What does your pediatrician mean when she says "short stature?" It is important to understand that short stature is not a specific diagnosis. Nor is it a definite indication that something is wrong with your child. Short stature is simply a descriptive term indicating that a child's height is less than expected for his/her age. Short stature does require evaluation by the pediatrician or family practitioner, and in some cases even a pediatric endocrinologist (a specialist that deals with glandular disorders in children). To give you a better understanding of what all of this means, the following article will review the way growth is assessed in children and then describe some of the common problems identified as a result of this evaluation.

How We Assess Growth

Growth is one of the major characteristics of childhood and one of the better indicators of overall well-being in children. For this reason, during check-ups, pediatricians will carefully measure the head circumference in infants, and the height and weight of infants and children. These measures are then compared to reference values for children of the same age, usually in the form of a growth chart. There is one chart for children from birth to 3 years old and another for children from 2 to 18 years old. Normal growth rates are different for boys and girls, so they use separate charts.

Current reference standards, in use since 1977, were derived from a mixed population of healthy children through two sources: the National Center for Health Statistics' national health examination surveys for children age 2 to 17 years, and the Fels Research Institute in Yellowsprings, Ohio, for infants from birth to age 2 years. These charts have been adopted by the World Health Organization for international use.

The Center for Disease Control of the US Public Health Service is currently in the process of revising these standards, using more data on the growth of children obtained through the national health examination surveys of 1988-1994. New infant charts will be developed that reflect this national data set rather than that of a single research institution's data. Thus, within the next one to two years we will have new reference standards to apply to children's growth.

This change in reference standard will not affect the interpretation of growth in most children. However, it will demonstrate that assessment of growth is not absolute. It is relative. Assessment of growth is a comparison against a population. In other words, when we assess growth, we are asking the question, "Is this child behaving like other children in his population?"

Growth charts also permit us to ask whether a child continues to grow according to the pattern she has established. Each chart has lines representing the path of a child's growth from a younger to an older age, plus lines representing average growth rate of children versus a slower or faster, but still acceptable, rate. Each child is expected to parallel or follow along one of those lines.

Deviation from the path may be considered an abnormality when at least two lines have been crossed. Thus a child may be within the lines that describe normal children, yet still have a problem if his growth pattern crosses different lines. We make the diagnosis of short stature when a child is either below all the lines on the growth chart for his age (i.e., below the fifth percentile) or that he has crossed two or more lines down from a previous point.



Evaluation of Short Stature

When a child is first diagnosed with short stature, it only means that she is shorter than the average child in her age group. It is important to remember that short stature does not necessarily represent a disease process or even a significant problem for the child. The goal of the next evaluation is to determine whether this short stature diagnosis represents a problem or if it is the child's normal height.

History and physical examination: To make such a determination, we must obtain a complete medical and family history identifying growth patterns of family members, genetic disorders associated with poor growth, and past medical history of disease processes in the child. In addition, we perform a complete physical examination, looking for any sign of organ system failure, status of pubertal development, and physical features associated with genetic disorders.

Bone age: An important examination involving an x-ray of the hand and wrist, known as bone age, is obtained early in the evaluation to determine the maturation of the child's bones. Bone maturation is known to be a sensitive indicator of adverse health experiences in a child and can be used as a tool to predict growth potential.

Laboratory and other studies: Finally, laboratory studies are used to evaluate organ systems, such as the liver and kidneys, and glandular systems, such as the thyroid, parathyroid, adrenals, and the pituitary, whose functions are not easily assessed by a simple physical examination. The purpose of these studies is to determine whether there is any organ system failure (e.g., hypothyroidism, kidney disease, cystic fibrosis) or if there are genetic abnormalities associated with growth disturbances (e.g., Turner's syndrome, a disorder in females in which one of the two sex chromosomes is missing). If abnormalities are identified in these first lab tests, it may be decided that more laboratory and/or radiographic tests (e.g., MRI, CT scans, sonograms) are necessary before a specific diagnosis can be made.

The pediatric endocrinology examination: The pediatric endocrinologist will review laboratory and genetic tests to ensure that no evidence of organ system failure or genetic disorder has been overlooked. The doctor will also evaluate the child's growth in comparison to that of the parents. Some questions the doctor should consider are:


Does this child resemble the growth pattern of other family members?
Is he/she a slow, average, or fast maturer, similar to his/her parents?
Is the child's growth potential appropriate for his/her family-i.e., is the child expected to reach a height within the target range of his/her parents?
How fast is the child changing and is this rate of change appropriate for age?

Finally, if the child appears to be growing abnormally without evidence of organ system failure or dysfunction, the pediatric endocrinologist may perform a series of blood tests to evaluate hormone function of the pituitary, particularly that of growth hormone.

Common Causes of Short Stature

Most children with short stature will fit into one of three categories:

Familial short stature: indicating that short stature runs in the family.

Constitutional delay: indicating that height potential is normal and appropriate for the family, but the rate of maturation is slow. Therefore the child will reach the final, normal height at an older than average age.

Psychosocial dwarfism: indicating that psychological and social stresses in the child's life have affected the child's ability to grow normally.

Familial short stature
Familial short stature is usually the easiest to recognize. First of all, the parents of the child will be documented to have short adult stature. The child himself will be short, but growing at a normal rate as established by a series of measures in the physician's office taken every three to six months during a one-year period of time. Usually the only study that is required in this case is a bone age evaluation. This will show bone development that is appropriate for the child's actual age. The expectation in familial short stature is that children will ultimately grow to a height similar to that of their parents.

Constitutional delay and psychosocial dwarfism
Constitutional delay and psychosocial dwarfism are more difficult to diagnose, since in each case there is no one test that clearly identifies the diagnosis. In both conditions, examinations confirm delayed bone age, with all other laboratory studies being normal. Generally, in constitutional delay, there is a family history of late maturation, while in psychosocial dwarfism there is a history of major stress in the family (e.g., separation from parents, divorce, disasters, homelessness, and/or poverty).

Frequently, patients diagnosed with constitutional delay or psychosocial dwarfism undergo extensive laboratory studies to ensure that no medical cause for growth failure has been overlooked. Patients with psychosocial dwarfism can be expected to increase their growth with a change in environment, while patients with constitutional delay are expected to reach appropriate final height without intervention.


Medical Causes of Short Stature

Organ system failure or dysfunction of the heart, lung, kidney, or GI tract are by far the most common medical cause of short stature. These are usually identified on the initial medical history, physical examination and screen of laboratory data. Two well known medical causes of short stature, not readily identified in this manner, are growth hormone deficiency and Turner's syndrome.

Growth hormone deficiency: Of the medical causes for short stature, one of the most difficult to diagnose is growth hormone deficiency. This is a disorder caused by inadequate production of the growth hormone, which is made in the pituitary, a small gland lying at the base of the brain.

Children with growth hormone deficiency generally have either poor growth or low blood sugar, neither of which produces dramatic symptoms. In fact, children with growth hormone deficiency appear much like children with constitutional delay or psychosocial dwarfism. To make the diagnosis, laboratory tests of other systems must be normal, and the patient must fail to respond to medicines known to stimulate growth hormone production and release. An MRI of the brain is usually done to ensure that a pituitary gland tumor is not causing the deficiency.

Turner's syndrome: In girls with short stature, a genetic test called a karyotype (a special blood test which looks at the number, shape, and size of a person's chromosomes) should be done to determine whether their short stature is the result of Turner's syndrome. In Turner's syndrome, girls are missing one of their X chromosomes.

There are a number of problems that can occur in Turner's syndrome. In addition to having short stature, girls with Turner's syndrome may have a variety of malformations involving the head and neck, heart, and kidneys. Since their ovaries usually do not function, these girls will fail to develop during adolescence and will be infertile. If the disorder is recognized at a young enough age, treatment can be provided to achieve normal female sexual development at puberty and to ensure increased height.


Treatments for Short Stature

Appropriate treatment for short stature depends on the specific diagnosis as well as the rate of growth. If the problem is traced to a specific organ system, treatment will focus primarily on correcting that system. For example, if a child is found to have hypothyroidism (low thyroid hormone), then thyroid hormone replacement will be the primary treatment. Further treatment, if any, will depend on the response to thyroid hormone therapy.

In the absence of a specific diagnosis, as well as in situations of poor growth due to genetic disorders, the decision to treat or not is frequently based on the child's rate of growth-i.e., how much height has changed between any two visits. Therapy under these circumstances may include giving androgens (the male hormone), or growth hormone.

Growth hormone therapy
Growth hormone therapy involves the injection of growth hormone. The growth hormone used as a medication is currently derived from recombinant DNA technology - in other words, it is synthesized from genetic material in the laboratory rather than extracted from human beings. It has been shown that growth hormone is most effective when it is given to the child on a daily schedule rather than a more intermittent schedule. Thus, families must learn the technique of giving their children daily injections of the hormone.

Side effects of growth hormone therapy: Side effects are most often related to the dose of the medication used. Too much growth hormone can result in an increase in blood glucose level in a diabetic-like pattern. It can also cause an overgrowth of soft tissues of the body, including the heart muscle, which can result in heart disease.

In patients with tumors of the pituitary that produce excessive growth hormone, an increase in the incidence of other tumors has caused some concern about cancer with growth hormone therapy. Furthermore, growth hormone treatment has been associated with leukemia in a small group of children, most of who had previously been treated for leukemia and were thought to be in remission. While no study has been able to demonstrate a direct link between growth hormone therapy and the development of cancer, these associations with tumors suggests one should not use this treatment indiscriminately, and only with caution.

Androgen therapy
Androgens, the male hormones, are commonly given to pubertal male children with growth failure both to increase their growth and to make them more like their peers in terms of physical maturation. Certain androgens with limited ability to produce male physical features are also used at low doses in girls to promote height growth.

Side effects of androgen therapy: Androgens cause the bones to mature rapidly and ultimately stop growing. They must therefore be administered with care and frequent monitoring to ensure that the goal of increased height is attained. Furthermore, androgens are known to have adverse effects on the liver. A range of abnormalities has been described. These include a mild cholestasis (blockage of bile excretion by the liver resulting in jaundice) with minimal injury to the liver cells themselves that clears with withdrawal of the medication to a condition called peliosis hepatis in which there are fluid filled areas throughout the liver that can rupture causing life threatening hemorrhage. The cholestatic injury is most often associated with prolonged, high dose use and can be avoided by appropriate medical supervision. On the other hand, peliosis hepatis is a rare entity that may be associated with hepatic cancer as well. Given the seriousness of these side effects, which on occasion result in death, it is felt by some that androgens pose an unacceptable risk for a problem such as short stature, which in many cases is a cosmetic problem rather than a disorder resulting in loss of function. In any case, caution should be exercised in choosing androgen therapy. All children receiving it should be monitored frequently for both physical changes and changes in bone age.


Conclusions

Short stature can be hard to live with for many reasons. No matter what treatment is selected, the goal of therapy is to help a child reach a final height appropriate for his or her family and within the acceptable range for adults. How successful these treatments are in achieving this goal is still unknown. They have been shown to increase an individual's growth rate, at least initially. Final height, however, is the result of both growth rate and duration of that growth rate. Thus, the length of time that the child is treated also contributes to his/her final height.

Most studies that demonstrate benefits have evaluated only short-term treatment. With growth hormone therapy, the effect of treatment decreases with time of treatment. Studies must follow children until final height is measured to ensure that the net effect is a taller individual.

At the moment, it is not yet possible to answer this question of final height with absolute clarity, because recombinant growth hormone therapy has been available only since 1985. The accumulating evidence suggests that final height is indeed greater in at least some groups of children with short stature who are treated with growth hormone therapy.

Given the limitations of our knowledge regarding the outcome of therapy and the risks associated with treatment of short stature combined with the fact that most children with short stature do not have a medical problem, it is clear we must exercise caution in our use of medications. Fortunately, we have reached a time in which those with extreme short stature have therapeutic options with a reasonable expectation of improved height.