Evaluation of short stature

In the third part of our endocrinology series, H S Randeva and P M G Bouloux explain how to distinguish between normal variants of growth and growth disturbances caused by pathological processes

Short stature is the commonest reason for a child to be seen by a paediatric endocrinologist. Most children referred with short stature are normal. It is important to differentiate normal variants of growth from growth disturbances secondary to underlying pathology or disease processes, thereby preventing the child from being exposed to unnecessary investigations.

Normal growth patterns

The fastest growth rate is achieved prenatally, birth size predominantly relating to maternal factors (for example, nutrition) than fetal factors. Several months after birth, maternal influences lessen and genetic factors become predominant. In the first year of life, growth velocity is most rapid (up to 22 cm/year) but declines during childhood, to around 5-7 cm per year in mid-childhood, decelerating further before puberty until the pubertal growth spurt (10-12 cm/year). The onset of puberty is her- alded by breast enlargement in girls and testicular enlargement in boys. Although the growth spurt in girls occurs earlier in the course of puberty than in boys (11.5 years and 13.5 years, respectively), the peak height velocity attained is less than that seen in boys. This, together with a longer duration of increased growth, accounts for the higher average adult height in males.

Growth charts

The normality of a child's height is deter- mined by reference to growth charts show- ing population norms. In 1994, the Child Growth Foundation (UK) introduced nine centile growth charts (figure 1), based on seven cross sectional growth surveys conducted between 1978 and 1990, to facilitate height screening in the community and appropriate referral of children with growth disorders (figure 2). The lowest centile is the 0.4 line-only one normal child in 250 will fall below that line. Altogether 2% of the normal population will have a height below the 2nd centile. The recommendations are that children whose height is below the 0.4th centile should be referred for assessment of growth. Any children between the 2nd and 0.4th centile should be monitored to see whether their growth is normal, and referral should be considered. In addition, any child undergoing sequential measurements should be referred for further assessment if the growth curve crosses two centile lines or a single centile line for those aged between two and five years of age.

Fig 1-Child Growth Foundation chart for girls

For monitoring the growth in an individual child the Buckler-Tanner charts are preferable. These are revised charts (1995) based on the Tanner-Whitehouse growth standards (longitudinal growth surveys in the 1960s) and by definition 3% of normal children will be below the lowest centile, the 3rd centile. If a 10 year old boy is on the 50th centile it means that 50% of boys of his age are taller and 50% are shorter than him.

Assessment of growth

History

A careful and detailed history is an important part when assessing growth. Details of pregnancy, maternal health and birth should be addressed. In addition to inquiring about birth weight and length, the occurrence of specific prenatal, perinatal, or postnatal complications should be questioned. For example, at birth a hypoxic insult may cause hypothalamic hypopituitarism, and neonatal hypoglycaemia may imply growth hormone deficiency. Early health, past medical history and treatment, and age of recognition of short stature are important questions to ask. For example, treatment of asthma with chronic systemic or inhaled glucocorticoids can cause poor growth.

Fig 2-Treatment of short stature depends on the underlying aetiology (JOHN PAUL KING/PETER ARNOLD INC/SPL)

Obtaining old growth records with data on height and weight is pertinent when assessing growth. It is important to remember that a single height measurement does not give any information regarding growth patterns. Only serial measurements and calculation of growth velocity (assessment over six months to one year) will differentiate normality from abnormality. The height of both parents, age of onset of puberty, nutritional status, and social background are also relevant.

A child's shortness, although it may be in keeping for his short parents, may reflect poor nutrition or emotional deprivation passed down the generations. A family history of pubertal delay is often found in children with constitutional short stature. The mean height of children from families from social classes IV and V remains significantly below that of those from social classes I and II. Finally, genetic potential can be predicted on the basis of parental heights, and it is the midparental height which provides information necessary to determine if the child's height is appropriate for his or her family; it is calculated as follows:

(MPH (boys)=father's height±(mother's height±12.5 cm))/2

(MPH (girls)=mother's height±(father's height-12.5 cm))/2

Using this information, the child's predicted adult height (mid-parental target height) is calculated as the MPH±2 standard deviations (SD), where one SD is 5 cm, that is MPH +- 10 cm.

Examination

Initially, it is useful to define whether short stature is proportionate or disproportionate, and whether the child otherwise looks "normal," or might be suffering from a syndrome (for example, hypochondroplasia). Accurate standing, sitting, and supine (for children aged up to 18 months) height, weight measurements, and head circumference are essential. A wall mounted device (stadiometer) is appropriate for measuring standing height. The sitting height plotted against total height on an appropriate chart will help in the differential diagnosis of short stature (proportionate versus disproportionate). In addition, the ratio of upper to lower body segment is most often disproportionate in patients with primary bone disorders. On the other hand, this ratio is normal (proportionate) in patients with chronic diseases, both endocrine and non-endocrine. The lower segment is the distance between the top of the symphysis pubis and the floor when the patient is standing; the upper segment is calculated by subtracting the lower segment from the standing height. Finally, arm span is another indicator of extremity growth.

Physical examination should include pubertal staging and documentation of testicular volume using a Prader orchidometer. Both visual acuity and visual fields ought to be checked, bearing in mind the possibility of a hypothalamic pituitary lesion. Finally, general physical examination may disclose features of recognised syndromes (for example, Turner's syndrome) or chronic disorders.

Investigations

At the initial visit certain laboratory studies (box 1) are used to screen for chronic occult diseases, such as inflammatory bowel disease, coeliac disease, and chronic renal failure, to name but a few. Chromosome karyotype is indicated in all girls to exclude Turner's syndrome. A bone age study (x ray films of the left hand and wrist) is usually performed at the initial assessment, although its contribution to the diagnosis is minimal, as most disorders causing poor growth are associated with a delay in skeletal maturity. Instead, it provides more information related to growth potential given that final adult height is dependent on both growth velocity and degree of skeletal maturity. If the screening programme is not diagnostic, then further assessment should include pituitary function tests and in particular an evaluation of the growth hormone axis by a paediatric endocrinologist.

Growth hormone secretion is pulsatile, with most pulses occurring at night. A number of physiological and pharmacological tests have been used to assess the growth hormone axis however, physiological tests are now less frequently used. The insulin hypoglycaemic tolerance test remains the standard for assessing the status of growth hormone in many paediatric endocrine units, although some units no longer use the insulin tolerance test because it is potentially dangerous in inexperienced hands. Therefore tests of growth hormone secretion must only be undertaken in specialist endocrine units experienced in their performance.

It should be observed that all the available tests give both false negative and false positive responses. Therefore, at present, the diagnosis of growth hormone deficiency and growth hormone insufficiency, or both, is based upon a combination of auxology, clinical assessment, and biochemical analysis. Once a diagnosis of growth hormone deficiency has been established, the most common cause of which is idiopathic, magnetic resonance imaging of the hypothalamic pituitary region is indicated to exclude an underlying aetiology of growth hormone deficiency or insufficiency - for example, pituitary hypoplasia or an intracranial tumour.

Causes of short stature

The differential diagnosis of short stature and slow growth is summarised in box 2. The following are some examples.

Normal variants

Familial (genetic) short stature and constitutional short stature are common variations of normal, although with differences. Individuals with familial short stature have a normal growth rate even though it is below the 5th percentile. They do not have skeletal delay, puberty and pubertal growth spurt occur at the usual chronological age, and final height is appropriate for mid-parental target height (see above). Those with constitutional short stature have growth deceleration in the first two years of life, with normal growth velocity being achieved by age three and continuing throughout childhood. Skeletal maturity is delayed, and because timing of puberty correlates with skeletal age, both puberty and pubertal growth spurt are delayed. The growth spurt can be blunted, and consequently individuals with constitutional short stature often reach a final height at or just below the mid-parental target height. With familial as well as constitutional short stature, reassurance is often all that is needed.

Non-endocrine causes

Non-endocrine causes of short stature are commoner than endocrine causes. Patients with non-endocrine disease tend to have normal body proportions. Chronic malnutrition is the commonest cause of poor growth globally. In the developed world, malnutrition may occur as part of more complex disease - for example, inflammatory bowel disease, coeliac disease, or anorexia nervosa, rather than frank malnutrition. Short stature is also commonly associated with renal disease, and conditions associated with hypoxia or hypoxaemia, such as congenital heart disease, pulmonary disease, and haemoglobinopathies. Finally, psychosocial deprivation often causes short stature and delayed bone age with a delay in pubertal development are other features of the condition. Placing the child in a different environment results in growth catching up.

Endocrine causes

Growth hormone deficiency or insufficiency is an uncommon cause of short stature, with a prevalence of the condition being reported as 1 in 4000. The diagnosis is suspected if growth velocity is low, skeletal maturation is delayed, and no other endocrine or non-endocrine disease can be identified. The typical phenotype is that of a short child with increased subcutaneous fat, dry skin, and crowding of facial features, maxillary hypoplasia, and poor development of the nasal bone. The calvarium seems to be relatively overgrown (delayed closure of fontanelles), with prominence of the frontal bone. Early referral to a paediatric endocrinologist is warranted so adequate diagnosis can be made (confirmation of growth hormone deficiency, exclusion of other anterior pituitary hormone deficiency, and imaging of the hypothalamopituitary region to exclude structural lesions) and growth hormone treatment initiated. Early diagnosis of growth hormone deficiency or insufficiency is mandatory if treatment is to yield the best results.

Hypothyroidism, which may present with short stature and poor growth velocity, is associated with low growth hormone pulsatility, which returns to normal on starting treatment with thyroxine. It is important to recognise that classic signs of hypothyroidism are rarely present. In boys, curiously, testicular enlargement without other features of pubertal development is sometimes seen.

The impairment of growth in Cushing's syndrome is predominantly the result of a direct effect at the growth plate. The commonest cause is iatrogenic (treatment with glucocorticoids), with endogenous glucocorticoid excess (Cushing's syndrome dependent on the pituitary and adrenal glands) being much rarer.

Chromosomal abnormalities

The incidence of Turner's syndrome is 1 in 2500 live births of girls. About 50% of patients with Turner's syndrome have a 45XO karyotype; the remainder are mosaics and have structural abnormalities of the X chromosome (or a Y chromosome). Short stature is the most consistent finding in girls with Turner's syndrome, and skeletal age in these patients is delayed only minimally during childhood, although the delay is greater in adolescence. Short stature in patients with Turner's syndrome may be a result of low birth weight (1 SD below the mean), feeding difficulties in the first year of life, skeletal dysplasia, and blunted secretion of growth hormone and production of insulin growth factor-1 (IGF-1) at puberty. Studies have shown a significant increase in growth velocity and predicted adult height to exogenous growth hormone; enough to warrant its use in patients with Turner's syndrome.

Summary

Short stature is a common reason for a child to be referred to a paediatrician. Most children whose height falls below the 3rd centile are "normal," with only a small number having endocrine abnormalities. When evaluating a child for short stature the importance of previous history, growth data, parents' heights, and pubertal history, cannot be overemphasised. In addition, an assessment of growth requires reliable growth measurements with data plotted on appropriate growth charts. In some cases specialised tests are performed such as chromosomal analysis, pituitary function tests, or growth hormone testing, when the diagnosis is not readily discernible by history, examination, and screening laboratory studies. Finally, the treatment of short stature will depend on the underlying aetiology, although often reassurance is all that is required.

H S Randeva, senior registrar in endocrinology,

P M G Bouloux,reader in endocrinology,, Centre for Neuroendocrinology, Royal Free Hospital, London NW3 2QG


studentBMJ 2000;08:131-174 May ISSN 0966-6494