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 clonidine and the short-ACTH test instead of the sometimes dangerous insulin-induced hypoglycemia test as a screening procedure, for the simultaneous assessment of growth hormone reserve and hypothalamic‐pituitary‐adrenal axis integrity in children with growth retardation. Design: Evaluative study. Method: Seventy-three children (52 males) aged 11 6 3 years with attenuated growth (group 1) were tested by combined clonidine (150 mg/m 2 ) and short-ACTH test (either the standard 250 mg or the lowdose 1 mg/1.73 m 2 ). Thirty-one children received no pretreatment (nonprimed) (subgroup 1NP), and 42 were primed with ethynylestradiol 40 mg/m 2 /day two days before testing (subgroup 1P). The control group for the short-ACTH test (group 2) consisted of 42 children and adolescents (13 males) aged 12 6 3 years with early or accelerated puberty or premature closure of epiphyses, who received ACTH only (21 standard, 21 low-dose) with no evidence of adrenal or pituitary pathology. The peak GH response was compared between the primed and the nonprimed group 1 subjects, and the cortisol levels were compared between the combined test subgroups and the controls. The peak pass level for growth hormone was 10 ng/ml; the peak pass level for cortisol was 520 nmol/l. Results: Sixty-four of the 73 children in group 1 (87.7%) showed a growth hormone level of $ 10 ng/ml on the first stimulation test, including 26/31 (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 primed subjects. Peak 30-min cortisol in response to ACTH stimulation was similar in the patients who underwent the 250 mg or the 1 mg test within each group (subgroup 1NP, subgroup 1P and group 2); therefore, the results for the two tests were considered together. Compared with group 2, subgroup 1NP patients had a similar 30-min cortisol response (Pa NS), and subgroup 1P patients had a much higher response (P < 0.05) (group 2a 690 6 145 nmol/l, subgroup 1NPa 772 6 195 nmol/l, subgroup 1Pa 934 6 209 nmol/l). However, there was no significant difference in the increment in cortisol response between the three groups. Conclusions: Our results suggest that the combined clonidine‐short-ACTH test is a reliable and safe tool for the simultaneous assessment of growth hormone reserve and hypothalamic‐pituitary‐ adrenal axis integrity in children.