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Normal puberty is the result of the maturation of the hypothalamo-pituitary-gonadal (HPG) axis. Primary and secondary sexual characteristics develop by the increase in the serum levels of gonadal steroids: oestradiol in girls and testosterone in boys. The main players in the process of normal puberty are the hypothalamus, by producing pulsatile Gonadotrophin Releasing Hormone (GnRH), and the pituitary. GnRH influences the pituitary via the portal vein system and the pituitary secretes the gonadotrophins Luteinizing Hormone and Follicle Stimulating Hormone (LH and FSH). LH and FSH in turn stimulate the gonads to develop the cells essential for reproduction and to secrete the gonadal steroids. In girls this maturational process primarily leads to the development of the breasts and internal genitalia. Menarche follows as a result of ong...
The secular changes in growth and maturation can be seen as indicators of socio-economic and health status. In most European countries the age of onset of puberty and of menarcheal age has been decreasing during the past few decades. The duration of puberty seems also to decrease, though few studies provide sufficient data to support this postulation. The four Dutch nationwide growth surveys are useful examples assessing the secular trend in pubertal development over the past 45 years. Genetic and environmental factors contribute to the secular changes. Environmental factors seem to be the most important. Recently, attention has been given to substances with oestrogen-like actions that are present in nutrients. The possible role of these...
Background: Renal tubular acidosis (RTA) is a rare cause of growth failure, therefore it is uncertain whether routine screening with blood gas analysis of short infants and children is cost-effective. Objective: To investigate the clinical, growth and laboratory parameters in children with RTA to estimate the possible value of laboratory screening for this disorder in infants and children referred for short stature according to a recent guideline. Method: Retrospective chart analysis of 30 children diagnosed between 1978 and 2005 in The Netherlands and 3 centers in Belgium. Results: The current guideline for short stature detected 33% of children with RTA. Assuming a pre-test probability of RTA of 0.6 per 100,000 births, the likelihood ratio of poor growth was 58 and 17 below and above 3 years, respectively. Sensitivity was 17/30 and 1...
We investigated pubertal development of 4019 boys and 3562 girls >8 y of age participating in a cross-sectional survey in The Netherlands and compared the results with those of two previous surveys. Reference curves for all pubertal stages were constructed. The 50th percentile of Tanner breast stage 2 was 10.7 y, and 50% of the boys had reached a testicular volume of 4 mL at 11.5 y of age. Median age at menarche was 13.15 y. The median age at which the various stages of pubertal development were observed has stabilized since 1980. The increase of the age at stage G2 between 1965 and 1997 is probably owing to different interpretations of its definition. The current age limits for the definition of precocious are close to the third percentile of these references. A high agreemen...
We assessed the effectiveness and safety of 3 yr combined GH and GnRH agonist (GnRHa) treatment in a randomized controlled study in children with idiopathic short stature (ISS) or intrauterine growth retardation (IUGR). Gonadal suppression, GH reserve, and adrenal development were assessed by hormone measurements in both treated children and controls during the study period. Thirty-six short children, 24 girls (16 ISS/8 IUGR) and 12 boys (8 ISS/4 IUGR), with a height SD score of -2 SD or less in early puberty (girls, B2-3; boys, G2-3), were randomly assigned to treatment (n = 18) with GH (genotropin 4 IU/m(2). day) and GnRHa (triptorelin, 3.75 mg/28 days) or no treatment (n = 18). At the start of the study mean (SD) age was 11.4 (0.56) o...
Background: GnRH analogue (GnRHa) combined with GH treatment has been proposed to increase adult height. Effect on metabolic profile and GH, IGF1, and IGFBP3 levels in short small for gestational age (SGA) children is unknown. Objective: To assess fat mass and lean body mass SDS, percentage trunk fat, blood pressure (BP), insulin sensitivity (Si), β-cell function (disposition index, DI), lipid profile, and GH, IGF1, and IGFBP3 levels during 2 years of combined treatment. Subjects: Forty-one pubertal short SGA children with a mean (±S.D.) age of 12.1 (±1.0) years. Design: Children received 3.75 mg of leuprolide acetate depot subcutaneously every 4 weeks, and they were randomly assigned to receive 1 mg (group A) or 2 mg (group B) of GH/m2per day. Results: Percentage trunk fat increased in both groups, but to a lower extent in group B. Le...
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