34 Methods of assessing abnormal growth

Suman Dua

Contents:

Introduction

Short stature

Growth velocity

Causes of short stature

Nutrition and systemic diseases

Bone disorders

Intrauterine growth retardation

Growth and puberty

Bone age

Obesity

Summary

Learning Objectives:

To understand:

1.      What is growth?

2.      What is abnormal growth?

3.      What causes short stature?

4.      About Growth velocity, metabolic disorders, hormonal disorders

Introduction

Growth is the progressive increase in the size of a person or parts of a person. Development is the acquisition of various skills to perform specific functions. Growth and development go together but at different rates. The healthy state of a person can be assessed by his growth and development. Measurement of growth therefore is very essential to know whether the growth is normal or abnormal. Failure to grow normally indicates symptom of disease.

Growth takes place when bones of the arms, legs, and back increase in size. This usually occurs before the ages 16 to 18 years. The bone age or the maturation of the bone can be assessed by taking the X-ray of the hand or knee. There are many causes of abnormal growth ,some are temporary and merely variations of the normal pattern of growth. Abnormal growth may result due genetic factors or may be associated with other physical problems. The proper health and growth of a child can only be maintained by regularly getting the child examined and measured.

There are a number of conditions that may lead to decreased or increased growth rate and / or short or tall stature, which could be detected through growth monitoring. Conditions in which stature outside the normal range is often the only or most significant presenting feature are growth harmone deficiency and Turner’s syndrome (TS) .Such conditions justify growth screening in childhood.

1. Short stature may result from hypothyroidism, psychosocial deprivation, and intrauterine growth retardation or other chronic diseases. Tall stature may be due to Marfan syndrome and Klinefelter syndrome, or a sign of treatable endocrine disorders. Early detection of organic causes of abnormal growth is important. When a child is born the size is almost same in everyone but postnatally every individual varies in size and shape. Established growth standards i.e. established range of normal height and weights for different age groups can be used to monitor growth of children.

A growth chart is used to compare a child’s height and growth rate with those of others of the same age. A standard growth chart is the one in which the researchers take a large number of children of different ages and make a graph of their heights and weights. The most commonly used growth charts are from the National Center for Health Statistics (NCHS) and are age and gender specific. The height at the 50th percentile means the height at which half of the children of that age are taller and half are shorter. The 25th percentile means 75 percent of the children are taller at that age, and 25 percent are shorter. The 75th percentile means that 75 percent will be shorter and 25 percent taller.

As there is a lot of variation, and if children are between the 3rd and 97th percentile but if they are growing at a normal rate, they will be regarded as normal. The reasons for such differences are searched for. These children simply may have inherited “short” or “tall” genes from their parents.In most of the cases, they will however continue to grow at a normal pace. What is the normal growth rate during childhood? Most children establish a pattern of growth by 3 years of age and do not deviate from this pattern until the onset of puberty. During this time, the normal growth rate is 2-2.5 inches/year (5-6.5 cm/year). When children in this age group cross over or change growth channels, this may signal a growth problem and should be evaluated further.

1.1. Mid-parental Height: This calculation provides a target mean and range for the genetic potential of a child based upon the biologic parents’ heights. This calculation alone is not sufficient to predict final height; it only calculates a reference range for assessing growth .mid-parental height = (father’s height – 5 in.) + (mother’s height) for girls (inches) 2 mid-parental height = (mother’s height + 5 in.) + (father’s height) for boys (inches) 2 Target height = mid-parental height ± 2 SD (1 SD = 2 in).

Single Height measurement identifies children, whose height is outside the normal range. In contrast, repeated height measurements over time allow for calculation of a growth rate (or growth velocity) and can be used to define abnormal growth in terms of a crossing of the height centiles, thereby identifying abnormality through the pattern of growth within the individual (Rogol et a.2000).

1.2. Growth velocity provides a superior measure because changes in actual height only become evident after altered growth rates have been sustained for a period of time. A normal child tends to follow a given centile line or pattern, deviations in growth away from the percentile are difficult to detect over short intervals using the growth curve. This is one of the most important reasons for calculating the growth rate or growth velocity(Brooke et al.,1986). Evaluating the growth velocity at each routine and acute illness visit provides the earliest identification of problems with growth.

Growth velocity is normal if growth is maintained along an isobar line. When growth slows and crosses the height centiles, even if still within the normal range on the growth chart, a pathological aetiology is more likely. Growth deceleration is defined as a growth velocity that is below the 5th percentile for age and gender (e.g. <5 cm/year after the age of 5 years) or a height drop across two or more percentiles on the growth chart. When growth velocity is abnormally decreased, height measurements will progressively fall across isobars, sometimes termed ‘falling off the curve’. Conversely, acceleration of growth velocity results in crossing the upper isobars but not all growth acceleration is beneficial, exposure to abnormal sex steroid whether from an exogenous or endogenous source can lead to early accelerated growth, premature fusion of the epiphyses and ultimately, short adult stature.

Growth velocity must therefore be interpreted in conjunction with attained height because position on the growth curve is essential for interpreting the growth rate and determining the effectiveness of interventions. Short stature with decreased weight-for-height ratio may indicate the presence of a chronic systemic disease. Indeed, almost all systemic diseases may attenuate growth to a degree that is dependent on the severity and treatment of the underlying disease. In some cases (e.g. irritable bowel syndrome, coeliac disease, chronic renal insufficiency), growth may be impaired for several years before the gastrointestinal or renal symptoms are evident.

In contrast to these more subtle diseases, growth failure associated with other chronic disease (e.g. heart, immunological, etc.) is clinically evident and obviously related to the underlying condition. Children who are undernourished or suffer malnutrition also present with similar symptoms; short stature and reduced weight for height. In children with a nutritional deficiency despite access to food (e.g. anorexia nervosa or poorly controlled type 1 diabetes), weight loss is more pronounced than the decline in linear growth, and there may also be delayed sexual maturity and bone age.

Genetic or syndromic causes of short stature are often diagnosed because of abnormalities found during clinical examinations.

The intrinsic biological complexity of the dynamics of human growth, however, makes the use and interpretation of measurements of growth challenging. Growth velocities of individual children are characterized by very high variability in consecutive growth intervals. Intermittent short growth arrests and growth spurts are frequent in child development. It is not unusual for a child to grow at the 95th velocity centile during one month and at the 20th velocity centile in the following month. Correlations between subsequent different patterns of growth are generally low; this reflects both a natural pattern of saltatory growth and possible catch-up or catch-down growth that contributes to overall narrowly canalized patterns in the attained growth trajectories of individual children.

Growth velocity is best assessed using measurements taken at 3- to 4-monthly intervals in infants and at 6-monthly intervals in older children. As young children often have growth spurts, the most accurate estimates of yearly growth velocity are derived from averaging 12-monthly height (or length) measurements as compared with averaging measurements from intervals of < 12 months. Although the latter approach may intuitively appear more useful, imprecision in height measurements means that, in the short term, height velocity may not adequately identify reduced growth during routine growth monitoring (Voss et al.1991).

Although obtaining and plotting height measurements does not require expensive or sophisticated equipment, training and attention to detail are warranted(Cole, 2002). Indeed, two of the most common reasons for the misdiagnosis of growth disorders and inappropriate referrals for further evaluation are errors in height measurement or inaccurate plotting of values on a growth curve(Voss,1994).

An appropriate growth chart is an essential tool for the screening, surveillance and monitoring of children’s growth.

The growth of preterm children differs from that of children born at full term and is dependent on their gestational age. Evidence suggests that boys, in particular, may be vulnerable to the complications of preterm birth that influence growth (Bocca-Tjeertes et al., 2012).When assessing height on a growth chart it is therefore important to correct for premature birth and to use their corrected age, rather than their actual age since birth. For example, a child born at 31 weeks’ gestation was born nine weeks early (40–31 = 9 weeks). The corrected age for this child will always be nine weeks less than his or her actual age since birth. The large number of clinical conditions associated with short stature can make the task of identifying the cause of short stature challenging.

The European Society of Paediatric Endocrinology (ESPE) classified the main causes of short stature into three groups:

(i)    primary growth disorders,where the condition is intrinsic to the growth plate;

(ii)  secondary growth disorders, where the milieu of the growth plates change as a consequence of the condition; and

(iii)  when there is no identifiable cause of short stature (idiopathic short stature [ISS] or growth failure of unknown aetiology) ( Wit et al.2007).

1.3 Causes of short stature

1. Primary growth failure

Clinically defined syndromes including Down syndrome, Turner syndrome, Noonan syndrome, Prader–Willi syndrome and Silver–Russell syndrome, Small for gestational age (SGA) ,with failure of catch-up growth, Congenital bone dysplasia, for example, achondroplasia, Hypochondroplasia

2.  Secondary growth disorders

Endocrine causes

Growth hormone deficiency (GHD) either congenital or acquired (hypothalamic-pituitary region lesions such as craniopharyngioma or head trauma)

Multiple pituitary deficiencies

Cushing syndrome

Hypothyroidism

Consequences of precocious puberty

Other disorders of the GH–IGF-I axis

IGF-I deficiency

ALS-deficiency

IGF-I resistance

Metabolic disorders

Poorly controlled diabetes mellitus

Disorders of lipid, carbohydrate, protein metabolism, for example, chronic renal insufficiency Disorders in organ systems and systemic disorders, for example, cardiac, pulmonary (cystic fibrosis), liver, intestinal (short bowel syndrome and coeliac disease), renal, chronic anaemia, juvenile arthritis Psychosocial conditions such as emotional deprivation, anorexia nervosa Systemic or local glucocorticoid therapy. Treatment of childhood malignancy, for example, chemotherapy, total body irradiation.

2.1  NUTRITION AND SYSTEMIC DISEASES

There are many diseases and disorders that can cause short stature and growth failure. Malnutrition in some parts of the world leads to abnormal growth. There are a number of intestinal disorders which may lead to poor absorption of food. Failure to absorb nutrients and energy from food then leads to growth failure. Children with these conditions may have complaints that involve the stomach or intestines. Treatment of these conditions often involves a special diet. Normal growth usually resumes after proper treatment is taken. Chronic diseases that may impair growth include diabetes, congenital heart disorders, sickle cell disease.

2.2 BONE DISORDERS

Several inherited bone diseases influence growth and maturation. In achondroplasia, a dominant inherited abnormality, the cartilage cells mature less rapidly than normal. This leads to short long bones and the skin of limbs tends to hang in folds. Physical performance is not much affected. A recessive abnormality known as Osteochondrodystrophy, results in decreased growth of articular cartilage and consequently metaphysical development is delayed. Degenerative changes in joints, sclerosis may lead to restriction of movement. The underlying causes of most of these skeletel dysplasias are not known. Researches are being done to identify the genetic and biochemical mechanisms.

2.3 INTRAUTERINE GROWTH RETARDATION

Some infants are small at birth, as they are born earlier than usual time. Such babies are premature. Some infants are shorter and weigh less than they should at birth. In other words, they had a chance to grow in the womb, but did not reach the length and weight they should have for their gestational age (length of the time in the womb). This failure to grow normally in the womb is called intrauterine growth retardation.

A problem with the placenta, the organ in the mother’s womb that supplies nutrients and oxygen to the baby may result in such conditions. During pregnancy, German measles a viral infection may affect the placenta , causing intrauterine growth retardation. This condition cannot be identified in some case. Such children will remain small throughout life, whereas some of them may reach normal size. Intrauterine growth retardation may result because of so many reasons. Researches are being done to see if growth hormone is effective in increasing the growth rate and adult height of these children.

2.4 GROWTH AND PUBERTY

At the time of adolescence, a growth spurt normally occurs. Girls experience growth spurt about two years earlier than boys. Rates of growth and changes during puberty vary from person to person. Parent’s growth and puberty patterns often are passed on through their genes to their children. If one or both parents had a late puberty, then their children are more likely to reach puberty later and to experience a later growth spurt. This is also known as constitutional growth delay.

2.4.1. SEX HORMONES

The increase in growth rate during puberty is marked by the increase in production of sex hormones which is estrogen from ovaries in girls, and testosterone from the testicles in boys. These hormones are responsible for skeleton growth and maturation. Hormones produced by the adrenal glands at puberty contribute to the development of secondary hair and under arm hair. They have little effect on bone growth. Disorders of pubertal development can affect a child’s growth pattern and ultimate height. Disorders during puberty are usually grouped into two categories. (i) Precocious or premature puberty. (ii) delayed or late puberty.

2.4.2 PRECOCIOUS PUBERTY

Puberty is considered precocious (early) if changes in sexual development manifest before age eight for girls and before age ten for boys. Most symptoms of precocious puberty are similar to normal puberty. The early risk in sex hormone levels in children with precocious puberty experience early growth spurts. Although initially this causes these children to grow taller than others of their age, their skeletons mature more rapidly, which results in stopping the growth at an early age. Therefore precocious puberty if left untreated may lead to a decrease in a child’s ultimate height.

There are many possible causes for precocious puberty, including brain tumors or genetic abnormality and other disorders of the central nervous system; and tumors or other conditions that cause the gonads or adrenal glands to overproduce sex hormones. In girls, however, the majority of cases of precocious puberty are idiopathic, which means a cause cannot be identical. Precocious puberty can be divided into two categories central precocious puberty and peripheral precocious puberty.

Central Precocious Puberty also known as gonadotropin-dependent precocious puberty, occurs when the abnormality is located in the brain. Central precocious puberty is the most common form of precocious puberty and affects many more girls than boys. The causes of central precocious puberty include: brain tumors, or infection.

2.4.2 DELAYED PUBERTY

Delayed puberty occurs when the hormonal changes of puberty occur later than occurring at normal range of ages. Puberty is considered late if it has not begun by age 13 in girls or by age 15 in boys. Most children who experience delayed puberty are following the normal pattern called constitutional growth delay.

Several disorders, such as disorders of the hypothalamus, pituitary, ovaries, and testicles can result in delayed puberty by interfering with the rise in sex hormones during puberty. Many chronic disorders of other body organs and systems (such as the intestines and lungs), as well as long-term medical treatments also may cause delayed puberty. Children with delayed puberty go through an otherwise normal puberty, just at a late age. This delay is due to the fact that the is maturing slowly than average, also known as constitutional delay of puberty. This condition often runs in families.

Improper nutrition due to long-term illnesses can delaying puberty strenuous physical training (running or gymnastics) may cause delayed puberty in girls. A medical condition, in which the sex glands (the testes in men and the ovaries in women) produce few or no hormones may cause delayed puberty. Hypogonadism can be divided into two categories: secondary hypogonadism and primary hypogonadism.

The pattern of skeletal maturity is also helpful in differentiating the type of short stature.

3.  BONE AGE – skeletal maturity is observed directly by visualization of epiphyseal growth plates on X-ray. X-rays are useful to determine skeletal age –

1.      <1 year: shoulder x-ray.

2.     1-13 years: hands and wrists

3.     >13 years: elbow and hip

Bone age is necessary for interpreting hormone levels in pubertal age; for diagnosis of precocious puberty or hyperandrogenism; for deciding whether to treat or not the above mentioned conditions; for predicting adult height in normal children; in evaluating any child with growth and/or puberty disorders; in deciding the time to start replacement therapy in hypogonadism; in monitoring children on growth hormone therapy.

4. GENETIC DISORDERS

4.1. TURNER SYNDROME

Short stature in girls may be caused by a genetic condition that affects the X chromosome. Chromosomes are small thread-like bodies in the nucleus of each cell; they contain the genetic material that determines the characteristics we inherit. Two of these chromosomes determine sexual development-the X and Y chromosomes. Boys have one X and one Y chromosome, and girls have two X chromosomes. In girls with Turner Syndrome, one of the X chromosomes is misshapen or missing in many or all body cells. Because of this, affected girls are short and may have undeveloped ovaries. Intelligence is normal. Turner Syndrome may be present because of the presence of certain physical features, but poor growth is sometimes the only sign. A special blood test (karypotype) is done to look for damaged or missing sex chromosomes. Replacement of the missing ovarian hormones in these girls help to develop normal female sexual characteristics.

4.2. MARFAN SYNDROME

Some genetic conditions cause abnormal tall stature. Marfan syndrome is a hereditary condition affecting connective tissue and is associated with tall stature. People with Marfan syndrome have very long arms and legs, eye problems, and differences in facial features. Other physical problems, such as heart abnormalities, also may be present. It is commonly believed that Abraham Lincoln had Marfan syndrome. Klinefelter’s syndrome is also one such example of abnormal tall stature.

4.3. HORMONES AND GROWTH DISORDERS

Growth is controlled by hormones (chemical messengers) from various glands. One of the most important, growth hormone is secreted by the pituitary gland. The gland looks like a peanut sitting at the base of the brain. Other hormones also are essential for growth. The thyroid gland in the neck secretes thyroxine, a hormone required for normal bone growth. Sex hormones are secreted from the ovaries.

4.4. PITUITARY HORMONES

The pituitary gland is attached by a stalk to the hypothalamus, an area of the brain that controls the function of the pituitary. The anterior or front part of the pituitary gland secretes the following hormones that can affect growth:-

• Growth hormone to regulate bone growth
• Thyroid-stimulating hormone to control the production and secretion of thyroid hormones.
• Gonad-stimulating hormones for development of the sex glands (gonads) and secretion of sex hormones.
• Adrenal-stimulating hormone to regulate the secretion of adrenal gland hormones.

    4.5. Too little growth hormone (hypopituitarism)

Sometimes the pituitary gland does not make enough growth hormone so Child’s growth rate is slowed down. The deficiency may appear at any time during infancy or childhood. When doctors have ruled out other causes of growth failure, they may recommend special tests for growth hormone (GH) deficiency. Children with growth hormone deficiency are treated with daily injections of the hormone, often for a period of years. With early diagnosis and treatment, these children usually increase their rate of growth, and may catch up to achieve average or near-average height as adults.

In pituitary dwarfism, caused by low amounts of growth hormone, the person is short but has normal body proportions. This is different from other forms of dwarfism due to genetic skeletal dysplasia. In these cases, the person with dwarfism is short, and the growth of the arms, legs, torso, and head often is out of proportion. For example, the person’s arms and legs may appear relatively smaller than the head or torso.

4.6. Too much growth hormone (hyperpituitarism)

Two conditions arise from excessive amounts of growth hormone in the body: acromegaly and gigantism. The cause usually is a, tumor in the pituitary.

(i) Acromegaly, a condition caused by increased secretion of growth hormone after normal growth has been completed, occurs in adults. The condition is rare, occurring in 6 out of 100,000 people. As the adults cannot grow taller, the excess growth hormone in acromegaly causes there bones to thicken as well as other structures and organs to grow larger. This occurs usually in middle age.

(ii) Gigantism occurs when excessive secretion of growth hormone occurs in children before normal growth has stopped. This results in the overgrowth of long bones. The vertical growth in height is accompanied by growth in muscle and organs. The person becomes very tall, with a large jaw, large face, large skull, and very large hands and feet. Many health problems may be associated with gigantism, such as heart disease and vision problems, etc.

4.6.1. Too little thyroid hormone (hypothyroidism)

The thyroid gland looks like a big butterfly at the base of the neck. One wing is on one side of the windpipe or trachea, and the other on the other side. The wings are joined by a thin strip of thyroid tissue. The thyroid gland makes the hormone thyroxine.

The thyroid is controlled by the pituitary gland, which makes thyroid-stimulating hormone. The hormone thyroxine controls the rate of chemical reactions (or metabolism) in the body. Too much thyroxine, or hyperthyroidism, speeds up metabolism.

Hypothyroidism is the opposite. Hypothyroidism is caused by the body’s underproduction of thyroid hormone, and this affects many different body processes. A child with thyroid hormone deficiency has slow growth and is physically and mentally sluggish. The lack of this hormone may be present at birth, if the thyroid gland did not develop properly in the fetus. Or the problem may develop during childhood or later in life as a result of certain diseases of the thyroid. In most states, babies are tested for hypothyroidism at birth. Blood tests can detect the problem, and treatment usually is a daily pill that replaces the missing thyroid hormone. Early diagnosis and continuing treatment help these children grow and develop normally.

4.7. Cushing’s syndrome.

The adrenal glands, which are located on top of the kidneys in the abdomen, secrete the hormone cortisol. If too much cortisol is made by the child’s adrenals, or if large-doses of the hormone are given to the child to treat certain diseases, Cushing’s syndrome may develop. Children with this syndrome grow slowly, gain weight excessively, and may experience delayed puberty due to the effects of the abnormally large amounts of cortisol in the body.

4.8. Obesity

The hormones leptin and insulin, sex hormones and growth hormone influence our appetite, metabolism (the rate at which our body burns kilojoules for energy), and body fat distribution. People who are obese have levels of these hormones that encourage abnormal metabolism and the accumulation of body fat.

Summary

Normal growth is a sign of good health. Monitoring for growth disturbances is fundamental to children’s health care. Early detection and diagnosis of the causes of short stature allows management of underlying medical conditions, optimizing attainment of good health and normal adult height.Failure to grow is an important clinical condition for the general practitioner to recognize. Short stature should be identified, diagnosed and treated appropriately and without delay. Normal growth is a sign of good health, but ill children and adolescents often grow slowly, making monitoring for growth disturbances of critical importance in paediatric health care. The principal reason to study abnormal growth in infants and children is to identify conditions that may threaten good health and life. The most useful tests in distinguishing the short normal child from one with a pathologic condition are accurate height measurements over time and calculation of the growth velocity. Most apparently, healthy children who are short but growing at a normal growth velocity are healthy. In contrast, a child whose growth velocity is declining, irrespective of their absolute height, deserves thorough evaluation. Prompt recognition of the cause of short stature, by measuring children early and often, provides the best chance for a child to achieve an ideal health outcome as well as the potential to reach an adult height within the normal population range. In light of our ability to diagnose remediable diseases using accurate growth assessment, the clinical significance of early recognition of short stature is clear. When doctors have ruled out other causes of growth failure, they may recommend special tests for growth hormone (GH) deficiency. Children with growth hormone deficiency are treated with daily injections of the hormone, often for a period of years. With early diagnosis and treatment, these children usually increase their rate of growth, and may catch up to achieve average or near-average height as adults.

References

• Rogol AD, Clark PA, Roemmich JN. Growth and pubertal development in children and adolescents: effects of diet and physical activity. Am J Clin Nutr 2000; 72(Suppl): 521S–8S
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    Suggested Readings

• Cowell  CT.   Short   Stature.   In  Brook   CGD,  editor.  Clinical   Paediatric  Endocrinology. Oxford: Blackwell Science LTD.; 1995. pp. 136-172.
• Linder B, Cassoria F. Short Stature, etiology, diagnosis, and treatment. Journal of the American Medical Association 1988; 260:3171-3175.
• Mahoney CP. Evaluating the child with short stature. Pediatric Clinics of North America 1987;34:825-849.
• Nwosu BU, Lee MM; Evaluation of short and tall stature in children. Am Fam Physician. 2008 Sep 1;78(5):597-604.

    Hypothyroidism

Lafranchi S. Thyroiditis and acquired hypothyroidism. Pediatric Annals 1992;21:29-39.

Obesity

Arslanian S. Obesity. In: Sperling MA, editor. Pediatric Endocrinology. Philadelphia: W.B. Saunders Co; 1996. p. 535-543.

Precocious puberty

Bridges NA, Brook CGD. Sexual Precocity. In Brook CGD, editor. Clinical Paediatric Endocrinology.

Oxford: Blackwell Science LTD; 1995, p. 253-262.

Mahoney CP. Evaluating the child with short stature. Pediatric Clinics of North America 1987; 34:825-(A timeless review article, which describes normal growth patterns, the evaluation of short stature, and diseases causing short stature.)

Shulman DI, Beru BB. Growth hormone therapy: An update. Contemporary Pediatrics 1998;15:95-110.

E<ahref=”http://www.betterhealth.vic.gov.au/bhcv2/bhcarticles.nsf/pages/Obesity_and_hormones?ope n”> http://www.betterhealth.vic.gov.au/- Better Health Channel</a><br/>ducational Resources on the World Wide Web

Jones, R. E., & López, K. H. (2006) Human Reproductive Biology, 3rd Edition. Academic Press.

The National Center for Health Statistics

http://www.cdc.gov/nchswww/ (Home page)

http://www.cdc.gov/growthcharts/ (Growth charts)