And It's About Time There Was Some Support For Cushing's!
Growth hormone is a protein made up of a sequence of 191 amino acids, which is released by the pituitary gland. The pituitary produces several hormones that control many of the body's vital functions. The production of hGH drops about 25% between the ages of 20 and 65, through its release may actually drop 90%. This means that there exists a relative deficiency state even though our pituitary is capable of producing additional amounts.
The pituitary releases hGH in response to the hypothalamic release of somatotropin. Other factors which cause the release of hGH include deep sleep, fasting, and intense physical exercise. The pituitary releases hGH into the circulation in a pulsatile fashion. One series of pulses occurs just after falling asleep, and another about 2 hours after getting up in the morning. The amount of hGH in the blood is very minute and varies rapidly over time. This renders it unsuitable as a monitor of hGH activity.
HGH travels through the general circulation and binds to receptor sites on nearly all cells of the body, though predominantly in liver cells. Once the receptor site is occupied by a molecule of hGH, the liver cell produces several messenger chemicals which include IGF-1, IGF-2, and other growth factors. These messengers are responsible for doing most of the work mediated by hGH. Insulin-like Growth Factor-1, (IGF-1), is the biochemical marker used to monitor the hGH activity in our bodies. IGF-1 is much more abundant, is produced in direct response to hGH, and has a consistent diurnal pattern. IGF-1 is also called somatmedin C.
In addition to somatotropin, the hypothalamus also releases a hormone called somatostatin that inhibits pituitary release of hGH. The reason for diminished secretion of hGH as we get older may be related to an increase in somatostatin.
The laboratory diagnosis of Growth Hormone Deficiency can be made by biochemical markers or provocative testing.
Serum IGF-1 level is a useful indicator of the adequacy of Growth Hormone. A normal level does not exclude GHD. IGF-1 levels may also be reduced by poor nutrition, hepatic disease, poorly controlled diabetes, and hypothyroidism.
The insulin tolerance test is the study of choice for provacative testing. A growth hormone release of less than ng/ml is response to insulin induced hypoglycemia is considered indicative of GHD. Alternative tests that use glucagon, propranolol, or levadopa may be used but have a lesser established diagnostic value.
The goal of therapy is to correct any current abnormalitites or conditions associated with the GHD and to prevent the development of the abnormilties associated with long-term deficiency.
To maintain hGH at youthful levels requires an integrated, monitored approach. A solid nutritional platform needs to be maintained, including select supplementation. An appropriate exercise program should be initiated. Other hormone deficiencies, especially hypothyroidism, should be corrected prior to the initiation of Growth Hormone therapy. Blood testing is essential to insure that adequate, but not excessive levels are achieved.
There are a variety of ways to increase hGH levels. These include the use of a secretogogue, homeopathic recombinant hGH available as a sublingual tablet, injectable recombinant hGH, GHRH mimics and finally injectable growth hormone releasing hormone. In 1996, the FDA approved the use of hGH in adult patients. Numerous studies have documented the benefits of hGH therapy. Please note that to date, the only scientific validated method of hGH therapy is by injection.
Secretogogues or releasers are substances that stimulate secreting organs. There are many substances that stimulate the release of growth hormone from the pituitary; these include several amino acids and drugs. Exercise is also a powerful releaser of growth hormone. Most good secretogogues elevate the IGF-1 level about 25-40%. The effect on individuals varies quite widely. These substances are particularly sensitive to the condition in which they are administered. If any other substances is taken that degrade the signal induced by the secretogogue, a reduced response will occur. For this reason it is important that they be taken on an empty stomach. Many authors and researchers recommend that secretogogues be cycled (stopped at intervals). The common interval is the 12-week on, 2 weeks off combination.
Another alternative is homeopathic sublingual hGH. This results in an elevation in the baseline IGF-1 amounting to about a 25%. There should be a two-minute period before and after the tablet that nothing else is put into the mouth.
Other products are available that may be used in combination with the above and include the amino acid L-Arginine. Please see the section below for injectable hGH protocol
The best biochemical marker for Growth Hormone is serum IGF-1 (Insulin-Like Growth Factor - 1) level. The target range for IGF-1 should be 300 - 350 mcg/ml. Testing should be performed the same time of day using the same reference laboratory.
Initially, IGF-1 measurements for dose titration should be performed monthly after the initiation of injectable rhGH therapy for every third month of oral therapy. Subsequently, IGF-1 levels should be performed every 6 months.
Thyroid function and blood glucose levels should be monitored periodically. Anthropometric determinations should be recorded and bone density measured.
GH is a protein that tells a child's body to grow. In adults, as well as in children, GH is essential to the maintenance of healthy body composition and metabolism. It is produced by the pituitary gland (an organ about the size of a pea, located at the base of the brain) and released into the bloodstream. GH travels to the cartilage and causes it to grow and turn into bone. GH also affects many other parts of the body. GH helps in the development of muscles and causes fat to be used for energy. Throughout adulthood, GH plays an important role in maintaining an improved ratio of body fat to lean mass, "bad" to "good" cholesterol levels, and proper bone mineral density.
Your doctor may give you a test to find out if you are still GH-deficient and need to continue GH replacement therapy as an adult. Although growth hormone is vital for developmental growth, our bodies continue to produce GH throughout our lives—even long after we have stopped growing. Scientists have discovered that adults who lack naturally occurring GH may experience many symptoms, including: weight gain, especially around the abdomen; lower energy and strength; a decreased sense of well-being; and sleep problems. These adults may also have abnormal cholesterol levels and an increased risk for fractures due to lower bone densities. GH therapy for AGHD may increase spine bone mineral density in certain patients, as well as improve fat distribution and body composition.
The goal of GH therapy for a child with pediatric GH deficiency is to help the child reach his or her growth potential. GH therapy may also help children with chronic renal insufficiency (up to the time of renal transplantation) or Turner syndrome to help achieve their adult height potential. GH therapy for adult GH deficiency may increase spine bone mineral density in certain patients, as well as improve fat distribution and body composition. Growth Hormone therapy is indicated to treat pediatric GH deficiency, chronic renal insufficiency, Turner syndrome, and adult GH deficiency.
GH therapy should not be used in patients with active cancer or tumors. GH therapy should be discontinued if evidence of cancer develops. GH should not be initiated to treat patients with acute critical illness due to complications following open-heart or abdominal surgery, multiple accidental trauma, or to patients having acute respiratory failure. GH therapy should not be used for growth promotion in patients with closed epiphyses—that is, whose long bones have stopped growing. GH is contraindicated in patients with Prader-Willi syndrome who are severely obese or have severe respiratory impairment (see WARNINGS in full prescribing information). Unless patients with Prader-Willi syndrome also have a diagnosis of growth hormone deficiency, Growth Hormone therapy is not indicated for the long-term treatment of pediatric patients who have growth failure due to genetically confirmed Prader-Willi syndrome.
Why must Growth Hormone therapy be given by injection?
Growth Hormone therapy must be given by injection because it is a protein. If the medication were taken by mouth, it would be broken down by digestion in the stomach and intestines and would never get to the rest of the body to do its job.
What causes adult onset growth hormone deficiency?
In adults, GH deficiency may often result when the pituitary gland becomes diseased or damaged. Particular tumors of the pituitary gland (pituitary adenomas), physical injury to the brain (hemorrhage, trauma, surgery), or radiation therapy can all injure the pituitary gland severely enough to cause GH deficiency. In the U.S. approximately 50,000 adults have GH deficiency and 6,000 new cases of adult GH deficiency are diagnosed each year. Children who receive GH therapy may need to continue with the therapy into adulthood if adult GH deficiency is confirmed.
How is Growth Hormone therapy administered?
Growth Hormone therapy is injected into the subcutaneous tissue (the fatty layer under the skin). Your healthcare provider will instruct you on the method of administration that has been prescribed for you or your child. Almost anyone can learn to administer Growth Hormone after receiving instructions from his or her healthcare team.
What should I do if an injection is missed?
Missing injections can interfere with the effectiveness of the medication. Talk to your healthcare professional if this should happen. Don't try to make up for missed injections by "doubling up" on injections.
When can I expect to see results from my GH replacement therapy?
It may be a number of months until you see the results of your replacement therapy. The changes may be so gradual at first that they are difficult to notice, but try not to get discouraged. Take your replacement therapy when and how your healthcare professional instructs. If you take it every day and don't miss doses, you can improve the likelihood of positive results.
I am taking other hormone medicines—why do I need to take GH therapy?
Depending on the cause of AGHD, many patients need to take other hormones. GH is produced by the pituitary gland—a small gland located at the base of the brain. This small gland is actually responsible for releasing and controlling many hormones in our bodies. Each of these hormones is released in tiny amounts into the blood stream. Once in the blood, each hormone travels to a different part of the body to perform a specific function. GH released from the pituitary is important for growth, body composition, lipid metabolism, and strength. Each of the other hormones released from the pituitary are important for other reasons—from salt and water regulation to helping our bodies deal with stress. GH cannot replace the function of these other hormones. Remember to tell your doctor about all of the medications that you take, including nonprescription medications and vitamins.
Why did my doctor order a DEXA scan before I started taking GH therapy?
Dual-energy x-ray absorptiometry (DEXA) is a special kind of x-ray that uses a very low amount of radiation. It is the method that doctors use to determine body composition or the proportion of your body that is made up of fat. DEXA is also considered the "gold standard" for measuring bone density. Patients with AGHD may experience changes in decreased bone density and body composition. By taking a DEXA scan before you begin treatment, your doctor will have a baseline measurement of your bone density and the composition of your body.
How is the effectiveness of GH therapy measured?
The primary criteria for judging the effectiveness of pediatric GH therapy are the child's growth rate (the number of centimeters or inches grown per year) and his or her change in height percentile on a standard growth chart (that is, how the child's height compares with the average height of other children the same age). For adults on GH therapy, success may be gauged using measures such as assessments of body fat and muscle mass, spine bone mineral density (in certain patients), and ratio of LDL to HDL cholesterol.