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The Utility of the Growth Hormone (GH) Releasing Hormone-Arginine Test for Diagnosing GH Deficiency in Adults with Childhood Acute Lymphoblastic Leukemia Treated with Cranial Irradiation

Competence Center for Clinical Research (J.B.), Department of Endocrinology (K.L., E.M.E.), Lund University Hospital, SE 221 85 Lund, Sweden

Address all correspondence and requests for reprints to: Dr. Eva Marie Erfurth, Department of Endocrinology, Lund University Hospital, SE-221 85 Lund, Sweden. E-mail: eva-marie.erfurth{at}med.lu.se.

Context: The insulin tolerance test (ITT) is the current standard diagnostic test for the diagnosis of adult GH deficiency (GHD), but alternative tests, such as the GHRH-arginine test, have been proposed.

Objective: We investigated the sensitivity and specificity of the GHRH-arginine test using ITT as the gold standard in diagnosing GHD in a group of young adults treated with cranial irradiation (CRT) for childhood acute lymphoblastic leukemia (ALL). We estimated the positive and negative predictive values of the GHRH-arginine test among patients as well as a number of individual characteristics and therapy-related factors during both the GHRH-arginine test and ITT.

Design: Forty-three young adults, treated for childhood ALL with 18–30 Gy CRT and chemotherapy, were studied, and comparison was made with matched controls.

Results and Conclusions: We evaluated four different cutoff levels for GHD in the GHRH-arginine test: 5, 7.5, 9, and 16.5 µg/liter. Using 7.5 µg/liter as the cutoff yielded high specificity (94%), but at the same time the sensitivity was only 66%, which leads to a low negative predictive value (27%). In contrast, a failed GH response to the GHRH-arginine test accurately reflects the presence of radiation-induced GHD, illustrated by a high positive predictive value (95% at 7.5 µg/liter). Only age at CRT and body mass index remained significant predictors of the peak GH during the GHRH-arginine test. Because a high proportion of GHD patients show a normal response to the GHRH-arginine test, it cannot be used reliably to exclude GHD in these patients. Complementary ITT is also warranted to confirm GHD in obese patients.

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