Growth hormone deficiency

Definition

Growth hormone (hGH), or somatotropin, is a hormone responsible for normal body growth and development by stimulating protein production in muscle cells and energy release from the breakdown of fats. Tests for growth hormone include Somatotropin hormone test, Somatomedin C, Growth hormone suppression test (glucose loading test), and Growth hormone stimulation test (Arginine test or Insulin tolerance test).

Purpose

Growth hormone tests are ordered for the following reasons:

• To identify growth deficiencies, including delayed puberty and small stature in adolescents which can result from pituitary or thyroid malfunction
• To aid in the diagnosis of hyperpituitarism that is evident in gigantism or acromegaly
• To screen for inadequate or reduced pituitary gland function
• To assist in the diagnosis of pituitary tumors or tumors related to the hypothalamus, an area of the brain
• To evaluate hGH therapy.

Precautions

Taking certain drugs such as amphetamines, dopamine, corticosteroids, and phenothiazines may increase and decrease growth hormone secretion, respectively. Other factors influencing hGH secretion include stress, exercise, diet, and abnormal glucose levels. These tests should not be done within a week of any radioactive scan.

Description

Several hormones play important roles in human growth. The major human growth hormone (hGH), or somatotropin, is a protein made up of 191 amino acids which is secreted by the anterior pituitary gland and coordinates normal growth and development. Human growth is characterized by two spurts, one at birth and the other at puberty. hGH plays an important role at both of these times. Normal individuals have measurable levels of hGH throughtout life. Yet levels of hGH fluctuate during the day and are affected by eating and exercise. Receptors which respond to hGH exist on cells and tissues throughout the body. The most obvious effect of hGH is on linear skeletal development. But the metabolic effects of hGH on muscle, the liver, and fat cells are critical to its function. Humans have two forms of hGH, and the functional difference between the two is unclear. They are both formed from the same gene, but one lacks the amino acids in positions 32-46.

hGH is produced in the anterior portion of the pituitary gland by somatotrophs under the control of hormonal signals in the hypothalamus. Two hypothalamic hormones regulate hGH; they are growth hormone-releasing hormone (GHRH) and growth hormone--inhibiting hormone (GHIH). When blood glucose levels fall, GHRH triggers the secretion of stored hGH. As blood glucose levels rise, GHRH release is turned off. Increases in blood protein levels trigger a similar response. As a result of this hypothalamic feedback loop, hGH levels fluctuate throughout the day. Normal plasma hGH levels 1 to 3 ng/ML with peaks as high as 60 ng/ML. In addition, plasma glucose and amino acid availability for growth is also regulated by the hormones adrenaline, glucagon, and insulin.

Most hGH is released at night. Peak spikes of hGH release occur around 10 p.m., midnight, and 2 a.m. The logic behind this night-time release is that most of hGH's effects are mediated by other hormones, including the somatomedins, IGH-I and IGH-II. As a result, the effects of hGH are spread out more evenly during the day.

A number of hormonal conditions can lead to excessive or diminished growth. Because of its critical role in producing hGH and other hormones, an aberrant pituitary gland will often yield 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 (2.5m) or more. Acromegaly results when hGH is overproduced after the onset of puberty. In this condition, the epiphyseal plates of the long bone 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 is used to identify hGH deficiency in adolescents with short stature, delayed sexual maturity, and other growth deficiencies. It also aids in documenting excess hGH production that is responsible for gigantism or acromegaly, and confirms underactivity or overproduction of the pituitary gland (hypopituitarism or hyperpituitarism). However, due to the episodic 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 negate these variables and obtain more accurate readings, a blood sample can be drawn 1 to 1.5 hours after sleep (hGH levels increase during sleep), or strenuous exercise can be performed for 30 minutes before blood is drawn (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 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 does not influence the 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. As a result, somatomedin C levels are low when hGH levels are deficient. Abnormally low test results of somatomedin C require an abnormally reduced or absent hGH during an hGH stimulation test in order 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 identify suspected hGH deficiency. A normal patient can have low hGH levels, but if hGH is still low after stimulation, a diagnosis can be more accurately made.

Insulin-induced hypoglycemia (via intravenous injection of insulin) stimulates hGH and corticotropin secretion as well. If such stimulation is unsuccessful, then there is a malfunction of the anterior pituitary gland. Blood samples may be obtained following an energetic exercise session lasting 20 minutes.

A substance called hGH-releasing factor has recently been used for hGH stimulation. This approach promises 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 chronologic age. At present, the best method to identify hGH-deficient patients is a positive stimulation test followed by a positive response to a therapeutic trial of hGH.

Growth hormone suppression test

Also called the glucose loading test, this procedure is used to evaluate excessive baseline levels of human growth hormone, and to confirm diagnosis of gigantism in children and acromegaly in adults. The procedure requires two different blood samples, one drawn before the administration of 100 g of glucose (by mouth), and a second sample two hours after glucose ingestion.

Normally, a glucose load suppresses hGH secretion. In a patient with excessive hGH levels, failure of suppression indicates anterior pituitary dysfunction and confirms a diagnosis of acromegaly and gigantism.

Preparation

Somatotropin: This test requires a blood sample. The patient should be fasting (nothing to eat or drink from midnight the night before the test). Stress and/or exercise increases hGH levels, so the patient should 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 on both days, preferably between 6 am and 8 am.

Somatomedin C: This test requires a blood sample. The patient should have nothing to eat or drink from midnight the night before the test.

Growth hormone stimulation: This test requires intravenous administration of medications and the withdrawal of frequent blood samples, which are obtained at 0, 60, and 90 minutes after injection of arginine and/or insulin. The patient should have nothing to eat or drink after midnight the night before the test.

Growth hormone suppression: This test requires two blood samples, one before the test and another two hours after administration of 100 g of glucose solution by mouth. The patient should have nothing to eat or drink after midnight, and physical activity should be limited for 10-12 hours before the test.

Risks

Growth hormone stimulation: Only minor discomfort is associated with this test, and results from the insertion of the IV line and the low blood sugar (hypoglycemia) induced by the insulin injection. Some patients may experience sleepiness, sweating and/or nervousness, all of which can be corrected after the test by ingestion of cookies, juice, or a glucose infusion. 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. With the close observation required for the test, these are unlikely.

Growth hormone suppression: Some patients experience nausea after the administration of this amount of glucose. Ice chips can alleviate this symptom.

Normal results

Normal results may vary from laboratory to laboratory but are usually within the following ranges:

Somatotropin:

• Men: 5 ng/ml
• Women: less than 10 ng/ml
• Children: 0-10 ng/ml
• Newborn: 10-40 ng/ml.

Somatomedin C:

• Adult: 42-110 ng/ml
• 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.

Growth hormone suppression: Normally, glucose suppresses hGH to levels of undetectable to 3 ng/ml in 30 minutes to two hours. In children, rebound stimulation may occur after 2-5 hours.

Abnormal results

Somatotropin hormone: Excess hGH is responsible for the syndromes of gigantism and acromegaly. Excess secretion is stimulated by anorexia nervosa, stress, hypoglycemia, and exercise. Decreased levels are seen in hGH deficiency, dwarfism, hyperglycemia, failure to thrive, and delayed sexual maturity.

Somatomedin C: Increased levels contribute to the syndromes of gigantism and acromegaly. Stress, major surgery, hypoglycemia, starvation, and exercise stimulate hGH secretion, which in turn stimulates somatomedin C.

Growth hormone stimulation: Decreased levels are seen in pituitary deficiency and hGH deficiency. Diseases of the pituitary can result in failure of the pituitary to secrete hGH and/or all the pituitary hormones. As a result, the hGH stimulation test will fail to stimulate hGH secretion.

Growth hormone suppression: The acromegaly syndrome elevates base hGH levels to 75 ng/ml, which in turn are not suppressed to less than 5 ng/ml during the test. Excess hGH secretion may cause unchanged or rising hGH levels in response to glucose loading, confirming a diagnosis of acromegaly or gigantism. In such cases, verification of results is required by repeating the test after a one-day rest.

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 inadequate amounts of growth hormone (as opposed to late growth spurt or genetics), hGH deficiency results in abnormally slow growth and short stature with normal proportions.

Gigantism

Excessive growth, especially in height, resulting from overproduction during childhood or adolescence of growth hormone 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 pituitary is the most important of the endocrine glands (glands that release hormones directly into the bloodstream). Sometimes referred to as the "master gland," the pituitary regulates and controls the activities of other endocrine glands and many body processes.

Further Reading

For Your Information

Books

• Cahill, Mathew. Handbook of Diagnostic Tests. Springhouse Corporation, 1995.
• Jacobs, David S. Laboratory Test Handbook, Fourth Edition. Lexi-Comp Inc., 1996.
• Pagana, Kathleen Deska. Mosby's Manual of Diagnostic and Laboratory Tests. Mosby, Inc., 1998.

Gale Encyclopedia of Medicine. Gale Research, 1999.