Comparison of adrenal function tests in children--the glucagon stimulation test allows the simultaneous assessment of adrenal function and growth hormone response in children.

The accurate assessment of adrenal function is necessary in many children with suspicion of pituitary insufficiency. The objective of this study was to evaluate the adrenal response during the glucagon stimulation test (GST) and its diagnostic utility in children. A total of 290 children, aged 10.1 +/- 5.0 years, were evaluated for adrenal function using the corticotrophin releasing hormone (CRH) test, the GST, and/or the insulin tolerance test (ITT). Glucagon stimulation provoked a substantial rise in cortisol and adrenocorticotropin (ACTH) that was independent of gender, age, or underlying growth hormone deficiency. There were no differences in peak cortisol levels in the GST compared to the CRH test in pair-wise intra-individual analyses in children with both tests performed within one year (615.4 +/- 30.5 vs 602.8 +/- 22.4 nmol/l, n=52). Similarly, there were no differences in the cortisol response between the ITT and CRH test. Peak cortisol levels in the CRH test correlated with the GST and the ITT. The magnitude of ACTH response, in contrast, was highest in the ITT with a 9.8-fold increase over baseline, while the increase in the GST (3.1-fold) and CRH test (1.6-fold) were more subtle. Since there is controversy concerning reliable cut-off values for adrenal function tests in children, we analyzed cut off levels in 186 children, including 26 children with adrenal insufficiency, using the CRH test. A peak cortisol level of 450 nmol/l provided the best balance of sensitivity (88.5%) and specificity (86.8%), while higher cut-off levels did not increase sensitivity but lost in specificity. In summary, the GST constitutes an1 equally sensitive test for the assessment of adrenal function in children that is not confounded by anthropometric parameters and is generally not accompanied by major side effects. It allows the simultaneous assessment of corticotroph and somatotroph function and may thus constitute a valuable alternative to the ITT.

PROP1 mutations cause progressive deterioration of anterior pituitary function including adrenal insufficiency: a longitudinal analysis.

Mutations in the PROP1 gene are the most frequent genetic defects in patients with combined pituitary hormone insufficiency. However, controversy exists about the timing and extent of pituitary insufficiency, and it remains unclear whether adrenal failure is a typical feature of this condition. We performed a retrospective longitudinal analysis of nine patients with PROP1 mutations who were under medical supervision at our clinic for 15.7 +/- 3.4 yr. All patients initially presented with growth failure (height sd score, -3.7 +/- 0.3) at a mean age of 4.9 +/- 0.8 yr. They were first diagnosed with GH and TSH deficiency, and replacement therapy was instituted at 6.1 +/- 1.1 and 6.8 +/- 1.2 yr, respectively. All seven patients who reached pubertal age required sex hormone substitution at 15.0 +/- 0.7 yr. Repeated functional testing of the anterior pituitary axes revealed a progressive decline with age in peak levels of GH, TSH, prolactin, and LH/FSH. All patients developed at least partial adrenal insufficiency, with a gradual decline of the function of the pituitary adrenal axis and eventually required substitution with hydrocortisone at a mean age of 18.4 +/- 3.5 yr. It is concluded that anterior pituitary function in patients with PROP1 mutations deteriorates progressively and includes adrenal insufficiency as a feature of this condition, which has important clinical relevance in childhood and adolescence.

Medical care of obese children and adolescents. APV: a standardised multicentre documentation derived to study initial presentation and cardiovascular risk factors in patients transferred to specialised treatment institutions.

UNLABELLED: So far in Europe, no studies have been published on the structuring of medical care for obese children and adolescents. Besides anthropometric parameters, evaluations of the cardiovascular risk factors hypertension, dyslipidaemia, impaired glucose metabolism and treatment modalities were documented in a standardised multicentre evaluation survey (APV) of 18 primarily outpatient and nine rehabilitation institutions. In total, 3837 children (aged 2-20 years) took part in the years 2000 up to March 2003, of whom 1985 were treated in outpatient institutions and 1852 in rehabilitation institutions. Of these children, 10% were overweight, 37% obese, 49% extremely obese and 4% of normal weight at initial presentation. The frequencies of diagnostic procedures performed and documented were low (measurement of blood pressure 43%, lipids 40%, glucose metabolism 21%). In the subgroup of obese children who were screened for cardiovascular risk factors, 23% suffered from hypertension, 11% displayed increased cholesterol, 9% increased low-density lipoprotein-cholesterol, 29% increased triglycerides, 11% decreased high-density lipoprotein-cholesterol and 6% had impaired glucose metabolism. CONCLUSION: Despite the high prevalence of cardiovascular risk factors in obese children and adolescents confirmed in this report, diagnostic procedures failed in a considerable percentage even in specialised treatment centres for obese children and adolescents. In future, the feedback based on standardised evaluation of diagnostic and treatment procedures should aim to improve the quality of medical care.

Gender differences of adiponectin levels develop during the progression of puberty and are related to serum androgen levels.

Adiponectin is an adipocytokine with profound antidiabetic and antiatherogenic effects that is decreased in obesity. With the increasing prevalence of obesity and the emergence of related disorders, including type 2 diabetes in children, the regulation of adiponectin and its relationship to childhood obesity is of great interest. In this study we aimed to elucidate the impact of gender, pubertal development, and obesity on adiponectin levels in children. We investigated two phenotypically characterized cohorts of 200 normal weight and 135 obese children and adolescents covering a wide range of age (3.4-17.9 yr) and body mass index (-2.1 to +4.8 sd score). In healthy lean boys, adiponectin levels significantly declined in parallel with physical and pubertal development, subsequently leading to significantly reduced adiponectin levels in adolescent boys compared with girls (5.6 +/- 0.5 vs. 7.1 +/- 0.5 mg/liter; P = 0.03). This decline was inversely related to testosterone (r = -0.42; P < 0.0001) and dehydroepiandrosterone sulfate (r = -0.20; P = 0.0068) serum concentrations and may account for the gender differences seen in adults. Using a stepwise forward multiple regression model, pubertal stage was the strongest independent predictor of adiponectin (r(2) = 0.206; P < 0.0001), with additional influences of body mass index sd score and testosterone. Adiponectin levels were decreased in obese children and adolescents compared with lean peers of corresponding age and pubertal stage (5.18 vs. 7.13 mg/liter; P = 0.015). In obese children, adiponectin levels were closely associated with parameters related to the metabolic syndrome, such as insulin resistance, hyperinsulinemia, blood pressure, and uric acid, in univariate and multivariate analyses, with the insulin sensitivity index being the strongest independent parameter identified by stepwise forward multiple regression (r(2) = 0.226; P < 0.0001). Hence, there is a strong association of adiponectin serum concentrations with obesity, pubertal development, and metabolic parameters in children indicating epidemiological and pathophysiological relevance already in childhood.

Pharmacoeconomics of obesity management in childhood and adolescence.

The level of fatness of a child at which morbidity acutely increases is operationally determined by calculating the body mass index (BMI). An increased risk of death from cardiovascular disease in adults has been found in subjects whose BMI had been > 75(th) percentile as adolescents. Childhood obesity seems to substantially increase the risk of subsequent morbidity whether or not obesity persists into adulthood. Among the most common sequelae of primary childhood obesity are hypertension, dyslipidaemia, back pain and psychosocial problems. Environmental/exogenous factors largely contribute to the development of body fatness early in life. Therapeutic strategies include psychological and family therapy, lifestyle/behaviour modification and nutrition education. The role of regular exercise and exercise programmes is emphasised. Surgical procedures and drugs used in adult obesity are not generally recommended in children and adolescents. Appetite suppressants and thermogenic drugs have not been approved for use in children. Digestive inhibitors such as lipase inhibitors and fat substitutes have been used in children and adolescents in off-label use and in only a few clinical studies. As obesity is the most common chronic disorder in the industrialised societies, its impact on individual lives, as well as on health economics, has to be recognised more widely. One should aim to increase public awareness of the ever increasing health burden and economic dimension of the childhood obesity epidemic that is present around the globe.

A season of aseptic meningitis in Germany: epidemiologic, clinical and diagnostic aspects.

OBJECTIVE: We assessed epidemiologic, clinical and laboratory features of aseptic meningitis during one season of multiserotype enteroviral meningitis in East Germany in 70 consecutive patients with aseptic meningitis admitted to the Children's University Hospital Leipzig. RESULTS: Patients, age 1 to 16 years, typically presented with headache, emesis and fever, whereas signs of meningeal irritation were only moderately expressed in one-half of the patients. The median number of leukocytes in the CSF was 151 cells/mm(3) (range, 2 to 1,820) with a high percentage of polymorphonuclear cells (PMNs). Initial blood counts showed mild leukocytosis and pronounced PMN predominance (78.9 +/- 1.3%). The percentage of PMNs in the peripheral blood decreased in favor of mononuclear cells after 3 days to a pattern more compatible with viral infection as opposed to that suggestive for bacteria in the beginning. Mean cerebrospinal fluid values of protein, glucose and lactate and the C-reactive protein were mildly elevated or normal. Nonpolio enteroviruses were detected in 30 of 70 patients. Subsequent serotyping revealed echovirus type 13 (13 patients), type 6 (2), type 30 (1) and coxsackie B virus type 5 (2). There were no differences in demographic or clinical data between enterovirus positive and negative patients. CONCLUSIONS: Even though individual laboratory values do not solely allow discrimination between viral and bacterial meningitis, the combined epidemiologic, clinical and laboratory data facilitate the diagnosis of aseptic meningitis in most cases. Viral diagnostics, identifying echovirus type 13 that thus far has not been associated with epidemics of meningitis, adds important epidemiologic information.