Growth hormone (GH) is a protein hormone secreted by the pituitary gland which stimulates growth and cell reproduction. In the past growth hormone was extracted from human pituitary glands. GH is now produced by recombinant DNA technology, and prescribed for a variety of reasons. GH therapy has been a focus of social and ethical controversies for 50 years. Growth hormone (GH or somatotropin) is a 191-amino acid, single chain polypeptide hormone which is synthesised, stored and secreted by the somatotroph cells within the lateral wings of the anterior pituitary gland, which stimulates growth and cell reproduction in humans and other animals. ... Norepinephrine A hormone (from Greek όρμή - to set in motion) is a chemical messenger from one cell (or group of cells) to another. ... Located at the base of the skull, the pituitary gland is protected by a bony structure called the sella turcica. ... Growth can mean increase in spatial number or complexity for concrete entities in time or increase in some other dimension for abstract or hard-to-measure entities. ... Drawing of the structure of cork as it appeared under the microscope to Robert Hooke from Micrographia which is the origin of the word cell being used to describe the smallest unit of a living organism Cells in culture, stained for keratin (red) and DNA (green) The cell is the...

This article describes the history of GH treatment, current uses, risks, and social controversies arising from GH use. Other articles describe GH physiology, diseases of GH excess (acromegaly and pituitary gigantism), deficiency, the recent phenomenon of HGH controversies, and growth hormone for cows. Growth hormone (GH or somatotropin) is a 191-amino acid, single chain polypeptide hormone which is synthesised, stored and secreted by the somatotroph cells within the lateral wings of the anterior pituitary gland, which stimulates growth and cell reproduction in humans and other animals. ... Acromegaly (from Greek akros high and megas large - extremities enlargement) is a hormonal disorder that results when the pituitary gland produces excess growth hormone (hGH). ... Anna Haining Bates with her parents Greek gigas, gigantus (giant) is a condition characterized by excessive height growth and bigness. ... Growth hormone deficiency is the medical condition of inadequate production of growth hormone (GH) and its effects on children and adults. ... There are many controversies around the claims, products, and businesses related to the use of growth hormone as an anti-aging therapy. ... Bovine somatotropin (bST), or bovine growth hormone (BGH), is a protein hormone that occurs naturally in the pituitary gland of cattle. ...

Terminology and glossary

Growth hormone (GH) is also called somatotropin (British: somatotrophin). The human form of growth hormone is known as human growth hormone, or hGH (similarly ovine growth hormone, or sheep growth hormone, is abbreviated oGH). GH can refer either to the natural hormone produced by the pituitary (somatotropin), or biosynthetic GH for therapy.

HGH is an abbreviation sometimes used for counterfeit or fake "growth hormone" products^{[citation needed]}. See HGH controversies for a fuller discussion of the origins and changing usages of HGH. There are many controversies around the claims, products, and businesses related to the use of growth hormone as an anti-aging therapy. ...

Cadaver growth hormone is the term for GH extracted from human pituitary glands between 1960 and 1985 for therapy of deficient children. In the U.S., cadaver GH, also referred to as NPA growth hormone, was provided by the (National Pituitary Agency), and by other national programs and commercial firms as well. In 1985 it was associated with the development of Creutzfeldt-Jakob Disease, and was withdrawn from use. Creutzfeldt-Jakob disease (CJD) is a very rare and incurable degenerative neurological disorder (brain disease) that is ultimately fatal. ...

rhGH refers to recombinant human growth hormone (somatropin). It contains the identical amino acid sequence of human GH and is "natural sequence" GH. It is chemically identical to the growth hormone produced by the pituitary gland. A long-acting somatropin was previously available, but has recently (March 2007) been put on hold by the FDA. Human growth hormone is currently available through multiple pharmacutical companies in the US. Recombinant DNA technology adds/replaces DNA in an organism resulting in the recipient organism containing exogenous DNA. Recombinant proteins are proteins that are produced by different genetically modified organisms following insertion of the relevant DNA into their genome. ...

Coincidentally, rhGH also refers to rhesus monkey GH, using the accepted naming convention. Rhesus growth hormone was never used by physicians to treat human patients, but rhesus GH was part of the lore of the underground anabolic steroid community in those years and fraudulent versions may have been bought and sold in gyms. Crystal structure of human sex hormone-binding globulin, transporting 5-alpha-dihydrotestosterone. ...

met-GH refers to methionyl-growth hormone. This was the first recombinant GH product marketed (Protropin by Genentech). It had the same amino acid sequence as human GH with an extra methionine at the end of the chain to facilitate the manufacturing process. It was discontinued in the late 1990s. Phenylalanine is one of the standard amino acids. ... Methionine is an α-amino acid with the chemical formula HO2CCH(NH2)CH2CH2SCH3. ...

rBST refers to recombinant bovine somatropin (cow growth hormone), or more properly, recombinant bovine GH (rbGH). Bovine somatotropin (bST), or bovine growth hormone (BGH), is a protein hormone that occurs naturally in the pituitary gland of cattle. ...

Treatment of GH deficiency in children

Growth hormone deficiency is treated by replacing GH. All GH prescribed in North America, Europe, and most of the rest of the world is a 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. Nearly painless insulin syringes make this less trying than is usually anticipated but perceived discomfort is a subjective value. Growth hormone deficiency is the medical condition of inadequate production of growth hormone (GH) and its effects on children and adults. ... Recombinant DNA technology adds/replaces DNA in an organism resulting in the recipient organism containing exogenous DNA. Recombinant proteins are proteins that are produced by different genetically modified organisms following insertion of the relevant DNA into their genome. ... Insulin (from Latin insula, island, as it is produced in the Islets of Langerhans in the pancreas) is an anabolic polypeptide hormone that regulates carbohydrate metabolism. ... A syringe nowadays nearly always means a medical syringe, but it can mean any of these: A simple hand-powered piston pump consisting of a plunger that can be pulled and pushed along inside a cylindrical tube (the barrel), which has a small hole on one end, so it can...

When a person has had a long-standing deficiency of GH, benefits of treatment are often obvious, and side effects of treatment are rare. When treated with GH, a deficient child will begin to grow faster within months. Other benefits may be noticed, such as increased strength, progress in motor development, and reduction of body fat. Side effects of this type of physiologic replacement are quite rare. Known risks and unsettled issues are discussed below, but GH deficient children receiving replacement doses are at the lowest risk for problems and receive the greatest benefit. In vertebrates, the term motor neuron (or motoneuron) classically applies to neurons located in the central nervous system (CNS) which project their axons outside the CNS and directly or indirectly control muscles. ... It has been suggested that Subcutaneous fat be merged into this article or section. ...

Still, costs of treatment in terms of money, effort, and perhaps quality of life, are substantial. Treatment of children usually involves daily injections of growth hormone, usually for as long as the child is growing. Lifelong continuation may be recommended for those most severely deficient as adults. Most pediatric endocrinologists monitor growth and adjust dose every 3-4 months. Assessing the psychological value of treatment is difficult but most children and families are enthusiastic once the physical benefits begin to be seen. Treatment costs vary by country and by size of child, but $US 10,000 to 30,000 a year is common. The well-being or quality of life of a population is an important concern in economics and political science. ... Pediatric endocrinology is a medical subspecialty dealing with variations of physical growth and sexual development in childhood, as well as diabetes and other disorders of the endocrine glands. ...

Little except the cost of treating severely deficient children is controversial, and most children with severe growth hormone deficiency in the developed world are offered treatment. Most accept. The story is very different for adult deficiency.

Treatment of adult GH deficiency

Research has shown that GH treatment can provide 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. Bone density is a medical term referring to the amount of matter per cubic centimeter of bones. ... A top-down view of skeletal muscle Muscle (from Latin musculus little mouse [1]) is contractile tissue of the body and is derived from the mesodermal layer of embryonic germ cells. ... It has been suggested that Subcutaneous fat be merged into this article or section. ... A polyunsaturated triglyceride. ...

GH for severe adult deficiency is usually prescribed as daily injections at a weekly dose about 25% of children's doses and comparably lower cost. Despite the potential benefits, most adults with GH deficiency are not being treated due to a combination of factors such as unwillingness of young adults to seek medical care, unacceptability of injections, inadequate insurance coverage, and significantly lower rates of diagnosis and treatment offer by internist endocrinologists. Endocrinology is a branch of medicine dealing with disorders of the endocrine system and its specific secretions called hormones. ...

See growth hormone deficiency for further details of treatment for this specific condition. Growth hormone deficiency is the medical condition of inadequate production of growth hormone (GH) and its effects on children and adults. ...

Other GH uses and treatment indications

In the last two decades, GH has also been increasingly used for children and adults who are not severely deficient, either to enhance growth or for other reasons.

GH treatment for other types of shortness

Many conditions besides GH deficiency cause poor growth. GH therapy has been shown to improve short-term growth in many conditions, but long-term height gains are usually poorer than those achieved when GH deficiency is the cause of shortness. Higher ("pharmacologic") doses are typically required to achieve efficacy; side effects are uncommon and vary according to the condition being treated.

As of 2004, GH has been approved by the U.S. Food and Drug Administration for treatment of five other types of short stature: hi “FDA” redirects here. ...

• Turner syndrome epitomizes the response of non-deficient shortness. At doses 20% higher than those used in GH deficiency, growth accelerates. With several years of treatment the median gain in adult height is about 2-3 inches (5-7.5 cm) on this dose. The gains appear to be dose-dependent.

• Chronic renal failure results in many problems, including growth failure. GH treatment for several years both before and after transplantation may prevent further deceleration of growth and may narrow the height deficit, though even with treatment net adult height loss may be about 4 inches (10 cm).

• Prader-Willi syndrome represents a unique combination both encouraging and discouraging GH treatment. Many of the children have at least partial deficiency, so that the adipose reduction and muscle strength benefits are amplified. These two benefits are specifically helpful in this syndrome. On the other hand, these children are intellectually and socially limited by their condition such that it is difficult to imagine that 2 or 3 more height inches would make much difference to quality of life. Furthermore, a handful of sudden deaths during treatment of older children has raised questions about safety and an official warning.

• Children short because of intrauterine growth retardation are small for gestational age at birth for a variety of reasons. If early catch-up growth does not occur and their heights remain below the third percentile by 2 or 3 years of age, adult height is likely to be similarly low. High dose GH treatment has been shown to accelerate growth, but data on long term benefits and risks is limited.

• Idiopathic short stature (ISS) is one of the most controversial indications for GH as pediatric endocrinologists do not agree on its definition, diagnostic criteria, or limits. The term has been applied to children with severe unexplained shortness that will result in an adult height below the 3rd percentile. In the late 1990's, the pharmaceutical manufacturer Eli Lilly and Company sponsored trials of Humatrope (their brand of rhGH) in children with extreme ISS, those at least 2.25 standard deviations below mean (in the lowest 1.2 percent of the population). These boys and girls appeared to be headed toward heights of less than 63" (160 cm) and 59" (150 cm) respectively. They were treated for about 4 years and gained 1.5 to 3 inches (3.8-7.6 cm) in adult height. Controversy has arisen as to whether all of these children were truly "short normal" children, since the average IGF1 was low. Not surprisingly, approval for this extreme degree of shortness led to an increase in the number of parents seeking treatment to make otherwise healthy children a little taller.

A variety of other causes of shortness is occasionally treated with growth hormone off-label. An organ transplant is the transplantation of an organ (or part of one) from one body to another, for the purpose of replacing the recipients damaged or failing organ with a working one from the donor. ... Prader-Willi syndrome is a genetic disorder, in which seven genes (or some subset thereof) on chromosome 15 are missing or unexpressed (chromosome 15q partial deletion) on the paternal chromosome. ... Intrauterine growth retardation or Intrauterine growth restriction (IUGR) refers to the condition during pregnancy where a fetus is considered to be too small for its gestational age (generally in the 10th percentile). ... Idiopathic short stature (ISS) refers to extreme short stature that does not have a diagnostic explanation (idiopathic designates a condition that is unexplained or not understood) after an ordinary growth evaluation. ... In general, a diagnosis (plural diagnoses) has two distinct dictionary definitions. ... Eli Lilly and Company (NYSE: LLY) is a global pharmaceutical company and one of the worlds largest corporations. ... Insulin-like growth factor 1 (IGF-1) is a protein hormone similar in molecular structure to insulin. ...

• Chronic high dose glucocorticoid use results in growth failure, diminished bone density, reduced muscle mass and strength, increased fat, skin fragility, and poor healing. Growth hormone reduces many of these complications without interfering with the anti-inflammatory benefits of the steroid. Unfortunately, GH cannot completely prevent or reverse them. GH is currently used for only a small percentage of people with this problem.

• Post-transplant growth failure sometimes improves with GH. Many children who suffer from chronic renal, liver, and heart disease grow poorly for years before a transplant is required (or available). While growth may improve after correction of organ function by successful transplantation, the immunosuppressive drugs taken to protect the transplanted organ may continue to interfere with growth. Growth hormone may help offset these effects and is often offered in these circumstances.

• X-linked hypophosphatemic rickets is an inherited disorder of phosphorus metabolism that results in growth failure and rickets. GH has been shown to accelerate growth modestly.

• Inflammatory bowel disease (ulcerative colitis and Crohn's disease) can impair growth before producing obvious bowel symptoms. Trials of GH have shown at least modest acceleration of growth.

• Poor growth is a part of Noonan syndrome and many other genetic syndromes. Many short children with various syndromes have been treated with GH. As a broad generalization, GH for several years usually produces faster growth, and perhaps 1-2 inches (2.5-5 cm) of extra adult height.

• Small numbers of children with various forms of bone dysplasia (dwarfism in common parlance) have been treated with GH with modest increases in short-term height velocity. No long-term studies have demonstrated increased adult height, and dwarfism due to bone dysplasia remains the prime example of extreme shortness considered not very amenable to GH treatment.

• If the onset of Celiac's Disease occurs in children prior to reaching their growth potential then stunted growth can result due to Celiac's Disease damaging the intestines and preventing proper nutrient absorption. HGH treatment can be used to recover lost growth due to this effect once a gluten free diet is follwed and the instestines begin to repair themselves.

Glucocorticoids are a class of steroid hormones characterised by an ability to bind with the cortisol receptor and trigger similar effects. ... An abscess on the skin, showing the redness and swelling characteristic of inflammation. ... The liver is an organ present in vertebrates and some other animals. ... The heart and lungs, from an older edition of Grays Anatomy. ... An organ transplant is the transplantation of an organ (or part of one) from one body to another, for the purpose of replacing the recipients damaged or failing organ with a working one from the donor. ... Immunosuppression is the medical suppression of the immune system. ... General Name, Symbol, Number phosphorus, P, 15 Chemical series nonmetals Group, Period, Block 15, 3, p Appearance waxy white/ red/ black/ colorless Standard atomic weight 30. ... Rickets is a softening of the bones in children potentially leading to fractures and deformity. ... In medicine, inflammatory bowel disease (IBD) is a group of inflammatory conditions of the large intestine and, in some cases, the small intestine. ... Noonan Syndrome (NS) is a relatively common congenital genetic condition which affects both males and females. ... In medicine, the term syndrome is the association of several clinically recognizable features, signs, symptoms, phenomena or characteristics which often occur together, so that the presence of one feature alerts the physician to the presence of the others. ... This page is about the medical condition. ...

GH treatment for other benefits beyond height

GH has occasionally been used for other purposes than accelerating growth or replacing deficiency. Nearly every hormone available for administration has been given to non-deficient people in hope of obtaining improvement for various conditions for which other treatments are unsatisfactory. With a few exceptions, benefits are modest and side effect risk is higher. Experience with GH has yielded the same results. The following is not an exhaustive list.

• Advanced acquired immunodeficiency syndrome is often accompanied by muscle wasting ("AIDS wasting"). GH has been shown to ameliorate this condition.

• GH has been given to promote healing of large burns by reducing the amount of protein breakdown during the early post-injury period.

• GH has been used as an adjunct to severe calorie restriction for obesity. GH promotes lipolysis and reduces proteolysis. It was hoped that GH would reduce muscle breakdown without interfering with use and reduction of fat as the body shifted to a near-starvation economy. Results showed benefit, but this has not been widely adopted for a variety of reasons (cost, injections, potential aggravation of insulin resistance, etc).

• Fibromyalgia and chronic fatigue syndrome are poorly understood and vaguely defined conditions with overlapping features. After demonstration of disorderd GH secretion and higher rates of tissue breakdown in patients with these conditions, a few people tried growth hormone treatment to see if energy or healing could be improved. Disturbances of GH secretion may be secondary phenomena and not causal. Despite anecdotal reports of improvement, no large, controlled trials have demonstrated significant, persistent improvement and GH is not a common or standard treatment for either condition.

• GH has been used to slow or reverse some of the debilities of aging based on the following observations: (1) as adults get older, production and levels of GH and IGF1 decline, and (2) many of the effects of aging (diminished muscle strength and bone mass, reduced energy, reduced resilience) also occur with adult growth hormone deficiency and are improved with GH treatment. See HGH controversies for more on GH use to retard aging.

• GH has been taken by athletes and muscle builders to increase either strength or bulk. Rumors of surreptitious athletic use date back to the days of cadaver GH. Since GH is a protein hormone, it is not detected by assays that screen for steroids and similar drugs-- the primary laboratory clue would be elevated IGF1 levels. However, despite decades of rumors and presumably some amount of black market or surreptitious use, the magnitudes of both benefits and risks remain unestablished. See HGH controversies for more.

AIDS (Acquired Immunodeficiency Syndrome or Acquired Immune Deficiency Syndrome, sometimes written Aids) is a human disease characterized by progressive destruction of the bodys immune system. ... For other uses, see Burn. ... Lipolysis is the breakdown of fat stored in fat cells. ... Proteolysis is the directed degradation (digestion) of proteins by cellular enzymes called proteases or by intramolecular digestion. ... A female child during the Nigerian-Biafran war of the late 1960s, shown suffering the effects of severe hunger and malnutrition. ... Insulin resistance is the condition in which normal amounts of insulin are inadequate to produce a normal insulin response from fat, muscle and liver cells. ... Fibromyalgia (FM or FMS) is a chronic syndrome (constellation of signs and symptoms) characterized by diffuse or specific muscle, joint, or bone pain, fatigue, and a wide range of other symptoms. ... Chronic fatigue syndrome (CFS) is one of several names given to a poorly understood, highly debilitating disorder of uncertain cause, which is thought to affect approximately 4 per 1,000 adults[1] in the United States and other countries, and a smaller fraction of children. ... Ageing or aging is the process of getting older. ... Growth hormone deficiency is the medical condition of inadequate production of growth hormone (GH) and its effects on children and adults. ... There are many controversies around the claims, products, and businesses related to the use of growth hormone as an anti-aging therapy. ... Bodybuilder Anders Graneheim (Sweden) Bodybuilding is the sport of developing muscle fibers through the combination of weight training, increased caloric intake, and rest. ... Insulin-like growth factor 1 (IGF-1) is a protein hormone similar in molecular structure to insulin. ... It has been suggested that this article or section be merged into underground economy. ... There are many controversies around the claims, products, and businesses related to the use of growth hormone as an anti-aging therapy. ...

Risks of GH treatment

Known risks of GH are few and rare. Few reasonable parents or physicians would incur a high risk of harm to a child to add a few inches to height. Most of the complications have been reported in children over 10 years of age or in adults. Though rare, the following harmful side effects have been reported during GH treatment often enough to be assumed noncoincidental.

• Slipped capital femoral epiphysis (SCFE) causes hip pain due to separation of the head of the femur from the shaft. Incidence in GH-treated children may be about 1 in 1000. SCFE usually requires casting or surgical pinning to reverse.

• Pseudotumor cerebri (also known as benign intracranial hypertension) is manifested by severe headache, papilledema, nausea, and visual changes. Incidence is also perhaps 1 in 1000. All cases have been reversed, usually by temporary discontinuation or reduced dose of the GH.

• Fluid retention and edema in early months of treatment is rare in children but more common and occasionally more severe in adults. It typically disappears with temporary interruption of treatment.

• Pancreatitis has been reported in a few patients receiving GH, but a causal relationship seemed unlikely but possible.

• Joint pains are occasionally experienced by children or adults being treated with GH.

• Carpal tunnel syndrome has also occurred in adults being treated with GH, presumably due to a combination of tissue growth and fluid retention causing pressure on the tightly confined nerves and tendons of the wrists.

• A small but controlled study of GH given to severely ill adults in an intensive care unit setting for the purpose of increasing strength and reducing the muscle wasting of critical illness showed a higher mortality rate for the patients who received GH. The reason is unknown, but GH is now rarely used in ICU patients unless they have severe growth hormone deficiency.

The following effects are common, but of questionable harm. Slipped capital femoral epiphysis is a medical term refering to chronic fracture of the epiphyseal growth plate known as a slipped capital femoral epiphysis. ... Bones of the Hip In anatomy, the hip is the bony projection of the femur, known as the greater trochanter, and the overlying muscle and fat. ... The femur or thigh bone is the longest, most voluminous, and strongest bone of the mammalian bodies. ... Benign intracranial hypertension (BIH), also known by the obsolete term pseudotumor cerebri is a neurologic disease that is caused by increased intracranial pressure in the subarachnoid space surrounding the brain without any indication of intracranial pathology. ... A headache (cephalalgia in medical terminology) is a condition of pain in the head; sometimes neck or upper back pain may also be interpreted as a headache. ... Pancreatitis is inflammation of the pancreas. ... This article is about the medical condition. ... Intensive care medicine or critical care medicine is concerned with providing greater than ordinary medical care and observation to people in a critical or unstable condition. ...

• Altered body composition refers to the tendency of GH to build bone and muscle mass and reduce body fat.

• GH treatment usually decreases insulin sensitivity^[1]. This effect does not seem to cause problems in most people but it is possible to envision a combination of factors which would make this a more significant effect.

• When GH is given to children and adults who are not deficient, IGF1 levels may be raised above normal. Though no effects are obvious, prolonged periods of extremely high IGF1 levels occur in acromegaly, and a small amount of evidence suggests that higher IGF1 levels in older adults (not receiving GH) are associated with a slightly higher risk of certain cancers; a causal relationship has not been established.

• When GH is given to a child in high doses for many years, it can subtly affect the facial bone structure. It rarely is recognized as a change by patients and parents and even less often causes problems.

The following serious problems have been linked by one or two small reports but a true risk has not been confirmed by larger surveillance studies. In physical fitness, body composition is used to describe the percentages of fat, bone and muscle in human bodies. ... Insulin sensitivity is the opposite of insulin resistance. ... Insulin-like growth factor 1 (IGF-1) is a protein hormone similar in molecular structure to insulin. ... Cancer is a class of diseases or disorders characterized by uncontrolled division of cells and the ability of these to spread, either by direct growth into adjacent tissue through invasion, or by implantation into distant sites by metastasis (where cancer cells are transported through the bloodstream or lymphatic system). ... It has been suggested that temporal fenestra be merged into this article or section. ...

• Type 2 diabetes has been reported in a few adolescents treated with GH. It uncertain whether this is a causal association because the incidence of adolescent type 2 diabetes is rising so rapidly in most countries that we no longer have reliable incidence statistics for diabetes in the untreated adolescent population.

• Leukemia is the most common childhood cancer, occurring in about 1 in 40,000 children each year. Because leukocytes have GH receptors, leukemia cases have been carefully counted since recombinant GH was introduced. Although a few children with no risk factors treated with GH have developed leukemia, the numbers have been no more than would be expected in a similarly sized group. For a variety of reasons, it has been harder to achieve the same level of reassurance for children who do have a higher leukemia risk. These are primarily children who became GH deficient as a result of treatment for leukemia or a brain tumor. Available statistics are reassuring, but numbers are not large enough to exclude any amplification of risk.

• Several extra cases of colon cancer were found in a study of lifelong health and mortality of a group of middle-aged British adults with severe GH deficiency from childhood. All had been treated as children with cadaver GH. This association has not been confirmed and even if it were, it would need to be established whether the GH treatment in childhood or the untreated GH deficient state in adult life represented the true association.

Finally, in any discussion of side effects, our experience with Creutzfeldt-Jacob disease 20 years after cadaver GH treatment reminds us that side effects of an apparently safe treatment may be unforeseeable and long-delayed. See diabetes mellitus for further general information on diabetes. ... Leukemia or leukaemia (see spelling differences) is a cancer of the blood or bone marrow and is characterized by an abnormal proliferation (production by multiplication) of blood cells, usually white blood cells (leukocytes). ... Cancer is a class of diseases or disorders characterized by uncontrolled division of cells and the ability of these to spread, either by direct growth into adjacent tissue through invasion, or by implantation into distant sites by metastasis (where cancer cells are transported through the bloodstream or lymphatic system). ... White Blood Cells is also the name of a White Stripes album. ... In biochemistry, a receptor is a protein on the cell membrane or within the cytoplasm or cell nucleus that binds to a specific molecule (a ligand), such as a neurotransmitter, hormone, or other substance, and initiates the cellular response to the ligand. ... A brain tumor is any intracranial tumor created by abnormal and uncontrolled cell division, normally either in the brain itself (neurons, glial cells (astrocytes, oligodendrocytes, ependymal cells), lymphatic tissue, blood vessels), in the cranial nerves (myelin-producing Schwann cells), in the brain envelopes (meninges), skull, pituitary and pineal gland, or... Diagram of the stomach, colon, and rectum Colorectal cancer includes cancerous growths in the colon, rectum and appendix. ... This article needs to be cleaned up to conform to a higher standard of quality. ... Adverse effect, in medicine, is an abnormal, harmful, undesired and/or unintended side-effect, although not necessarily unexpected, which is obtained as the result of a therapy or other medical intervention, such as drug/chemotherapy, physical therapy, surgery, medical procedure, use of a medical device, etc. ...

Ethical issues

Hormone treatment seems an unlikely source of social controversy, but for four decades, growth hormone has been second only to estrogens and progestins (diethylstilbestrol, contraception, abortifacients, and post-menopausal replacement) in its ability to engender challenging ethical issues. The principal controversies of the last two decades arise from the intersection of two factors: high cost and the difficulty of defining a boundary between disease and variation of normal. In other words, if GH were inexpensive, it would be no more controversial than orthodontics. If there were zero potential benefit to all but the most easily defined, severely deficient persons, GH would be one more expensive treatment for a rare disease. But neither condition is true. Estriol. ... A progestin is a synthetic progestagen. ... Diethylstilbestrol (DES) is a drug, a synthetic nonsteroidal estrogen that was first synthesized in 1938. ... An abortion is the removal or expulsion of an embryo or fetus from the uterus, resulting in or caused by its death. ... Menopause is the physiological cessation of menstrual cycles associated with advancing age in women. ... Human variability, or human variation, refers to the range of possible values for any measurable characteristic, physical or mental, of human beings. ... Orthodontics is a specialty of dentistry that is concerned with the study and treatment of malocclusions (improper bites), which may be a result of tooth irregularity, disproportionate jaw relationships, or both. ...

• Growth hormone is one of the most expensive treatments in all of medicine. The cost of adult GH replacement for deficiency (or for “aging”) is about US$2000 per year. The cost of treatment for a non-deficient child (e.g., with Turner syndrome or idiopathic short stature) is about US$25,000 per year. A typical treatment course of 5 years yielding about 2 inches (5 cm) of extra adult height would cost approximately US$125,000. The highest cost, for treatment from infancy to age 70 of severe, congenital GH deficiency, could exceed US$300,000.

The high cost has been a subject of criticism of the pharmaceutical companies. A high cost was originally justified by the new technology and unusually extensive clinical trials. Orphan drug status in the United States (which blocks competing products for several years) was granted to the first two recombinant products (Genentech's Protropin and Lilly's Humatrope) introduced in the mid-1980s. Continuing production costs have been much lower than the drug price. When orphan drug status expired in the early 1990s it was hoped that introduction of additional brands into the market would result in a lower price. Instead, the 5 major companies offering synthetic GH have competed on other grounds than price. While the dollar price has not been increased to keep up with inflation over 2 decades, it hasn't been reduced as net manufacturing costs have fallen. Despite a similar manufacturing process, pricing of synthetic GH for use in cattle (see Bovine somatotropin) is inexpensive compared to the human product.

• Assessing the value of treatment to balance against the cost is made difficult by the range of severity of conditions treated and the difficulty of cleanly distinguishing disease from human variability. The most expensive treatment cost cited above for lifetime replacement of severe deficiency purchases for that person a 12"; (30 cm) height difference, enough to prevent shortness severe enough to be a physical handicap, enhanced marriage and employment prospects (compared with those under 56”). It also enhances bone and muscle strength, and perhaps even psychological resilience. It can prevent obesity, and may even prolong employability and life span. These are substantial benefits in return for the high cost, but less than 1 in 5000 children is born with this type of severe deficiency. At the other extreme is a child whose only diagnosable disease is a height in the lowest 2% of the population, who may gain 1 inch from 2 years of treatment. In between these extremes is a continuum of more or less severe shortness, greater or lesser response to treatment, and greater or smaller abnormalities to testing.

Questions and dilemmas arise from the previous facts. A pharmaceutical company, or drug company, is a commercial business whose focus is to research, develop, market and/or distribute drugs, most commonly in the context of healthcare. ... The granting of the orphan drug status is designed to encourage the development of drugs which are necessary but would be prohibitively expensive/un-profitable to develop under normal circumstances. ... Bovine somatotropin (bST), or bovine growth hormone (BGH), is a protein hormone that occurs naturally in the pituitary gland of cattle. ... This article is about the medical term. ... Human variability, or human variation, refers to the range of possible values for any measurable characteristic, physical or mental, of human beings. ...

• Is GH a wise use of finite health care resources? Is there anything wrong with an insurer or government health program declining to spend US$ 100 000 or more to make an otherwise healthy child a few inches taller?
• A physician usually assumes the responsibility of advocating for a patient to get coverage for a treatment. If the family of a normal but slightly short child thinks GH treatment is worth the cost and trouble, does the physician have a duty to support it? If the physician declines, is she being “paternalistic” rather than “respecting the patient’s autonomy”? Or is the physician merely giving the expert advice that the patient requested?
• If the cost of GH drops, and is given to short children whose parents can afford it, will shortness become a lifelong mark of lower social origins, like crooked teeth?
• Some have compared treating a child to protect him from the disadvantages of social heightism to lightening the skin or straightening hair to protect him from racism. Instead should we try to help the child recognize height prejudice, and try to immunize his self-esteem against it, since treating him would reinforce the message that being short is so bad that it justifies years of injections?
• If two children of the same height might gain the same benefit from treatment, is the reason for the shortness (diagnosis) an ethically relevant consideration? Does the child who tests more abnormally have a better claim to treatment?
• Is “idiopathic short stature” a medical condition worthy of treatment if it is defined simply as the shortest 1% of the population? Would it make a difference if many or most of this lowest 1% could be shown to have a defect of IGF1 production or responsiveness? If ISS were defined as the shortest 3%, 5%...?
• What is the difference between enhancement and therapy?
• Should mentally handicapped children be as eligible for GH treatment as those with more “normal” social prospects? Are parents the best judges of potential benefits?

See Synopsis of symposium on ethical aspects of GH treatment. It has been suggested that Health plan be merged into this article or section. ... Social class refers to the hierarchical distinctions between individuals or groups in societies or cultures. ... Heightism is a form of discrimination based on height. ... Racism is the prejudice that members of one race are intrinsically superior or inferior to members of other races. ... Mental retardation is a term for a pattern of persistently slow learning of basic motor and language skills (milestones) during childhood, and a significantly below-normal global intellectual capacity as an adult. ...

Legal issues

It is illegal to take growth hormone without a valid prescription from a doctor in many countries. In 2007, the actor Sylvester Stallone was prosecuted by Australian customs officials for bringing Jintropin into the country. Sylvester Stallone (born Michael Enzio Sylvester Stallone on July 6, 1946) is a two-time Academy Award-nominated American actor, director, producer and screenwriter. ...

History

Perhaps the most famous person who exemplified the appearance of untreated congenital growth hormone deficiency was Charles Sherwood Stratton (1838-1883), who was exhibited by P.T. Barnum as General Tom Thumb, and married Lavinia Warren. Pictures of the couple show the typical adult features of untreated severe growth hormone deficiency. Despite the severe shortness, limbs and trunks are proportional. Growth hormone deficiency is the medical condition of inadequate production of growth hormone (GH) and its effects on children and adults. ... The wedding party comprised, from left to right: George Washington Morrison Nutt (1844-1881), Charles Sherwood Stratton (1838-1883), Lavinia Warren Stratton (1841-1919), Minnie Warren (1841-1878). ... Phineas Taylor Barnum (July 5, 1810 – April 7, 1891), American showman who is best remembered for his entertaining hoaxes and for founding the circus that eventually became Ringling Brothers and Barnum and Bailey Circus. ... The wedding party comprised, from left to right: George Washington Morrison Nutt (1844–1881), Charles Sherwood Stratton (1838–1883), Lavinia Warren Stratton (1841–1919), Minnie Warren (1841–1878). ...

Like many other nineteenth century medical terms which lost precise meaning as they gained wider currency, “midget” as a term for someone with extreme proportional shortness acquired pejorative connotations and is no longer used in medical contexts. In the 19th century, midget was a medical term referring to an extremely short but normally-proportioned person and was used in contrast to dwarf, which denoted disproportionate shortness. ...

By the middle of the twentieth century endocrinologists understood the clinical features of growth hormone deficiency. GH is a protein hormone, like insulin, which had been purified from pig and cow pancreases for treatment of type 1 diabetes since the 1920's. However pig and cow GH did not 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). Insulin (from Latin insula, island, as it is produced in the Islets of Langerhans in the pancreas) is an anabolic polypeptide hormone that regulates carbohydrate metabolism. ... The pancreas is a gland organ in the digestive and endocrine systems of vertebrates[2]. It is both exocrine (secreting pancreatic juice containing digestive enzymes) and endocrine (producing several important hormones, including insulin, glucagon, and somatostatin). ...

Extraction for treatment

In the late 1950s Maurice Raben purified enough GH from human pituitary glands to successfully treat a GH-deficient boy. A few endocrinologists began to help parents of severely GH deficient children to make arrangements with local pathologists to collect human pituitary glands after removal at autopsy. Parents would then contract with a biochemist to purify enough growth hormone to treat their child. Few families could manage such a complicated undertaking. The pituitary gland, or hypophysis, is an endocrine gland about the size of a pea that sits in a small, bony cavity (sella turcica) covered by a dural fold (sellar diaphragm) at the base of the brain. ... To meet Wikipedias quality standards, this article or section may require cleanup. ... Post-mortem, postmortem and post mortem redirect here. ... Biochemistry is the study of the chemical processes and transformations in living organisms. ...

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, UK, 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. National Institutes of Health Building 50 at NIH Clinical Center - Building 10 The National Institutes of Health (NIH) is an agency of the United States Department of Health and Human Services and is the primary agency of the United States government responsible for biomedical research. ...

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. Pediatric endocrinology is a medical subspecialty dealing with variations of physical growth and sexual development in childhood, as well as diabetes and other disorders of the endocrine glands. ...

In 1976 physicians became aware that Creutzfeldt-Jacob disease could be transmitted by neurosurgical procedures and cornea transplantation. CJD is a rapidly fatal dementing disease of the brain also known as spongiform encephalopathy, related to “mad cow disease”. This article needs to be cleaned up to conform to a higher standard of quality. ... Insertion of an electrode during neurosurgery for Parkinsons disease. ... For other uses, see Dementia (disambiguation). ... Transmissible spongiform encephalopathies (TSEs, also known as prion diseases) are a group of progressive conditions that affect the brain and nervous system of humans and animals and are transmitted by prions. ... Bovine spongiform encephalopathy (BSE or commonly mad cow disease) is a fatal, neurodegenerative disease of cattle, which infects by a mechanism that shocked biologists on its discovery in late 20th century and appears transmissible to humans. ...

In 1977 the NPA GH extraction and purification procedure was refined and improved.

A shortage of available cadaver GH worsened in the late 1970’s as the autopsy rate in the U.S. declined, while the number of pediatric endocrinologists able to diagnose and treat GH deficiency increased. GH was "rationed." 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. Only those pediatric endocrinologists who remained at university medical centers with departments able to support a research program had access to NPA growth hormone.

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. Although an additional source of GH was welcomed, Crescormon was greeted with ambivalence by pediatric endocrinologists in the United States. The first concern was that Kabi would begin to purchase pituitaries in the U.S., which would quickly undermine the NPA, which relied on a donation system like blood transfusion. As the number of autopsies continued to shrink, would pathologists sell pituitaries to a higher bidder? The second offense was Kabi-Pharmacia’s marketing campaign, which was directed at primary care physicians under the slogan, “Now, you determine the need,” implying that the services of a specialist were not needed for growth hormone treatment anymore and that any short child might be a candidate for treatment. Although the Crescormon controversy in the U.S. is long forgotten, Kabi’s pituitary purchase program continued to generate scandal in Europe as recently as 2000. A primary care physician, or PCP, is a physician who provides both the first contact for a person with an undiagnosed health concern as well as continuing care of varied medical conditions, not limited by cause, organ system, or diagnosis. ...

Synthetic HGH

In 1981, the new American corporation Genentech, after 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, approval was deferred as lengthy safety trials continued over the next four years. Recombinant DNA technology adds/replaces DNA in an organism resulting in the recipient organism containing exogenous DNA. Recombinant proteins are proteins that are produced by different genetically modified organisms following insertion of the relevant DNA into their genome. ... For a non-technical introduction to the topic, see Introduction to Genetics. ...

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 use of human pituitary GH rapidly ceased. Between 1985 and 2003, a total of 26 cases of CJD occurred in adults who had received NPA GH before 1977 (out of 7700), comparable numbers of cases occurred around the world. 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 methionyl growth hormone, which was introduced in 1985 as Protropin in the United States. Although this previously scarce commodity was suddenly available in “bucketfuls,” the price of treatment (US$10,000–30,000 per year) was the highest at the time. Genentech justified it by the prolonged research and development investment, orphan drug status, and a pioneering post-marketing surveillance registry for tracking safety and effectiveness. The granting of the orphan drug status is designed to encourage the development of drugs which are necessary but would be prohibitively expensive/un-profitable to develop under normal circumstances. ...

Within a few years, GH treatment had become “big business” in more than one sense. In the United States, Eli Lilly launched a competing natural sequence 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 (but without cutting price). Most children with severe deficiency in the developed world are now likely to have access to a pediatric endocrinologist and be diagnosed and offered treatment. Eli Lilly and Company (NYSE: LLY) is a global pharmaceutical company and one of the worlds largest corporations. ... Pfizer Incorporated (NYSE: PFE) is the worlds largest research-based pharmaceutical company[1].[1] The company is based in New York City. ...

Pediatric endocrinology became a recognizable specialty in the 1950s, but did not reach board status in the U.S. until the late 1970s. Even 10 years later, as a cognitive, procedureless specialty dealing with mostly rare diseases, it was one of the smallest, lowest paid, and more obscure of the medical specialities. Pediatric endocrinologists were the only physicians interested in the arcana of GH metabolism and children’s growth, but their previously academic arguments took on new practical significance with major financial implications. Pediatric endocrinology is a medical subspecialty dealing with variations of physical growth and sexual development in childhood, as well as diabetes and other disorders of the endocrine glands. ...

The major scientific arguments dated back to the days of GH scarcity:

• Everyone agrees on the nature and diagnosis of severe GH deficiency, but what are the edges and variations?
• How should marked constitutional delay be distinguished from partial GH deficiency?
• To what extent is “normal shortness” a matter of short children naturally making less growth hormone?
• Can a child make GH in response to a stimulation test but fail to make enough in “daily life” to grow normally?
• If a stimulation test is used to define deficiency, what GH cutoff should be used to define normal?

It was the ethical questions that were new. Is GH a wise use of finite health care resources, or is the physician’s primary responsibility to the patient? If GH is given to most extremely short children to make them taller, will the definition of “extremely short” will simply rise, negating the expected social benefit? If GH is given to short children whose parents can afford it, will shortness become a permanent mark of lower social origins? More of these issues are outlined in the ethics section. Whole meetings were devoted to these questions; pediatric endocrinology had become a specialty with its own bioethics issues. Puberty is described as delayed when a boy or girl has passed the usual age of onset of puberty with no physical or hormonal signs that it is beginning. ... People who are shorter have short stature. ... {{}} Bioethics are the ethics of biological science and medicine. ... {{}} Bioethics are the ethics of biological science and medicine. ...

Despite the price, the 1990s became an era of experimentation to see what else growth hormone could help. The medical literature of the decade contains hundreds of reports of small trials of GH use in nearly every type of growth failure and shortness imaginable. In most cases the growth responses were modest. For conditions with a large enough potential market, 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. Similar expansion of use occurred in Europe. hi “FDA” redirects here. ... Prader-Willi syndrome is a genetic disorder, in which seven genes (or some subset thereof) on chromosome 15 are missing or unexpressed (chromosome 15q partial deletion) on the paternal chromosome. ... Intrauterine growth retardation or Intrauterine growth restriction (IUGR) refers to the condition during pregnancy where a fetus is considered to be too small for its gestational age (generally in the 10th percentile). ...

One obvious potential market was adult GH deficiency. By the mid-1990s, several GH companies had sponsored or publicized research into the quality of life of adults with severe GH deficiency. Most were people who had been treated with GH in childhood for severe deficiency. Nearly all of them had been happy to leave the injections behind as they reached final heights in the low normal range. However as adults in their 30s and 40s, these people had more than their share of common adult problems: reduced physical, mental, and social energy, excess adipose and diminished muscle, diminished libido, poor bone density, higher cholesterol levels, and higher rates of cardiovascular disease. Research trials soon confirmed that a few months of GH could improve nearly all of these parameters. However, despite marketing efforts, most GH deficient adults remain untreated. The well-being or quality of life of a population is an important concern in economics and political science. ...

Though GH use was slow to be accepted among adults with GH deficiency, similar research to see if GH treatment could slow or reverse some of the similar effects of aging attracted much public interest. The most publicized trial was reported by Daniel Rudman in 1990.^[2] As with other types of hormone supplementation for aging (testosterone, estrogen, DHEA), confirmation of benefit and accurate understanding of risks has been only slowly evolving. Use of GH for effects of aging is discussed in more detail in HGH controversies. Testosterone is a steroid hormone from the androgen group. ... Estriol. ... Dehydroepiandrosterone (DHEA), is a natural steroid prohormone produced from cholesterol by the adrenal glands, the gonads, adipose tissue, brain and in the skin (by an autocrine mechanism)]. DHEA is the precursor of androstenedione, testosterone and estrogen. ... It has been suggested that Longevity genes be merged into this article or section. ... There are many controversies around the claims, products, and businesses related to the use of growth hormone as an anti-aging therapy. ...

There are always entrepreneurs who don't need much evidence to see a business opportunity. In 1997, Ronald Klatz published Grow Young With HGH: The Amazing Medically Proven Plan To Reverse the Effects Of Aging,^[3] an uncritical touting of GH as the answer to aging. This time the internet amplified the proposition and spawned a hundred frauds and scams. Fortunately, their adoption of the "HGH" term has provided an easy way to distinguish the hype from the evidence. For more, see HGH controversies. There are many controversies around the claims, products, and businesses related to the use of growth hormone as an anti-aging therapy. ...

In 2003, growth hormone hit the news again, when the US FDA granted Eli Lilly approval to market Humatrope for the treatment of idiopathic short stature. The indication was controversial for several reasons, the primary one being the difficulty in defining extreme shortness with normal test results as a disease rather than the extreme end of the normal height range; in fact, the definition offered by Lilly for ISS is a height in the shortest 1.2% of the population. While this is an extreme degree of shortness, critics suggested that the company could afford to be extremely restrictive to earn approval, yet be confident that the definition, as well as actual use, would be driven upward by parents and physicians. Meanwhile, pediatric endocrinologists are still arguing about whether ISS is a "pathologic" or a statistical condition. Eli Lilly and Company (NYSE: LLY) is a global pharmaceutical company and one of the worlds largest corporations. ... Idiopathic short stature (ISS) refers to extreme short stature that does not have a diagnostic explanation (idiopathic designates a condition that is unexplained or not understood) after an ordinary growth evaluation. ...

As of 2004, GH use continues to rise, though it is no longer the most expensive prescription drug in the formulary. Synthetic growth hormone available in the U.S. (and their manufacturers) included Nutropin (Genentech), Humatrope (Lilly), Genotropin (Pfizer), Norditropin (Novo), Tev-Tropin (Teva) and Saizen (Serono). The products are nearly identical in composition, efficacy, and cost, varying primarily in the formulations and delivery devices. Saizen® is a commercial preparation of synthetic somatropin (growth hormone, a. ...

References

1. ^ Bramnert M, Segerlantz M, Laurila E, Daugaard JR, Manhem P, Groop L (2003). "Growth hormone replacement therapy induces insulin resistance by activating the glucose-fatty acid cycle". The Journal of Clinical Endocrinology & Metabolism 88 (4): 1455-1463. PMID 12679422. 
2. ^ Rudman D, Feller AG, Nagraj HS et al. "Effect of human growth hormone in men over 60 years old," New England Journal of Medicine 323:1–6 PMID 2355952
3. ^ New York: Harper-Collins

Support organizations

• The Most Frequently Asked Questions when Beginning GH Treatment-The MAGIC Foundation for Children's Growth

External links

• Human Growth Foundation
• Growth Section of The Hormone Foundation
• Magic Foundation for Children's Growth
• Other support groups
• General overview of GH use for physicians
• National Organization of Short Statured Adults
• Short Persons Support