Bioassay Of Growth Hormone Biology Essay

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Also known as: GH; Human Growth Hormone; HGH; Somatotropin

Formal name: Growth Hormone

Why Get Tested?

To identify diseases and conditions caused by either a deficiency or overproduction of growth hormone (GH), to evaluate pituitary function, and to monitor the effectiveness of GH treatment

When to Get Tested?

As part of an evaluation of pituitary function; symptoms suggestive of giantism (in children) or acromegaly (in adults) may be a result of excess GH production. Slow growth in stature, delayed maturational development (in children), decreased bone density and/or muscle strength, and increased lipids (in adults) all could be related to insufficient GH production.

Sample Required?

Usually several blood samples, drawn at timed intervals from veins in your arm; sometimes a single sample of blood, drawn following a fast or after a period of strenuous exercise

The Test Sample

What is being tested?

Growth hormone (GH) is essential for a child's normal growth and development and promotes proper linear bone growth from birth through puberty. Children with insufficient GH production grow more slowly and are smaller in size for their age, one of the first symptoms of growth hormone deficiency (GHD). It should be noted that short stature in itself can also be related to familial traits or other genetic disorders. Excess GH is most often due to a GH-secreting pituitary tumor (usually benign). Too much GH can cause children's long bones to continue to grow beyond puberty, resulting in gigantism with heights of 7 or more feet tall. Those with excess GH may also have thickening of facial features, general weakness, delayed puberty, and headaches.

Although GH is not as active in adults, it does play a role in regulating bone density, muscle mass, and lipid metabolism. Deficiencies can lead to decreased bone densities, less muscle mass, and altered lipid levels. Excess GH in adults can lead to acromegaly, marked not by bone lengthening but by bone thickening. Although symptoms such as skin thickening, sweating, fatigue, headaches, and joint pain can be subtle at first, increased GH levels can lead to enlarged hands and feet, enlarged facial bones, carpal tunnel syndrome, and abnormally enlarged internal organs. If untreated, acromegaly (and gigantism in children) can lead to complications such as type 2 diabetes, increased cardiovascular disease risk, high blood pressure, arthritis, and in general, a decreased life span.

GH stimulation and suppression tests are most often used to diagnose GH abnormalities. Since growth hormone is released by the pituitary gland in bursts throughout the day, random measurements of GH levels are not usually clinically useful.

How is the sample collected for testing?

Usually GH suppression or stimulation testing is done. After you have fasted for 10 to 12 hours, a blood sample is drawn from a vein in your arm. Then, under medical supervision, you are given either a standard glucose solution to drink (for a suppression test) or you are given an intravenous (IV) solution of insulin or arginine (for a stimulation test) through a vein in your arm. Blood samples are then drawn from your veins (or from the IV) at timed intervals. GH tests are run on each sample collected to monitor the change in levels of growth hormone over time.

Sometimes, a single sample of blood is drawn following a fast or after a period of strenuous exercise.

NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.

Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.

Is any test preparation needed to ensure the quality of the sample?

In healthy adults, GH levels remain stable, but rise sharply 3-4 hours after a meal and within 60 minutes after sleep. Thus, one should be fasting before testing.

How is it used?

GH testing is not recommended for general screening. It is primarily ordered on those with symptoms of growth hormone abnormalities, as a follow-up to other abnormal hormone test results, or to help evaluate pituitary function.

Periodic GH measurements may also be performed on children who have had radiation treatment of the central nervous system or whole body irradiation prior to stem cell transplants. This is common in acute lymphoblastic leukemia (ALL), where irradiation of the brain can affect the hypothalamus and pituitary gland, thus affecting growth.

Growth hormone tests help identify excess and diminished GH production and give your doctor information about the severity of your condition. They are part of the diagnostic work-up required to find a cause for abnormal hormone production. Testing most often involves either a GH stimulation test or a GH suppression test to track GH levels over time.

GH stimulation tests help to diagnose hypopituitarism. For a stimulation test, a sample of blood is drawn after you have fasted for 10-12 hours. Then, under close medical supervision, you are given an intravenous solution of insulin or arginine. Blood samples are then drawn at timed intervals, and GH levels are tested in each to see if your pituitary gland was stimulated by the insulin (or arginine) to produce expected levels of GH.

GH suppression tests help to diagnose hyperpituitarism, which, in addition to other blood tests and imaging scans, can help identify and locate pituitary tumors. For a suppression test, a sample of blood is drawn after you have fasted for 10-12 hours. Then you are given a standard glucose solution to drink. Blood samples are drawn at timed intervals, and GH levels are tested in each to see if your pituitary gland is sufficiently suppressed by the dose of glucose.

Often other blood tests that reflect pituitary function, such as T4, TSH, cortisol, FSH, LH, and testosterone (in men), are also ordered. These tests are usually performed prior to GH testing to make sure that they are normal and/or controlled with medication before GH testing is done. Glucose levels are run on the samples collected during the GH suppression test, both to track glucose levels and to make sure that the patient's system is sufficiently challenged by the glucose solution.

IGF-1 (Insulin-like growth factor - 1) is often measured once during GH provocation testing and is often used by itself or with GH as a monitoring tool. Produced in the liver, IGF-1 mirrors GH excesses and deficiencies, but its level is stable throughout the day, making it a useful indicator of average GH levels.

GH and IGF-1 levels are often monitored for extended periods of time following treatment for GHD, gigantism, and acromegaly, and are monitored following surgery, drug treatment, and/or radiation for a pituitary tumor.

When is it ordered?

GH stimulation testing is ordered when your child has symptoms of GHD, such as when:

his growth rate slows down in early childhood and he is significantly shorter than others his age;

TSH tests show that your child is not hypothyroid (low thyroid levels can also cause slowed growth);

X-rays show delayed bone development;

your doctor suspects that your child's pituitary gland is under-active.

Once GHD is diagnosed, your doctor may use stimulation testing to confirm the diagnosis, along with IGF-1 to monitor the effectiveness of GH replacement (if indicated), and as a child reaches adulthood to see if continued supplementation is necessary.

GH levels are also monitored in children who have received radiation therapy.

Stimulation testing is ordered in adults when patients have symptoms of GHD and/or hypopituitarism, such as decreased bone density, fatigue, adverse lipid changes, and reduced exercise tolerance. Other hormone testing is done first to rule out other conditions that may cause similar symptoms.

GH suppression testing is done when children show signs of gigantism, when adults show signs of acromegaly, and/or when their doctor suspects hyperpituitarism. Suppression testing may be done when a pituitary tumor is suspected and may be used along with IGF-1 levels and other hormone levels to monitor the effectiveness of treatment for these conditions. Monitoring may continue at regular intervals for many years to watch for recurrence.

Since GH is released by the pituitary in bursts, random GH levels are not very useful. There is too much overlap between abnormal results and normal daily variation. GH levels will be higher first thing in the morning and will increase with exercise and stress.

What does the test result mean?

GH suppression test:

If your GH levels are not significantly suppressed during a GH suppression test (they stay higher than they should) and:

you have symptoms of gigantism or acromegaly

other pituitary hormone levels are normal and/or controlled

your IGF-1 levels are high

then it is likely that you are producing too much GH and it is causing complications. If you have other pituitary hormones that are abnormal, then you may have a condition causing hyperpituitarism. If a mass shows up on an X-ray, CT scan, or MRI, then you may have a pituitary tumor (or very rarely a malignancy). If you are being monitored for a previous tumor, then you may be having a recurrence.

GH stimulation test:

If your GH levels are not significantly stimulated during a GH stimulation test (they stay lower than they should) and:

you have symptoms of GHD

other pituitary hormone levels are normal and/or controlled

your IGF-1 level is low

then it is likely that you have a deficiency of GH that your doctor may treat. If your TSH level is low, then that should be addressed first as thyroid deficiencies can cause symptoms similar to GHD. You may also have a more general decrease in pituitary function.

Is there anything else I should know?

Pituitary tumors are the most common cause of excess GH production but may also cause deficiencies. Presence of a pituitary tumor not only can affect GH production, but may also affect production of other pituitary hormones, such as ACTH (Cushing's syndrome) or prolactin (galactorrhea). If the tumor is relatively large, it may inhibit all pituitary hormone production and cause damage to the surrounding tissues.

Factors that can interfere with GH testing include:

Stress, exercise, and low blood glucose levels

Drugs that can increase GH include: amphetamines, arginine, dopamine, estrogens, glucagon, histamine, insulin, levodopa, methyldopa, and nicotinic acid

Drugs that can decrease GH levels: corticosteroids and phenothiazines

Radioactive scan within week of test (with some laboratory methods)

Abnormal GH levels can usually be modified once the causes are identified. Synthetic GH is available to alleviate deficiencies in children (treatment of adults with GHD is more controversial). Combinations of surgery, medication, and radiation can be used to treat pituitary tumors that are causing excess GH production. The important thing is to identify GH abnormalities as soon as possible for good outcomes. The bone growth changes associated with gigantism and acromegaly are permanent and, if left untreated, the GH deficient child's short stature will remain.

There can be long term complications from GH abnormalities. Acromegaly, for instance, can cause colon polyps (increasing a patient's risk of developing colon cancer), diabetes, high blood pressure, and visual abnormalities. If a pituitary tumor permanently damages pituitary cells, then multiple hormone replacement may be necessary. Increased bone growth may also lead to trapped nerves (carpal tunnel syndrome), arthritis, and weak bones.

1.  What conditions are treated with GH therapy?

Besides GHD, children may be treated with growth hormone replacement if they have:

Chronic renal insufficiency

Prader Willi syndrome

Turner's syndrome

Treating children with GH replacement who are short but do not have GHD is controversial. This is also true of adults, whether or not they have documented GHD. The medicine has associated risks and side effects, is expensive, and there are not enough data to support its benefits.

GH replacement is sometimes given to those with HIV/AIDS-related wasting (loss of lean muscle mass) to help maintain body weight.

2.  Why would athletes be tested for GH?

Because GH promotes muscle growth in adults, it may be taken by some adults as a performance enhancing steroid. Athletes may be tested for GH when they are being tested for other performance enhancing drugs.

3.  What other tests might be ordered to evaluate my GH production?

Although they are not routinely ordered, other tests, such as insulin-like growth factor-1, binding protein-3 (IGFBP-3), and growth hormone releasing hormone (GHRH) are sometimes ordered to help evaluate GH production.