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The Impact of Irradiation on Growth Hormone Responsiveness to Provocative Agents Is Stimulus Dependent: Results in 161 Individuals with Radiation Damage to the Somatotropic Axis¹

Department of Endocrinology, Christie Hospital National Health Service Trust, Manchester, United Kingdom M20 4BX

Address all correspondence and requests for reprints to: Prof. S. M. Shalet, Department of Endocrinology, Christie Hospital National Health Service Trust, Wilmslow Road, Manchester, United Kingdom M20 4BX.

GH provocative tests remain the mainstay for the diagnosis of GH deficiency and at present the insulin tolerance test (ITT) is the gold standard. There are, however, a variety of other stimulation tests used in clinical practice. Each necessitates the use of a specific cut-off derived from normative data, but there remains a widely held view that the implications from a "failed" test are independent of the nature of the stimulus. We sought to examine whether this is the case in individuals with evidence of radiation damage to the somatotropic axis.

One hundred and sixty-one nonacromegalic patients were identified who had undergone an arginine stimulation test (AST) and an ITT within a 3-month period as part of routine testing between 1975 and 1999. They were divided into those tested before (n = 81; 48 males) and those tested after (n = 80; 36 males) completion of growth and puberty. Patients were considered for inclusion in the study if they had a history of cranial irradiation and a GH response to one provocative test of less than 8 µg/L, taken as indicating that some damage to the GH axis may have occurred. The patients were compared with 2 control groups. The first comprised 35 adults (18 males) and the second consisted of 16 prepubertal children (10 males).

The median peak (range) GH response to the ITT was significantly greater (P < 0.0001) than that to the AST in the adult controls: 24.9 (4.1–76.9) vs. 12.2 (0.88–35.0) µg/L, respectively. However, in the patients the GH responses were similar (P = 0.28): 2.2 (0.2–25.7) vs. 1.4 (0.2–12.8) µg/L to the ITT and AST, respectively. In contrast to the pattern seen in the adult controls, the response to an ITT in childhood controls was of similar magnitude (P = 0.5) to that to the AST: 17.5 (8.1–40.0) vs. 19.4 (7.3–53.8) µg/L, respectively. However in the patients, the GH response to the AST was greater than that to the ITT (P < 0.0001): 4.3 (0.7–17.2) vs. 3.0 (0.4–18.1) µg/L, respectively.

In summary, we have shown that the impact of irradiation on GH responsiveness to provocative agents is stimulus dependent. The GH response to an AST appears to be more resistant to the effects of irradiation than that to the ITT. When investigating the impact of irradiation on GH secretory status, the GH response to an AST may be a less sensitive guide to the functional ability of the GH axis.

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