Clinical review: Is lack of recombinant growth hormone (GH)-releasing hormone in the United States a setback or time to consider glucagon testing for adult GH deficiency?

CONTEXT: The use of the combined GHRH and arginine (GHRH-ARG) test has gained increasing acceptance in the United States as a reliable alternative test to the insulin tolerance test (ITT) for diagnosing adult GH deficiency (GHD). In July 2008, the only manufacturer of recombinant GHRH in the United States, EMD Serono, Inc., announced the discontinuation of Geref, thus raising the question of which reliable alternative GH stimulation test should practicing endocrinologists be considering in place of the GHRH-ARG test. In this article, we review the existing published data and consensus guidelines and provide recommendations for alternative stimulation tests to the GHRH-ARG test. EVIDENCE ACQUISITION: The major source of data acquisition included PubMed search strategies and personal experience of the authors from clinical experience. EVIDENCE SYNTHESIS: Previous consensus guidelines and previous data assessing the reliability and discriminatory value of the GHRH-ARG, glucagon, ARG, and GH secretagogues on assessing GH reserve are discussed. Our recommendations for performing the glucagon stimulation test, potential drawbacks in conducting this test, and caveats in interpreting this test are also discussed. CONCLUSIONS: The ITT should remain the test of choice in diagnosing adult GHD. However, when the ITT is not desirable and recombinant GHRH remains unavailable in the United States, we recommend the alternative to the GHRH-ARG test to be the glucagon stimulation test, based on its reliability and availability. Nevertheless, further studies into alternative GH stimulation tests that are available in the United States, comparable, and simpler to perform than the ITT in diagnosing adult GHD are still needed.