Pediatric Growth Hormone Deficiency
Hormones are chemicals produced by special cells in glands and other organs of the body; most hormones are produced by cells in the endocrine glands. These hormones, which are produced in very small amounts, are released into the bloodstream and travel to the “target organ” or tissue where they exert their effect.
Several hormones are involved in regulating growth. Some act directly on target organs, while others act by triggering the production of other hormones, which activate specific organ functions necessary for growth. This finely tuned system can malfunction in several ways, causing abnormal growth.
The pituitary gland is often called the master gland because it produces several hormones that control the functions of other glands. It is located in the middle of the skull below the part of the brain called the hypothalamus. The pituitary gland has two distinct parts: An anterior (front) lobe and a posterior (rear) lobe. The pituitary gland secretes its hormones in response to chemical messages from the hypothalamus, the part of the brain to which it is connected.
Growth hormone is an anterior pituitary hormone whose main effect is to promote the growth of body tissues. Other anterior pituitary hormones affect growth indirectly by working through other glands.
These other hormones include:
Thyroid Stimulating Hormone (TSH) – causes the thyroid gland to produce thyroid hormone, which regulates body metabolism and is essential for normal growth.
Adrenocorticotropic Hormone (ACTH) – causes the adrenal glands to produce cortisol (stress hormone) and other hormones that enable the body to respond to stress. Too much cortisol will cause growth failure in a child.
Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH) – cause the sex glands (ovaries or testes) to produce sex hormones, which are necessary for adolescent sexual development and the growth spurt that accompanies puberty.
The major hormone produced by the posterior pituitary gland -is called vasopressin, or anti-diuretic hormone (ADH). It controls water output through the kidneys.
CAUSES OF GROWTH HORMONE DEFICIENCY
Growth hormone deficiency may occur by itself or in combination with one or more other pituitary hormone deficiencies. It may be total (no growth hormone is produced) or partial (some growth hormone is produced, but not enough to support normal growth).
Hypopituitarism may be congenital, resulting from abnormal formation of the pituitary or hypothalamus before the child is born, or acquired, stemming from damage to the pituitary or hypothalamus during or after birth. Congenital hypopituitarism is present at birth, although it may not be apparent for many months. Acquired hypopituitarism may become evident any time during infancy or childhood, and may occur after a severe head injury or a serious illness such as meningitis or encephalitis. Many cases of acquired hypopituitarism result from a tumor called craniopharyngioma. This tumor may press on the hypothalamus or pituitary, causing one or more hormone deficiencies. Deficiency consists of surgical removal of the tumor, which usually results in permanent hypopituitarism.
Sometimes no cause for hypopituitarism can be identified, or- if a cause is suspected, it may be difficult to prove. Researchers are trying to learn more about the causes of growth hormone deficiency and hypopituitarism.
DIAGNOSIS OF GROWTH HORMONE DEFICIENCY
The child with growth hormone deficiency is often small, with an immature face and chubby body build. The rate of growth of all body parts is slow so that the child’s proportions remain normal. Intelligence is normal. If the child’s height has been plotted on a growth chart, it will appear to be leveling off and falling away from the child’s established growth curve. If growth failure has been present for a long time, the child may be much shorter than other children the same age. This is why height and weight measurements plotted on a growth chart are so important – the earlier a treatable growth problem is detected, the better the child’s chance of maintaining a normal height throughout childhood and realizing his or her full growth potential.
Any child who is only as tall as children two or more years younger or who falls away from a previously normal growth curve should be evaluated by a doctor. Pediatric endocrinologists are doctors who specialize in treating children with growth and hormone problems. Depending on the situation, the doctor may measure the child over a six to twelve month period in order to accurately determine the child’s growth rate.
The evaluation starts with gathering information on the heights of relatives and the presence of any health problems in the family. A history of early or late puberty (sexual development and growth spurt) in family members should be mentioned. The doctor will want to know about the mother’s pregnancy, labor, and delivery. All measurements of the child’s height and weight from birth on should be gathered so the doctor can plot them on a growth chart. The doctor will ask questions about the child’s general health and nutritional state, past illnesses, injuries, and stresses.
A thorough physical examination will be performed, and an x-ray of the hand and wrist may be obtained to see how bone development compares to height and chronologic age. A small amount of blood may be drawn to look for evidence of thyroid hormone deficiency and kidney, bone, and gastrointestinal (stomach and bowel) diseases. The amount of insulin-like growth hormone-I (IGF-I) in the blood may be measured. IGF-I is the “middle-man” in the growth process. Growth hormone stimulates the liver and other body tissues to produce IGF-I, which then acts as the link between growth hormone in the blood and the machinery inside cells that causes growth. The amount of IGF-I in the blood provides an indirect measure of the amount of growth hormone present.
This simple evaluation often provides the doctor with enough information to identify the cause of the growing problem or to decide that no growth problem exists. If the doctor suspects that a pituitary problem may exist, further testing is necessary. A series of blood tests can measure concentrations of hormones in the blood and the ability of the pituitary gland to respond to various stimuli. These tests may be done in the clinic or during a brief hospitalization.
Growth hormone deficiency is moderately difficult to diagnose because the pituitary gland produces growth hormone in bursts. This means that the level of growth hormone in a single random blood sample is likely to be very low. One way of testing for growth hormone deficiency is to give the child a substance that causes the release of a growth hormone burst in normal children and measure the amount of growth hormone present in several blood samples obtained over a period of time. Since any child may not respond to any given test on a given day, more than one stimulus may be needed to evaluate the child’s ability to produce growth hormone. Several growth hormone stimulators have been identified. These include vigorous exercise and several chemicals and drugs (insulin, arginine, glucagon, L-dopa, clonidine).
Another way of testing growth hormone secretion involves hospitalizing the child and measuring the amount of growth hormone present in blood samples obtained overnight during sleep or even during an entire 24 hour period. Since about two-thirds of total growth hormone production occur during deep sleep, this test provides a better reflection of how much growth hormone the child’s pituitary gland normally produces.
If several tests show that no growth hormone is present or that the amount of growth hormone being produced is not enough to support normal growth, the diagnosis of growth hormone deficiency is established. A great deal of research is being done to develop more accurate and reliable ways of diagnosing growth hormone deficiency. Even the definition of growth hormone deficiency is being revised as researchers learn more about conditions that may cause partial growth hormone deficiency.
TREATMENT OF GROWTH HORMONE DEFICIENCY
Growth hormone deficiency is treated with injections of growth hormone. Most children receive injections daily; others receive it six times a week; and, a few receive it three times a week.* There is usually a prompt increase in growth rate after treatment starts, which may be noticeable to the child and parent in 3 to 4 months. This faster than-normal growth rate slowly declines over time, but it continues to be greater than would occur without treatment. Many parents notice an increase in the child’s appetite and loss of body fat after treatment begins.
The treatment of growth hormone deficiency usually is carried out over several years, until the child achieves an acceptable adult height or maximum growth potential is reached. As with other conditions, children and parents may become impatient to see faster or more impressive results from therapy. They may become discouraged, even when treatment iis going according to plan. It is important to remember that growth is a slow process that is measured over months; children who expect to grow overnight when they start Deficiency will be disappointed. Your child’s doctor will discuss realistic short and long-term expectations of therapy with you.
If testing reveals other hormone deficiencies, medications are available to replace them; thyroid hormone, cortisol and sex hormones can be administered easily when found to be lacking. It is important that these hormones are taken as directed, because normal growth can occur only when all hormones are present in the proper amounts. Good nutrition and adequate rest are important for normal growth in all children.
SOURCES OF HUMAN GROWTH HORMONE
Until recently, the only source of human growth hormone was the pituitary glands of deceased people, obtained at autopsy. In April, 1985, pituitary-derived growth hormone was removed from distribution in the United States and many foreign countries following the deaths of several young adults from a very rare viral disease that may have been transmitted through the pituitary growth hormone they had received many years earlier. Fortunately, the first biosynthetic growth hormone, which is produced using recombinant DNA technology, was in the- final stages of testing and was approved as safe and effective for use in growth hormone deficient children by the Food and Drug Administration in October, 1985. Because this type of growth hormone does not come from human beings, there is little possibility that human diseases can be transmitted through it.
Biosynthetic growth hormone is supplied as a powder in sterile vials. Parents and children are taught how to mix the powder into a solution and administer the injections. Treatment is continued as long as potential for growth exists and the child is responding to therapy. With early diagnosis and a good response to treatment, children with growth hormone deficiency can expect to reach normal adult height.
PSYCHOLOGICAL ASPECTS OF SHORT STATURE
OIur society places great emphasis on height. Children who are short for their age sometimes have problems because playmates and teachers treat them as though they are younger rather than just smaller. Parents tend to do this too and decrease their expectations of the child. These children then may not act their age because it’s not expected of them. Teasing and name-calling may be hard to take. Some of these problems may be helped by a frank and open discussion with teachers and classmates.
It is very important to provide emotional support for the child with GH deficiency and to emphasize the child’s many good and valuable characteristics, so that the child’s stature does not limit his horizons. More about psychosocial adaptation to short stature can be learned from parents of short children and from your growth clinic doctor, nurse and psychologist.
HOPE FOR THE FUTURE
Biosynthetic growth hormone is available in unlimited quantity for the Deficiency of all growth hormone deficient children. It is possible that substitutes for growth hormone may become available as research continues. These may include growth hormone releasing factor (GHRF), the hypothalamic chemical that directs the pituitary to produce growth hormone, and IGF-I that links growth hormone with linear growth.
Much research is being done to better understand the causes of growth hormone deficiency, and to develop more accurate ways of diagnosing it. Many children with growth hormone deficiency can look forward to reaching normal height as a result of the research that has been done over the years and is continuing today.