-16 recommendations from current consensus guidelines,7,8,10
and is gradually gaining acceptance in the US.13
and the
GHRH-ARG test has in recent years emerged as the best and most reliable alternative GH stimulation test to the ITT in diagnosing adult GHD. However, when EMD Serono, Inc decided to discontinue the manufacture of recombinant GHRH (Geref®) in the US in July 2008,17 this inevitably left a significant gap for an alternative reliable test for evaluation of patients suspected to have GHD in place of the GHRH-ARG test. This is particularly important for endocrinologists in the US who are not comfortable or do not have the necessary logistical or staff support to conduct ITTs in their office or patients who have contraindications to hypoglycaemia in whom the ITT would be inappropriate. With the lack of reliable GH stimulation tests available in the US, we recommended the glucagon stimulation test (GST) as the alternative test to the ITT for diagnosing adult GHD based on its availability, reproducibility, safety, lack of influence by gender and hypothalamic cause of GHD, and relatively few contraindications.13
© TOUCH BRIEFINGS 2011
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