Relation between hydration status in children and their dietary profile - results from the DONALD study.

OBJECTIVE: To describe associations between hydration status and dietary behaviour in children, as current research indicates that hydration status is influenced by nutrition vice versa, hydration status may influence dietary behaviour. DESIGN: Cross-sectional analyses of data from the Dortmund Nutritional and Anthropometric Longitudinally Designed Study, (DONALD) using 24-h urine samples to determine the hydration status and 3-day weighed food records to describe the dietary profile of the children. SETTING: Secondary analyses of data from an observational study. SUBJECTS: A group of 4-11 year old children living in Dortmund, Germany; N=717. METHODS: Hydration status was determined by calculating the 'free water reserve', using analyses of the 24-h urine samples. Nutrient intake per day was calculated from the 3-day weighed food records. Children were categorized into groups of hydration status and analysed for significant differences in their dietary profile. RESULTS: Children in the highest group of the hydration status had significant higher total water intake, lower energy density of the diet and a lower proportion of metabolic water compared to children in the lowest group of the hydration status. In addition, analyses showed - although not significant in all subgroups - that better hydrated children consumed more water from beverages and water-supplying foods and less energy from fat. CONCLUSIONS: Euhydrated children, that are children in the highest group of hydration status, had a more preferable dietary profile than children at risk of insufficient hydration. SPONSORSHIP: Funding for the DONALD Study and its analyses is provided by the Ministry of Innovation, Science, Research and Technology of the State of North Rhine-Westphalia, Germany.

The muscle-bone unit in adulthood: influence of sex, height, age and gynecological history on the bone mineral content and muscle cross-sectional area.

Bone and muscle development are both strongly influenced by sex hormones. The purpose of this study was to examine the changes in bone and muscle parameters (bone mineral content - BMC, muscle cross-sectional area - MA) in 130 men aged 31 -60 years, and in 180 pre-menopausal women aged 30-53 years with respect to age, body height and, with the women, their gynecological history (age-at-menarche, number of pregnancies, duration of lactation and use of oral contraception). The study was performed using peripheral quantitative computed tomography (pQCT) at a 65% site of the forearm length. Both BMC and MA were dependent on body height (p<0.0001), but not on age. The BMC/MA ratio was dependent neither on age nor on body height in both genders. MA as well as BMC were found significantly higher in males than in females (p<0.0001 for both variables). We observed a significantly higher BMC/MA ratio in females than in males (p<0.0001). We found no effect either of the analyzed variables of gynecological history on bone/muscle characteristics. The findings highlight the necessity of involving height-adjusted parameters and BMC/MA ratio into bone analysis in adults.

The development of metaphyseal cortex--implications for distal radius fractures during growth.

Fractures of the distal radial metaphysis are very common in otherwise healthy children. The reasons for this high fracture incidence are not entirely clear. To address this problem, we undertook a detailed analysis of distal radius development using peripheral quantitative computed tomography (pQCT) at a site 4% proximal to the radial articular surface. The study population comprised 337 healthy children and adolescents (aged 6-18 years; 171 girls) and 107 adults (aged 29-40 years; 88 women). Total volumetric bone mineral density (vBMD) remained stable at about 70% of the adult value between the ages of 6-7 years and 14-15 years in both genders. Cortical thickness increased little between 6-7 years and 12-13 years in girls and 14-15 years in boys. Strength-Strain Index (SSI; a parameter combining geometry and density) was still at only 20% of the adult value in girls aged 10-11 years and at 21% of the adult level in boys aged 12-13 years. At these ages, factors that contribute to the mechanical challenge to the distal radius in case of a fall (forearm length and body weight) had already reached 49% and 36% of the adult value in girls and boys, respectively. The shaping of the distal radius cortex (metaphyseal inwaisting) was assessed by analyzing the decrease in cross-sectional bone size between adjacent bone slices in a separate population of 44 children (aged 8-19 years; 26 girls). The rates of periosteal resorption and endocortical apposition were estimated to average 8 microm/day and 10 microm/day, respectively, during the growth period. In conclusion, during growth the increase in distal radius strength lags behind the increase in mechanical challenges caused by a fall, because metaphyseal cortical thickness does not increase sufficiently. The endocortical apposition rate is already very high at that site and apparently cannot be further increased to levels that would be necessary to keep bone strength adapted to the mechanical requirements.

The midgrowth spurt in healthy children is not caused by adrenarche.

A small transient increase in growth, the midgrowth spurt, has been observed in several growth studies in healthy children around the age of 7 yr. During this time adrenarche (the physiological increase in adrenal androgen secretion) also occurs. Although it is now well established that estrogen, not androgen, has a critical role in the male (and female) pubertal growth spurt, a direct effect of androgens on growth cannot be excluded. In accordance with published observations that growth is frequently accelerated in infants and young children with late-diagnosed 21-hydroxylase deficiency (before adequate androgen suppression), it has been speculated that the adrenarchal increase in adrenal androgen secretion in healthy children could be responsible for the midgrowth spurt. To test this hypothesis we studied long-term serial changes in urinary 24-h excretion rates of dehydroepiandrosterone sulfate and total 17-ketosteroid sulfates in a group of healthy children (n = 12) in which yearly auxological measurements allowed the identification of a midgrowth spurt. Annual measurements of standing height were performed over periods of 6-9 yr before the onset of puberty. All children collected five to seven serial 24-h urine samples (1-yr intervals) each at the time of anthropometric examination. The peak of the midgrowth spurt was found to occur at a mean age of 6.8 +/- 1.0 yr. The average height of the midgrowth peak, i.e. average maximum gain in height velocity, was 0.9 cm/yr. In a peak-centered examination of individual 24-h excretion rates of dehydroepiandrosterone sulfate and 17-ketosteroid sulfates, primarily weak 1-yr changes in adrenal androgens were observed until the peak was attained. Only after the peak did increments in urinary adrenal androgen output become more pronounced. ANOVA performed on the peak-centered dehydroepiandrosterone sulfate and 17-ketosteroid sulfate excretion rates revealed a highly significant overall increase in adrenal androgen secretion from 2 yr before to 2 yr after the midgrowth spurt. After multiple testing, however, significant increments, when compared with the respective preceding androgen excretion levels, were for the first time seen 1 yr after the midgrowth spurt (dehydroepiandrosterone sulfate) or 2 yr later (17-ketosteroid sulfates). In conclusion, our longitudinal analysis of prepubertal growth and urinary adrenal androgen excretion in healthy children disproves the speculation that the midgrowth spurt is primarily caused by the adrenarchal increase in adrenal androgen secretion. However, the present results do not rule out a growth-accelerating effect of clearly higher androgen levels, as in premature adrenarche.

Role of nutritional status in the regulation of adrenarche.

The factors regulating adrenarche are unknown. Recent in vitro studies have demonstrated that insulin and insulin-like growth factor I induce major adrenal steroidogenic enzyme genes and increase the production of adrenal androgens. Literature findings strongly suggest that changes in body mass index (BMI) reflect an integrated nonhormonal index of changes in serum levels and/or bioactivities of insulin and insulin-like growth factor I. We therefore longitudinally investigated individual changes in BMI and urinary 24-h excretion rates of dehydroepiandrosterone sulfate (DHEAS) in a prepuberty (PreC; n = 22, 11 boys and 11 girls) and a puberty (PubC; n = 20, 10 boys and 10 girls) cohort of healthy children. Twenty-four-hour urine samples were collected at yearly intervals during observation periods that lasted at least 4 yr (comprising > or = 5 consecutive 24-h urine collections). For 4-yr intervals highly significant tracking coefficients (P < 0.001) of 0.73 (PreC) and 0.93 (PubC) were observed for DHEAS, emphasizing the importance of individual (and genetic) influences on adrenal androgen excretion. In both cohorts almost 3-fold higher median increases in urinary DHEAS excretion rates (P < 0.05) were observed during the 1-yr period of the individually highest rises in BMI compared with the 1-yr period of significantly lower rises in BMI (P < 0.01) in the same children after the factor age was controlled for. However, no consistently significant associations were found between urinary DHEAS output and BMI from simple cross-sectional correlations at defined age points. These findings provide the first in vivo evidence that a change in the nutritional status, measurable in the form of delta-BMI (but not BMI alone), is an important physiological regulator of adrenarche regardless of individual adrenal androgen excretion level, age, and developmental stage.

Short-term impact of a lactovegetarian diet on adrenocortical activity and adrenal androgens.

The aim of this study was to determine whether definite diet changes affect adrenocortical activity and/or adrenal androgen metabolism. A controlled experimental diet study with four consecutive diet periods (repeated measure design) was carried out in six healthy adult volunteers. Four nearly isoenergetic diets, two normal (N) moderately protein-rich, one protein-rich (P), and one low protein lactovegetarian (L), were fed. At the end of each 5-day diet period a blood sample and two 24-h urine specimens were obtained from each subject. Plasma levels of dehydroepiandrosterone sulfate (DHEAS) were elevated with diet L (6.5 +/- 1.4 vs. 5.3 +/- 1.1 mumol/L; P < 0.05) compared to diet N, whereas other plasma hormones, including cortisol and insulin-like growth factor I did not vary markedly. A marked increase of 60% was seen in the urinary 24-h output of 3 alpha-androstanediol glucuronide with diet P. Urinary 24-h excretion rates for C peptide, free cortisol, DHEAS, and total 17-ketosteroid sulfates were clearly reduced with diet L compared to those with diet N or P. Our results show that a lactovegetarian diet can reduce adrenocortical activity (at least after a short term diet change). In addition, this vegetarian nutrition leads to a particular metabolic situation (elevated plasma DHEAS and reduced urinary DHEAS output) that usually is characteristic of fasting. Peripheral androgen metabolism as reflected by urinary 3 alpha-androstanediol glucuronide appears to be influenced only by high protein intake (diet P). Further research (controlled dietary long term investigation) is required 1) to validate whether the effects of diet on adrenocortical activity represent sustained endocrine changes and 2) to elucidate the underlying mechanism.

Influence of puberty on muscle area and cortical bone area of the forearm in boys and girls.

The aim of the current study is to analyze the interaction of the muscle and bone system (muscle-bone unit) during puberty in males and females by computed tomography of the nondominant forearm. The data presented here are the first results from 318 healthy children (159 boys and 159 girls), aged 6-22 yr, and 336 adults (parents) participating in the DONALD Study (Dortmund Nutritional and Anthropometric Longitudinally Designed Study). Cortical area (CA) of the radius representing bone strength and muscle area (MA) representing muscle strength were measured with peripheral quantitative computed tomography (XCT 2000; Stratec, Pforzheim, Germany). A single slice measurement at a site corresponding to 65% of the ulnar length proximal to the radial endplate was used. MA and CA of the radius have been determined by a built-in software algorithm using density differences. There was a strong correlation between MA (x) and CA (y) in all children, adolescents, and adults (y = 0.019x + 10.93; r2 = 0.77). Before puberty, boys and girls displayed a similar relation between MA and CA. CA in relation to MA was greater in girls than in boys during puberty. Analysis of covariance was performed investigating the dependency of CA on MA, five pubertal stages, sex, and interaction of sex and pubertal stages. MA representing muscle strength was the strongest predictor of CA (P < 0.001) representing bone mass. Pubertal stage (P < 0.001) and interaction of pubertal stage*sex (P = 0.002) also had a significant influence on CA. r2 of the model was 0.85. These data suggest that in pubertal girls and women rather than in pubertal boys and men an additional factor shifts the relationship between MA and CA to higher values of cortical area. The present data confirm previous studies of the influence of puberty and estrogens or related factors on the muscle-bone interaction.

The development of bone strength at the proximal radius during childhood and adolescence.

Current investigations of bone development mostly focus on bone mass, but bone strength may be functionally more important than mass. Therefore, we compared the developmental changes in cortical bone mass (BMCcort) and parameters of cortical bone strength [polar moment of inertia, section modulus, and strength strain index (SSI)]. Analyses were performed at the 65% site of the proximal radius using peripheral quantitative computed tomography. The study population comprised 469 healthy subjects, 6-40 yr of age (273 females). Both in prepubertal children (pubertal stage 1) and after puberty (pubertal stage 5 and adults) all studied parameters were significantly higher in males. During puberty (pubertal stages 2-4) the gender-specific differences were generally somewhat smaller. All of the measured parameters increased significantly with age and pubertal stage. However, although the percent increase in BMCcort between the youngest children and adults was similar between the genders, the increases in polar moment of inertia, section modulus, and SSI were higher in males. The ratio between section modulus and BMCcort was consistently higher in males after the age of 11 yr and after pubertal stage 2. Similar results were found for ratios between polar moment of inertia or SSI and BMCcort. These results show that for a given bone mass, males have stronger bones than females after pubertal stage 2. This reflects the fact that in puberty males add bone mostly on the periosteal surface, where the effect on bone strength is highest, whereas females add bone on the endocortical surface, which has a small effect on bone stability. The purpose of the mechanically inefficient endocortical apposition in female puberty might be to create a reservoir of calcium for future pregnancy and lactation.

Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis maps to chromosome 3q27 and is associated with mutations in the PCLN-1 gene.

Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC, MIM 248250) is a complex renal tubular disorder characterised by hypomagnesaemia, hypercalciuria, advanced nephrocalcinosis, hyposthenuria and progressive renal failure. The mode of inheritance is autosomal recessive. A primary defect in the reabsorption of magnesium in the medullary thick ascending limb of the loop of Henle (mTAL) has been proposed to be essential in FHHNC pathophysiology. To identify the underlying genetic defect we performed linkage analysis in eight families, including three with consanguineous marriages. We found linkage to microsatellite markers on chromosome 3q27 with a maximum two-point lod score (Zmax) of 5.208 for D3S3530 without evidence for genetic heterogeneity. Haplotype analysis revealed crucial recombination events reducing the critical interval to 6.6cM. Recently, mutations in the gene PCLN-1, mapping to 3q27 and coding for paracellin-1, were identified by Simon et al (1999) as the underlying genetic defect in FHHNC. Paracellin-1 represents a renal tight junction protein predominantly expressed in the TAL. Mutational analysis in our patient cohort revealed eight different mutations in the PCLN-1 gene, within six novel mutations. In seven of 13 mutant alleles we detected a Leu151 substitution without evidence for a founder effect. Leu151 is a residue of the first extracellular loop of paracellin-1, the part of the protein expected to bridge the intercellular space and to be important for paracellular conductance. This study confirms the implication of paracellin-1 defects in FHHNC and points to a predominant role of this protein in the paracellular reabsorption of divalent cations in the TAL.

Estimation of the renal net acid excretion by adults consuming diets containing variable amounts of protein.

The object of this study was to determine whether it is possible to reliably estimate the renal net acid excretion (NAE) produced by adults consuming different amounts of dietary protein. A physiologically based calculation model that corrects for intestinal absorption of minerals and sulfur-containing protein and assumes a rate of urinary excretion of organic acids proportional to body surface area was used to estimate NAE. Urinary excretion of different minerals and NAE was measured during the last 48 h of each of four separate 5-d diet periods in six healthy adults. On the basis of food tables, the four nearly isoenergetic diets (one lacto-vegetarian and one high- and two moderate-protein diets) were estimated to yield the following NAE values: 3.7, 117.5, 62.2, and 102.2 mEq/d, respectively. The analytically determined urinary NAE (24.1 +/- 10.7, 135.5 +/- 16.4, 69.7 +/- 21.4, and 112.6 +/- 10.9 mEq/d) corresponded reasonably well to these estimates, suggesting that the calculation model is appropriate to predict the renal NAE from nutrient intake and anthropometric data.

Gender-specific pubertal changes in volumetric cortical bone mineral density at the proximal radius.

It is well established that puberty affects the geometry of cortical bone differently in females and males. In the present study we investigated whether there are also gender differences in the volumetric bone mineral density of the cortical compartment (BMDcort). BMDcort was determined at the proximal radial diaphysis in 362 healthy children and adolescents (age 6-23 years; 185 females, 177 males) and in 107 adults (age 29-40 years; 88 women, 19 men) using peripheral quantitative computed tomography (pQCT). The densitometric result for BMDcort was similar in prepubertal girls and boys, but was significantly higher in females after pubertal stage 3. pQCT results for BMDcort are influenced by cortical thickness due to the partial volume effect. Therefore, these gender differences were reanalyzed in groups of subjects of the same developmental stage who were matched for cortical thickness. Thus calculated, no gender difference in BMDcort was detected in prepubertal children. However, adolescent females after pubertal stage 3 and adult women had a 3%-4% higher BMDcort than males at the same developmental stage. BMDcort is an integrated measure of both cortical porosity and mean material density of cortical bone. The metabolic activity of cortical bone (intracortical remodeling) increases cortical porosity and decreases the mean material density of cortical bone. Our results therefore suggest that intracortical remodeling is lower in postpubertal females than in males.

Bone densities and bone size at the distal radius in healthy children and adolescents: a study using peripheral quantitative computed tomography.

Peripheral quantitative computed tomography (pQCT) has the ability to improve the diagnostic utility of densitometry in children and adolescents, because bone size and volumetric bone mineral density (vBMD) can be measured independently. Nevertheless, detailed reference data are lacking. We therefore performed pQCT (XCT-2000 scanner, Stratec, Inc., Pforzheim, Germany) at the distal radius in 371 healthy children, adolescents, and young adults (185 males and 186 females, ages 6-23 years) and in 107 of their parents (19 men and 88 women, ages 29-40 years). Total vBMD, trabecular, and "cortical + subcortical" vBMD as well as cross-sectional area (CSA) were determined at the "4% site" of the distal radius. This location was defined as the site whose distance to the most distal portion of the growth plate or to the radial articular surface corresponded to 4% of the forearm length. In both genders, total vBMD remained stable between 6 and 15 years of age and then increased by 30% in girls and by 46% in boys. Regarding pubertal development, total vBMD remained almost constant throughout pubertal stages 1-4 and thereafter increased in both genders. Trabecular vBMD did not change with age in girls, whereas in boys an increase with age of about 10% was noted after 15 years of age. Males had higher trabecular vBMD than females. This gender difference increased from 6% in prepubertal children to 23% in adults. The variation with age and pubertal stage in "cortical + subcortical" vBMD-cort was similar to that of total vBMD. CSA roughly doubled between 6 and 15 years of age in both genders. In conclusion, the availability of this reference material will provide a basis for the use of pQCT in the assessment of pediatric bone diseases.

A moderate increase in daily protein intake causing an enhanced endogenous insulin secretion does not alter circulating levels or urinary excretion of dehydroepiandrosterone sulfate.

To study the effect of a moderate increase in insulin secretion produced by an increased daily protein intake on dehydroepiandrosterone sulfate (DHEAS), a balanced randomized crossover trial consisting of three strictly controlled dietary regimens was performed in six healthy male volunteers. The basic diet (B) contained 50 g protein/d; diets P and M (also basic diets) were enriched with either 32 g protein/d (P) or 10 mmol L-methionine/d (M). Methionine was given (as a specific nonprotein source of endogenously derived sulfate) to control for possible confounding effects on DHEAS due to an increased sulfate supply. At the end of each 4-day diet period, blood and 24-hour urine samples were collected. Fasting plasma levels of testosterone, cortisol, insulin-like growth factor-I (IGF-I), and insulin, as well as urinary output of total (hot acid-cleaved) testosterone conjugates and 3alpha-androstanediol glucuronide, did not show significant changes in response to dietary manipulations. Endogenous sulfate availability (as reflected by renal sulfate output per 24 hours) approximately doubled with diets P and M. However, plasma levels (6.3 +/- 1.5, 6.8 +/- 1.8, and 6.9 +/- 2.1 micromol/L for B, P, and M, respectively) and urinary excretion (8.8 +/- 9.8, 9.4 +/- 11.2, 8.0 +/- 8.3 micromol/d) of DHEAS remained unaffected. Considering the clear increments (P < .01) in urinary C-peptide excretion with diet P (20.4 +/- 10.3 nmol/d) versus diets B and M (12.6 +/- 5.1 and 13.2 +/- 3.6 nmol/d), respectively, our results suggest that a moderately strong diet-induced increase in daily insulin secretion does not alter urinary and plasma levels of DHEAS.

Predictability of the progression of chronic renal failure.

The progression of chronic renal failure has been claimed to be predictable by means of mathematical models. The present study assesses, in 110 adult patients, the prediction error caused by the application of these models. The study shows that the prediction error has a wide range, which indicates that these models should be used with caution for prediction purposes in individual patients. Improvements of the models are proposed, and a new approach is demonstrated.

[Orbicularis oculi reflexes and evoked response of orbicularis oris muscle in Bell's palsy. A prognostic study (author's transl)]. / Orbicularis oculi-Reflexe und Summenpotentiale des Orbicularis oris bei idiopathischer Facialislähmung. Eine prognostische Studie

In 84 patients with idiopathic, clinically complete Bell's palsy the electrically induced blink reflexes with their two components (OOR I and II) were electromyographically recorded on both sides using skin electrodes. In 67 of these patients the evoked responses of the orbicularis oris muscle were also studied. The latencies and amplitudes were measured and related to the clinical outcome of the facial paralysis. The patients were divided into two groups, one with good recovery of the palsy (46 patients), the other with significant residual paresis and/or strong associated movements of the facial musculature (38 patients). In the group with good recovery the following results were obtained: 1. the OOR I remained elicitable or reappeated during the first 12 days after the onset of palsy; 2. the OOR II began to rise during the first 10 days of palsy; 3. the amplitude of the orbicularis oris response did not decrease to below 10%. In the group with poor recovery: 1. both components of the OOR were absent or diminished to below 4% for more than 12 days after the onset of palsy; 2. the latency difference of the OOR I exceeded 8 msec; 3. the amplitude of the orbicularis oris responses decreased to below 10%. Using these criteria it appears to be possible in about 85% of patients to make a prognosis between the 3rd to 5th and the 10th to 12th day after the onset of Bell's palsy.

Type 2B muscle fibre deficiency in myotonia and paramyotonia congenita. A genetically determined histochemical fibre type pattern?

The histochemical ATPase fibre type pattern was examined in muscle biopsy samples obtained from patients with recessive myotonia, paramyotonia and from one patient with dominant myotonia. Absence (less than or equal to 5%) of 2B fibres was a genuine finding in the minority of the cases. In additional cases of recessive myotonia, a deficiency (less than or equal to 15%) of 2B fibres was observed. Absence or deficiency of 2B fibres was not related to the minor myopathic alterations or to (para-)myotonic activity. It is hypothesised that absence of 2B fibres is a dominant or a recessive autosomal trait, and deficiency of 2B fibres is a recessive trait. Reported findings and our own observations suggest the possibility of a genetic combination of myotonia and absence/deficiency of 2B fibres. Implications of these hypotheses are proposed.

Determination of inorganic plasma sulfate by indirect atomic absorption spectrophotometry.

An indirect method for the determination of inorganic sulfate in small plasma volumes is presented. After removal of protein and phosphate by uranylacetate, sulfate is precipitated by barium chloride. Excess barium in the supernatant is measured by atomic absorption spectrophotometry. The sulfate content of the sample corresponds to the difference of the added and the measured barium. The mean concentration of inorganic plasma sulfate of healthy children, determined by this method, was 0.241 +/- 0.059 mmol/l.

Measurement of urinary androgen sulfates without previous hydrolysis: a tool to investigate adrenarche. Validation of a commercial radioimmunoassay for dehydroepiandrosterone sulfate.

A commercial 125I radioimmunoassay designed for the quantification of dehydroepiandrosterone sulfate (DHEAS) in blood samples was tested for its direct applicability to 24-hour urine samples from children and adults. Average recoveries in parallelism and spiking experiments were found to be near 100%. Intra- and inter-assay coefficients of variation were below 10%. Urinary DHEAS concentrations determined directly by the radioimmunoassay (x) differed only slightly from corresponding radioimmunoassay values (y) obtained after C18 reversed-phase extraction and LH-20 chromatography (y = 0.85x + 0.12; r = 0.99). Cross-reactivity data from related steroids suggested only a small contribution to the DHEAS titer by other steroids. In 8-year-old children compared to preadrenarchal children (4 years old) a clearly increased median daily urinary DHEAS output could be observed both for absolute excretion data (0.163 versus 0.05 mumol/d, P < 0.01) and for excretion values related to body surface area (0.181 versus 0.071 mumol/d/1.73 m2, P < 0.05). However, this "onset of adrenarche" was no longer statistically significant when urinary creatinine was taken as adjustment parameter for renal androgen sulfate output. After correction with the individual body surface area, rises of urinary DHEAS from childhood to adulthood were nearly in the order of the literature data on age-corresponding serum increases of DHEAS. In conclusion, the direct radioimmunological quantification of DHEAS in 24-hour urine samples with subsequent correction for individual body surface area appears to present a physiologically meaningful way to assess the adrenal gland's secretory activity for this androgen sulfate.

Measurement of urinary androgen sulfates without previous hydrolysis: a tool to investigate adrenarche. Determination of total 17-ketosteroid sulfates.

According to published data the group of urinary total 17-ketosteroid sulfates appears to represent an index of overall adrenal androgen production, at least before the onset of puberty. To quantify total 17-ketosteroid sulfates a modified colorimetric assay based on the Zimmermann reaction was validated. 17-ketosteroid sulfates were measured without previous hydrolysis (as conjugated Zimmermann chromogens against authentic dehydroepiandrosterone sulfate (DHEAS) as assay standard) after C18 reversed-phase extraction and LH-20 chromatography. Intra- and inter-assay coefficients of variation were 8.4% (15.0%) and 5.9% (17.6%), respectively, at urinary 17-ketosteroid sulfate concentrations of 10.8 (1.9) nmol/ml. Recoveries observed in spiking and parallelism experiments varied between 88 and 102%. In a group of 4-year-old children showing a renal DHEAS output of less than 0.1 mumol/d/1.73 m2 (measured by radioimmunoassay) a relatively high median 17-ketosteroid sulfate excretion of 1.29 mumol/d/1.73 m2 was found. Older children aged 8 years as well as a group aged 12-14 years demonstrated only moderately higher urinary 17-ketosteroid sulfates whereas excretion of DHEAS/d/1.73 m2 more than tripled from age group to age group. For children from 8 years onwards, adolescents, and adults, linear regression analysis indicated that urinary DHEAS elevations seem to contribute with a constant proportion of approximately 70% to the increments of total urinary 17-ketosteroid sulfates. These findings suggest that the attainment of such a constant relationship (between the total 17-ketosteroid sulfates and their major component) from about 8 years of age onwards could represent the hormonal correlate of the completion of the continuous zona reticularis in the adrenal gland (developing around this age from a focal reticularis zone).

Re-examination of the effect of hCG on plasma levels and renal excretion of dehydroepiandrosterone sulfate in healthy males.

To reinvestigate the effect of hCG on circulating and urinary dehydroepiandrosterone sulfate (DHEAS), a hCG stimulation test (5000 IU administered i.m. at 8.30 h on 3 consecutive days) was performed in 6 healthy males (aged 24 to 35 years). Blood specimens and 24-h urine samples were collected immediately before the first and directly after the last hCG administration. Contrary to previous findings in normal men, the present study revealed significant DHEAS responses after testicular stimulation with hCG: plasma DHEAS increased from 7.9 +/- 2.3 to 9.6 +/- 2.2 mumol/L (P < 0.05) and urinary DHEAS from 5.7 +/- 3.6 to 9.3 +/- 5.2 mumol/day (P < 0.05). There was also a marked rise (P < 0.05) in the urinary excretion of total 17-ketosteroid sulfates. Clear increases of unconjugated plasma dehydroepiandrosterone as well as of circulating and renally excreted androstenedione and testosterone definitely confirmed an adequate Leydig cell stimulation. Significant post-hCG changes were additionally observed for plasma and urinary 3 alpha-androstanediol glucuronide (149% and 79% increases, respectively) and for urinary cortisol (21% decrease). Significant correlations were found for the post-hCG percent increases of plasma androstenedione versus plasma DHEAS (r = 0.86) and for the percent increases of plasma testosterone versus urinary DHEAS (r = 0.98), indicating that the extent of gonadal androgen elevations in the circulation of normal men is a determinant of DHEAS increases in blood or urine. These findings provide an explanation for the frequently observed sex differences for DHEAS in adults.(ABSTRACT TRUNCATED AT 250 WORDS)