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|Department of Paediatrics, Paediatric Endocrinology and Diabetes
Medical University of Silesia, Katowice, Poland
|View Author’s Full BiographyHigh Boots Calvin Leather Heeled Klein Selene Jeans Black qwTOtRSn|
Postnatal linear growth is controlled by genetic, endocrine and nutrition factors. Although adequate nutrition is essential for normal growth of the child, excessive fat tissue accumulation may cause abnormalities in the trajectory of linear growth. Obesity in children and adolescents has been long associated with tall stature. First studies presenting the hypothesis that overnutrition accelerates linear growth were published in 1960s 1. On the other hand some studies suggest that taller children may be wrongly labelled as ‘overweight’ because body mass index (BMI) is dependent of height 2.
Annual height velocity approximates 25 cm in the first year of life, and then decreases over time until a plateau-like phase of 5.5 cm is reached before the onset of puberty. Distinct sex-specific differences exist in annual height velocity in childhood and they are accentuated during puberty. Girls attain a peak height velocity of 8.3 cm per year at an average chronological age of 11.5 years. By contrast, boys gain height at the pre-pubertal rate until the mean age of 11 years and then experience a peak height velocity of 9.5 cm per year from approximately 13.5 years of age. The overall pubertal increment of stature in boys exceeds that of girls by only 3–5 cm, which means that the mean adult height difference of ~13 cm between the sexes is largely due to a more prolonged period of pre-pubertal growth in boys 3,4.
Growth during fetal life, infancy, childhood and adolescence is controlled by many factors such as genes, nutrition status and hormones. Fetal growth is mediated by insulin, insulin-like growth factor 1 (IGF-1), insulin-like growth factor 2 (IGF-2) and maternal nutrition. Growth hormone (GH) plays the main role in the post fetal life together with thyroid hormones and sex steroids are active growth stimulators during puberty 3,4.
GH acts mainly through IGF-1. IGF-1 is a single chain polypeptide involved not only in the regulation of growth but responsible for several metabolic actions. It interacts with insulin through the specific receptors in regulating body metabolism both in fasting and overnutrition state. It serves a role in beta-cell mass regulation in the pancreas, insulin secretion and insulin sensitivity, integrating lipolysis, proteolysis and insulin resistance 4-6. On the other hand hyperinsulinemia was found to be associated with advanced bone age (BA) in obese children 7 so it also active in modulation of skeletal growth in humans. Increased insulin secretion is a normal feature in adolescence and it probably plays a role in activating the insulin receptor at the growth plate. At a given degree of obesity children may be either insulin sensitive or insulin resistant. In Pinhas-Hamiel et al study7 hiperinsulinemia >30mIU/l was the strongest predictor of advanced BA.
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GH-IGF-1 axis in obesity
Intact GH/IGF-1 axis is essential for somatic growth in children. However overweight and obese children experience either normal or most often accelerated growth in spite of several abnormalities in GH and IGF-1 secretion. Compared to normal weight peers they have reduced GH secretion, decreased frequency of GH bursts and reduced GH half-life 6. Moreover, GH response to several stimulation tests is blunted. However increased GH binding protein (GHBP) values have been found in obese children by Bouhours-Nouet et al.10 suggesting increased GH receptor number in peripheral tissues. IGF-1 levels were found either normal or high, that may suggest an increased responsiveness to GH. GH responsiveness in prepubertal children, as measured by the IGF-I increment in response to a single dose of GH, was increased in obese children compared with tall normal weight peers. It was also dependent on the fat mass percentage which suggests a link between the energy stores and the anabolic action of GH.
Kratzsch et al 9 have shown that obese girls have increased levels of growth hormone binding protein (GHBP) possibly reflecting elevated GH receptor tissue density. This mechanism could play a role in accelerating growth in obese children, as demonstrated by a significantly positive relationship between GHBP and height SDS. Wabitsch et al 10 have demonstrated that obese girls have increased IGF-I levels until maturity and suggested that the advanced development seen in overnutrition is due to increased IGF-I production. The large population-based Avon Longitudinal Study of Parents and Children (ALSPAC) showed that circulating IGF-1 levels in childhood were influenced by infant growth rate. The authors concluded that they may positively mediate the effects of early postnatal nutrition on later growth and maturation 11Trainers nbsp;leather Grey Garment Project Flash Lace Lining qO764Saw. Denzer et al have found that IGF-I levels correlated with the degree of BA acceleration independently of gender and pubertal stage. 12
The potential link between obesity and impaired GH secretion is leptin that is produced by the adipose tissue 13,14. Serum leptin levels are elevated not only in simple obesity but also in other clinical conditions associated with increased body fat accumulation, such as Cushing’s syndrome or adult GH deficiency. In rodents leptin had a stimulating effect on GH secretion and a similar effect has been hypothesized to occur in humans15. The coexistence of high leptin and low GH serum levels in obesity would suggest a status of leptin resistance. Animal models have shown that leptin can act as a skeletal growth factor, able to stimulate proliferation and differentiation of chondrocytes in the growth plateOf Bow Textile Mules And Teal Lining Lining Bianco Loafer nbsp;combination Leather Dark 15 .
Growth in obese children
Obese children usually present with greater height than their normal weight peers although they do not tend to attain taller height as adults16-18. The increased linear growth is associated with accelerated skeletal maturation. In the study of Johnson et al 18 difference in skeletal age between obese and normal weight children was significant from 6 to 14 years of age in boys and from 7 to 16 years of age in girls. It reached its maximum at 14 years of age in girls and at 12 years in boys, bone age being approximately one year advanced with respect to normal weight peers. Large differences in stature were also found by Stovitz et al 14 in the cohort of 1375 boys and 1433 girls followed in CATCH study. According to them the difference peaked at approximately 11 years of age. Accelerated growth in childhood followed by reduced subsequent height gain was also reported by He and Karlberg in 3650 Swedish children16. These authors have calculated that each unit of increased BMI between two and eight years of age was associated with a 0.23 cm increase in height in boys and 0.29 cm increase in girls.
Interestingly, Johnson et al 20 have reported that advanced skeletal maturity preceded linear growth acceleration in overweight individuals. They suggested that factors involved in physical maturity are linked etiologically with the risk of becoming overweight. According to these authors early maturation combined with unrelated to mid-parental height tall stature in prepubertal children may herald obesity in young adulthood. The authors concluded that in children who are at risk to become obese or overweight adults increased BMI precedes the advancement in skeletal development and subsequently tall stature at puberty.
Belsky et al. measured polygenic risk of the obesity development using a multilocus genetic risk score derived from GWAS of obesity-related phenotypes 21. In their 38-year prospective longitudinal study they found out that polygenic risk for obesity was partially mediated by rapid growth in the early childhood. Moreover, genetic associations with growth and obesity risk were independent of birth weight and the family history.
Differences in linear growth of obese children are due to the differences in the pace of maturation between overweight and normal weight children and adolescents. He and Kalberg 18 clearly shown that earlier age of puberty onset in obese children diminished the final height. In their study the impact of each BMI unit accelerated pubertal timing by 0.6 years in boys and by 0.7 years in girls. Therefore the temporary increase in height in childhood was compensated by a smaller gain in adolescence. These findings probably reflect growth plate maturation in response to early estrogenization. Despite acceleration of BA and decreased growth spurt during puberty, children with obesity generally attain expected adult height16-20,.
Tall stature or accelerated growth rate accompanied by early appearance of pubertal signs may raise the suspicion of hormonal pathology. Careful assessment of pubertal status and determination of bone age are helpful in prediction of adult height and reassurance of the patients and their guardians of normal growth pattern. Child’s height should be always related to midparental height. However final height correction should be applied for height prediction in obese children at different bone age17 .
Nevertheless it is critical to identify situations in which tall stature or abnormal growth rate in overweight child are clinical manifestations of underlying pathology. Causes of statural overgrowth are listed in table 1.
Tab. 1 Pathology causing tall stature in children
Syndromes associated with tall stature and overweight/obesity
- Klinefelter’s syndrome (XXY or other less common chromosomal aneuploidy)
- Beckwith –Wiedeman syndrome
- Sotos syndrome
- Weaver’s syndrome
Syndromes associated with tall stature and leanness
- Marshall-Smith syndrome
- Fragile X syndrome
- Aromatase deficiency
- Estrogen receptor deficiency
- Marfan’s syndrome
- Androgen insensitivity
Endocrine causes of tall stature
- GH excess (pituitary adenoma)
- Hypogonadrotrophic hypogonadism
- Precocious puberty (tallness at precocious growth spurt but reduced final height)
- Hyperthyroidism (untreated may cause significant weight loss)
Diagnosis of tall stature in obese children
Detailed family history including the measurement of parental height and physical examination of obese or overweight child with growth acceleration in most cased will exclude pathology and the need for further investigation22,23. Establishing a growth curve from serial height measurements and assessing pubertal status are useful in excluding hormonal pathology. Height and weight measurement, calculation of BMI together with plotting it on a BMI chart to calculate SD score is a helpful tool in discussion of the problem with parents or guardians. So is the final height prediction based on midparental height, pubertal stage and bone age advancement, however the standard error is always considerable.
If clinical examination suggests the need for subsequent investigation, the baseline studies should include;
- Assessment of pubertal stage according to Tanner’s scale
- X-ray of the no dominating hand for bone age assessment
- TSH and fT4 to exclude hyperthyroidism
- IGF-1 and IGFBP3
- Gonadotrophins (LH and FSH) and sex steroids if pubertal disturbances present
- Magnetic resonance of the pituitary gland if IGF-1 level high
- Karyotype if body disproportions, delayed puberty, psychosocial problems or mental retardation present
- GH glucose suppression test to exclude pituitary adenoma
- Plasma homocysteine if marfanoid features present
Childhood obesity is related to the acceleration of the linear growth during prepuberty and early puberty with a subsequent trend toward a reduction of height velocity due to the less pronounced growth spurt as compared to the lean peers (Fig 1.). Therefore a vast majority of tall obese children will have a final height according to their genetic potential of growth. Nevertheless abnormal growth may be in some patients caused by an important pathological causes that need to be considered.
Figure 1: Tall Stature
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- Metcalf BS, Hosking J, Fremeaux AE, Jeffrey AN, Voss LD, Wilkin TJ. BMI was right all along: taller children really are fatter (implications of making childhood BMI independent of height) EarlyBird 48. Int J Obes 2011;35:541-7
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- Pinhas-Hamiel O, Benary D, Mazor-Aromovich K, et al. Advanced bone age and hyperinsulinemia in overweight and obese children. Endocr Pract 2013 doi:10.4158/EP13193.OR
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