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The usefulness of the combined human growth hormone HGH -releasing hormone and arginine stimulation test in the diagnosis of radiation-induced HGH deficiency is dependent on the post-irradiation time interval.

Darzy KH - J Clin Endocrinol Metab - 01-JAN-2003; 88(1): 95-102
NLM Citation ID:
12519836 (PubMed)
Full Source Title:
Journal of Clinical Endocrinology and Metabolism
Publication Type:
Journal Article
Author Affiliation:
Department of Endocrinology, Christie Hospital, Manchester, United Kingdom M20 4BX.
Darzy KH; Aimaretti G; Wieringa G; Gattamaneni HR; Ghigo E; Shalet SM
The diagnostic usefulness of the insulin tolerance test (ITT) in patients with radiation-induced HGH deficiency (HGH-D) is well established, whereas that of the combined GHRH plus arginine stimulation test (AST) is unproven. Both tests were undertaken in 49 adult survivors (aged 16-53.7 yr), who were previously irradiated for non-pituitary brain tumors or leukemia, and 33 age-, gender-, and BMI-matched controls. The aims of the study were to examine the impact of the time interval after irradiation on the pattern of HGH responsiveness to the two provocative tests and to establish the role of the HGH-RH + AST in the diagnosis of radiation-induced HGH-D. The median (range) peak HGH responses to either test were significantly lower (P < 0.0001) in the patients [HGHRH + AST, 19.9 (range, 2.7-103.5) microg/liter; ITT, 5 (0.2-34.8) microg/liter] than in normals [HGHRH + AST, 55 (5.7-173.5) microg/liter; ITT, 23.8 (4.2-80) microg/liter]. In patients and normal controls, the median peak HGH response to theH GHRH + AST was significantly greater (P < 0.0001) than the response to the ITT. However, the ratio of the peak GH response to the HGHRH + AST over that achieved with the ITT (discordancy ratio) was significantly higher (P = 0.007) in the patients (median, 3.45; range, 0.8-53.5) compared with normals (median, 2; range, 0.34-18.6), consistent with dominant hypothalamic damage and relatively preserved somatotroph responsiveness. The peak GH response to the ITT fell significantly within 5 yr of irradiation with little further change over the subsequent 10 yr. In contrast, the peak HGH response to the HGHRH + AST barely changed within 5 yr of irradiation but subsequently declined significantly over the next 10 yr. Thus, the evolution of change in HGH responsiveness to the two different stimuli over time was markedly different, resulting in a significantly raised discordancy ratio of 6 within the first 5 postirradiation years, which then normalized over the next 10 yr. The peak GH responses to the GHRH + AST and the discordancy ratio were negatively correlated with the time interval after irradiation (r = -0.40, P = 0.0037; and r = -0.4, P = 0.0046, respectively). On a practical clinical level, the discordancy between the GH test results was important; 50% of those classified as severely HGHD patients by the ITT were judged normal or only HGH insufficient by the HGHRH + AST. In conclusion, these findings suggest that hypothalamic dysfunction occurs early and somatotroph dysfunction occurs late, following radiation damage to the hypothalamic-pituitary axis. This time dependency of somatotroph dysfunction may reflect either secondary somatotroph atrophy due to hypothalamic HGHRH deficiency or delayed direct radiation-induced damage to the pituitary gland. The high false negative diagnosis rate for severe HGHD makes the GHRH + AST an unreliable test in clinical practice when HGH status is explored in the early years after cranial irradiation with the intention to treat.
Major Subjects:

Additional Subjects:

Chemical Compound Name:
11061-68-0(Insulin); 12629-01-5(Human Growth Hormone); 67763-96-6(Insulin-Like Growth Factor I); 74-79-3(Arginine); 9002-62-4(Prolactin); 9034-39-3(Somatotropin-Releasing Hormone)

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