The relationship between osteocalcin levels and sexual stages of puberty in male children

Osteocalcin is a specific and reliable marker which increases with rapid bone turnover and gives data about bone metabolism. The pubertal growth spurt is also known as a good example of rapid bone turnover. The aim of this study was to determine whether osteocalcin is a useful marker for the pubertal growth spurt period. In this study, osteocalcin levels in male adolescents were examined in relation to their sexual maturation stage and age. The osteocalcin levels and alkaline phosphatase levels were compared during the pubertal growth spurt. Serum osteocalcin and alkaline phosphatase levels were evaluated in 100 eligible healthy male children and adolescents (aged 10 to 17 years). Five groups (n: 20 each) of children and adolescents were formed according to their sexual maturation stages. Finally, the subjects were divided into three main groups in relation to the pubertal growth spurt and sexual maturation stages. Data were evaluated and compared among these three groups: First group = Stage 1 (prepuberty) + Stage 2 (early puberty) consisted of 40 (20 + 20) children and adolescents. Their mean osteocalcin value was 17.2 +/- 6.3 ng/ml and alkaline phosphatase 573.8 +/- 143.9 IU/L. Second group: Stage 3 + Stage 4 consisted of 40 (20 + 20) children and adolescents. These groups were known as the pubertal growth spurt groups. Their mean osteocalcin value was 29.4 +/- 10.6 ng/ml and alkaline phosphatase 728.4 +/- 233.9 IU/L. Third group: In this group, there were 20 children and adolescents who reached Stage 5 of sexual maturation and whose pubertal growth spurt was slowing. Their mean osteocalcin value was 15.3 +/- 5.8 ng/ml and alkaline phosphatase 435.8 +/- 184.8 IU/L. During the pubertal growth spurt, there is a relationship between bone remodelling and increasing osteocalcin and alkaline phosphatase levels. When sexual maturation reaches Stage 4 at 14 years old, osteocalcin and alkaline phosphatase levels make a peak, associated with the rapid growth in height. As sexual maturation reaches Stage 5, osteocalcin and alkaline phosphatase levels gradually decrease with growth maturation and their levels decline to the level of adults at the completion of this period. Our study showed that osteocalcin and alkaline phosphatase levels can be used as markers for evaluation of the growth spurt period.     

Effects of 12 months rhGH treatment on bone and collagen turnover in children with constitutional growth delay

Serum bone Gla protein (BGP), marker of osteoblast function, serum carboxyterminal cross-linked telopeptide of type I collagen (ICTP) and urinary free deoxypyridinoline (DPD), markers of bone resorption, and the aminoterminal propeptide of type III procollagen (PIIINP), marker of type III collagen turnover, were determined in eight prepubertal children (8 males, age range 7-9.6 yr, Tanner stage I) with constitutional growth delay (CGD), before and after 6-12 months of treatment with rhGH (Saizen, Serono, 0.6 IU/kg/week, s.c.). Serum BGP (mean+/-SD: 15.4+/-1.7 ng/ml), ICTP (9.4+/-1.6 ng/ml) and urinary DPD/creatinine (11.3+/-1.7 nmol/mmol) levels were significantly lower (p<0.02, p<0.0001 and p<0.02, respectively) in children with CGD than in healthy age-matched controls (BGP: 18.9+/-3.6 ng/ml, ICTP: 14.3+/-2.6 ng/ml, DPD: 20.7+/-10.0 nmol/mmol), while PIIINP levels of patients were similar to those recorded in controls (6.3+/-0.7 vs 6.7+/-2.3 ng/ml, respectively). Serum BGP, urinary free DPD/creatinine and PIIINP levels significantly increased after 6 (BGP: 20.9+/-2.1 ng/ml, p<0.0001; DPD/creatinine: 16.3+/-3.6 nmol/mmol, p<0.001; PIIINP: 8.1+/-1.6 ng/ml, p<0.005) and 12 months (BGP: 19.2+/-2.0 ng/ml, p<0.0001; DPD/creatinine: 19.7+/-5.1 nmol/mmol, p<0.001; PIIINP: 8.8+/-1.9 ng/ml, p<0.002) of GH treatment. Serum ICTP levels did not significantly change after 6 months (10.6+/-2.1 ng/ml), while a significant increase (p<0.002) was evident after 12 months of therapy (13.6+/-1.3 ng/ml). Our study shows that BGP, ICTP and DPD/creatinine levels are significantly reduced in children with CGD, thus indicating the presence of low bone turnover in this form of short stature. Since GH treatment is able to reactivate bone remodeling and increase collagen synthesis, it is tempting to speculate that a partial GH-IGF-I defect (i.e. locally at bone level) might be one of the factors involved in determining the biochemical alterations of bone metabolism found in this clinical condition.     

Impaired response of growth hormone-releasing hormone (GHRH) measured in plasma after L-dopa stimulation in patients with idiopathic delayed puberty

In order to investigate the regulation of GH secretion in patients with idiopathic delayed puberty (IDP), either prepubertal (stage P1) or early pubertal (P2), GHRH levels in plasma were measured after stimulation with L-Dopa in a group of 16 patients with IDP. The results were compared to those obtained in 12 patients with constitutional short stature (CSS) at the same stages of puberty, who underwent L-Dopa test for insufficient height. Plasma GHRH levels were measured, after extraction and concentration on C18 Sep Pack columns, by radioimmunoassay using an antibody against 1-40 GHRH, which cross-reacts 100% with 1-44 GHRH. The sensitivity of the assay is 6-8 pg/ml. After L-Dopa intake, the peak of GH was mean +/- SEM 8.6 +/- 1.4 ng/ml in IDP and 12.0 +/- 0.8 ng/ml in CSS (NS). The peak of GHRH after L-Dopa was 41 +/- 10 pg/ml in IDP and 96 +/- 25 pg/ml in CSS (p less than 0.02). A significant (p less than 0.02) decrease of plasma GHRH peak values (mean +/- SEM 17.3 +/- 4.4 pg/ml) was noted in the five patients with IDP whose growth velocity was below -2 SD for their bone age compared to the patients with normal growth velocity (mean +/- SEM 75.0 +/- 14.5 pg/ml). These results suggest a hypothalamic dysfunction in patients with IDP, and a relationship between the well-known partial and transitory somatotropic deficiency found in some adolescents having a pubertal delay and their secretion of the releasing hormone GHRH.     

Plasma thyroglobulin in treated hypothyroidism in children

In order to appreciate the value of the dosage of thyroglobulin (Tg) in the reappraisal of the classification of hypothyroidism after the onset of substitutive treatment and the supervision of patients treated with L-thyroxin (LT), plasma Tg and FT4 levels were studied in 42 samples from 21 hypothyroid children (ages ranging from 18 months to 16 years) under LT treatment. These patients were divided into 2 groups according to the results of scanning: group I: a thyroid (n = 8) and group II: ectopic or hypoplastic thyroid gland (n = 13). A control group consisted of 60 apparently healthy children of the same ages. Tg was undetectable in 11 samples of 6 children but significant levels (6.8 to 17 ng/ml) were found in 5 samples of 2 children. In group II, Tg could be measured in 20 of 26 samples, the mean level (+/- SEM) not being different from that in the control group (14.32 +/- 2.25 and 18.12 +/- 1.28 ng/ml, respectively). However, in this group, Tg levels seemed to be lower (9.75 +/- 3.94 ng/ml) in samples from patients with LT excess than in euthyroid or hypothyroid patients whose values of Tg were 15.8 +/- 3.36 ng/ml and 16 +/- 3.91 ng/ml, respectively.     

Autoantibodies in children with type 2 diabetes mellitus

To evaluate the frequency of autoantibodies to glutamic acid decarboxylase (GAD), protein tyrosine phosphatase-like protein (IA-2), and insulin (IAA) in children with type 2 diabetes mellitus (DM), we studied 37 children and adolescents whose type 2 DM was defined by fasting and 90-min standard liquid meal-stimulated serum C-peptide levels of >0.2 and >0.5 nmol/l (0.7 and 1.5 ng/ml), respectively. Mean fasting-stimulated serum C-peptide levels were 1.1 +/- 0.10 nmol/l (3.38 +/- 0.29 ng/ml) and 1.9 +/- 0.17 nmol/l (5.79 +/- 0.50 ng/ml), respectively. Eleven out of 37 patients (29.7%) were positive for at least one autoantibody: 8.1% (n = 3) had positive GAD, 8.1% (n = 3) had positive IA-2, and 27% (n = 10) had positive IAA. Nine of the 10 IAA-positive patients were on insulin treatment at the time of testing. Three of the 10 IAA-positive patients were also positive for GAD or IA-2. Since insulin treatment can stimulate IAA, we considered this to be less informative in classifying autoimmunity in DM. Therefore, GAD and IA-2 were considered primary autoimmune markers. Four out of 37 patients (10.8%) were positive for GAD (n = 3) or IA-2 (n = 3) or both (n = 2). Thus, low (10.8%) frequency of autoimmunity in children and adolescents is consistent with their clinical classification of type 2 DM based on the presence of residual C-peptide.     

Systemic hypertension and plasma renin activity in children with the hemolytic-uremic syndrome

A group of 21 children with HUS underwent serial estimations of PRA and blood pressure. At time of administration PRA was 13.2 divided by 1.59 ng/ml/hr (mean + SE), in seven who were hypertensive the mean was 14.1 +/- 3.2 ng/ml/hr and despite the wide range PRA was considered to be elevated in 6 of this group. The 14 normotensive children had a mean PRA of 12.8 +/- 1.8 ng/ml/hr, only 1 patient having a value within the normal range. In 9 children PRA was normal once diuresis had been established (9 +/- 1.4 ng/ml/hr) and only two patients of this group were hypertensive at time of the study. PRA measured in 8 children 4 weeks after presentation was 7 +/- 1.6 ng/ml/hr, and 3 hypertensive children having a mean value of 7.5 ng/ml/hr and the 5 normotensive children a mean of 2.5 ng/ml/hr. The data indicate that activation of the renin-angiotensin system in HUS occurs irrespective of hypertension. Furthermore blood pressure levels were not correlated to the degree of hydration.     

Peritoneal clearance of biochemical markers of bone turnover in children with end stage renal failure on peritoneal dialysis

Renal osteodystrophy is one of the important complications in children with end stage renal disease. Non-invasive tools for evaluation of bone metabolism have been proposed in recent years. The aim of this study was to investigate the markers of metabolic bone disease and peritoneal clearance of these markers in children treated with continuous ambulatory peritoneal dialysis (CAPD). In this study, serum osteocalcin (OC) levels were found significantly higher in patients (107.98 +/- 99.99 ng/ml) than in the healthy control group (41.94 +/- 12.94 ng/ml; p<0.05). Mean peritoneal clearance (Clp) of OC was 0.87 +/- 0.91 ml/min. There was no correlation between serum OC and Clp-osteocalcin. There was a positive correlation between serum phosphorus (P) and OC (r=0.394, p=0.031), alkaline phosphatase (ALP) and OC (r=0.520, p=0.003), and parathyroid hormone (PTH) and OC (r=0.441, p=0.017), whereas no correlation was found between OC and calcium (Ca) and OC and magnesium (Mg). There was also a significant correlation between serum ALP and PTH (r=0.714, p=0.0001). A positive correlation was found between serum PTH and Clp of PTH (r=0.471, p=0.009). In conclusion, Clp-osteocalcin is of no interest as a non-invasive marker of metabolic bone disease in children treated with CAPD. But significant correlation between serum OC and PTH, P, and ALP shows that serum OC could be used as a valuable non-invasive biochemical marker of metabolic bone disease.     

Calciotropic hormones in osteoporosis caused by anorexia nervosa

The authors evaluated bone mineralization by single photon absorptiometry and mineral homeostasis in 7 patients with anorexia nervosa. The patients with anorexia nervosa showed a reduction of bone mineralization in respect to age-sex matched normal values. Serum levels of calcium, ionized calcium, phosphate, magnesium, alkaline phosphatase, calcitonin and 25-hydroxyvitamin D were normal as well as phosphate and hydroxyproline urinary excretion. Osteocalcin levels were significantly low as compared to normal values (5.0 +/- 3.0 ng/ml vs 14.3 +/- 5.2 ng/ml, p less than 0.01) as well as urinary calcium excretion (0.02 +/- 1.01 vs 0.08 +/- 0.06, p less than 0.05); 1,25-dihydroxyvitamin D values were low only in 4 patients. Parathyroid hormone means levels were increased in respect to normal values (74.1 +/- 12.7 pg/ml vs 38.0 +/- 12.0, p less than 0.02). We confirm that adolescents with anorexia nervosa showed a reduced bone mineral content and alterations of mineral homeostasis that may contribute to the development of bone mineral loss.     

Growth hormone secretion in patients with constitutional delay of growth and pubertal development

Growth hormone levels were measured every 30 minutes during sleep over 9 hours in 20 prepubertal patients with constitutional delay of growth and puberty (CGD) and in 10 age-matched controls, all of whom had had normal GH responses to an orally administered dose of clonidine. We found no significant difference in the mean 9-hour overnight GH concentration between groups (4.5 +/- 1.8 ng/ml (mean +/- SD) in the CGD group, 4.4 +/- 2.8 ng/ml in the control group). Total GH output (258 +/- 99 U vs 222 +/- 135 U), total number of nocturnal GH pulses (3.6 +/- 0.8 vs 3.3 +/- 1.3), mean peak GH response during nocturnal sampling (13 +/- 1.2 ng/ml vs 13.2 +/- 1.3 ng/ml), and basal somatomedin C concentrations were not different in the children with growth delay and controls. We conclude that prepubertal patients with constitutional delay of growth and puberty secrete GH normally and do not seem to have any abnormality in GH regulation.     

Prolactin and cortisol levels in various paroxysmal disorders in childhood

The hormonal response of the anterior pituitary to various epileptic and nonepileptic events in children was studied. Postictal serum prolactin and cortisol levels were measured in 17 children with epilepsy, 23 with febrile seizures, and 10 with syncope or breath-holding spells. The levels were compared with those of 30 children with nonspecific fever, and 23 afebrile children served as control subjects. Significantly higher (P less than .01) prolactin levels (26.5 +/- 3.3 ng/mL, mean +/- SEM) were found in the epileptic group, compared with levels in children with febrile seizures (13.2 +/- 1.0 ng/mL), fever (11.2 +/- 0.9 ng/mL), syncope (7.3 +/- 0.9 ng/mL), and the control group (7.9 +/- 0.6 ng/mL). In contrast, serum cortisol levels were nonspecifically elevated in the epileptics and patients with febrile seizures or fever only. These findings suggest that elevated prolactin levels may be found after epileptic seizures and much less after febrile seizures, but not after breath-holding spells or syncopal events. Cortisol secretion appears to be nonselectively triggered by all stressful events, such as epileptic and febrile seizures, and fever. Elevated prolactin levels (greater than 15 ng/mL) associated with seizures may help in differentiating epileptic from febrile seizures or syncope.     

Serum 25-hydroxyvitamin D levels in Finnish children aged 2 to 17 years

Serum levels of 25-hydroxyvitamin D (25-OHD) in summer and winter were studied in 564 children aged 2-17 years living in the northern, central or southern parts of Finland. The mean levels of 25-OHD were significantly lower in winter (13.3 +/- 10.8 ng/ml) than in summer (27.2 +/- 10.3 ng/ml) in all age groups (p less than 0.001). The mean 25-OHD levels in the northern part of the country did not differ significantly from the others. In both seasons the levels of 25-OHD were lower in the 11-17 year age group than in younger children. In that age group 22.4% of the children had serum levels of 25-OHD below 5 ng/ml (the limit of risk for rickets), compared to 16.8% of children 6-10 years old and 7.5% of children 2-5 years old, but none of the children showed any laboratory evidence of rickets.     

哮喘患儿血清IL 12 TGFβ1 与IgE 水平变化的研究

目的：检测哮喘患儿不同病期的白细胞介素12 ( IL-12) 、转化生长因子β1 ( TGFβ1 ) 与免疫球蛋白E( IgE) 水平变化的规律,并探讨不同病期IL-12,TGFβ1水平与IgE水平的相关性,据此阐述它们在哮喘中的临床意义。方法：采用ELISA 方法检测85例哮喘患儿及30例正常儿童的血清IL-12,TGFβ1与总IgE 水平。结果：哮喘组血清IL-12,TGFβ1水平明显低于对照组,而IgE 水平则哮喘组明显高于对照组,且发作期IL-12,TGFβ1 水平（28.42±10.73 ng/L,40.25±11.73 pg/mL）明显低于缓解期（40.42±15.26 ng/L,65.41±22.38 pg/mL）,差异有显著性 (P< 0. 01),缓解期血清IL-12,TGFβ1 水平明显低于对照组（67.42±20.58 ng/L,178.54±90.56 pg/mL）,差异有显著性(P<0.01),发作期血清IgE 水平（280.35±80.54 IU/mL）明显高于缓解期（145.67±51.25 IU/mL）, 差异有显著性(P< 0.01), 缓解期血清IgE 水平明显高于对照组（53.61±13.32 IU/mL）, 差异有显著性(P<0.01),哮喘患儿血清IL-12,TGFβ1水平与IgE呈负相关(P< 0.01)。结论：哮喘患儿存在IL-12,TGFβ1及IgE 水平失衡,提示IL-12,TGFβ1 在哮喘的发病中起着重要作用,检测它们的水平可为哮喘的诊断及判断病情提供依据。     

Pyridoxal 5'-phosphate levels in children with sickle cell disease

Pyridoxal 5'-phosphate (PLP), the major coenzyme form of vitamin B6, is known to have antisickling properties in vitro. Recently, low plasma PLP levels were reported in a group of adults with sickle cell anemia. We measured the plasma PLP levels in a group of 55 asymptomatic nontransfused children with sickle cell diseases (SCD) to determine the prevalence of low plasma PLP levels in this population. Comparative studies were made with the measurement of PLP in three other groups serving as controls: Group A (black children, n = 36); Group B (white children, n = 37); and Group C (black adults, n = 13). PLP was measured directly in plasma by a radioenzymatic technique. The results of these comparisons showed that there was no statistically significant difference in plasma PLP of black children with SCD (10.7 +/- 10.0 ng/ml) as compared with black control children (group A, 9.0 +/- 12.3 ng/ml). The low plasma levels PLP in these two groups were significantly lower than that of the plasma PLP of white control children (group B, 15.85 +/- 15.92 ng/ml). This data suggest that a high prevalence of low PLP levels exists in black children seen at Grady Memorial Hospital, both with and without SCD.     

An open label 12-month pilot trial on the effects of the aromatase inhibitor anastrozole in growth hormone (GH)-treated GH deficient adolescent boys

OBJECTIVE: To investigate whether 12 mo treatment with the aromatase inhibitor anastrozole can achieve sustained suppression of estrogen production and delay epiphyseal fusion in growth hormone deficient (GHD) adolescent males. STUDY DESIGN: 20 adolescents with GHD were recruited (mean age +/- SE: 14.7 +/- 0.5 yr). Ten continued on GH (control group), and 10 on GH and anastrozole (Rx group) for 12 mo. RESULTS: After 12 mo E2 concentrations declined 60% in the Rx group (from 1.8 +/- 0.5 to 0.7 +/- 0.3 pg/ml, p <0.05) whereas they increased in controls (from 1.2 +/- 0.7 to 1.8 +/- 0.7, p <0.05). Testosterone increased 117% in the Rx group (from 304 +/- 31 to 626 +/- 64 ng/dl), 47% in controls (from 274 +/- 89 to 398 +/- 51) (p = 0.03, ANOVA between groups). IGF-I increased 42% in controls (454 +/- 22 to 711 +/- 109 ng/ml, p <0.05), but remained invariant in the Rx group (446 +/- 29 to 540 +/- 80, p = NS). Bone markers, plasma lipids, insulin, glucose, and liver function tests were all unchanged between groups with no differences either in body composition or bone mineral density accrual. There were no differences in growth velocity, height SDS, bone age advancement, predicted adult height or testicular volumes between groups after 12 mo. CONCLUSIONS: Anastrozole treatment potently decreases estrogen concentrations in adolescent males with GHD while allowing normal virilization, without deleterious effects on body composition, plasma lipids, bone metabolism or the tempo of puberty. Twelve months of treatment, however, did not increase predicted adult height. Further studies are needed to ascertain whether more prolonged estrogen blockade is helpful in the treatment of growth retardation in puberty.     

Oral clonidine: an effective growth hormone provocative test

Twenty normal statured healthy children (8 M; 12 F) aged 9-16 years were subjected to growth hormone (GH) provocative tests. The mean basal GH level was 2.0 +/- 0.42 ng/ml (+/- SEM). The mean peak levels of GH were 11.9 +/- 2.19 ng/ml (+/- SEM) after exercise, 9.82 +/- 2.81 ng/ml (+/- SEM) after insulin and 15.2 +/- 2.54 ng/ml (+/- SEM) after oral clonidine. A significant rise (peak level greater than 7 ng/ml) of serum GH was found in 70, 80 and 85% of children after exercise, insulin and oral clonidine tests, respectively. The observation in the present study indicates that oral clonidine test, a safer, easier and more economical test than insulin hypoglycemia, is equally potent and can be done in out patients.     

Leptin levels in children with insulin dependent diabetes mellitus

Leptin, a product of the ob gene, is a polypeptide hormone produced in adipose tissue that informs the brain about the amount of energy storage of body fat. It has very important effects on neuroendocrine functions and energy expenditure. The aim of our study was to determine leptin levels of children with insulin dependent diabetes mellitus (IDDM), which is known to affect body metabolism, and to investigate the relationship between duration of the disease, insulin dosage, HbA1c levels, body mass index (BMI), serum lipids and IGF-1 levels. Sixteen patients with IDDM (chronological age 13.8 +/- 2.6 years) whose HbAlc levels were 10.2 +/- 1.9 %, BMI 21.2. +/- 2.7 kg/m2, insulin dosage 0.9 +/- 0.4 U/kg/day and duration of the disease 6.7 +/- 2.6 years, and 12 healthy controls (13.4 +/- 2.6 years) were included in the study. Fasting plasma leptin levels were measured by radioimmunoassay method. The mean plasma leptin levels of the patient and the control groups were 19.1 +/- 7.6 ng/ml and 6.1 +/- 2.9 ng/ml, respectively, and significant difference was found between the two groups (p < 0.05). No correlation was found between leptin values and IGF-1, cholesterol, HDL-cholesterol, LDL-cholesterol, triglyceride levels, atherogenic index, insulin dosage or HbA1c levels in the patient group. A weak statistical correlation was determined between BMI and leptin levels in the IDDM group (r = 0.28, p < 0.05). A positive correlation was also found between leptin levels and the duration of the disease (r = 49, p < 0.05). As a result, it seems that leptin levels of children with IDDM differed from the levels of the control group significantly, and that the duration of insulin therapy was responsible for this difference.     

Growth hormone secretion in response to the administration of thyrotropin releasing hormone (TRH) in children with insulin-dependent diabetes mellitus]

In this study the Authors examined the response in growth hormone (GH) to thyrotrophin releasing hormone (TRH) administration in a group composed of 29 children (17 males, 12 females) suffering from insulin-dependent diabetes mellitus (IDDM) (group 1). All subjects were prepubertal, had a chronological age of 8.82 +/- 1.76 years (m +/- SD), a bone age of 8.60 +/- 1.65 years; the time elapsed since the diagnosis was 2.45 +/- 1.51 years, glycosylated hemoglobin (HbA1c) was 7.33 +/- 1.80%. Some of the same subjects (all those with a response in GH to TRH higher than 4 ng/ml; no. 11; group 2) were examined again 12-18 months later; as controls, 13 short children were also examined (group 3). All the subjects of the three groups showed a TSH peak ranging from 10-25 microU/ml, whereas GH peak resulted higher than 4 ng/ml ("paradoxical" response) in 6 subject of the group 1 and in an only subjects of the group 2. All the responders of the 3 groups showed a value in HbA1c higher than 8%. A significant difference was not present between males and females in GH and TSH values. Cortisol levels and glycaemia remained almost constant during the performance of the tests. By considering all the groups, TSH and GH values during TRH-test were not correlated with glycaemia, chronological age, bone age, the time elapsed since the diagnosis, height, height velocity, HbA1c values. In conclusion, our data demonstrated that "paradoxical" response in GH to TRH administration was present only in some subjects and particularly in those with a poor metabolic control of the disease.     

Low dose of insulin for assessment of growth hormone and cortisol release in short children

OBJECTIVE: In 55 prepubertal children with growth failure, aged 8.62 +/- 2.89 years, we evaluated the efficacy of a test using only half the usual dose of insulin by comparing the results with those obtained during a classical arginine tolerance test, performed separately. PATIENTS AND METHODS: The patients were randomly divided into two groups: group A consisting of 37 children received 0.05 U/kg insulin, while group B consisting of 18 patients received 0.1 U/kg insulin. Each child received the same dose of arginine per kg during the second test. RESULTS: Serum growth hormone (GH) peak levels were significantly (p < 0.01) lower in children of group A (6.59 +/- 4.10 ng/ml) than in those of group B (10.12 +/- 5.80 ng/ml). No differences of GH peak levels were found in patients of the two groups after arginine infusion. The injection of 0.05 U/kg insulin induced a significantly (p < 0.0001) lower percent decrease of serum glucose than 0.1 U/kg. No difference of the percent increase of serum cortisol induced by insulin at 0.05 U/kg and 0.1 U/kg was observed. CONCLUSION: The diagnosis of GH deficiency in children can be supported by a blunted GH response after two or more pharmacological stimuli including hypoglycaemia induced by only half the usual dose of insulin.     

Growth hormone response to clonidine in obese children.

Basal and stimulated serum growth hormone (GH) levels after exercise, insulin induced hypoglycemia (IIH) and oral clonidine were evaluated in 20 (16 M, 4 F) normal statured obese (body mass index greater than or equal to 25 kg/M2) children. Basal serum GH levels (mean +/- SEM, 2.0 +/- 0.38 ng/ml) were not different from basal levels in non-obese children. The mean peak levels were 3.16 +/- 1.17 ng/ml, 2.15 +/- 0.36 ng/ml and 3.15 +/- 1.12 ng/ml (+/- SEM) after exercise, IIH and oral clonidine, respectively. The positive responses (peak level of serum GH greater than 7 ng/ml) were seen in 10% with exercise, in 10% with clonidine and in none with IIH test. These observations suggest that GH response to oral clonidine is subnormal in obese children.     

Serum levels of Midkine in children and adolescents without malignant disease

Background:  Midkine (MK), a heparin-binding growth factor, is a secreted protein and can be detected in a patient's sera.
Method:  MK was studied in the sera of 215 children and adolescents without malignant disease using an enzyme-linked immunosorbent assay in order to determine the distribution of concentrations in a control population for pediatric oncology patients. Tested subjects either underwent surgical procedures or suffered from endocrinological diseases.
Results:  Elevated MK levels were found in patients with short stature, diabetes mellitus, obesity, and cleft lip and palate. These patients were subsequently excluded from the "non-cancer" group. MK serum levels did neither correlate with sex, age, weight or height nor showed a normal distribution ( n = 152, range: 0.0–5.58 ng/ml, median: 0.0 ng/ml, mean: 0.26 ng/ml, SD: ±0.61).
Conclusion:  MK serum values in children and adolescents are widely spread and not normally distributed. The present results indicate that the MK expression is influenced by many factors apart from cancer, which have not yet been identified.