Study describes U.S. experience with glucagon stimulating test

The Endocrine Society 92nd Annual Meeting

SAN DIEGO — The glucagon stimulation test was well tolerated and may be performed in the outpatient setting, according to a new study that described the experience with glucagon stimulating tests at four U.S. centers.

"Until 2008, the growth hormone-releasing hormone test had been the accepted alternative test to the insulin tolerance test to diagnose adult GH deficiency in the United States," Kevin C. J. Yuen, MD, from the department of endocrinology, diabetes and clinical nutrition at Oregon Health and Science University, Portland, said during an oral session. "When Serono, maker of the recombinant GH-releasing hormone stopped making the compound almost 2 years ago, it raised the question as to what would be the alternative test to take the place of the GH-releasing hormone plus arginine test."

Yuen and colleagues proposed the glucagon test because of its availability, reproducibility and safety.

Although popular in other countries, the United States has little experience using the glucagon stimulating test. Thus, Yuen and colleagues conducted a retrospective study of four U.S. centers where 143 patients underwent glucagon stimulation tests from 2008 to 2010 (41 men; mean age, 45.6 years; mean BMI, 31.5). Intramuscular glucagon 1 mg to 1.5 mg was administered and blood was collected at baseline and every 30 minutes for 240 minutes.

Most peak glucose levels occurred from 30 to 60 minutes (89%), most peak nadir glucose levels occurred from 150 to 240 minutes (86%) and most peak GH levels occurred from 120 to 180 minutes (78%).

“Samples at 120, 150 and 180 minutes yielded the most information,” the researchers wrote in the abstract.

Peak GH levels were negatively correlated with fasting glucose, peak glucose, nadir glucose and BMI.

According to the results, 66 patients (46%) failed the glucagon stimulation test; 20 in this group had hyperglycemia (glucose ≥100 mg/dL) and 45 were obese.

Peak cortisol levels with glucagon stimulation tests were lower, had higher failure rates (44.4% vs. 33.3%) and the peak cortisol of 17.5 mcg/dL achieved 100% sensitivity and 67% specificity.

The most commonly reported adverse events were nausea, fatigue, headache, weakness and hunger. The majority of adverse events resolved by 240 minutes without intervention.

Further studies are needed to determine whether glucagon stimulation tests may result in increased false diagnosis of GH deficiency in patients with fasting hyperglycemia and a high BMI, and until those data are available the researchers recommended consideration of a second GH stimulation test for these patients. Other future considerations may include lower cortisol cut-points if the glucagon stimulation test is used to evaluate the HPA axis, they said. – by Matthew Brannon

The glucagon stimulation test fills the much-needed role of an alternative method for testing for GH deficiency. This study shows persuasive preliminary data in a large group of people. I believe that the investigators will go on to perform the same test in a matched control group and different set of subjects, and through those data we can clearly define what the limits of normal and abnormal are.

– Ken Ho, MD

Senior Principal Research Fellow and Head of the Pituitary Research Unit,
Neuroscience Research Program, Garvan Institute of Medical Research, Sydney, Australia

For more information:

• Yuen KCJ. OR25-2. Presented at: The Endocrine Society 92nd Annual Meeting and Expo; June 19-22, 2010; San Diego.