Growth hormone tests measure the levels of specific hormones that regulate human growth. These hormone levels are measured in blood serum samples obtained by venipuncture. To study growth hormone function under specific conditions, certain medications may be administered before blood is taken and hormone levels are measured. Human growth hormone (hGH) (somatotropin) is produced by somatotropes in the anterior pituitary gland. Its role in normal body growth and development is to stimulate protein production in muscle cells and trigger energy release from the breakdown of fats. Diagnostic tests for growth hormones include the somatotropin hormone test, somatomedin C test, growth hormone stimulation test (also known as the arginine test or insulin tolerance test), and growth hormone suppression test (glucose loading test).
Purpose
Growth hormone tests are ordered by physicians to determine whether levels of hGH and other related hormones in the blood are normal, increased, or decreased, and to help diagnose conditions that may result from abnormal hormone levels or pituitary gland dysfunction. Some of the common reasons for testing are:
to identify growth abnormalities that may cause delayed puberty and small stature in adolescents
to aid in the diagnosis of hyperpituitarism, which can cause gigantism or acromegaly
to assist in the diagnosis of pituitary tumors or tumors related to the hypothalamus, an area of the brain
to monitor the effects of hGH therapy administered for certain conditions
Description
Human growth hormones play an important role in normal human growth and development. The major human growth hormone is a protein made up of 191 amino acids, the building blocks of proteins. The production of this protein is controlled by two other hormones secreted by the hypothalamus: growth hormone releasing hormone (GHRH), which controls secretion of hGH; and growth hormone-inhibiting hormone (GHIH), which inhibits secretion of hGH. All healthy individuals have measurable levels of hGH throughout life, but there are two notable growth spurts, one at birth and the other at puberty, and hGH plays a vital role at each time. The most obvious effect of hGH is on linear skeletal growth (height), but metabolic effects of hGH (the results of hGH activity in the body) on muscle, the liver, and fat cells are a critical part of its function. When any question arises about growth or development, pediatricians may investigate the levels of the major growth hormone hGH, its receptors and stimulants, the glands that produce the hormones, and the complex hormone interactions that control normal development.
Somatotropin (hGH) is secreted by somatotropes in the anterior pituitary gland. It is typically secreted during sleep, with peak release occurring around 10 p.m., midnight, and 2 a.m. Most of the effects of hGH are mediated by other hormones, including the somatomedins, IGH-I (somatomedin C) and IGH-II, which are insulin-like growth hormones that also influence linear growth, and the two hypothalamic hormones (GHRH and GHIH) that regulate hGH by responding to changes in the individual's blood sugar (glucose) and protein levels. When blood glucose levels fall, GHRH triggers the secretion of stored hGH. As blood glucose levels rise, hGH secretion is turned off by GHIH activity. Increases in blood protein levels trigger a similar response. This feedback loop, along with the effects of eating and exercise, is responsible for the fluctuating levels of hGH throughout the day. In addition, blood glucose and amino acid availability for growth is also regulated by the hormones adrenaline, glucagon, and insulin. All of these growth factors may be evaluated in order to understand hormone deficiencies or gland dysfunction when growth deficiencies are suspected.
A number of hormonal conditions can lead to excessive or diminished growth. Because of its critical role in producing hGH and other hormones, a dysfunctional pituitary gland will often lead to altered growth. Dwarfism (very small stature) can be due to underproduction of hGH, lack of IGH-I, or a flaw in target tissue response to either of these growth hormones. Overproduction of hGH or IGH-I, or an exaggerated response to these hormones, can lead to gigantism or acromegaly, both of which are characterized by a very large stature.
Gigantism is the result of hGH overproduction in early childhood leading to a skeletal height up to 8 feet (2.5 m) or more. Acromegaly results when hGH is over-produced after the onset of puberty. In this condition, the epiphyseal plates of the long bones of the body do not close, and they remain responsive to additional stimulated growth by hGH. This disorder is characterized by an enlarged skull, hands and feet, nose, neck, and tongue.
Somatrotropin
Somatrotropin (hGH) is measured in the clinical laboratory to identify hGH deficiency in adolescents with short stature, delayed sexual maturity, and other growth or development abnormalities. The somatotropin test also aids in documenting the excess hGH production responsible for gigantism or acromegaly, and confirms underactivity or overproduction of the pituitary gland (hypopituitarism or hyperpituitarism, respectively). However, due to variable secretion of hGH, as well as hGH production in response to stress, exercise, or other factors, random assays are not an adequate determination of hGH deficiency. To obtain more accurate readings, a blood sample can be drawn one to one-and-a-half hours after sleep (hGH levels increase during sleep), or strenuous exercise can be performed for 30 minutes before blood is drawn. (A person's hGH levels increase after exercise.) The hGH levels at the end of an exercise period are expected to be maximal.
Somatomedin C
The somatomedin C test is usually ordered to help detect pituitary abnormalities, hGH deficiency, and acromegaly. Also called insulin-like growth factor (IGF-1), somatomedin C is considered a more accurate reflection of the blood concentration of hGH because such variables as time of day, activity levels, or diet do not influence test results. Somatomedin C is part of a group of peptides, called somatomedins, through which hGH exerts its effects. Because it circulates in the bloodstream bound to long-lasting proteins, it is more stable than hGH. Levels of somatomedin C do depend on hGH levels, however, and typically somatomedin C levels will be low when hGH levels are deficient. Abnormally low levels of somatomedin C will require further investigation, so doctors may perform the hGH stimulation test to diagnose hGH deficiency. Nonpituitary causes of reduced somatomedin C include malnutrition, severe chronic illness, severe liver disease, hypothyroidism, and Laron's dwarfism.
Growth hormone stimulation test
The hGH stimulation test, also called hGH provocation test, insulin tolerance, or arginine test, is performed to test the body's ability to produce human growth hormone and to confirm suspected hGH deficiency. A normal patient can have low hGH levels, but if hGH is still low after stimulation, a more definitive diagnosis can be made. The test involves creating a condition of insulin-induced hypoglycemia (via intravenous injection of insulin) to stimulate production of hGH and corticotropin secretion as well. If such stimulation is unsuccessful, a malfunction of the anterior pituitary gland is likely. It may be necessary to obtain blood samples following an energetic exercise session lasting 20 minutes.
A substance called hGH-releasing factor has also been used for hGH stimulation. This approach is believed to be more accurate and specific for hGH deficiency caused by the pituitary. Growth hormone deficiency is also suspected when x-ray determination of bone age indicates retarded growth in comparison to chronological age. As of 2004, the best method to identify hGH-deficient patients was a positive stimulation test followed by a positive response to a therapeutic trial of hGH.
Growth hormone suppression test
This procedure, also called the glucose loading test, is performed to evaluate excessive baseline levels of hGH and to confirm diagnosis of gigantism in children (and acromegaly in adults). The procedure requires drawing two different blood samples, one before the child ingests 100 grams of glucose by mouth and a second sample two hours after glucose ingestion. Normally, a glucose load such as this will suppress hGH secretion. In a child with excessive hGH levels, failure of suppression indicates anterior pituitary dysfunction and confirms a diagnosis of gigantism (or acromegaly).
Precautions
Taking certain drugs such as amphetamines, dopamine, corticosteroids, and phenothiazines may increase or decrease growth hormone secretion. A pediatrician may discontinue certain medications prior to the performance of growth hormone tests. Other factors that may influence hGH secretion include stress, exercise, diet, and abnormal glucose levels. The pediatrician may make recommendations for the child's activity prior to testing. Growth hormone tests should not be done within a week after any radioactive scan such as an x ray, MRI, or CT scan.
Preparation
The hGH or somatotropin test requires that a fasting blood sample be drawn from a vein, usually in the arm. The child should have nothing to eat or drink from midnight the night before the test until after the blood sample is drawn. Since stress and exercise increase hGH levels, the child must be at complete rest for 30 minutes before the blood sample is drawn. If the physician has requested two samples, they should be drawn on consecutive days at approximately the same time, preferably between 6 a.m. and 8 a.m.
The somatomedin C test also requires a fasting blood sample. The patient should have nothing to eat or drink from midnight the night before until after the blood sample is drawn.
Growth hormone suppression testing requires two fasting blood samples, one before the test and another two hours after the child is given a glucose solution by mouth. The child should have nothing to eat or drink from midnight the night before until after the blood samples are drawn, and physical activity should be limited for at least 10 to 12 hours before the test.
Aftercare
Usually there will be no effects from hormone testing and normal activities can be resumed. A bandage may be applied to keep the site of venipuncture or intravenous administration of medications clean and to stop any bleeding that may occur. Unusual bleeding or bruising of the site should be reported to the pediatrician. The child should be observed closely after the more extensive growth hormone stimulation test and growth hormone suppression test. A pediatrician may limit activities for the immediate pre-test period.
Risks
Growth hormone tests do not have significant risks. Minor discomfort may be experienced during and after the growth hormone stimulation test because of the intravenous line for delivery of insulin. A low blood sugar (hypoglycemia) will result from the insulin injected into the child's system, which may make some children light-headed or lethargic. Some children may experience sleepiness, sweating, and/or nervousness, all of which can be corrected after the test by ingestion of juice or a glucose infusion, as recommended by the pediatrician. Severe cases of hypoglycemia may cause ketosis (excessive amounts of fatty acid byproducts in the body), acidosis (a disturbance of the body's acid-base balance), or shock. Medical personnel provide close observation during the test to help prevent or react to these unlikely reactions. Growth hormone suppression tests can cause some children to feel nauseous after the administration of glucose. Ice chips can help alleviate this symptom.
Normal results
Results are reported in nanograms per milliliter (ng/ml). Normal results may vary from laboratory to laboratory depending upon the method used for measurement, but results are usually within the following ranges.
child: 0–8 years; girls 7–110 ng/ml; boys 4–87 ng/ml
9–10 years: girls 39–186 ng/ml; boys 26–98 ng/ml
11–13 years: girls 66–215 ng/ml; boys 44–207 ng/ml
14–16 years: girls 96–256 ng/ml; boys 48–255 ng/ml
Growth hormone stimulation: greater than 10 ng/ml
KEY TERMS
Acromegaly—A rare disease resulting from excessive growth hormone caused by a benign tumor. If such a tumor develops within the first ten years of life, the result is gigantism (in which growth is accelerated) and not acromegaly. Symptoms include coarsening of the facial features, enlargement of the hands, feet, ears, and nose, jutting of the jaw, and a long face.
Dwarfism, pituitary—Short stature. When caused by hGH deficiency, as opposed to late growth spurt or genetics, abnormally slow growth and short stature with normal proportions may be seen.
Gigantism—Excessive growth, especially in height, resulting from overproduction of growth hormone during childhood or adolescence by a pituitary tumor. Untreated, the tumor eventually destroys the pituitary gland, resulting in death during early adulthood. If the tumor develops after growth has stopped, the result is acromegaly, not gigantism.
Pituitary gland—The most important of the endocrine glands (glands that release hormones directly into the bloodstream), the pituitary is located at the base of the brain. Sometimes referred to as the "master gland," it regulates and controls the activities of other endocrine glands and many body processes including growth and reproductive function. Also called the hypophysis.
Regarding growth hormone suppression, normally, glucose suppresses hGH to levels ranging from undetectable to 3 ng/ml within 30 minutes to two hours. In children, rebound stimulation may occur after two to five hours.
Parental concerns
Parents may be concerned about the child's response to venipuncture or reaction to intravenous administration of medications prior to testing. The parents can play a calming role by reassuring the child and explaining the procedure beforehand. Medical personnel and the pediatrician may provide instruction before, during, and after the tests, as well as close observation to minimize any risks. Parents can be prepared for post-testing sleepiness or lightheadedness by having juice handy and ice chips to help relieve any feelings of nausea.
BOOKS
Czernichow, P., et al. Growth and Metabolic Disorders in Chronic Pediatric Diseases: Cambridge December 2001 Hormone Research. Basel, Switzerland: S. Karger AG, 2002.
DeGroot, Leslie, et al. Hormone Action, Pituitary Growth, and Maturation, Immunology, Nutrition, Diabetes Mellitus. Kent, UK: Elsevier—Health Science Division, 2001.
WEB SITES
"Growth Hormone." Lab Tests Online: American Association for Clinical Chemistry, 2001–2004. Available online at <www.labtestsonline.org/understanding/analytes/growth_hormone/test.html> (accessed October 21, 2004).
