Human sympathoadrenal system and adrenal cortex in prepubertal and pubertal periods

A complex study of the functional state of the sympathoadrenal system and adrenal cortex in 10–15-year-old children of both sexes was carried out using the indices of daily excretion of adrenaline, noradrenaline, 17-ketosteroids, and 17-hydroxycorticosteroids. A synchronism in the functional activity of the mediator component of the sympathoadrenal system as well as of the androgenic and glucocorticoid functions of the adrenal cortex was observed with age and during pubertal development of children. At the same time, heterochronic maturation was observed in the sex groups: in girls at the age of 10 and 12 years and in boys at the age of 14–15 years. The changes of different direction and intensity in the excretion of the studied hormones and hormonal metabolites were observed in the sex and age groups. A sharp increase in the daily excretion of glucocorticoid metabolites accompanied by a considerable decrease in the age index of noradrenaline secretion was observed in 14-and 15-year-old boys from beginning to end of school year; in addition, an increase in the daily excretion of sex hormones was observed at the age of 15 years. In girls, these indices varied within the age range, which points to a more sophisticated neuroendocrine control of physiological functions in girls during puberty.     

Age- and sex-related characteristics and mechanisms of adaptations during the prepubertal and pubertal periods of development

Integrated study of the functional state of the sympathoadrenal system and the adrenal cortex in children of both sexes aged 10–15 years. The study was conducted on the basis of the daily adrenaline, noradrenaline, 17-ketosteroid, and 17-oxycorticosteroid excretion values, which allowed certain synchrony to be established in the manifestation of the activity of the transmitter link of the sympathoadrenal system and the adrenal cortex androgenic and glucocorticoid functions with age, during sexual maturation. The heterogeneous character of maturation was found in the sex groups: in girls at an age of 10 and 12 years and in the boys at an age of 14–15 years. Changes in the excretion of the hormones and hormone metabolites with different directions and rates in the age-sex groups were observed throughout the academic year. In 14- to 15-year-old boys, a sharp increase in the daily excretion of the glucocorticoid metabolites accompanied by a substantial decrease in the age-related noradrenaline excretion values and the sex hormone metabolite values at an age of 15 years was observed. In the girls, these values varied within the age range, which indicates a more perfect character of the neuroendocrine regulation of their physiological functions in the period of sexual maturation.     

Interrelations between the sympathoadrenal system,adrenal cortex,and autonomic tone in seven- to nine-year-old children

Comprehensive study of the functional state of the sympathoadrenal system (SAS) and adrenal cortex (AC) and the specific features of the autonomic regulation of the cardiac rhythm revealed close correlations between the excretion of catecholamines (CAs) and androgens, on the one hand, and the initial autonomic tone (IAT) of the cardiovascular system of children, on the other hand. Most schoolchildren of both sexes with a predominant dependence of their cardiac rhythm on sympathetic influences were shown to excrete more noradrenaline (NA), 17-hydroxycorticosteroids, and 17-ketosteroids and less dopamine than their normotonic and vagotonic counterparts, which was accompanied by an increase in the NA-to-adrenaline ratio. In contrast, eight-and nine-year-old girls exhibited a relatively decreased activity of glucocorticoid functions of the AC associated with sympathicotonia. A local static effort performed as a functional test caused similarly directed changes in the functional states of the SAS and AC in a manner dependent on the child’s IAT, age, and sex. In the states of sympathicotonia or normotonia, nine-year-old girls exhibited a decrease in the excretion of CAs and DOPA or their insignificant increase accompanied by strengthening of the functional activity of the AC, especially of its androgen function. This may be interpreted as a manifestation of specific neuroendocrine interrelations in the adaptive mechanisms of nine-year-old girls and a higher stability of the pituitary-adrenal system, which controls metabolic processes in the growing body. In contrast, in normotonic and vagotonic seven-year-old boys (as well as in sympathicotonic eight-year-old boys), the local static effort revealed simultaneous decreases in the reserve potentials of the SAS and AC, probably caused by fatigue and asthenization of these children during their schoolwork.     

The impact of increased physical exertion on the state of adrenal cortex and pubertal development in boys

The study of the functional state of the adrenal cortex (AC) in young athletes aged 11 to 15 years, which was assessed by daily free (C_f) and bound (C_b) cortisol excretion levels, and the comparison of these levels with those of the boys from the control group made it possible to conclude that the increased physical exertion in the form of regular athletic training had a dominating effect on the age-related changes in the AC and pubertal development in the young athletes. It was found that the 12- to 14-year-old athletes had stably high C_f excretion levels, which were significantly decreased by the age of 15 years on the background of high C_b levels, as compared to the nonathletes, whose urinary cortisol levels were significantly lower (p < 0.05) and were progressively increased (p < 0.05) from 13 to 15 years of age. It was found that pubertal development (the development of secondary sex characteristics) was relatively delayed in the athletes, and pubertal changes in the glucocorticoid function of the AC reflected mainly its adaptive responses providing the increased resistance of the child’s body to increased physical exertion.     

Characteristics of cardiac activity in 5- to 7-year-old children during graded exercise

The characteristics of cardiac activity in 5–7-year-old children were studied at rest and during graded veloergometric exercise. The indices of central hemodynamics strongly correlated at rest and the closest correlations were in girls compared to boys. Minute volume increased with an increasing load (from 0.5 to 1.5 W/kg) which could be attributed to an increase in stroke volume. In the groups of 5- to 7-year-old boys and 7-year-old girls the stroke volume increased with an increasing load reaching a maximum at 1.5 W/kg. In the groups of 6-year-old boys and 5-year-old girls the stroke volume increased up to a load of 1.0 W/kg. Heart rate represents another mechanism of cardiac output regulation. The chronotropic response to physical exercise in 5- to 7-year-old children was found to be sex specific, which was especially pronounced at the loads of 1.0 and 1.5 W/kg. Sex difference in the chronotropic heart response to graded physical exercise appeared at the age of 5, and the difference in inotropic response at the age of 7 years substantiates the heterochronous development of chrono- and inotropic cardiac functions.     

Adrenal steroid hormones and metaphyseal bone in children

BACKGROUND/OBJECTIVES: The responses of metaphyseal bone tissue to physiological variations of endogenous adrenal steroid hormones during childhood are unclear. Therefore, we studied potential hormonal influences in children before the appearance of pubic hair (onset of pubarche). METHODS: Excretions of major glucocorticoid metabolites (C21), cortisol, sum of adrenarchal dehydroepiandrosterone and its immediate 16-hydroxylated metabolites (DHEA&M), and 5-androstene-3beta,17beta-diol (hermaphrodiol) were analyzed in a cross-sectional study in 24-hour urine samples of 109 healthy boys and girls, aged 6-13 years, using steroid profiling by gas chromatography-mass spectrometry. Total and trabecular volumetric bone mineral densities, bone mineral content (BMC) and bone strength strain index were determined with peripheral quantitative computed tomography at the distal forearm. RESULTS: In multiple regression analyses significant associations with the metaphyseal radius were seen for grip force, age, or BMI depending on gender and bone variable analyzed. DHEA&M did not contribute to the explanation of the variance of any bone variable. However, hermaphrodiol positively explained a significant part of variation of bone mineral densities, and BMC (p < 0.01) in girls. Significantly negative associations with all bone variables were seen in boys for cortisol. CONCLUSIONS: The steroid hormones, cortisol and hermaphrodiol, in their physiological ranges, but not the adrenarche marker DHEA&M, appear to associate with metaphyseal bone in a sex-dependent manner during childhood.     

Influence of cognitive load on the body functional state in children aged 9 to 12 years during early stages of puberty

This article analyzes heart rate variability (HRV), the glucocorticoid function of adrenal glands, and brain electrical activity (EA) in children aged 9 to 12 years to study their functional state during early stages of puberty. The cognitive load (mental arithmetic) caused low-frequency waves in the heart rate spectrum in all subjects, regardless of the puberty stage and gender. With respect to the age range under study, the hormonal response to the arithmetic test, expressed in a decrease in the level of cortisol, was observed in boys only at the third stage of puberty. The visual analysis of the background electrical encephalogram showed frequent generalized bilateral and synchronous changes in the electrical activity (EA) in the form of diencephalic signs in children. The features of the relationship between the autonomic nervous system and the hypothalamic pituitary-adrenal system have been revealed in children aged 9 to 12 years during cognitive load. The closest correlations between HRV indices and cortisol levels have been found in girls at the first stage and boys at the third stage of puberty.     

Development of centrality indices of subcutaneous fat during growth

Changes of fat distribution were followed up in Czech and Slovak children from 1.5 to 15 years of age, using centrality indices, which relate the values of skinfolds on the trunk to the skinfolds on the extremities, head and neck. Up to 5 years of age, subcutaneous fat was deposited relatively more on the extremities, head and neck than on the trunk, which was expressed by lower values of the centrality indices. After the age of 5 years, the accumulation of subcutaneous fat was greater on the trunk, which was also expressed by higher values of the centrality indices. The comparison of the individual indices revealed in both genders a relatively higher amount of subcutaneous fat on the trunk in boys until 12 years of age. During puberty subcutaneous fat over triceps and on the forearm was reduced. In girls the deposition of the subcutaneous fat was relatively greater at different sites of the trunk than in boys, with the exception of the age of 14-15 years. The deposition of subcutaneous fat was greater on the trunk than on the head (cheek) and on the extremities in Czech compared to Slovak children, except for 12-year-old girls. During the period between the fifties and the seventies of the last century, in Czech children, especially in girls, the deposition of subcutaneous fat on the trunk was relatively smaller than on other parts of the body surface, which was expressed by the reduction of the centrality indices. Index 12 was therefore considered as the most valuable for the characterization of fat distribution on the body surface.     

Blood pressure in patients after unilateral adrenalectomy for aldosterone producing adrenal adenoma]

Forty five patients (35 women and 10 men) who underwent adrenalectomy for aldosterone-producing adrenal adenoma were followed up for 5.7 +/- 4.7 years (1-17 years). Stable normalization of blood pressure was noted in 27 (60%) patients. In 16 patients the primary hypertension and in 1 patient the second adrenal adenoma were diagnosed after surgery. Statistically significant decrease in daily excretion of adrenaline and noradrenaline with the urine, reduced adrenaline/noradrenaline ratio and reduced catecholamines and their metabolites ratio were noted in the operated patients in comparison to healthy volunteers indicating catecholamines metabolism disorders. Surgical treatment of adrenal adenoma besides normalization of blood pressure diminishes biochemical abnormalities. Development of the primary blood hypertension may be expected in some patients.     

The functional state of the sympathoadrenal system and the autonomic regulation of the cardiac rhythm in younger schoolchildren

A comparative analysis of functional states of the sympathoadrenal system (SAS) and its reactions to isometric muscular effort was performed in seven-year-old schoolchildren of both sexes with different types of cardiac regulation. Children with a predominance of sympathetic influences displayed a higher excretion of noradrenaline and a lower excretion of dopamine than their counterparts with normal or vagal tone. A graded isometric exercise changed the functional state of the SAS in a manner dependent on the initial autonomic tone, baseline excretion of catecholamines, and sex. Boys displayed more strained reactions of the SAS than girls did, which was associated with a decrease in its reserve potential, especially pronounced in the states of vagal and normal tones. This suggests imperfect mechanisms of adaptation to static loads.     

Serum IGF-I and IGFBP-3 levels of Turkish children during childhood and adolescence: establishment of reference ranges with emphasis on puberty

AIMS/METHODS: We established age- and sex-related reference ranges for serum insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) levels in 807 healthy Turkish children (428 boys, 379 girls), and constructed a model for calculation of standard deviation scores of IGF-I and IGFBP-3 according to age, sex and pubertal stage. RESULTS: Serum IGF-I and IGFBP-3 concentrations tended to be higher in girls compared to boys of the same ages, but the differences were statistically significant only in pubertal ages (9-14 years) for IGF-I and only in prepubertal ages for IGFBP-3 (6-8 years) (p < 0.05). Peak IGF-I concentrations were observed earlier in girls than boys (14 vs. 15 years, Tanner stage IV vs. V) starting to decline thereafter. IGFBP-3 levels peaked at age 13 and at Tanner stage IV in both sexes with a subsequent fall. Serum levels of IGF-I and IGFBP-3 increased steadily with age in the prepubertal stage followed by a rapid increase in IGF-I in the early pubertal stages. A relatively steeper increase in IGF-I but not in IGFBP-3 levels was observed at age 10-11 years in girls and at 12-13 years in boys which preceded the reported age of pubertal growth spurt. At late pubertal stages, both IGF-I and IGFBP-3 either did not change or decreased by increasing age. Interrelationships between growth factors and anthropometric measurements have been described, and the physiologic consequences of these have been discussed in detail. CONCLUSIONS: Differences in the pattern of IGF-I and IGFBP-3 in the present paper and those reported in other studies emphasize the importance of locally established reference ranges. Establishment of this reference data and a standard deviation score prediction model based on age, sex and puberty will enhance the diagnostic power and utility of IGF-I and IGFBP-3 in evaluating growth disorders in our population.     

Intelligence in Taiwan: Progressive Matrices means and sex differences in means and variances for 6- to 17-year-olds

Data for Raven's Progressive Matrices are reported for a sample of 6290 6- to 17-year-olds in Taiwan. The Taiwanese obtained a mean IQ of 109.5, in relation to a British mean of 100. There was no difference in mean scores of boys and girls at age 7 years. At age 10 years girls obtained significantly higher scores than boys, and at ages 13 and 16 years boys obtained significantly higher scores than girls. There was no sex difference in variance at age 7 years. At ages 10, 13 and 16 years variance was significantly greater in boys.     

Sexual dimorphism in cortisol secretion starts after age 10 in healthy children: urinary cortisol metabolite excretion rates during growth

Detailed data on the physiological pattern of adrenocortical activity during normal growth are lacking. An established method to determine adrenocortical glucocorticoid secretion is the measurement of 24-h excretion rates of major urinary cortisol metabolites (C21). To test the hypothesis that the frequently reported higher cortisol secretion in men than in women develops during puberty, we examined C21 together with excretions of combined urinary free and conjugated cortisol (F(comb)) in 400 healthy boys and girls aged 3-18 yr using GC-MS. Daily excretion rates of C21, F(comb), and body surface area (BSA)-corrected F(comb) significantly increased with age in both sexes. In contrast, C21/BSA (microgxm(-2).day(-1)) declined from the age of 3-4 yr to 7-8 yr in boys and girls (P < 0.01; e.g., in boys: from 3,991 +/- 1,167 to 3,193 +/- 804), then increased in both sexes, and finally became discordant after the age of 11-12 yr with a further rise in males only (17- to 18-yr-olds: boys, 5,275 +/- 1,414; girls 3,939 +/- 1,586, P < 0.01). This pattern was associated with the occurrence of a lower index for 5alpha-reductase activity (allotetrahydrocortisol/tetrahydrocortisol) in females compared with males. Our results demonstrate dynamic changes in adrenocortical activity in healthy children resulting in an emerging sexual dimorphism in cortisol secretion after age 11. The latter can be explained, at least partly, by diverging 5alpha-reductase activities in boys and girls. F(comb), a frequently analyzed GC-MS parameter, proved not to reflect dynamic changes in cortisol secretion. In conclusion, the varying metabolic need for cortisol during normal growth may have implications for future improvements in glucocorticoid replacement therapy.     

Urinary excretion of immunoreactive prostaglandin F2 alpha in healthy children and adults

The 24-hours urinary excretion of immunoreactive prostaglandin F2 alpha (U-iPGF2 alpha) in normal children on a free diet was not significantly different in 30 boys (aged 3-15 years; geometric mean 589 ng/24 h) compared to 27 girls (aged 4-14 years; mean 473 ng/24 h). In both sexes this excretion rose with age until adolescence where it reached a plateau. In normal adults the men had significantly higher (p less than 0.001) excretions of U-iPGF2 alpha than the women; also body weight and urinary creatinine excretion were higher in men (p less than 0.001). In the children, as well as in the total population, U-iPGF2 alpha correlated best with body weight (r = 0.44 and r = 0.48 respectively; p less than 0.001) and the urinary creatinine excretion (r = 0.53 and 0.57 respectively; p less than 0.001); both body weight and urinary creatinine excretion are reflections of total body development. After the correction for urinary creatinine excretion or for body weight, the sex difference in the adult U-iPGF2 alpha totally disappeared.     

Sex matters during adolescence: testosterone-related cortical thickness maturation differs between boys and girls

Age-related changes in cortical thickness have been observed during adolescence, including thinning in frontal and parietal cortices, and thickening in the lateral temporal lobes. Studies have shown sex differences in hormone-related brain maturation when boys and girls are age-matched, however, because girls mature 1-2 years earlier than boys, these sex differences could be confounded by pubertal maturation. To address puberty effects directly, this study assessed sex differences in testosterone-related cortical maturation by studying 85 boys and girls in a narrow age range and matched on sexual maturity. We expected that testosterone-by-sex interactions on cortical thickness would be observed in brain regions known from the animal literature to be high in androgen receptors. We found sex differences in associations between circulating testosterone and thickness in left inferior parietal lobule, middle temporal gyrus, calcarine sulcus, and right lingual gyrus, all regions known to be high in androgen receptors. Visual areas increased with testosterone in boys, but decreased in girls. All other regions were more impacted by testosterone levels in girls than boys. The regional pattern of sex-by-testosterone interactions may have implications for understanding sex differences in behavior and adolescent-onset neuropsychiatric disorders.     

Planning Steps Forward in Development: In Girls Earlier than in Boys

The development of planning ability in children initially aged four and five was examined longitudinally with a retest-interval of 12 months using the Tower of London task. As expected, problems to solve straightforward without mental look-ahead were mastered by most, even the youngest children. Problems demanding look-ahead were more difficult and accuracy improved significantly with age and over time. This development was strongly moderated by sex: In contrast to coeval boys, four year old girls showed an impressive performance enhancement at age five, reaching the performance of six year olds, whereas four year old boys lagged behind and caught up with girls at the age of six, the typical age of school enrollment. This sex-specific development of planning was clearly separated from overall intelligence: young boys showed a steeper increase in raw intelligence scores than girls, whereas in the older groups scores developed similarly. The observed sex differences in planning development are evident even within a narrow time window of twelve months and may relate to differences in maturational trajectories for girls and boys in dorsolateral prefrontal cortex.     

Evaluation of Body Composition in Patients With and Without Adrenal Tumors and Without Overt Hypersecretory Syndromes

ObjectiveTo compare body composition between patients with autonomous cortisol secretion (ACS), those with nonfunctioning adrenal incidentalomas (NFAIs), and control subjects without adrenal tumors.MethodsA cross-sectional study was performed, incluidng the following 3 groups: patients with ACS (cortisol post–dexamethasone suppression test [DST] >1.8 μg/dL), NFAIs (cortisol post-DST ≤ 1.8 μg/dL), and patients without adrenal tumors (control group). Patients of the 3 groups were matched according to age (±5 years), sex, and body mass index (±5 kg/m²). Body composition was evaluated by bioelectrical impedance and abdominal computed tomography (CT) and urinary steroid profile by gas chromatography mass spectrometry.ResultsThis study enrolled 25 patients with ACS, 24 with NFAIs, and 24 control subjects. Based on CT images, a weak positive correlation between the serum cortisol level post-DST and subcutaneous fat area (r = 0.3, P =.048) was found. As assessed by bioelectrical impedance, lean mass and bone mass were positively correlated with the excretion of total androgens (r = 0.56, P <.001; and r = 0.58, P <.001, respectively); visceral mass was positively correlated with the excretion of glucocorticoid metabolites and total glucocorticoids (r = 0.28, P =.031; and r = 0.42, P =.001, respectively). Based on CT imaging evaluation, a positive correlation was observed between lean mass and androgen metabolites (r = 0.30, P =.036) and between visceral fat area, total fat area, and visceral/total fat area ratio and the excretion of glucocorticoid metabolites (r = 0.34, P =.014; r = 0.29, P =.042; and r = 0.31, P =.170, respectively).ConclusionThe urinary steroid profile observed in adrenal tumors, comprising a low excretion of androgen metabolites and high excretion of glucocorticoid metabolites, is associated with a lower lean mass and bone mass and higher level of visceral mass in patients with adrenal tumors.     

Incidence of asthma in children in Tuzla Canton--Bosnia and Herzegovina

Asthma is one of the most common chronic diseases whose incidence shows constant growth in childhood. The objective of this work was to look into asthma incidence in children in relation to their age group and sex in a retrospective study, at Tuzla Canton area. The study comprised children of both sexes, age 0-14 who fell sick with asthma within the period from January 1st 2003 to December 31st 2007. The overall incidence and the incidence in relation to age group and sex was calculated as the number of children suffering from asthma, within the age group 0-14 years per 1000 children of the same age group in the Tuzla Canton. Asthma was diagnosed in 277 children (66.1% male and 33.9% female). The difference between asthma frequency in boys and girls was significant (chi2 = 56.16; df = 1; p < 0.0001). The average difference in proportion between the boys and girls was 32.2% (95% CI = 24.32-40.08). From this sample group the boys had a 3.8 times greater risk (OR = 3.79; %95 CI = 2.67-5.39) of contracting asthma. The average rate of incidence of asthma for both sexes in the observed period was 0.67/1000 (95% CI; 0.6-0.7; for boys 0.86/1000; for girls 0.47/1000). There was a statistically significantly higher incidence of asthma in boys in relation to girls (t = 6.3836, df = 32; p < 0.0001). The epidemiological data obtained could be useful for early detection and adequate treatment of children with asthma in the mentioned area.     

Urinary growth hormone excretion in 657 healthy children and adults: normal values, inter- and intraindividual variations.

Urinary growth hormone (u-GH) excretion was measured in 547 healthy children and 110 adults by ELISA with a detection limit of 1.1 ng/l u-GH after prior concentration of the urine samples (20- to 30-fold). u-GH excretion values were significantly dependent on the pubertal stage (p less than 0.0001) with maximum values in Tanner stage 3 for girls and 4 for boys. This corresponded to a peak in u-GH excretion between 11.5-14.5 years in girls and 12.5-16 years in boys. Additionally, u-GH excretion in adults was significantly higher than in prepubertal children (p less than 0.001). The day/night ratio of u-GH excretion (pg/h) was significantly higher in females than in males (p less than 0.01). In Tanner stages 1-4, u-GH excretion during the day was lower than that at night, whereas the opposite was true in late puberty and in adult women. The interindividual variation of u-GH excretion within the same Tanner stage was considerable and approximately double the intraindividual variation. The day-to-day variation could be further reduced by collection of three consecutive urine samples. The variations were larger if night samples instead of 24-hour samples were considered. The expression of u-GH excretion in nanograms per gram creatinine did not diminish the observed variation and blunted the pubertal increase in u-GH excretion. In conclusion, (1) u-GH excretion depends significantly on age, sex and pubertal maturation as does the day/night ratio of u-GH excretion. (2) The interindividual variation in u-GH excretion is considerable.(ABSTRACT TRUNCATED AT 250 WORDS)     

The determination of the adrenal medullary cell fate during embryogenesis

One subset of neural crest cells, the sympathoadrenal precursors, undergoes a switch in phenotype expression, when they invade the adrenal anlagen and become associated with adrenocortical cells. To investigate the mechanisms responsible for the conversion of noradrenaline synthesizing precursors to adrenaline producing endocrine chromaffin cells we studied the role of glucocorticoids on the initial induction of adrenaline synthesis in embryonic adrenals and cultures of highly purified chromaffin precursor cells. We could show that in vivo differentiation of rat chromaffin precursors commences between 16.3 and 17.3 days of gestation. While adrenaline and the activity of the enzyme phenylethanolamine N-methyltransferase (PNMT), which converts noradrenaline to adrenaline, were present at Embryonic Day 17.3 (E17.3), they were not detectable in E16.3 adrenals. Small amounts of corticosterone were present in E16.3 adrenals and plasma, but in parallel with the initial induction of adrenaline biosynthesis, a sharp rise in organ and plasma glucocorticoid levels occurred until E17.3. Chromaffin precursor cells, isolated at E16.3 and cultured for 4 days, failed to express PNMT activity and adrenaline. However, 0.1 nM dexamethasone was already sufficient for the initial induction of adrenaline and its synthesizing enzyme. Specific glucocorticoid binding of freshly isolated chromaffin (precursor) cells revealed a developmental increase during embryogenesis, yet no glucocorticoid binding sites were detectable in chromaffin precursor cells at E16.3. They appeared at E17.3 in parallel with the initial induction of adrenaline biosynthesis and the enormous rise of adrenal and plasma corticosterone levels. We therefore conclude that glucocorticoids are essential and sufficient to trigger the differentiation of noradrenergic sympathoadrenal precursors to adrenergic chromaffin cells after a functional glucocorticoid receptor system has been established.