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The impact of gender, puberty and body mass on reference values for urinary growth hormone (GH) excretion in normally growing non-obese and obese children.

OBJECTIVE: There is a lack of normal reference data on urinary GH (u-GH) excretion in children. We have investigated the impact of age, gender, pubertal development and body mass on reference values for u-GH excretion in normally growing non-obese and obese children. STUDY DESIGN: u-GH levels were evaluated in 1153 healthy normal children (aged 5-14) and in 684 obese children (body mass index, BMI: > 75th). u-GH levels (ng/8 h) were determined by ELISA as the mean value of three consecutive first morning voidings. RESULTS: Reference values (5-95th centile) for u-GH excretion in obese and non-obese children of both sexes are reported. In normal prepubertal children median u-GH levels were relatively stable and superimposable in the two sexes; subsequently, u-GH levels increased, reaching a peak value at 13 years in both sexes. Significant increments (P < 0.0001) in u-GH levels were shown at B2 for females and at G3 for males. A slight decline was evident at 14 years. In obese children, median u-GH concentrations were significantly lower than those recorded in normal children of prepubertal age and at all stages of puberty (except in females at B2), in spite of their comparable normal height. u-GH levels significantly increased at puberty also in obese children, although the pubertal rise was significantly (P < 0.001) lower (1.7-fold in both sexes) than that observed in normal children (2.5-fold in boys and 2.3-fold in girls). A multiple regression analysis showed that both chronological age (beta: 0.20), BMI (beta: - 0.11), gender (beta: - 0.04) and pubertal stage (beta: 0.25) contributed significantly to the physiological variation in u-GH levels (multiple R: 0.44, P < 0.00001). CONCLUSIONS: This study provides reference values for u-GH in normally growing non-obese and obese children, analysing the impact of gender, puberty and body mass on this parameter. In agreement with previous studies, which demonstrate blunted GH-responses to provocative stimuli and reduced nocturnal GH concentration, obese children have significantly lower u-GH levels than age-matched normal weight children, both before and during puberty.

Adolescent↗

Puberty: mind and body.

Puberty is the attainment of fertility -- the ability to reproduce. It occurs because our brains begin to secrete one key hormone, gonadotropin-releasing hormone. This causes the pituitary gland to induce maturation of the testis and the ovary, which then produce sex steroid hormones and mature sperm and eggs. We should be concerned that the age at which puberty begins is decreasing in many countries. Puberty starts when adequate growth and energy storage has occurred, so the earlier age of puberty may reflect recent increases in adolescent obesity resulting from more sedentary lifestyles.

Adolescent↗

Pelvic sonography and uterine artery color Doppler analysis in the diagnosis of female precocious puberty.

OBJECTIVES: To evaluate the role of ultrasound and color Doppler analyses in the diagnosis of precocious puberty. METHODS: Gray-scale sonographic uterine and ovarian evaluation together with color Doppler analysis of the uterine artery were prospectively performed in 29 girls presenting with premature breast development and pubic hair growth. The values were compared with results obtained from the gonodotrophin releasing hormone stimulation test. Excluded from the study were patients with isolated thelarche or isolated pubarche and those patients with gonodotrophin releasing hormone-independent puberty and with polycystic ovaries. RESULTS: According to the Tanner scale, all the girls presented a breast stage of 2-3 and pubic hair stage 2-3. The uterine size was greater in those girls who presented a pubertal response to the gonodotrophin releasing hormone test (Group II; n = 20) (8.07 +/- 4.47 mL) than in those who did not (Group I; n = 9) (3.07 +/- 1.18 mL; P = 0.001). The ovarian volume and the number of small follicles was not significantly different between the groups. On Doppler analysis, more elevated impedances were observed in Group I (pulsatility index = 3.28 +/- 0.37) than in Group II (pulsatility index = 2.29 +/- 0.19; P = 0.001) girls. The presence of a low pulsatility index (< 2.5) at the level of the uterine arteries had a high diagnostic value for precocious puberty (sensitivity 86%, specificity 100%). CONCLUSIONS: Uterine artery Doppler analysis may assist the diagnosis of gonodotrophin releasing hormone-dependent precocious puberty, may be useful for the selection of those girls needing treatment, and may simplify the follow-up of girls treated for precocities.

Child↗

Puberty and chronic kidney disease.

Puberty is a period of dramatic physiologic changes when children become adults. Chronic kidney disease (CKD), like many disorders, may delay or blunt the onset and outcomes of puberty. These include attainment of adult height and reproductive capacity. Although nutrition and treatment effects may contribute to these phenomena, increasing evidence supports direct biological effects of CKD on the neurohypophyseal axis that controls these systems. Although CKD affects puberty, this life period also impacts the progression of CKD. Diabetes mellitus, posterior urethral valves, reflux nephropathy, and hypoplasia all appear to accelerate with sexual maturation. Potential mechanisms include increases in blood pressure and body size as well as altered endocrine physiology. Better understanding of the interactions of puberty and CKD may lead to better outcomes for children with CKD as well as longer preservation of native kidney function.

Adolescent↗

Insulin-like growth factor I correlations to changes of the hormonal status in puberty and age.

IGF-I is considered to be one of the most important growth factors during puberty. Information concerning its correlation to thyroid hormones (T3, T4), adrenal and sex steroids is limited to puberty and the elderly. The presented study included 455 subjects (among them 259 children) ranging in age from newborn to 100 years. Serum IGF-I concentrations increase from childhood to the end of puberty (2 years earlier in girls). There are close positive correlations between IGF-I concentrations and age, height and weight and between IGF-I and estradiol or testosterone concentration in girls and boys respectively, and the DHEA-S level in boys during puberty. Correlations also exist with T3, aldosterone and 17 OH-progesterone in boys and girls in the pubertal stages I-V and with T4 in stages I-IV. Compared to 20-30 year-old subjects IGF-I concentrations amounted to 59% after 60 years, 43% in men and 54% in women after 70 years and 29% after 90 years. It is suggested that increasing adrenal DHEA-S concentrations stimulate IGF-I synthesis and by means of gonadal steroidogenesis, increase the pubertal GH secretion and the further pubertal IGF-I increase. The low IGF-I concentrations in patients > 60 years reflect the more catabolic metabolism of the elderly.

Adolescent↗

Delayed puberty and amenorrhea.

The ability to diagnose and manage disorders that cause delayed puberty requires a thorough understanding of the physical and hormonal events of puberty. Wide variation exists within normal pubertal maturation, but most adolescent girls in the United States have begun to mature by the age of 13. Delayed puberty, a rare condition in girls, occurs in only approximately 2.5% of the population. Constitutional delay, genetic defects, or hypothalamic-pituitary disorders are common causes. Amenorrhea, often found as a symptom of delayed puberty, may be due to congenital genital tract anomalies, ovarian failure, or chronic anovulation with estrogen presence or with estrogen absence.

Adolescent↗

Differences in infantile growth patterns in Turner syndrome girls with and without spontaneous puberty.

OBJECTIVE: The role of prepubertal estrogen in child growth was modeled using Turner's syndrome, comparing growth patterns of girls who later did or did not enter puberty spontaneously. The hypothesis was that TS patients with normal prepubertal estrogen levels would have a different growth pattern from those with subnormal estrogen levels. STUDY DESIGN: Growth data from 78 full-term patients with Turner's syndrome were collected retrospectively. 24/78 later developed spontaneous puberty, (+Pub), and their growth data were compared to TS patients without spontaneous puberty (-Pub). A nonlinear mixed model was fitted using the bi-exponential model. RESULTS: The growth velocity difference between the -Pub and +Pub groups suggests an early infantile growth advantage in the -Pub group, which disappears before the end of the first year of life; growth velocity remains similar (+/- 1 cm/y) for the next 6 years and declines at age 7-8 years in the +Pub group faster than it does in the -Pub group. Bi-exponential analysis showed that both the 1st (restrictive) and 2nd exponent (forward) were different (p = 0.0003). CONCLUSIONS: Comparison of girls with or without spontaneous puberty suggests a role for estrogen in child growth. Estrogens restrict infantile growth, as well as growth during the mid-childhood spurt.

Adolescent↗

A simple test for the hormonal assessment of early puberty in boys.

The initial hormonal changes in male puberty occur at nighttime, with episodic rises of LH and testosterone (T). Only much later do the daytime levels of these hormones rise. Nocturnal sampling is impractical for routine clinical assessment, so we have examined the relationship between peak nocturnal T levels and those produced in the same subject by a single intravenous injection of gonadotrophin releasing hormone (GnRH, 100 micrograms) in the morning. Nocturnal T profiles and daytime GnRH tests have been conducted in eight boys in early (delayed) puberty, three with pubertal gynaecomastia in later puberty, two normal men, and one man with gynaecomastia. Excellent agreement was obtained between peak nocturnal and post-GnRH T levels. The serum testosterone level 3 hours after 100 micrograms IV GnRH is a simple and useful hormonal marker of pituitary-Leydig cell activity during puberty.

Adolescent↗

Impaired insulin action in puberty. A contributing factor to poor glycemic control in adolescents with diabetes.

Patients with insulin-dependent diabetes mellitus often have poor metabolic control during puberty. To determine whether puberty is associated with decreased insulin-stimulated glucose metabolism, we compared the results of euglycemic insulin-clamp studies in adults and prepubertal and pubertal children with and without insulin-dependent diabetes. In nondiabetic pubertal children, insulin-stimulated glucose metabolism (201 +/- 12 mg per square meter of body surface area per minute) was sharply reduced, as compared with that of prepubertal children and adults (316 +/- 34 and 290 +/- 21 mg per square meter, respectively; P less than 0.01), despite comparable hyperinsulinemia (insulin levels of 80 to 90 microU per milliliter). Similarly, the response to insulin was 25 to 30 percent lower in the diabetic pubertal children than in the diabetic prepubertal children (P less than 0.05) and adults (P = 0.07). At each stage of development, the stimulating effect of insulin on glucose metabolism was decreased by 33 to 42 percent in the children with diabetes (P less than 0.01). In all the groups of children studied, the response to insulin was inversely correlated with mean 24-hour levels of growth hormone (r = -0.52, P = 0.01). Among the diabetic children, the glycosylated hemoglobin levels were substantially higher in the pubertal children than in the prepubertal children (P less than 0.02), although the daily insulin doses tended to be higher. These data suggest that insulin resistance occurs during puberty in both normal children and children with diabetes. The combined adverse effects of puberty and diabetes on insulin action may help explain why control of glycemia is so difficult to achieve in adolescent patients.

Adolescent↗

Puberty and genetic susceptibility to breast cancer in a case-control study in twins.

BACKGROUND: Breast cancer is thought to result from excessive cumulative exposure to ovarian hormones. Different predictors of hereditary and sporadic breast cancer suggest different pathogenic mechanisms. Affected twin pairs may help to illustrate such differences. METHODS: We obtained information from 1811 pairs of female twins, one or both of whom had breast cancer. The pairs were stratified according to concordance or discordance for breast cancer, zygosity, the presence or absence of a family history of breast cancer, and the presence of bilateral or unilateral disease. Disease-concordant monozygotic pairs were assumed to have a higher genetic susceptibility than other subgroups of pairs. Paired twins were compared with respect to age at puberty and other factors. We calculated adjusted odds ratios for the diagnosis of breast cancer when only one twin was affected and for the first of the two diagnoses when both were affected. RESULTS: Within disease-discordant monozygotic pairs, the twin with an earlier onset of puberty did not have an increased risk of breast cancer (adjusted odds ratio, 0.8; 95 percent confidence interval, 0.6 to 1.2). Within disease-concordant monozygotic pairs, the twin with earlier puberty was much more likely to receive the diagnosis first (adjusted odds ratio, 5.4; 95 percent confidence interval, 2.0 to 14.5). In contrast, a later first pregnancy, lower parity, and later menopause within the pair were associated with an increased risk of breast cancer when one twin was affected but did not predict an earlier diagnosis when both were affected. CONCLUSIONS: Within the most genetically susceptible subgroup of twin pairs, the strong influence of earlier puberty on the age at the diagnosis of breast cancer and the absence of linkage to hormonal milestones later in life suggest that most cases of hereditary breast cancer are not related to cumulative hormone exposure and that they may instead result from an unusual sensitivity to pubertal hormones. Associations between breast cancer and early menarche and those with reproductive milestones in adulthood may reflect different genotypes.

Adult↗

Three-year follow-up of changes in aerobic fitness during puberty: the Muscatine Study.

To assess the tracking of aerobic fitness during puberty and its relationship to changes in body composition and indexes of growth, the authors of this study measured body fat, echocardiographic left ventricular mass (LVM), fat-free mass (FFM), height, physical activity, resting blood pressure, sexual maturation, and maximal aerobic fitness (VO2peak) in 123 children (ages 7-12 years). Measures were repeated 3 years later. Tracking was assessed by Spearman rank correlation coefficients between baseline and follow-up data. Predictors of changing aerobic fitness were examined using stepwise regression. Significant tracking of aerobic fitness was observed with correlations ranging from .70-.75. Increased FFM and increased LVM explained 51% of the variability in improved aerobic fitness (ml.min-1) in boys. Increased FFM and increased height explained 26% of the variability in improved aerobic fitness (ml.min-1) in girls. During puberty, children who gain the greatest amount of lean tissue (including cardiac) experience the greatest improvements in aerobic fitness (ml.min-1). Measures of aerobic fitness prior to and during early puberty tend to predict aerobic fitness during puberty.

Adipose Tissue↗

Weight/heightp compared to weight/height2 for assessing adiposity in childhood: influence of age and bone age on p during puberty.

Data from three American Health Examination Surveys and 11 other published studies were used to investigate the weight-for-height index W/Hp, adjusted for age and sex by expressing it as a fraction of the same ratio for an NCHS standard child. The appropriate power of height p was determined by regressing log weight-for-age on log height-for-age, giving an index of relative weight which is highly correlated with weight but uncorrelated with height for age. The optimal value of p was 2 in pre-school children, but it increased gradually to 3 at age 11 and fell back to 2 after puberty. The largest value of p occurred 18 months earlier in girls than in boys, and the pattern was the same for white and black children. The trend was summarized by the formula: p = 2 + exp [-0.5 (age - 11)2]. The index thus provides a compact way of adjusting weight for height and age throughout childhood, using standards of weight and height for age and sex. During puberty, W/Hp was found to be related to maturity as measured by Greulich-Pyle bone age. Each year's advancement relative to chronological age was associated with an increase of up to 5% in relative weight, adjusted for height and age. This maturity effect was shown to be the cause of the rise in the value of p early in puberty, so that after adjusting for it the value of p remained close to 2 throughout childhood. Thus the index W/H2 is appropriate for preschool children and adults, but early in puberty it tends to assess tall or physically advanced children as being overweight. This bias can be avoided by using instead the more general index, where the precise power of height is a function of the child's age.

Adipose Tissue↗

Psychological assessments before and after treatment of early puberty in adopted children.

UNLABELLED: Early puberty is frequently observed in adopted children. This randomized trial treated 30 adopted children with early puberty and short stature with either gonadotropin-releasing hormone agonist (GnRHa) alone or in combination with growth hormone (GH) for 3 y. Before the start of treatment (T1) in the trial and at discontinuation (T2) the children and their parents underwent a psychological evaluation. At the start of treatment the children did not have increased levels of behavioural or emotional problems as assessed by the Child Behaviour Checklist (CBCL). During treatment the CBCL scores did not increase. Self-perception of the children appeared to be normal, and after 3 y a significantly higher score for acceptance by peers was observed. At T1, an overestimation of future height was present in 80% of the children and 17% of the parents. Lower family stress was observed at T1 and T2 compared with reference values. Intelligence quotient levels decreased significantly during treatment. The findings are discussed with reference to the reported levels of behavioural and emotional problems in adopted children and the psychosocial effects of precocious puberty. CONCLUSION: This psychological evaluation did not reveal any consistent abnormalities in adopted children with early puberty. Treatment with GnRHa with or without GH did not increase emotional and behavioural problems in adopted children, nor was their self-perception decreased.

Adoption↗

Impaired sexual maturation associated with sleep apnea syndrome during puberty: a case study.

A 20-year-old hypogonadal man was discovered to have had obstructive sleep apnea syndrome--secondary to hypertrophied tonsils, adenoids, and uvula--spanning the years of puberty. All-night polysomnographic recordings and 24 hr measurements of plasma luteinizing hormone (LH) concentrations (sampling at 20 min intervals) were performed before and after combined tonsillectomy, adenoidectomy, and uvulectomy. Two weeks preoperatively, nocturnal sleep was markedly disturbed by 407 apneic episodes, and the patient was found to be hypogonadotropic. Daytime LH concentrations were in the low-normal range for an adult male, and concentrations fell dramatically during nocturnal sleep. This contrasts with both the sleep-related elevation of LH normally seen in puberty and the adult pattern, where no difference is observed in mean concentrations during waking and sleep. Two week and 6 month postoperative evaluations revealed complete alleviation of the sleep apnea syndrome and normalization of the 24 hr pattern of plasma LH, although LH values remained in the low-normal range. Plasma testosterone concentrations were in the low to low-normal range both pre- and postoperatively. No evidence of continued sexual development, beyond that achieved preoperatively, was observed 20 months after surgery, despite continued relief from apnea. These data suggest that sleep apnea during puberty may impair sexual development by preventing the sleep-related elevation in LH secretion normally observed during a critical period spanning puberty.

Adenoidectomy↗

Molecular profiling of human prostate tissues: insights into gene expression patterns of prostate development during puberty.

Testosterone production surges during puberty and orchestrates massive growth and reorganization of the prostate gland, and this glandular architecture is maintained thereafter throughout adulthood. Benign prostatic hyperplasia (BPH) and prostate adenocarcinoma (PCA) are common diseases in adulthood that do not develop in the absence of androgens. Our objective was to gain insight into gene expression changes of the prostate gland at puberty, a crucial juncture in prostate development that is androgen dependent. Understanding the role played by androgens in normal prostate development may provide greater insight into androgen involvement in prostatic diseases. Benign prostate tissues obtained from pubertal and adult age group cadaveric organ donors were harvested and profiled using 20,000 element cDNA microarrays. Statistical analysis of the microarray data identified 375 genes that were differentially expressed in pubertal prostates relative to adult prostates including genes such as Nkx3.1, TMEPAI, TGFBR3, FASN, ANKH, TGFBR2, FAAH, S100P, HoxB13, fibronectin, and TSC2 among others. Comparisons of pubertal and BPH expression profiles revealed a subset of genes that shared the expression pattern between the two groups. In addition, we observed that several genes from this list were previously demonstrated to be regulated by androgen and hence could also be potential in vivo targets of androgen action in the pubertal human prostate. Promoter searches revealed the presence of androgen response elements in a cohort of genes including tumor necrosis factor-alpha induced adipose related protein, which was found to be induced by androgen. In summary, this is the first report that provides a comprehensive view of the molecular events that occur during puberty in the human prostate and provides a cohort of genes that could be potential in vivo targets of androgenic action during puberty.

Adolescent↗

The effect of medroxyprogesterone acetate on gonadotropin secretion in girls with precocious puberty.

Plasma luteinizing hormone (LH) and follicle stimulating hormone (FSH) as detected by radioimmunoassay have been found to be present in prepubertal children and show a gradual rise until the onset of puberty. Children with idiopathic true precocious puberty have plasma gonadotropin levels which are appropriate for their advanced degree of sexual development. A potent progestational agent, 6-methyl-17-hydroxyprogesterone acetate or medroxyprogesterone has been used in the treatment of precocious puberty and will suppress its physical manifestations. In this study the effect of medroxyprogesterone on gonadotropin levels was investigated in seven girls with true precocious puberty. Plasma LH values were found to be significant lower in patients receiving this agent than in a group of normal prepubertal girls. FSH values did not differ from the control group. One patient was evaluated prior to treatment and showed decreasing levels of LH after therapy was begun. These data suggest that medroxyprogesterone may act on the pituitary-hypothalamic axis to suppress the pubertal levels of LH.

Adult↗

Case study: sexual hyperactivity treated with psychostimulants in familial male precocious puberty.

Familial male precocious puberty is a form of precocious puberty resulting from an activating mutation of the luteinizing hormone receptor. Behavior problems are associated with the early onset of puberty. In this case, sexual hyperactivity was treated with psychostimulants. Implications for the effectiveness of methylphenidate in reducing sexual hyperactivity with and without familial male precocious puberty are discussed, and testable hypotheses are proposed for the effects of stimulants on sexual behavior in adolescents.

Central Nervous System Stimulants↗

Ultrasensitive new immunoassays for gonadotropins in the evaluation of puberty.

The increased sensitivity and specificity of new immunometric gonadotropin assays make them particularly useful to study the ontogenesis of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion in normal and abnormal puberty. The results show that the gonadotropin-releasing hormone pulse generator is functionally active even in prepubertal children with selective occurrence of LH and FSH pulses after the onset of sleep. The onset of puberty is associated with a major increase in pulse amplitude and a small increase in pulse frequency, expressed as a progressive increase in day-time pulsatility, and a gradual reduction of sleep-entrained amplification. Daytime gonadotropin measurements may better distinguish pubertal stages than nighttime sampling because of less overlapping. As the changes are greater with the sensitive assays, the diagnosis of pubertal disturbances is improved. It is easier to differentiate constitutionally delayed puberty and hypogonadotropic hypogonadism, but biologically overlapping phenomena cannot be separated by even sensitive assays. The augmentation of LH secretion after onset of sleep might be missing in hypogonadotropic hypogonadism and is proposed as a new, somewhat complicated, diagnostic approach. As serum concentrations of FSH in prepubertal children are much higher than those of LH, the measurement of FSH in this age group is particularly useful, and lower-than-normal levels can be found in gonadotropin-releasing hormone-independent precocious puberty as well as in pituitary defects.

Adolescent↗