Sex hormone binding globulin concentration as a prepubertal marker for hyperinsulinaemia in obesity.

BACKGROUND: Overweight children become obese adults who are prone to develop the "metabolic syndrome" and premature coronary arterial disease (CAD). AIMS: To assess whether sex hormone binding globulin (SHBG) is a potential marker for hyperinsulinaemia/insulin resistance in prepubertal obese children. METHODS: Twenty five obese children (body mass index (BMI) >2SD) who warranted investigation on clinical grounds were enrolled. Their insulin response to an oral glucose tolerance test was assessed. RESULTS: Fourteen children were hyperinsulinaemic. Despite being matched for age and BMI, SHBG concentrations were below the sex related reference range in the hyperinsulinaemic group. CONCLUSION: Our results indicate that a subnormal SHBG concentration in a prepubertal child is strongly predictive of hyperinsulinaemia. By measuring the circulating SHBG concentration, it might be possible to identify those at most risk of premature CAD, targeting them for lifestyle changes.     

Sex hormone binding globulin (SHBG) in children with obesity.

Serum sex hormone binding globulin (SHBG) concentration of children with obesity was measured and relationships between SHBG level and body mass index (BMI), waist hip ration (WHR), serum insulin, C-peptide, thyroid hormones (thyroxine--T4, triiodothyronine--T3/ sexual hormones (testosterone--T, oestradiol--E2) were investigated. Significant negative correlations were found between SHBG concentration and BMI, serum insulin, C-peptide concentration; significant positive concentrations were found between BMI and serum insulin, C-peptide concentration. Thyroid hormone and sexual hormones did not associate with SHBG levels. These results suggest that insulin hypersecretion has an important role in determining the reduction of SHBG production in obesity.     

Sex hormone‐binding globulin levels and metabolic syndrome and its features in adolescents#

Oya I, Schoppen S, Lasunción MA, Lopez‐Simon L, Riestra P, Oya M, Garcés C. Sex hormone‐binding globulin levels and metabolic syndrome and its features in adolescents. Background: Low levels of sex hormone‐binding globulin (SHBG) are associated with obesity, insulin resistance, and metabolic syndrome (MS) in men and women, and it has been suggested that SHBG could be a useful marker for MS risk. Objective: The aim of this study was to analyze the relationship of SHBG levels with MS and its components in Spanish adolescents. Methods: The sample population of this cross‐sectional study was comprised of 386 male and 429 female adolescents, aged 12–16 yr. Anthropometric parameters and blood pressure (BP) were measured. Total cholesterol, high‐density lipoprotein (HDL)‐cholesterol, insulin, glucose, and SHBG levels were determined. The pediatric International Diabetes Federation (IDF) definition was used to classify adolescents for MS. Results: SHBG levels were lower in adolescents with MS or with some MS features. More than 90% of the abdominally obese adolescents were in the lowest and medium SHBG tertiles. In girls, BP was significantly higher in the lowest SHBG tertile than in the two others, whereas in boys BP levels were significantly higher in the lowest and medium tertiles than in the highest one. Insulin levels and homeostasis model assessment (HOMA) index were also significantly higher in the lowest SHBG tertile than in the two others. Conclusions: The associations of SHBG with MS and its components, such as abdominal obesity, high BP or insulin levels, are already present in normal adolescents. This may suggest the possibility of using SHBG levels as a biomarker for MS risk in adolescents as well as adults.     

The effect of tamoxifen on sex hormone binding globulin in adolescents with pubertal gynecomastia

We investigated the relationship between sex hormone binding globulin (SHBG) and pubertal gynecomastia in 21 adolescents evaluated longitudinally. Thirteen patients were given tamoxifen treatment after grading according to the Nydick classification (group 1). Group 2 consisted of eight patients followed without treatment. Gynecomastia existed bilaterally in 15 patients. There was a statistically significant breast size reduction in both groups. There was a significant decrease in serum SHBG only in group 2. These findings suggest that serum SHBG is increased by tamoxifen treatment in male adolescents. There was a decrease in SHBG levels through the duration of follow up in patients who recovered with or without treatment. However, this decrease was statistically significant in the untreated group, but not in the tamoxifen treated group. In conclusion, we suggest that the pubertal fall in SHBG levels is attenuated by tamoxifen treatment given for pubertal gynecomastia since tamoxifen increases SHBG levels in male adolescents.     

Misinterpretation of thyroid function caused by alteration in thyroxine binding globulin concentration (author's transl)

Two children with undiagnosed TBG alteration were incorrectly treated for hyperthyroidism and hypothroidism, respectively. The first child exhibited hyperthyroxinemia and hypertriiodothyroninemia caused by an increase of TBG. The unoccupied binding sites of serum for thyroid hormones measured by T3-uptake were elevated as usually seen in hypothyroidism. In contrast thyroxine and triiodothyronine were extremely low in the serum of the second patient due to inherited TBG deficiency. T3-uptake was decreased to a value normally found in hyperthyroidism. The paradoxical results of T3-uptake and thyroxine levels indicated changes of concentrations of thyronine binding proteins. The quantitative determination of TBG established the correct diagnosis of TBG elevation and TBG deficiency, respectively.     

Lipopolysaccharide binding protein is a potential marker for invasive bacterial infections in children

BACKGROUND: The aim of this study was to test the hypothesis that elevated lipopolysaccharide binding protein (LBP) serum concentration is a useful marker in the early diagnosis of invasive bacterial infection in children. We measured LBP in serum and cerebrospinal fluid (CSF) of children with proven invasive infection caused by Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis. PATIENTS AND METHODS: Samples were collected from 39 children (aged 2 months to 17 years) with bacterial sepsis (n = 19) or meningitis (n = 20). Bacterial infection was diagnosed when a blood or CSF culture was positive and clinical signs of invasive infection were present. The control group consisted of serum (n = 60) and CSF (n = 19) samples from children with neurologic disease, juvenile idiopathic arthritis or viral infection. In 10 patients with bacterial infection, follow-up samples (24 and 48 hours) were available. LBP values were measured by an immunochemiluminescence analyzer (IMMULITE; DPC Biermann, Bad Nauheim, Germany) and compared with tumor necrosis factor-alpha and interleukin-8 concentrations. RESULTS: The median LBP serum concentrations in patients with bacterial infection were markedly elevated compared with the control groups (45.0 [33.1-55.2] versus 8.3 [6.8-10.1] microg/mL [median and 5-95% confidence interval]; P < 0.0001). Follow-up serum values of LBP were persistently elevated despite adequate antibiotic treatment, whereas tumor necrosis factor-alpha and interleukin-8 concentrations decreased. In contrast, LBP concentrations in the CSF were below the detection limit of 0.5 microg/mL in 67% of patients with bacterial meningitis (median <0.5 microg/mL), whereas tumor necrosis factor-alpha and interleukin-8 levels were highly elevated. CONCLUSION: LBP serum concentration is elevated in serum of children with invasive bacterial infection and could be a promising diagnostic marker.     

The influence of growth hormone monotherapy and growth hormone in combination with oxandrolone or testosterone on thyroxid hormone parameters and thyrxine binding globulin in patients with Ullrich- Turner syndrome

 Administration of human growth hormone (GH) has yielded conflicting results concerning its role on thyroid function in patients with Ullrich-Turner syndrome. Therefore, we investigated the course of thyroid hormone parameters and thyroxin binding globulin in relation to GH therapy, IGF-I and additional oxandrolone-(Ox) or testosterone (T) treatment in 20 patients with Ullrich-Turner syndrome. During the 1st year the patients received only GH. There was no change in T4, fT4, and TSH levels, T3 increased significantly (P <  0.01) after 6 and 12 months, resulting in a higher T3/T4 ratio. TBG (P < 0.05) and IGF-I (P < 0.01) increased after 6 months and remained elevated at 12 months. A significant positive correlation was found between the change of T4 and TBG after 6 months (r = 0.47, P < 0.05) and after 12 months (r = 0.69, P < 0.005). Thirteen patients were further investigated after addition of an anabolic compound; 7 received Ox (0.0625 mg/kg/day po) and 6 low dose T (5 mg i.m. every 14 days). Chronological age was comparable in these groups (10.7 ±  2.7 vs 10.7  ± 3.6 years). After 6 months of combination therapy with Ox, T4, T3 and TSH decreased. As T4 and T3 showed a parallel decrease the T3/T4 ratio remained elevated. TBG declined after 6 and 12 months (P < 0.05), while IGF-I showed a further increment (P < 0.05). There was no correlation between the changes in T4 and IGF-I, TSH and TBG, respectively. In the T-treated group only IGF-I increased (P < 0.05) to the same extent as in the Ox-treated patients, whereas the thyroid parameters did not change. Conclusion The observed changes in thyroid hormone and TBG levels in the Ox group were not mediated by GH or IGF-I. The Ox-induced TBG decrease might be linked to altered pancreatic functions regulating carbo-hydrate metabolism. Received: 22 April 1996 / Accepted: 1 August 1996     

Somatic symptoms as a marker for severity in adolescent depression

Aim: This study aims to investigate the prevalence of somatic symptoms in depressed adolescents and in their healthy peers. A second aim is to investigate the correlation, in the depressed adolescents, between the number of somatic symptoms and severe concurrent symptoms, signs and life events. Methods: The total population of 16–17 year olds – in the city of Uppsala – was screened for depression and then interviewed using a structured interview questionnaire. Depressed subjects and matched controls were identified. A total of 177 pairs were used for pair‐wise analyses of somatic symptoms. Severe symptoms, signs and life events were selected for analysing their relation to depression with somatic symptoms. Results: The adolescents with depressive disorders experienced considerably more somatic symptoms than their healthy controls. The duration and depth of the depression correlated with the number of somatic symptoms. There was a strong correlation between depression with many somatic symptoms and suicidal plans/thoughts, suicidal attempts, disruptive behaviour, as well as multiple stressful relationships. Conclusion: This study demonstrates that somatic symptoms are common in adolescent depression. Multiple somatic symptoms within depression imply a higher severity in terms of duration, depth and psychiatric comorbidity. The strong correlation with suicidal plans, suicidal attempts and disruptive behaviour is concerning.     

兔抗人胸腺细胞球蛋白联合环孢素A治疗儿童再生障碍性贫血10例分析

目的 观察10例应用兔抗人胸腺细胞球蛋白(r-ATG)联合环孢素A(CsA)治疗儿童再生障碍性贫血的疗效及安全性.方法 回顾性分析我院血液科应用r-ATG联合CsA治疗10例患儿的临床资料.结果 10例患儿的中位年龄为7岁,男女比例为2∶3.6例患儿3个月内获得治疗反应,总反应率80%;目前总有效率为70%.不良反应可...     

Reduced levels of growth hormone,insulin-like growth factor-I and binding protein-3 in patients with shunted hydrocephalus

Accepted 25 March 1997
OBJECTIVE—Children with hydrocephalus are characterised by slow linear growth in prepuberty, accelerated physical maturation during puberty, and reduced final height. We aimed to study the possible roles of growth hormone, insulin-like growth factor-I (IGF-I), and IGF binding protein-3 (IGFBP-3) in this growth pattern.
STUDY DESIGN—One hundred and fourteen patients with shunted hydrocephalus (62 males) aged 5 to 20 years, of whom 17 had spina bifida (six males), and 73 healthy controls (38 males) were studied. Anthropometric measures, body mass index, and body fat mass were assessed and the stage of puberty was determined. Serum growth hormone and plasma IGF-I and IGFBP-3 concentrations were measured.
RESULTS—The patients comprised 44 (26 males) who were prepubertal and 70 (36 males) pubertal or postpubertal, while 32 of the controls (19 males) were prepubertal and 41 (19 males) pubertal or postpubertal. The prepubertal children with hydrocephalus had lower IGF-I (p = 0.002) and IGFBP-3 concentrations (p< 0.001) than the controls, and the pubertal children had four times lower basal growth hormone concentrations (p< 0.001). There was a correlation between height SD score and IGF-I levels in the total patientpopulation (r = 0.23; p = 0.01). Peripheral IGF-I concentrations peaked at pubertal stages 2-3 in the female patients and at stage 4 in the controls. The prepubertal patients on antiepileptic treatment, carbamazepine in most cases (73%), had higher IGF-I (p = 0.01) and IGFBP-3 concentrations (p = 0.03) than those who had never been treated with antiepileptic drugs, but still lower IGFBP-3 levels than the controls (p = 0.01).
CONCLUSION— Based on these findings, it can be concluded that reduced growth hormone secretion may contribute to the pattern of slow linear growth and reduced final height observed in these patients.

• Prepubertal children with shunted hydrocephalus have reduced circulating IGF-I and IGFBP-3 concentrations • Pubertal children with shunted hydrocephalus have reduced basal serum growth hormone concentrations • Reduced growth hormone secretion may contribute to slow linear growth and reduced final height in hydrocephalic children • Carbamazepine treatment may increase IGF-I and IGFBP-3 concentrations in the peripheral circulation     

Postnatal thyroid function in low birth weight infants: A cross-sectional assessment of free thyroxine and thyroid hormone binding globulin

To investigate the significance of low serum thyroxine in premature infants, serum FT4, T4, TSH and TBG were measured in 7 infants with BW<1000 g, 8 infants with BW 1001 to 1350 g, 9 infants with BW 1351 to 2499 g, and 11 full-term infants.FT4 concentrations were lower in the LBW infants than in the FT infants. Percent FT4 values in the infants with BW<1000 g were the highest in the groups studied, so that FT4 concentrations in those infants did not fall proportionally with the marked T4 decrease. TBG concentrations were lower in the VLBW infants (相似文献   

Neuropeptide Y as a marker in pediatric neuroblastoma

Neuropeptide Y (NPY) was investigated as a possible tumor marker in pediatric patients with tumors of the sympathetic nervous system. Seven patients with neuroblastoma, 3 patients with ganglioneuroblastoma, and 2 with ganglioneuroma, were compared with 12 matched healthy controls and 34 tumor controls. NPY-like immunoreactivity (NPYLI) was analyzed in extracted plasma using a competitive radioimmunoassay. At diagnosis, plasma NPYLI was significantly increased (p less than .001) in the neuroblastoma patients (352 +/- 99 pM; mean +/- SEM) when compared with healthy controls (36 +/- 4 pM) and tumor controls (30 +/- 2 pM). Ganglioneuroblastoma and ganglioneuroma patients had lower levels (57 +/- 8 pM) than neuroblastoma patients but still significantly higher than the controls. In all patients with sympathetic tumors, the NPYLI level was decreased after treatment. Five neuroblastoma patients relapsed; all had increasing NPYLI levels. In 3 of these patients, incresing NPYLI was the first sign of relapse. Plasma NPYLI correlated well to urinary levels of homovanillic acid. NPY in plasma (NPYLI) may be a clinically useful marker of pediatric neuroblastoma for diagnosis and differential diagnosis. NPYLI correlates well with the clinical course and can be the first sign of relapse. Plasma determinations of NPYLI make it possible to monitor rapid alterations of disease.     

Renal concentrating capacity as a marker for glomerular filtration rate

AIM: We have studied 160 children with a variety of renal diseases, 14 of them with chronic renal failure (CRF), to evaluate maximum urinary osmolality as a predictor of glomerular filtration rate (GFR) testing the hypothesis that a normal GFR is necessary to have a normal urinary concentrating capacity. METHODS: All patients had a serum creatinine measured. GFR was calculated according to the Schwartz formula. All patients underwent desmopressin (DDAVP) test to evaluate renal concentrating capacity. RESULTS: Patients with CRF were unable to concentrate the urine beyond 486 mosm/kg whereas all patients with a normal concentrating capacity (urine osmolality >835 mosm/kg) had a normal GFR. Desmopressin test sensitivity to detect CRF was 100% and specificity 70.5%. A significant negative correlation was found between urinary osmolality after DDAVP administration and serum creatinine levels and between urinary volume corrected by 100 mL of GFR (V/GFR) and urinary osmolality. CONCLUSION: In our series, a normal concentrating capacity was always associated with a normal GFR while all patients with decreased GFR had a concentrating capacity defect. Thus, in the evaluation of infants and children with renal disease, the finding of a normal urinary concentrating capacity will suggest and intact glomerular and tubular function.     

Transcobalamin I as a "marker" for fibrolamellar hepatoma

A 12 year old girl with a localised fibrolamellar hepatoma had a raised serum unsaturated vitamin B12 binding capacity (UBBC) and transcobalamin I (TCI) prior to complete resection and chemotherapy. Regular clinical and radiological follow-up detected no recurrence of her disease, but the UBBC and TCI slowly rose. Local recurrence and pulmonary metastases became detectable 2 1/2 years after diagnosis, 18 months after the UBBC and TCI level became elevated. Measurement of UBBC and TCI can help in the early detection of recurrence long before there is clinical or radiological evidence of recurrent fibrolamellar hepatoma.     

N-terminal-proB-type natriuretic peptide as a marker for acute anthracycline cardiotoxicity in children

BACKGROUND: Anthracyclines are widely used in the treatment of pediatric cancer but their use is associated with cardiotoxicity. The cardiotoxic effect may become clinically apparent many years after therapy, and no reliable method exists for early detection of cardiac damage while the patient is receiving the drug. The natriuretic peptides have been established as markers for anthracycline-induced cardiotoxicity in adults and markers for cardiac dysfunction in children. We examined whether N-terminal proB-type natriuretic peptide (NT-proBNP) may be used as a marker for anthracycline-induced cardiotoxicity in children. METHODS: Twenty-three consecutive pediatric patients with newly diagnosed cancer were enrolled in this study. All patients received anthracycline-containing chemotherapy. Fifty-four age-matched children served as controls. Serial measurements of plasma NT-proBNP levels were taken before and after each anthracycline-containing course. Echocardiograms were performed before initiation of treatment and at the end of the study. RESULTS: Plasma levels of NT-proBNP were within normal limits before treatment and increased significantly only after the first anthracycline dose (from 150+/-112 to 327+/-321 pg/mL, mean+/-SD, P=0.02) and not after subsequent doses. This increase was attributed mainly to a subgroup of patients who received more than 25 mg/m of doxorubicin. In 14 patients (61%), the highest NT-proBNP level occurred after the first anthracycline dose. All patients had normal echocardiograms and none developed heart failure. CONCLUSIONS: NT-proBNP increases significantly after the first anthracycline course in a subset of pediatric cancer patients. This increase is not associated with clinical or echocardiographic evidence of cardiac dysfunction. Anthracyclines may be more cardiotoxic in the first course than in subsequent courses. Longer follow-up of these patients is necessary to determine whether NT-proBNP can be used as an early marker for anthracycline-induced cardiotoxicity.     

Growth hormone replacement in patients with Langerhan's cell histiocytosis

OBJECTIVES—To assess the impact of growth hormone on growth and the underlying disease in children with growth hormone deficiency as a result of Langerhan''s cell histiocytosis.
STUDY DESIGN—Retrospective analysis of data from the Kabi (Pharmacia & Upjohn) international growth database (KIGS) for 82 children with Langerhan''s cell histiocytosis treated with recombinant growth hormone.
RESULTS—At the start of treatment the median (10-90th centile) age was 9.0 (5.2 to 14.7) years, with a median height standard deviation score (SDS) of −2.0 (−3.5 to −0.9). The median pretreatment height velocity (measured in cm/year) was 3.6 (0.9 to 6.4); this increased to 8.8 (3.8 to 12.0) in the first year of treatment with growth hormone, and then remained significantly greater than the pretreatment height velocity at 7.3 (4.4 to 9.7) and 7.1 (4.1 to 9.3) cm/year in the second and third years, respectively. The median height SDS increased from −2.0 to −0.8 (−2.3 to 0.6) by the end of three years of treatment. There was no increase in the recurrence rate of the underlying disease and no adverse event could be directly attributed to growth hormone treatment, apart from one case of benign intracranial hypertension that resolved on stopping treatment with growth hormone.
CONCLUSIONS—Growth hormone replacement treatment for patients with Langerhan''s cell histiocytosis with growth hormone deficiency is beneficial and safe.