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Combining Growth Hormone Releasing Hormone-Arginine and Synacthen Testing Diminishes the Cortisol Response

Endocrinology and Reproduction Section (S.S., V.I., A.D., R.J.R.), and Medical Statistics Group (M.J.C.), The School of Health and Related Research, University of Sheffield, Sheffield S10 2JF, United Kingdom; and University of Turin (E.G.), 10060 Turin, Italy

Address all correspondence and requests for reprints to: Professor Richard J. M. Ross, University of Sheffield, Room 112, Floor M, Royal Hallamshire Hospital, Glossop Road, Sheffield S10 2JF, United Kingdom. E-mail: r.j.ross{at}sheffield.ac.uk.

Objectives: The GHRH/arginine test and short synacthen test (SST) have been validated as safe alternatives to the insulin tolerance test for the assessment of the GH reserve and hypothalamic-pituitary-adrenal axis integrity, respectively. However, these two tests are usually performed separately. The objective was to see whether the synacthen and GHRH/arginine tests could be combined to save time and blood samples and minimize inconvenience to patients.

Patients/Methods: Twenty-four consecutive patients with adult onset pituitary disease requiring pituitary function testing were randomized to receive sequentially and in random order a SST, a GHRH/arginine test, and a combined SST and GHRH/arginine test on three different visits separated by at least 1 wk.

Results: There was no difference in basal cortisol or ACTH values for the SST done alone or during the combined test. However, when GHRH/arginine was given with synacthen, patients had a lower peak cortisol response with a mean difference of 116 nmol/liter (95% confidence interval, 52.54 to 179.37; P < 0.001), and one patient with a normal response on the SST had a subnormal cortisol response in the combined test. Similar lower peak cortisol responses were observed in males and females with combined test. The difference between the peak cortisol responses showed no significant correlation with age (r = 0.123; P = 0.58) or with the body mass index (r = –0.376; P = 0.09). There was no difference in GH measurements between the GHRH/arginine test done alone or in combination with the SST.

Conclusions: Combining the SST and GHRH/arginine test results in a lower cortisol response to synacthen. For this reason, the combined test cannot be recommended to assess the integrity of cortisol and GH reserve using current diagnostic criteria.