The impact of irradiation on growth hormone responsiveness to provocative agents is stimulus dependent: Results in 161 individuals with radiation damage to the somatotropic axis

GH provocative tests remain the mainstay for the diagnosis of GH deficiency and at present the insulin tolerance test (ITT) is the gold standard. Ther e are, however, a variety of other stimulation tests used in clinical pract ice. 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 "f ailed" test are independent of the nature of the stimulus. We sought to exa mine whether this is the case in individuals with evidence of radiation dam age to the somatotropic axis. One hundred and sixty-one nonacromegalic patients were identified who had u ndergone an arginine stimulation test (AST) and an ITT within a 3-month per iod as part of routine testing between 1975 and 1999. They were divided int o those tested before (n = 81; 48 males) and those tested after (n = 80; 36 males) completion of growth and puberty. Patients were considered for incl usion in the study if they had a history of cranial irradiation and a GH re sponse to one provocative test of less than 8 mug/L, taken as indicating th at 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 se cond consisted of 16 prepubertal children (10 males). The median peak (rang e) 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) <mu> g/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) mug/L to the ITT and AST, resp ectively. In contrast to the pattern seen in the adult controls, the respon se to an ITT in childhood controls was of similar magnitude (P = 0.5) to th at to the AST: 17.5 (8.1-40.0) vs. 19.4 (7.3-53.8) mug/L, respectively. How ever in the patients, the GH response to the AST was greater than that to t he ITT (P < 0.0001): 4.3 (0.7-17.2) us. 3.0 (0.4-18.1) <mu>g/L, respectivel y. In summary, we have shown that the impact of irradiation on GH responsivene ss to provocative agents is stimulus dependent. The GH response to an AST a ppears to be more resistant to the effects of irradiation than that to the ITT. When investigating the impact of irradiation on GH secretory status, t he GH response to an AST may be a less sensitive guide to the functional ab ility of the GH axis.