Growth: II Normal Growth
Clinical background
Short stature in children is a common presenting complaint. The majority
of short children do not have an identifiable abnormality and thus it is
important to make accurate measurements of height over a period of time and to
calculate growth velocity. Short stature can reflect a wide range of underlying
causes, ranging from nutritional and psychosocial factors, to endocrine
disorders and genetic dysmorphic syndromes.
Growth hormone deficiency (GHD; Fig. 10a) has numerous causes related to
congenital midline structural defects of the hypothalamus and pituitary, acquired
lesions following perinatal trauma or central nervous system infections,
primary and secondary tumours of the hypothalamus and pituitary, autoimmune
hypophysitis and following cranial irradiation. In the majority of cases the
cause is unknown (‘idiopathic’ GHD; Fig. 10b). Children with GHD present with
growth failure and typical features relating to GH effects on bone and body
com- position. Thus the facial appearance is immature with a depressed central
zone and prominent forehead related to lack of GH effects on skull maturation.
GHD children have reduced muscle bulk and increased central fat deposition
consistent with a lack of the metabolic effects of GH. Untreated they will
reach approximately 65 to 70% of predicted adult height and this can be
reversed by the introduction of GH replacement therapy at the earliest possible
age (Fig. 10a).
Normal growth
Prenatal growth
The growth rate is an informative index of mental and physical
development, both pre- and postnatally. Normal intrauterine growth and
development are critically dependent on maternal diet and state of health and
adversely affected by excessive maternal alcohol intake and smoking. Endocrine
influences on intrauterine growth and development are poorly understood.
Circulating maternal unconjugated estriol is an important index of
normal fetal growth. Estriol’s function is not understood but it is known to be
produced by the placenta using precursor steroids derived from both fetus and
mother. Table
10.1 shows expected ranges during pregnancy. Reduced values may point to
the possibility of intrauterine growth retardation or Down’s syndrome (Table
10.2).
Postnatal growth
Human postnatal growth in stature and weight is assessed relative to
standardized growth curves (Fig. 10c). Growth rates are highest during fetal
development and just after birth. There is a spurt in growth in boys and girls
between 6½ and 7 years, followed by a plateau and then the sharp pubertal
growth spurt. Growth ceases with the fusion of the long bone epiphyses by sex
steroids, reflecting full adult growth and maturation.
Normal growth is influenced by genetic, socioeconomic and nutritional
factors, and chronic disease. There is a good correlation between parental and
child height which is sex-specific. The correlations with respect to birth
length, rate of growth and final height are well documented in families. Poor
hygiene, poverty and malnutrition adversely affect growth before and after parturition. Smoking, alcohol and
drug abuse have deleterious effects on the fetus and growing child.
Malnutrition is associated with several adverse effects on the endocrine
system, including decreased concentrations of circulating IGF-1, decreased GH
receptors and post-GH receptor defects with the predicted elevation of serum
GH.
Any form of chronic disease, particularly when associated with malabsorption, such as coeliac
disease or inflammatory bowel disease, may impair growth and should be excluded
before subjecting a child to lengthy endocrine investigation of short stature.
Endocrine hormones are essential for postnatal growth. Growth hormone (GH)
exerts its effects directly and through the mediation of the insulin-like
growth factors. Disorders of GH synthesis, secretion or action may originate in
the hypothalamus, pituitary gland, at sites of IGF-1 production or at target
organs for the hormones. Thus GH abnormalities in children may present with low or absent circulating
GH concentrations (asinidiopathic GH deficiency) or with the
elevated GH levels seen in association with GH receptor abnormalities in the
Laron syndrome.
Thyroid hormones are essential for normal intrauterine and postnatal
development; fetal thyroid deficiencies cause mental impairment and delayed
development, but whilst postnatally acquired hypothyroidism inhibits growth it
does not usually affect mental development. Excess glucocorticoid treatment in
childhood can also impair growth. The gonadal sex steroids are essential for
the normal pubertal growth spurt and individuals with delayed puberty present
with short stature as well as developmental delay.
