Combined clonidine-short-ACTH test for the simultaneous assessment of growth hormone reserve and hypothalamic-pituitary-adrenal axis integrity in children

Objective: To determine the feasibility of using the combined oral clonidin e and the short-ACTH test instead of the sometimes dangerous insulin-induce d hypoglycemia test as a screening procedure, for the simultaneous assessme nt of growth hormone reserve and hypothalamic -pituitary- adrenal axis inte grity in children with growth retardation. Design: Evaluative study. Method: Seventy-three children (52 males) aged 11 +/- 3 years with attenuat ed growth (group 1) were tested by combined clonidine (150 mu g/m(2)) and s hort-ACTH test (either the standard 250 mu g or the low-dose 1 mu g/1.73 m( 2)). Thirty-one children received no pretreatment (nonprimed) (subgroup INP ), and 42 were primed with ethynylestradiol 40 mu g/m(2)/day two days befor e testing (subgroup 1P). The control group for the short-ACTH test (group 2 ) consisted of 42 children and adolescents (13 males) aged 12 +/- 3 years w ith early or accelerated puberty or premature closure of epiphyses, who rec eived ACTH only (21 standard, 21 low-dose) with no evidence of adrenal or p ituitary pathology. The peak GH response was compared between the primed and the nonprimed grou p 1 subjects, and the cortisol levels were compared between the combined te st subgroups and the controls. The peak pass level for growth hormone was 1 0 ng/ml; the peak pass level for cortisol was 520 nmol/l. Results: Sixty-fo ur of the 73 children in group 1 (87.7%) showed a growth hormone level of g reater than or equal to 10 ng/ml on the first stimulation test, including 2 6/31 (84%) nonprimed and 38/42 (90.5%) primed. Of the 9 patients who failed the first clonidine test, 4 also failed the second, primed test, including 1/5 nonprimed patients (20%) and 3/4 primed patients (75%). This yielded a GH deficiency/ insufficiency rate of 5.5% and a rather low false-positive rate of 13.3% (4/30) for the nonprimed subjects and 2.6% (1/39) for the pri med subjects. Peak 30-min cortisol in response to ACTH stimulation was simi lar in the patients who underwent the 250 mu g or the 1 mu g test within ea ch group (subgroup 1NP, subgroup 1P and group 2): therefore, the results fo r the two tests were considered together. Compared with group 2, subgroup 1 NP patients had a similar 30-min cortisol response (P = NS), and subgroup 1 P patients had a much higher response (P < 0.05) (group 2 = 690 +/- 145 nmo l/l, subgroup 1NP = 772 +/- 195 nmol/l, subgroup 1P = 934 +/- 209 nmol/l). However, there was no significant difference in the increment in cortisol r esponse between the three groups. Conclusions: Our results suggest that the combined clonidine-short-ACTH tes t is a reliable and safe tool for the simultaneous assessment of growth hor mone reserve and hypothalamic-pituitary-adrenal axis integrity in children.