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Growth HormoneWhat Is
Growth Hormone? As we go about the natural process of aging, our bodies start to release less and less of this growth hormone. As a result, we feel more tired, with less energy and zest for life. If you are over the age of 30, chances are you have experienced some symptoms of this decline in HGH in your body. Our Recommended Supplier Of Growth Hormone Products... Is HGH
Therapy Beneficial? Growth hormone releasers are not actual hormones. Rather, they stimulate the body to release more of it's own HGH, on an as needed basis. Benefits include increased vitality, better sleep, higher sex drive, more lean muscle mass, less body fat, and an overall elevated mood. Growth hormone (GH) is also called somatropin. GH is a polypeptide hormone which stimulates growth and cell reproduction in humans and other vertebrate animals. HGH refers to human growth hormone but this older abbreviation has begun to develop paradoxical connotations (see final paragraphs for fuller discussion of HGH). This article describes human growth hormone physiology, deficiency, and treatment. Outline
GH excess:
acromegaly and pituitary gigantism Structure of
the human GH molecule
Secretion of
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 somatotrophs. 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 mg/dl 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 quite 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 amplitude and frequency 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 GH receptor. Functions of
GH Height growth is the best known effect of GH action, and appears to be stimulated by at least two mechanisms. 1. GH directly stimulates division and multiplication of chondrocytes of cartilage. These are the primary cells in the growing ends (epiphyses) of children’s long bones (arms, legs, digits). 2. GH also stimulates production of insulin-like growth factor 1 (IGF1, also known as somatomedin C), a hormone homologous to proinsulin. The liver is a major target organ of GH for this process, and is the principal site of IGF1 production. IGF1 has growth-stimulating effects on a wide variety of tissues. Although height growth is the best known effect of GH, it serves many other metabolic functions as well. GH strengthens and increases the mineralization of bone. It increases muscle mass. It tends to promote lipolysis, which results in some reduction of adipose tissue (body fat). It induces growth of many different organ systems of the body. GH plays a role in fuel homeostasis. GH reduces liver uptake of glucose, an effect that opposes that of insulin. GH also contributes to the maintenance and function of pancreatic islets.
Clinical problems: too much and too little Growth
hormone excess: (acromegaly and pituitary gigantism) 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 There are many causes of GH deficiency. Some examples include: mutations of
specific genes (e.g., GHRHR, GH1) Severe prenatal deficiency of GH, as occurs in congenital hypopituitarism, does not affect fetal growth but can reduce the size of a male’s penis, especially when gonadotropins are also deficient. Besides micropenis, additional consequences of severe deficiency in the first days of life can include hypoglycemia and exaggerated jaundice (both direct and indirect hyperbilirubinemia). Female infants will lack the microphallus of course but may suffer from hypoglycemia and jaundice. Even congenital GH deficiency does not impair length growth until after the first few months of life. From late in the first year until mid teens, poor growth and/or shortness is the hallmark of childhood GH deficiency. Growth is not as severely affected in GH deficiency as in untreated hypothyroidism, but growth at about half the usual velocity for age is typical. It tends to be accompanied by delayed physical maturation so that bone maturation and puberty may be several years delayed. When severe GH deficiency is present from birth and never treated, adult heights can be as short as 48-58 inches (122-147 cm). Severe GH deficiency in early childhood also results in slower muscular development, so that gross motor milestones such as standing, walking, and jumping may be delayed. Body composition (i.e., the relative amounts of bone, muscle, and fat) is affected in many children with severe deficiency, so that mild to moderate chubbiness is common (though GH deficiency alone rarely causes severe obesity). Some severely GH-deficient children have recognizable, cherubic facial features characterized by maxillary hypoplasia and forehead prominence (said to resemble a kewpie doll) Though growth ends with sexual maturity, GH continues to be secreted throughout life. In adults, GH contributes to maintenance of muscle and bone mass and strength. Understanding of the effects and benefits of GH in adults increased in the 1980’s and the features of adult GH deficiency have not only been published, but can be said to have gained some notoriety. Reported effects of severe GH deficiency in adults have included: reduced
muscle mass and strength Diagnosis of
growth hormone deficiency Although GH can be readily measured in a blood sample, testing for GH deficiency is constrained by the fact, described above, that levels are nearly undetectable for most of the day. This makes simple measurement of GH in a single blood sample fairly useless for detecting deficiency and a combination of indirect and direct criteria are used. Several types of evidence are used to ascertain GH sufficiency or deficiency. • Auxologic criteria (defined by body measurements) • Indirect hormonal criteria (IGF levels from a single blood sample) • Direct hormonal criteria (measurement of GH in multiple blood samples to determine secretory patterns or responses to provocative testing) • Response to GH treatment • Corroborative evidence of pituitary dysfunction “Provocative tests” involve giving a dose of an agent that will normally provoke a pituitary to release a burst of growth hormone. An intravenous line is established, the agent is given, and small amounts of blood are drawn at 15 minute intervals over the next hour to determine if a rise of GH was provoked. Agents which have been used clinically to stimulate and assess GH secretion are arginine, levodopa, clonidine, epinephrine and propranolol, glucagon, insulin, and Bovril. Severe GH
deficiency in childhood has the following measurable
characteristics: When these features are accompanied by corroboratory evidence of hypopituitarism such as deficiency of other pituitary hormones, a structurally abnormal pituitary, or a history of damage to the pituitary, the diagnosis is considered established with absolute certainty. For GH deficiency, as for many other diseases, the practical purpose and effect of these diagnostic criteria is to determine who is to be treated with it. GH deficiency accounts for only a minority of shortness among children. GH deficiency accounts for an even smaller minority of fatigability, excessive fat, osteopenic bones, and underdeveloped muscles in adults. An ideal diagnostic test cleanly separates people who would benefit from a treatment from those who would not. Unfortunately, none of the criteria listed above do so, not even in various combinations. The common clinical problem is that most children and adults being evaluated meet some, but not all, of the above criteria. Since many children and adults who do not meet all of the diagnostic criteria may receive some of the benefits of treatment, small differences in the diagnostic criteria make large differences in the number of short or tired people diagnosed with deficiency. Because of uncertainties and complexities of diagnosis and the high costs of treatment, diagnosis of growth hormone deficiency has been a more persistent subject of debate and controversy in clinical endocrinology than any other aspect of endocrine diagnosis. Our Recommended Supplier Of Growth Hormone Products... Treatment of
GH deficiency When treated with GH, a severely deficient child will begin to grow faster within months. In the first year of treatment, the rate of growth may increase from half as fast as other children are growing to twice as fast (e.g., from 1 inch a year to 4 inches, or 2.5 cm to 10). Growth typically slows in subsequent years, but usually remains above normal so that over several years a child who had fallen far behind in his height may grow into the normal height range. Parents often notice increased strength, appetite, and energy. Increased muscle strength may allow young children to overcome delays of motor development. Excess adipose tissue may be reduced. Just as importantly, there are almost no significant side effects of this type of physiologic replacement. Nevertheless, costs of treatment in terms of money, effort, and perhaps quality of life, are substantial. Treatment usually involves daily injections of growth hormone for children. Treatment is usually extended as long as the child is growing, and lifelong continuation may be recommended for those most severely deficient. Nearly painless insulin syringes make this less trying than is usually anticipated but discomfort is a subjective value. Most pediatric endocrinologists request visits to monitor growth and adjust dose every 3-4 months and many of these visits involve blood tests. It is even more difficult to assess a positive or negative psychological value to treating severe deficiency but most children and families are quite enthusiastic once the benefits begin to be seen. However, no one except the stockholders of the pharmaceutical companies is enthusiastic at the cost. Treatment costs vary by country and by size of child, but $US 10,000 to 30,000 a year is common in the United States. Little except the cost of treating severely deficient children is controversial, and it is likely that the majority of children with severe growth hormone deficiency in North America, Japan, and much of Europe and the rest of the developed world are offered treatment, and most accept. The story is very different for adult deficiency.
It has been shown repeatedly in research studies that GH
treatment can confer a number of measurable benefits to
severely GH-deficient adults, such as enhanced energy and
strength, and improved bone density. Muscle mass may increase
at the expense of adipose tissue. Blood lipid levels improve,
but long term mortality benefit has not yet been demonstrated.
Other GH uses
and treatment indications Other causes
of shortness often treated with growth hormone Chronic
glucocorticoid use GH treatment to reverse aging GH treatment to aid muscle-building Risks of GH
treatment History By the middle of the twentieth century endocrinologists understood the clinical features of growth hormone deficiency. GH is a protein hormone, like insulin. However, insulin had been purified from pig and cow pancreases for treatment of type 1 diabetes since the 1920's, and pig and cow GH did not seem to work as well in humans due to greater species-to-species variation of molecular structure (i.e., insulin is considered more "evolutionarily conserved" than GH). In the late 1950’s Maurice Raben purified enough GH from collected human pituitary glands to successfully treat a GH-deficient boy. Over the next few years, endocrinologists began to encourage parents of severely GH deficient children to collect human pituitary glands (after removal at autopsy) from local pathologists. The parents would then contract with a biochemist to purify enough growth hormone to treat their child. This was an arduous and complicated undertaking that few families could manage. In 1960 the National Pituitary Agency was formed as a branch of the U.S. National Institutes of Health. The purpose of this agency was to supervise the collection of human pituitary glands when autopsies were performed, arrange for large scale extraction and purification of GH, and distribute it to a limited number of pediatric endocrinologists for treating GH-deficient children under research protocols. Canada, U.K., Australia, New Zealand, France, Israel, and other countries establish similar government-sponsored agencies to collect pituitaries, purify GH, and distribute it for treatment of severely GH deficient children. Supplies of this “cadaver growth hormone” were limited and only the most severely deficient children were treated. From 1963 to 1985 about 7700 children in the U.S. and 27,000 children worldwide were given GH extracted from human pituitary glands to treat severe GH deficiency. Physicians trained in the relatively new specialty of pediatric endocrinology provided most of this care, but in the late 1960’s there were only a hundred of these physicians in a few dozen of the largest university medical centers around the world. In 1976 physicians became aware of transmissibility of Creutzfeldt-Jacob disease by neurosurgical procedures. CJD is a rapidly fatal dementing disease of the brain also known as spongiform encephalopathy, a form of “mad cow disease”. In 1977 the NPA GH extraction and purification procedure was refined and improved. The shortage of available cadaver GH worsened in the late 1970’s as the autopsy rate in the U.S. declined, but the number of pediatric endocrinologists able to diagnose and treat GH deficiency increased. Often treatment would be stopped when a child reached an arbitrary minimal height, such as 5 feet (152 cm). Children who were short for reasons other than severe GH deficiency were told that they would not benefit from treatment. In the late 1970’s a Swedish pharmaceutical company, Kabi, contracted with a number of hospitals in Europe to buy pituitary glands for the first commercial GH product, Crescormon. In 1981, the new American corporation Genentech, in collaboration with Kabi, developed and started trials of synthetic human growth hormone made by a new technology (recombinant DNA) in which human genes were inserted into bacteria so that huge vats of bacteria could produce unlimited amounts of the protein. Because this was new technology, lengthy safety trials continued over the next 4 years, delaying approval. In 1985 four young adults in the U.S. who had received NPA growth hormone in the 1960’s developed CJD. The connection was recognized within a few months and there was a rapid cessation of use of human pituitary GH. Between 1985 and 2003, a total of 26 cases of CJD occurred in adults who had received NPA GH before 1977 (out of 7700 people treated). Comparable numbers of cases occurred around the world. Nevertheless, by 2003 there had been no cases in people who received only GH purified by the improved 1977 methods. Discontinuation of human cadaver growth hormone led to rapid Food and Drug Administration approval of Genentech’s synthetic growth hormone, which was introduced in 1985 under the brand name Protropin in the United States. The price of treatment (US$ 10,000 to 30,000 per year) was uniquely astronomical at the time, justified by the prolonged research and development investment, orphan drug status, and a pioneering post-marketing surveillance registry for tracking safety and effectiveness. Within a few years, GH treatment had become “big business” in more than one sense. In the United States, Eli Lilly launched a competing growth hormone, and in Europe, Pharmacia (formerly Kabi, now Pfizer), Novo, and Serono marketed nearly identical synthetic human growth hormone products and competed with dozens of different marketing strategies-- except cutting price. The 1990’s became an era of experimentation to see what else growth hormone could help. Most children with severe deficiency in the western world were likely to have access to a pediatric endocrinologist and be diagnosed and offered treatment. The medical literature of the decade contains hundreds of reports of small trials of GH use in nearly every type of growth failure imaginable. In most cases the responses were modest. For a few conditions, more rigorous trials were sponsored by growth hormone companies to achieve approval to market for those specific indications. Turner syndrome and chronic renal failure were the first of these “non GH deficient causes of shortness” to receive FDA approval for GH treatment, and Prader-Willi syndrome and intrauterine growth retardation followed. Parallel expansion of use was occurring in Europe. The biggest potential expansion of use was the adult market. Increasing indications Adult market Klatz ISS As of 2004,
synthetic growth hormones available in the U.S. (and their
manufacturers) included Nutropin (Genentech), Humatrope
(Lilly), Genotropin (Pfizer), Norditropin (Novo), and Saizen (Serono).
The products are nearly identical in composition, efficacy,
and cost, varying primarily in the formulations and delivery
devices. HGH quackery Content Provided by Wikipedia Try the leading HGH supplier NOW - Sytropin!
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