A comparison of clonidine and standard provocative agents of growth hormone

To evaluate the effectiveness of clonidine on growth-hormone (GH) release in prepubertal children, and to distinguish between a central alpha-adrenergic effect and a corticotropin-cortisol-mediated response, we measured serum glucose, corticotropin, cortisol, and GH concentrations following levodopa, arginine hydrochloride, and clonidine hydrochloride stimulation in 15 euthyroid children who had short stature. We found that clonidine is an effective and safe stimulator of GH release and provided a clearer distinction between GH-deficient and non-GH-deficient young persons than levodopa or arginine. The action of clonidine is not corticotropin-cortisol mediated.     

Screening test for growth hormone deficiency: Usefulness of L-dopa-propranolol provocative test

This is a retrospective review of 185 short children who were tested for growth hormone (GH) secretion using the L-dopa-propranolol provocative test. One hundred and thirty-three children were deemed to have passed the screening test when a GH concentration of greater than 15 miu/L was elicited after stimulation. Fifty-two failed the screening test, of which 33 were diagnosed as having growth hormone deficiency (GHD) when they had inadequate growth hormone response to insulin-induced hypoglycaemia. The other 19 were low-responders since they showed adequate GH response to insulin tolerance test (ITT). The low-responder rate to L-dopa-propranolol provocative test among short children who are not GH deficient was 12.5%. The low cost of L-dopa and propranolol, the simplicity and safety of the test, and the acceptable rate of low-responders make the test an effective screening test for GHD.     

Evaluation of growth hormone in thalassaemic boys with failed puberty: Spontaneous versus provocative test

Growth hormone (GH) secretion was determined by evaluating ultradian GH profiles for 12 h and GH responses to insulin stimulated hypoglycaemia (ITT) in 28 stunted boys with -thalassaemia major aged 15.2–17.4 years, who presented with pubertal failure (FP). Healthy non thalassaemia prepubertal boys (n=10) aged 7.5–8.8 years, were studied as controls. All patients had normal responses to ITT with peak GH levels 15 mU/l. Basal GH concentrations (mean±sem) (1.65±0.03 mU/l vs 2.58±0.27 mU/l;P<0.05) and the stimulated GH responses (peak GH=15.4±0.20 mU/l vs 21.08±0.78 mU/l;P<0.001) were significantly lower in the patients with failed puberty than in the controls, indicating that the FP patients had diminished GH reserve and secretory capacity. Moreover, all the GH peak parameters including the maximum spontaneous concentrations (MX-GH) and the area under the GH curve (AUC) were significantly lower in the thalassaemic patients than in the controls (MX-GH=5.2±0.21 mU/l vs 20.42±0.14 mU/l;P<0.001; AUCb=421.22±4.31 mU/l vs 712.20±3.42 mU/l;P<0.001). These observations suggest that the thalassaemic patients had endogenous neurosecretory GH deficiency (GHND). Priming with sex steroid did not cause any improvement in the spontaneous or stimulated GH secretory patterns in thalassaemic patients. It was noteworthy that in neither the patients nor the control subjects, was there a significant correlation between the maximum stimulated and the MX-GH concentrations. These data suggest that the provocative ITT underestimates spontaneous GH secretion and that measurement of spontaneous GH secretion was a more reliable method for identifying patients with GH insufficiency than the ITT.     

心得安运动激发试验对儿童生长激素缺乏症的诊断价值

目的 探讨心得安运动激发试验对儿童生长激素缺乏症(GHD)的诊断价值.方法 选择在2009年1月至2013年3月期间因身材矮小症住院,同时完善胰岛素激发和心得安运动激发两项试验的儿童,共120例,记录激发试验前后静脉血GH值.将激发试验后血GH峰值<10 ng/mL定义为激发阴性,GH峰值≥10 ng/mL定义为激发阳性.将两项激发试验后血GH峰值均<10 ng/mL者诊断为GHD.结果 120例矮小儿童中,诊断为GHD者29例(24.2%).胰岛素激发试验阳性率为48.3%.心得安运动激发试验阳性率为65.8%.两项激发试验的总符合率为62.5%,阳性符合率为79.3%.心得安运动激发后血GH峰值显著高于胰岛素激发试验的GH峰值.胰岛素激发试验血GH峰值多出现在试验后30~60 min,心得安运动激发试验GH峰值多出现在试验后的120 min.心得安运动激发试验未见不良反应发生.结论 心得安运动激发试验与胰岛素激发试验对GH的激发结果符合率较高,且比胰岛素激发试验更易刺激GH分泌,临床可考虑同时应用胰岛素激发试验、心得安运动激发试验联合诊断GHD.     

Low-dose oral clonidine. A simple and reliable growth hormone screening test for children

We evaluated the efficacy and side effects of a low dose of oral clonidine hydrochloride on growth hormone release in 24 healthy short children; ten received 100 micrograms (group A) and 14 received 50 micrograms (group B). The mean +/- SD growth hormone peak at 60 minutes was 14.5 +/- 6.3 mg/mL in group A v 11.6 +/- 6.1 mg/mL in group B. Failure rate (growth hormone less than 10 mg/mL) was 10% in group A and 36% in group B. The drop in cortisol levels was similar in both groups. Blood pressure did not change significantly, and only mild somnolence was noted in all. A single dose of oral clonidine hydrochloride approximating 100 micrograms/sq m, followed by one blood sample after 60 minutes seems to be an effective and safe screening test for growth hormone deficiency in short children.     

Hypoglycemia associated with clonidine testing for growth hormone deficiency

We have observed 4 cases of hypoglycemia associated with clonidine stimulation of growth hormone secretion; only one patient had growth hormone deficiency. Significant drowsiness after administration of clonidine may prolong the period of fasting in these children and mask early signs and symptoms, leading to severe hypoglycemia.     

Chronic growth retardation with normal growth hormone response to provocative stimuli and low somatomedin activity. Long-term therapy with human growth hormone

Four prepubertal children with chronic growth retardation (growth velocities less than or equal to 4 cm/yr), normal growth hormone (GH) response to provocative stimuli and low basal but increased somatomedin activity values after GH administration, received continuous GH-therapy (4 IU/three times a week) for an 18-24-month period. Growth velocity doubled during the first 12 months of therapy and remained 4-6 cm/yr until the end. Bone age progressed according to chronological age and adult height predictions improved. No thyroid function or carbohydrate and lipid metabolism anomalies were observed. After completion of this GH-therapy period, patients remained off treatment during the following six months. Growth velocities were similar to pre-GH-treatment values in two patients, lower in the third and higher in the fourth, who was by then pubertal. Thus, in these patients, long-term GH-therapy promoted growth and improved adult height prediction.     

Efficacy of insulin-like growth factor I levels in predicting the response to provocative growth hormone testing

Clinical testing of growth hormone (GH) sufficiency is a controversial area in endocrinology. Due to the episodic nature of endogenous GH secretion, diagnosis of GH deficiency has been defined as a failure to achieve normal GH levels in response to at least two stimuli. This testing is associated with significant patient morbidity and cost. We analyzed our experience over a 4-y period to determine whether clinical or biochemical variables could be used to predict the results of a specific GH testing procedure. Of 180 cases analyzed (67% male, mean age 8.89 +/- 4.39 y, range neonate-16 y), eight cases had incomplete GH testing results. Of the remaining 172, 19 were GH deficient (GH level less than 7 ng/mL). Younger age, higher body mass index and a greater degree of bone age delay were characteristic of the GH-deficient population; however, none of these variables alone was of diagnostic utility. Serum IGF-I level was below the normal range for 81% of the GH deficient and 47% of the GH-sufficient children; and was the only single variable that provided a reasonable between-group distinction. Discriminant analysis resulted in development of a new variable, based on IGF-I z scores, chronologic age, degree of bone age delay, and body mass index, which would have allowed exclusion of GH deficiency without provocative testing for 58% of the GH sufficient population, whereas permitting the diagnosis of GH deficiency for all GH-deficient subjects. Our data are dependent on the IGF-I assay method and the clinical definition for GH deficiency; therefore, the calculated predictive values are not applicable to all clinical populations.(ABSTRACT TRUNCATED AT 250 WORDS)     

Oral administration of arginine enhances the growth hormone response to growth hormone releasing hormone in short children

We have evaluated the effect of oral administration of arginine chlorhydrate on the growth hormone response to growth hormone releasing hormone in a group of nine short prepubertal children (six boys and four girls). Arginine chlorhydrate 10 g, administered orally 60 min before an iv bolus injection of growth hormone releasing hormone 1–29, 1 μg/kg, significantly enhanced the growth hormone response to the neuropeptidc, confirming the results of previous studies which used the iv route. Furthermore, our data strengthen the view that the effects of arginine chlorhydrate on growth hormone secretion are mediated by inhibition of endogenous somatostatin release.     

Oral administration of arginine enhances the growth hormone response to growth hormone releasing hormone in short children

We have evaluated the effect of oral administration of arginine chlorhydrate on the growth hormone response to growth hormone releasing hormone in a group of nine short prepubertal children (six boys and four girls). Arginine chlorhydrate 10 g, administered orally 60 min before an iv bolus injection of growth hormone releasing hormone 1–29, 1 μg/kg, significantly enhanced the growth hormone response to the neuropeptidc, confirming the results of previous studies which used the iv route. Furthermore, our data strengthen the view that the effects of arginine chlorhydrate on growth hormone secretion are mediated by inhibition of endogenous somatostatin release.     

Urinary growth hormone excretion as a screening test for growth hormone deficiency.

Overnight urinary growth hormone secretion was measured by an immunoradiometric assay incorporating commercially available reagents, in 41 normal prepubertal school-children from three age groups: 3-5 years, 6-7 years, and 9-10 years. There was no significant difference between the groups expressing the results as total microU/specimen and so they have been combined to provide a prepubertal reference range of 2.25-10.50 microU/night. Prepubertal children with growth hormone deficiency who had not been receiving growth hormone treatment for two days had overnight urinary growth hormone concentrations well below this range. Urinary growth hormone was assayed in 49 children undergoing investigation for short stature with conventional provocative testing, and those shown to have growth hormone deficiency had correspondingly low overnight urinary growth hormone concentrations. There was, in addition, a strong correlation between overnight urinary growth hormone concentrations and peak serum response to provocation. This simple urine assay may provide a useful screening test for growth hormone deficiency.     

Exercise test for growth hormone deficiency.

An exercise test measuring energy expenditure was performed on a bicycle ergometer by 98 patients in the outpatient clinic. Results concordant with the final diagnosis were obtained in 89% of the 75 children referred because of short stature and in 65% of the 23 children with associated chronic disorders.