Puberty In Children Research Articles

Absence of Mutation in the Follicle-Stimulating Hormone Receptor Gene in Severe Primary Hypothyroidism Associated with Gonadal Hyperstanulation

Severe hypothyroidism can cause a distinct form of precocious puberty in children, characterized by delayed skeletal maturation, predominance of FSH-mediated effects over LH-mediated function, and reversal of sexual precocity upon thyroid hormone replacement. The etiology of this unusual form of precocious puberty in children remains poorly understood. Recently, three mutations of the FSH receptor gene have been identified in women with spontaneous ovarian hyperstimulation during pregnancy. All three mutated receptors displayed abnormally high sensitivity to hCG which caused gonadal stimulation. Two of these mutations displayed concomitant increase in sensitivity of the mutated receptor to TSH. In this report, we describe four children with primary hypothyroidism and gonadal hyperstimulation. The aim of this study was to determine whether these patients' gonadal hyperstimulation is due to a mutation in their FSH receptor gene. DNA was extracted from all four patients with primary hypothyroidism and gonadal stimulation. The entire FSH receptor gene was sequenced and analyzed. Direct sequencing of these patients' FSH receptor gene did not demonstrate any mutation, proving that the cause of gonadal stimulation in these patients is not due to the increased sensitivity or constitutive activation of a mutated FSH receptor. The elevated TSH in these patients and prior demonstration of the in vitro ability of TSH to bind to the FSH receptor lead us to hypothesize that the gonadal stimulation in these patients is TSH-mediated. The fact that gonadal stimulation is not seen in all patients with severe hypothyroidism raises the question as to whether polymorphisms of the FSH receptor gene and/or possible changes in the TSH molecular structure may contribute to the TSH-mediated activation of the FSH receptor.

Leptin and its emerging role in children and adolescents.

Leptin is an adipocyte-secreted hormone which plays a key role in energy homeostasis. Recent “proof of concept” studies involving leptin administration to humans support its critical role in regulating energy homeostasis, neuroendocrine and immune function as well as insulin resistance in states of energy/ caloric deprivation. Moreover, interventional studies in leptin deficient children and observational studies in normal girls and boys support a role for leptin as a permissive factor for the initiation of puberty in children. The potential clinical usefulness of leptin in several disease states in children and adolescents, including hypothalamic amenorrhea, eating disorders and syndromes of insulin resistance is still under investigation.

Effect of Growth Hormone Dose on Bone Maturation and Puberty in Children with Idiopathic Short Stature

GH at 0.22 mg/kg.wk has been shown to have no effect on pubertal onset or pace, whereas GH at 0.5 mg/kg x wk has been shown to advance pubertal onset and bone maturation. Our objectives were to determine whether 0.37 mg/kg x wk GH advanced pubertal onset, pace, or bone maturation relative to 0.24 mg/kg x wk GH; whether 0.37 mg/kg x wk GH led to pubertal onset at an inappropriately early age; and whether age at start of GH therapy influenced pubertal onset. We conducted a randomized, open-label study to final height. We studied children with idiopathic short stature. Patients were treated with 0.24 mg/kg x wk, 0.24 increasing to 0.37 mg/kg x wk, or 0.37 mg/kg x wk. We assessed age at pubertal onset and rates of bone maturation, Tanner stage development, and increase in testicular volume (boys only). For the primary comparison between the 0.24 and 0.37 mg/kg x wk dose groups, median ages of pubertal onset (in years) were similar (13.7 vs. 13.5 for boys and 11.7 vs. 11.4 for girls) and were greater than those for the general population for each sex. Age at start of GH therapy did not appear to influence pubertal onset for either sex. Rates of pubertal pace and bone maturation were not significantly different between the 0.24 and 0.37 mg/kg x wk dose groups for either sex. GH at 0.37 mg/kg x wk does not appear to accelerate pubertal onset, pace, or bone maturation compared with GH at 0.24 mg/kg x wk in patients with idiopathic short stature. From a clinical standpoint, our results suggest that the approved dose range of up to 0.37 mg/kg x wk GH does not lead to pubertal onset at an inappropriately early age.

Getting Serious About Pediatric Chronic Kidney Disease

Getting Serious About Pediatric Chronic Kidney Disease

Diabetes and the Kidney

Diabetes and the Kidney

New developments in the use of peptide gonadotropin-releasing hormone antagonists versus agonists

Gonadotropin-releasing hormone (GnRH) stimulates the pituitary secretion of both luteinising hormone (LH) and follicle-stimulating hormone (FSH), and thus controls the hormonal and reproductive functions of the gonads. The blockade of the effects of GnRH may be sought for a variety of reasons; for example, to control premature LH surges and to reduce the cancellation rate with the aim of improving the pregnancy rate per treatment cycle or in the treatment of sex hormone-dependent disorders. Selective blockade of LH/FSH secretion and subsequent chemical castration have previously been achieved by desensitising the pituitary to continuously administered GnRH or by giving long-acting GnRH agonists. GnRH analogues are indicated for clinical situations in which the suppression of endogenous gonadotropins (precocious puberty, contraception and controlled ovarian hyperstimulation) or sexual steroids (endometriosis, prostate hyperplasia, cancer and uterine fibroids) is desired. The immediate suppression of the pituitary that is achieved by GnRH antagonists without an initial stimulatory effect is the main advantage of these compounds over the agonists. GnRH antagonists have been developed for clinical use with acceptable pharmacokinetic, safety and commercial profiles. In assisted reproduction, these compounds seem to be as effective as established therapy, but with shorter treatment times, less use of gonadotropic hormones, improved patient acceptance, and fewer follicles and oocytes. All of the current indications for GnRH agonist desensitisation may prove to be indications for a GnRH antagonist, including endometriosis, leiomyoma and breast cancer in women, benign prostatic hypertrophy and prostatic carcinoma in men, and central precocious puberty in children. However, the best clinical evidence has been in assisted reproduction and prostate cancer.

Anthropometric relationships between parents and children throughout childhood: the Fleurbaix–Laventie Ville Santé Study

The study of parent-child anthropometric relationships and their evolution over time may help to better understand familial risk factors for childhood obesity. In a population-based cohort of 124 nuclear families (Fleurbaix-Laventie Ville Santé Study (FLVS) I and II), various anthropometric parameters were measured in both parents and their children, first when the children were prepubescent and again at the end of puberty. Troncular adiposity repartition was estimated by calculating troncular to peripheral skinfolds ratio and waist-to-hip circumferences ratio. Birth and infancy heights and weights were also obtained from the children's health booklets. Parent-child correlations were estimated in infancy, before and at the end of the child's puberty. A prospective analysis was performed to predict the changes in the children's measurements over puberty according to their parents' corresponding baseline values. BMI and weight correlations at birth were high (>0.30) with the mother and low (<0.10) with the father, then they converged to an intermediate level at 2 y and remained between 0.2 and 0.3 thereafter. Correlations for waist circumference were already present at the prepubertal period and persisted on the same level at the postpubertal period, whereas correlations for subcutaneous adiposity - measured by four skinfolds - and for adiposity distribution - measured by ratios - were higher at the postpubertal period. Moreover, the prospective approach showed that mother's BMI predicted the evolution of her children's BMI over puberty, whereas this relationship was observed more specifically with the father concerning adiposity distribution parameters. Maternal adiposity may act early in life on the adiposity of the child. Maternal and paternal adiposities seem to have quite distinct effects at two key periods of the child's adiposity development such as the prenatal and pubertal periods.

Gender, age, and puberty in children’s experimental pain

Empirical experimental pain research suggests that women show greater pain responsivity than men. In children, this sex difference has not been as clearly demonstrated, perhaps due to developmental confounds associated with puberty. We sought to understand how gender (sex), age, and puberty relate to experimental pain in children (aged 8 to 18 years). The sample included 234 healthy children (mean age 12.7, SD 2.9): 109 in early puberty (54 female, 55 male) and 125 in late puberty (63 female, 62 male).

Postponing Puberty in Children with Growth Hormone Deficiency

Postponing Puberty in Children with Growth Hormone Deficiency

Changes in respiratory muscle endurance during puberty

The evaluation of respiratory muscle endurance provides clinically useful information on muscle function, especially in children with respiratory and neuromuscular diseases. However, endurance may be lower in young children than in older children because of the major physical changes of puberty. We thus compared respiratory muscle endurance in 15 healthy pre- and peripubertal children (S1-S2/P1 group) and 14 healthy children near the end of the pubertal process (S4P4 group). All performed a respiratory muscle endurance test threshold load fixed at 50% of the individual maximal inspiratory pressure; (Pi(max)), using a standardized method with a controlled breathing pattern. No significant difference was found between groups for Pi(max). The mean endurance time limit for the S1-S2/P1 group was 138 +/- 20 sec. The S4P4 group was able to breathe with the threshold valve for more than 20 min (1,200 sec) without task failure, except for one girl (385 sec). This study shows that inspiratory muscle endurance is significantly lower in children in early puberty compared to children at the end of the pubertal process. If the underlying mechanisms are not well-known, the present study revealed that if we use the same inspiratory load in prepubertal children as in adults during clinical testing, we are likely to underestimate the susceptibility to task failure of their respiratory muscles. To define a fatigue threshold for the respiratory muscles, as a function of age, thus appears clinically important in further studies, particularly for the management of children with respiratory diseases.

Early puberty in girls: The case of premature adrenarche

In this article we examine the issue of early puberty in girls. First, a brief overview of normal pubertal development is provided, including the two endocrine components of puberty: gonadarche and adrenarche. Second, we critically discuss the controversy regarding whether puberty truly is occurring earlier in girls. Third, we emphasize one type of early puberty, the case of premature adrenarche (PA). PA is used to illustrate the importance of identifying types of early puberty, evaluating the types to determine causality, determining whether follow-up of early puberty is necessary, and showing the potential ramifications of ignoring this variation in pubertal development. Findings from a pilot study comparing PA and on-time puberty children are used to show the importance of determining whether early puberty is normal in all cases.

The hypothalamic-pituitary axis in men and women with chronic kidney disease

Although the precise abnormalities that lead to failure of the hypothalamic-pituitary-gonadal axis in men and women with chronic kidney disease (CKD) and end-stage renal disease (ESRD) remains undefined, evidence exists for defects in both the hypothalamus and the pituitary. The lack of appropriate cyclic release of gonadotropin-releasing hormone (GnRH) by the hypothalamus leads to loss of normal pulsatile luteinizing hormone (LH) release by the pituitary, which results in impaired ovulation in women and reduced testosterone and sperm production in men. The cause of impaired cyclic release of GnRH is unclear, but hyperprolactinemia, elevated endorphins, and high levels of GnRH and LH caused by reduced clearance may contribute. Perturbations of the hypothalamic-pituitary-gonadaotropin axis in CKD lead to high rates of infertility, dysfunctional uterine bleeding, and impaired puberty in children. Only through additional study of the complex effects of CKD on the hypothalamic-pituitary-gonadal axis will the precise abnormalities in hormonal control of reproduction be explained. Although the precise abnormalities that lead to failure of the hypothalamic-pituitary-gonadal axis in men and women with chronic kidney disease (CKD) and end-stage renal disease (ESRD) remains undefined, evidence exists for defects in both the hypothalamus and the pituitary. The lack of appropriate cyclic release of gonadotropin-releasing hormone (GnRH) by the hypothalamus leads to loss of normal pulsatile luteinizing hormone (LH) release by the pituitary, which results in impaired ovulation in women and reduced testosterone and sperm production in men. The cause of impaired cyclic release of GnRH is unclear, but hyperprolactinemia, elevated endorphins, and high levels of GnRH and LH caused by reduced clearance may contribute. Perturbations of the hypothalamic-pituitary-gonadaotropin axis in CKD lead to high rates of infertility, dysfunctional uterine bleeding, and impaired puberty in children. Only through additional study of the complex effects of CKD on the hypothalamic-pituitary-gonadal axis will the precise abnormalities in hormonal control of reproduction be explained.

The hypothalamic-pituitary axis in men and women with chronic kidney disease

Although the precise abnormalities that lead to failure of the hypothalamic-pituitary-gonadal axis in men and women with chronic kidney disease (CKD) and end-stage renal disease (ESRD) remains undefined, evidence exists for defects in both the hypothalamus and the pituitary. The lack of appropriate cyclic release of gonadotropin-releasing hormone (GnRH) by the hypothalamus leads to loss of normal pulsatile luteinizing hormone (LH) release by the pituitary, which results in impaired ovulation in women and reduced testosterone and sperm production in men. The cause of impaired cyclic release of GnRH is unclear, but hyperprolactinemia, elevated endorphins, and high levels of GnRH and LH caused by reduced clearance may contribute. Perturbations of the hypothalamic-pituitary-gonadaotropin axis in CKD lead to high rates of infertility, dysfunctional uterine bleeding, and impaired puberty in children. Only through additional study of the complex effects of CKD on the hypothalamic-pituitary-gonadal axis will the precise abnormalities in hormonal control of reproduction be explained.

Estradiol negative feedback regulates nocturnal luteinizing hormone and follicle-stimulating hormone secretion in prepubertal female rhesus monkeys.

In recent years, animal models of puberty in children have focused on factors responsible for the developmental increase in gonadotropin secretion independent of gonadal negative feedback. Although the testis may play little if any role in timing the initial increase in gonadotropin secretion in the male, the situation may be different for the female. The present study tested the hypothesis that removal of endogenous estradiol by ovariectomy would produce an immediate increase in nocturnal but not daytime LH and FSH concentrations, an effect reversed by estradiol replacement. Morning (1000 and 1030 h) and evening (2200 and 2230 h) concentrations of bioactive LH and, in selected samples, immunoreactive FSH were evaluated in young juvenile female rhesus monkeys (n = 7) before and after ovariectomy at 13 months of age. Evening but not morning concentrations of gonadotropins were significantly increased within 2 wk of ovariectomy, whereas estradiol replacement returned these to presurgical levels and to those observed in age-matched, gonadally intact females (n = 7). By 145 d after ovariectomy, or approximately 17 months of age, evening as well as morning concentrations of LH were significantly higher than concentrations seen immediately after surgery. Estradiol replacement at approximately 18 months of age suppressed both morning and evening LH but not to the degree seen during a similar treatment after ovariectomy. These data support the hypothesis that, for the female, the developmental rise in diurnal gonadotropin secretion is controlled by a gonad-independent mechanism as well as a gonadal negative feedback inhibition. The importance of gonadal restraint on gonadotropin secretion in young juvenile females is evident only in samples obtained during the evening. These data underscore the notion that, for the female puberty, onset, at least in terms of gonadotropin secretion, is a misnomer and that puberty reflects a progression in multiple control mechanisms that ultimately time the attainment of fertility.

Sex steroid hormones, growth and puberty in children with portal hypertension.

Perturbations in sex hormones occur in adults with liver disease; however, little is known about how liver disease affects hormone levels in children. To address this issue, we recruited 19 patients with portal hypertension and 21 non-hormone-deficient short children as controls. Serum sex hormones, sex hormone binding globulin (SHBG), IGF-I, IGFBP-3, gonadotropins, and thyroid hormones were measured; growth and pubertal status were recorded. There was no significant difference between groups for any of the sex hormones, SHBG, gonadotropins, or thyroid hormones. In contrast, IGF-I and IGFBP-3 were significantly lower among patients than controls, despite the fact that height SDS for the control group was significantly lower. We conclude from this cross-sectional study that children with portal hypertension do not have clinical evidence of growth failure or abnormal puberty, despite subtle changes in the growth axis.

Role of a follow-up in puberty children with diffuse euthyroid goiter

То identify patients with autoimmune thyroiditis (AIT) in a random sample of children, a stepwise clinical examination was conducted among 427 ninth-form pupils (aged 14-15 years) from 4 Yekaterinburg districts. Among 58 children with goiter as shown by ultrasonography, 18 were initially diagnosed as having hypertrophic AIT; 38patients had diffuse euthyroid goiter; one patient had diffuse toxic goiter; and mixed euthyroid goiter was detected in one case. At one-year follow-up, re-examination rejected the diagnosis of AIT in 13 of the 18 patients. It was concluded that: (1) the follow-up of children with a presumptive diagnosis of AIT suggests that the latter plays a much less role in the etiological pattern of diffuse euthyroid goiter as compared with the data of the primary examination; (2) most changes originally interpreted as manifestations of AIT are reversible, which suggests that it is preferable to follow-up children with a presumptive diagnosis of AIT in the phase of euthyrosis under active therapeutic intervention.

Gonadotropin-releasing hormone antagonists: impact of IVF practice and potential non-assisted reproductive technology applications.

To provide the clinician with updated knowledge of the most recent findings on the clinical use of gonadotropin-releasing hormone antagonists. Gonadotropin-releasing hormone antagonists, which have recently been introduced in clinical practice, cause an immediate suppression of gonadotropin secretion by competitive blocking of pituitary gonadotropin-releasing hormone receptors. Thus, they are effective in preventing the premature luteinizing hormone surges during ovarian stimulation for in-vitro fertilization and may improve the patient's response to lower doses of gonadotropins. Better patient acceptance, shorter treatment cycles and fewer follicles and oocytes are also reported. Data existing so far concerning the necessity of luteal phase support after the use of gonadotropin-releasing hormone antagonists show that it might not be mandatory when used in clomiphene citrate costimulated cycles or in intrauterine insemination cycles. The use of gonadotropin-releasing hormone antagonists seems to be safe for pregnant women and their offspring. All sex-hormone-dependent disorders, currently treated with gonadotropin-releasing hormone agonists, may in future be indications for a gonadotropin-releasing hormone antagonist, including endometriosis, leiomyoma, and breast cancer in women, benign prostatic hypertrophy and prostatic carcinoma in men, and central precocious puberty in children. The vast majority of the available clinical data up till now, however, are in assisted reproduction and prostate cancer. It is expected that the availability of gonadotropin-releasing hormone antagonist will lead to the use of 'softer' ovarian stimulation protocols, which will be shorter, cheaper and safer compared with the conventional protocols.

Tumeur testiculaire bilatérale à cellules de Leydig : à propos d’un cas

Testicular Leydig cell tumours are uncommon. Bilateral synchronous lesions are exceptional. They cause isosexual pseudo precocious puberty in childhood. The histological diagnosis of malignancy is sometimes difficult to establish and it can be made retrospectively when lymph nodes involvement or visceral metastasis appear in the follow-up. We report a case of a 9 year-old boy presenting bilateral Leydig cell tumour of the testis treated by bilateral radical orchiectomy who developed 2 years after the intervention a pulmonary metastasis.

Energy balance, body composition, and puberty in children and adolescents: importance of ethnicity

Energy balance, body composition, and puberty in children and adolescents: importance of ethnicity

Cognitive efficiency on a match to sample task decreases at the onset of puberty in children

Electrocortical evidence indicates that a wave of synaptic proliferation occurs in the frontal lobes around the age of puberty onset. To study its potential influence on cognition, we examined 246 children (10–17 years) and 49 young adults (18–22 years) using a match-to-sample type of task to measure reaction times to assess emotionally related information. Based upon the instruction set, subjects made a yes/no decision about the emotion expressed in a face, a word, or a face/word combination presented tachistoscopically for 100 ms. The faces were images of a single individual with a happy, angry, sad or neutral expression. The words were ‘happy,’ ‘angry,’ ‘sad,’ or ‘neutral,’ In the combined stimulus condition, subjects were asked to decide if the face and word matched for the same emotion. Results showed that compared to the previous year, reaction times were significantly slower for making a correct decision at 11 and 12 years of age in girls and boys, the approximate ages of puberty onset. The peripubertal rise in reaction time declined slowly over the following 2–3 years and stabilized by 15 years of age. Analyses of the performance of 15–17 year olds revealed significantly longer reaction times in females to process both faces and words compared to males. However, this sex difference in late puberty appeared to be transient since it was not present in 18–22 year olds. Given the match-to-sample nature of the task employed, the puberty related increases in reaction time may reflect a relative inefficiency in frontal circuitry prior to the pruning of excess synaptic contacts.