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

Abstract

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 ®rst stimulation test, including 26/31 (84%) nonprimed and 38/42 (90.5%) primed. Of the 9 patients who failed the ®rst 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 de®ciency/ insuf®ciency 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 (P NS), and subgroup 1P patients had a much higher response (P < 0.05) (group 2 690 6 145 nmol/l, subgroup 1NP 772 6 195 nmol/l, subgroup 1P 934 6 209 nmol/l). However, there was no signi®cant 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.

Decreased Growth During Therapy With Selective Serotonin Reuptake Inhibitors

“…29 Among our 4 patients, only patient 4 had delayed puberty, with subnormal GH responses on 2 postpriming stimulation tests. According to our experience and that of others, 20,27 the probability of a false-positive response on 2 postpriming stimulation tests is very low.…”

Decreased Cortisol Secretion in Nonclassical 21-Hydroxylase Deficiency Before and During Glucocorticoid Therapy

“…Data are presented as means ± SD unless otherwise indicated. There was no significant correlation between the age at testing and the basal VOLUME 15 Cortisol levels during glucocorticoid therapy in lowdose test (Table 3) The patients had slightly higher basal Cortisol levels than the controls, but significantly lower 30min stimulated and incremental Cortisol levels. For multiple comparisons, we used the Bonferroni correction.…”

The Linear Relationship between Changes in Childhood Growth Velocity and Topical Glucoco'rticoid Dose

“…Combined clonidine-short-ACTH stimulation tests of GH reserve and hypothalamic-pituitary adrenal axis integrity may distinguish more subtle differences related to steroid effects on growth. 46 Sophisticated monitoring and statistical analysis of pulsatile release of GH, sex, and other hormones was required for these studies. Application of these methods may permit prediction of children at greater risk for steroid-induced growth suppression or other side effects.…”