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Growth hormone (GH) is also called somatropin and somatotropin (British: somatotrophin). HGH refers to human growth hormone and is used as an abbreviation for human GH measured in the blood or extracted from human pituitary glands. In 1985, biosynthetic human growth hormone replaced pituitary-derived human growth hormone for therapeutic use in the U.S. and other countries. Biosynthetic human growth hormone, also referred to as recombinant human growth hormone, is also called somatropin (British: somatrophin) and abbreviated as rhGH. Since the mid-1990s the abbreviation HGH has begun to carry paradoxical connotations and now rarely refers to real GH used for indicated purposes. See articles on GH treatment and HGH quackery for fuller discussions of GH therapy and the HGH issue.
Secretion of GH
GH is secreted into the blood by the somatotrope cells of the anterior pituitary gland, in larger amounts than any other pituitary hormone. The transcription factor PIT-1 stimulates both the development of these cells and their production of GH. Failure of development of these cells, as well as destruction of the anterior pituitary gland, results in deficiency GH .
Peptides released by neurosecretory nuclei of the hypothalamus into the portal venous blood surrounding the pituitary are the major controllers of GH secretion by the somatotropes. Growth hormone releasing hormone (GHRH) from the arcuate nucleus and ghrelin promote GH secretion, and somatostatin from the periventricular nucleus inhibits it.
Although the balance of these stimulating and inhibiting peptides determines GH release, this balance is in turn affected by many physiologic stimulators and inhibitors of GH release. Stimulators of GH release include (among others) sleep, exercise, hypoglycemia, dietary protein, and estradiol. Inhibitors of GH secretion include dietary carbohydrate and glucocorticoids.
Most of the physiologically important GH secretion occurs as several pulses or peaks of GH release each day. The level of GH during these peaks may range from 5 to 30 ng/mL or more. Peaks typically last from 10 to 30 minutes before returning to basal levels. The largest and most predictable of these GH peaks occurs about an hour after onset of sleep. Otherwise there is wide variation between days and individuals. Between the peaks, basal GH levels are low, usually less than 3 ng/mL for most of the day and night.
The amount and pattern of GH secretion change throughout life. Basal levels are highest in early childhood. The amplitude and frequency of peaks is greatest during the pubertal growth spurt. Healthy children and adolescents average about 8 peaks per 24 hours. Adults average about 5 peaks. Basal levels and the frequency and amplitude of peaks decline throughout adult life.
Several molecular forms of GH circulate. Much of the growth hormone in the circulation is bound to a protein (growth hormone binding protein, GHBP) which is derived from the growth hormone receptor.
Clinical problems
Growth hormone excess: (acromegaly and pituitary gigantism)
The most common disease of GH excess is a pituitary tumor comprised of somatotroph cells of the anterior pituitary. These somatotroph adenomas are benign and grow slowly, gradually producing more and more GH. For years, the principal clinical problems are those of GH excess. Eventually the adenoma may become large enough to cause headaches, impair vision by pressure on the optic nerves, or cause deficiency of other pituitary hormones by displacement.
Prolonged GH excess thickens the bones of the jaw, fingers and toes. Resulting heaviness of the jaw and increased thickness of digits is referred to as acromegaly. Accompanying problems can include pressure on nerves (e.g., carpal tunnel syndrome), muscle weakness, insulin resistance or even a rare form of type 2 diabetes, and reduced sexual function.
GH-secreting tumors are typically recognized in the 5th decade of life. It is extremely rare for such a tumor to occur in childhood, but when it does the excessive GH can cause excessive growth, traditionally referred to as pituitary gigantism.
Surgical removal is the usual treatment for GH-producing tumors. In some circumstances focused radiation or a GH antagonist such as bromocriptine or octreotide may be employed to shrink the tumor or block function.
Growth hormone deficiency
Deficiency of GH produces significantly different problems at various ages. In children, growth failure and short stature are the major manifestations of GH deficiency. In adults the effects of deficiency are more subtle, and may include deficiencies of strength, energy, and bone mass, as well as increased cardiovascular risk.
There are many causes of GH deficiency, including mutations of specific genes, congenital malformations involving the hypothalamus and/or pituitary gland, and damage to the pituitary from injury, surgery or disease.
Diagnosis of GH deficiency involves a multiple step diagnostic process, usually culminating in GH stimulation test(s) to see if the patient's pituitary gland will release a pulse of GH when provoked by various stimuli.
GH deficiency is treated by replacing GH. All GH in current use is a biosynthetic version of human GH, manufactured by recombinant DNA technology. As GH is a large protein molecule, it must be injected into subcutaneous tissue (or muscle) to get it into the blood. When the patient has had a long-standing deficiency of GH, benefits of treatment are often dramatic and gratifying and side effects of treatment are rare. Increased growth in childhood can result in dramatically improved adult height.
GH is used as replacement therapy in adults with GH deficiency of either childhood-onset (after completing growth phase) or adult-onset (usually as a result of an acquired pituitary tumor). In these patients, benefits have variably included reduced fat mass, increased lean mass, increased bone density, improved lipid profile, reduced cardiovascular risk factors, and improved psychosocial well-being.
Other GH uses and treatment indications
Many other conditions besides GH deficiency cause poor growth, but growth benefits (height gains) are often poorer than when GH deficiency is treated. Examples of other causes of shortness often treated with growth hormone are Turner syndrome, chronic renal failure, Prader-Willi syndrome, intrauterine growth retardation, and severe idiopathic short stature. Higher ("pharmacologic") doses are required to produce significant acceleration of growth in these conditions, producing blood levels well above physiologic. Despite the higher doses, side effects during treatment are rare, and vary little according to the condition being treated.
Sometimes GH is used for other benefits than height. It has been shown to improve muscle strength and slightly reduce body fat in Prader-Willi syndrome, benefits more important to these children than increased height. It has also been shown to help maintain muscle mass in AIDS wasting. GH can also be used in patients with short bowel syndrome to lessen the requirement for intravenous parenteral nutrition.
Uses that are considered controversial include
GH treatment to reverse effects of aging in older adults
GH treatment to aid bodybuilding
GH treatment to enhance weight loss in obesity
GH treatment for fibromyalgia
GH treatment for Crohn's disease and ulcerative colitis
Risks of GH treatment
Risks of treatment are quite rare when GH is given in replacement doses to deficient children and adults. Risks are uncommon even when used in "pharmacologic doses" for other reasons, but there are more unanswered questions about risk:benefit ratios for other uses. |
