Clonidine-stimulated growth hormone concentrations (cut-off values) measured by immunochemiluminescent assay (ICMA) in children and adolescents with short stature

Abstract

OBJECTIVES:To establish cut-off values for growth hormone concentrations using clonidine as a secretagogue and an immunochemiluminescent assay as the method of measurement and to analyze the response time as well as the influence of gender, nutritional status and pubertal stage.METHODS:A total of 225 tests were performed in 3 patient groups, categorized as group 1 (normal), group 2 (idiopathic short stature) and group 3 (growth hormone deficiency). Among the 199 disease-free individuals, 138 were prepubertal, and 61 were pubertal. Clonidine (0.1 mg/m2) was orally administered, and the growth hormone level was measured by immunochemiluminescent assay. The growth hormone peak and the difference between the growth hormone peak and the baseline level were then analyzed. Statistical analyses were performed using Student's t-test or the Mann-Whitney test and Kruskal-Wallis test followed by Dunn's post hoc test. Cut-off values were determined using a receiver operating characteristic curve.RESULTS:Group 1 and group 2 had no difference in growth hormone peak, gender, body mass index standard deviation score, or pubertal stage. Group 3 exhibited a significantly lower growth hormone peak than the other groups did. The receiver operating characteristic curve demonstrated that growth hormone concentrations ≥ 3.0 ng/mL defined responsiveness to clonidine. In total, 3.02% of individuals in group 1 and group 2 were considered false positive, i.e., these children lacked growth hormone deficiency and had a peak below 3.0 ng/mL.CONCLUSION:Clonidine-stimulated growth hormone concentrations ≥3 ng/mL, as measured by immunochemiluminescent assay, suggest responsiveness to the stimulus regardless of gender, body mass index standard deviation score or pubertal stage.

Reliability of clonidine testing for the diagnosis of growth hormone deficiency in children and adolescents

“…Puberty does not influence GH responsiveness after GHRH or PD+GHRH . Although CT is one of the most widely used GH stimulation test, it is still unclear whether the GH response is affected by pubertal maturation. Gil‐Ad et al in 1979 demonstrated for the first time in 18 children that clonidine was an effective GH‐stimulating agent in prepubertal and adolescent subjects .…”

“…Gil‐Ad et al in 1979 demonstrated for the first time in 18 children that clonidine was an effective GH‐stimulating agent in prepubertal and adolescent subjects . A number of studies have confirmed the utility of the CT in the diagnosis of GHD, but most of these studies have been performed in prepubertal children, and none has specifically addressed the effect of puberty on the rate of false positive responses in a large number of subjects. Fraser et al studied 41 children and adolescents and concluded that CT produces less false subnormal responses than ITT.…”

“…Cavallo et al tested 34 subjects and found no difference between prepubertal and pubertal children . More recently Borges et al aimed to establish cut‐off values of CT using a different dose of clonidine (0.10 mg/m 2 ) in a cohort of 225 short children and adolescents, and found no difference between prepubertal and pubertal subjects. Here, we have shown that the GH response to CT and the rate of subnormal false positive responses is similar between prepubertal and pubertal children.…”

“…Puberty does not influence GH responsiveness after GHRH or PD+GHRH. 49 Although CT is one of the most widely used GH stimulation test, [28][29][30][31][33][34][35][36][37][38]40,44,45,50,51 it is still unclear whether the GH response is affected by pubertal maturation. Gil-Ad et al in 1979…”

“…Most of these studies have been performed in prepubertal children, 29,31,[33][34][35][36] and some have included adolescents or young adults. 28,30,[37][38][39] Given the paucity of the data and the contrasting results, it is not clear whether puberty affects the GH response to CT and whether CT is a reliable GH-stimulating agent also in adolescents.…”