Growth hormone treatment
Encyclopedia
Growth hormone treatment refers to the use of growth hormone
(GH) in medical treatment. Growth hormone is a peptide hormone
secreted by the pituitary gland that 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 is prescribed for a variety of reasons. GH therapy has been a focus of social and ethical controversies for 50 years.
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
.
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 peptide molecule, it must be injected into subcutaneous tissue or muscle to get it into the blood. Nearly painless insulin
syringe
s make this less trying than is usually anticipated, but perceived discomfort is a subjective value.
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. .
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.
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.
. Increased Muscle
mass, decrease of adipose tissue
, faster hair
and nail growth, strengthened immune system
, increased circulatory system
, and improved blood lipid
levels, but long term mortality benefit has not yet been demonstrated.
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 some adults to seek medical care, unacceptability of injections, inadequate insurance coverage, and significantly lower rates of diagnosis and treatment offered by internist endocrinologists
.
A peer-review article published in 2010 indicates that "Growth hormone (GH) replacement unequivocally benefits growth, body composition, cardiovascular risk factors and quality of life. Less is known about the effects of GH on learning and memory."
for treatment of five other conditions in children and one other indication in adults:
Due to the immunostimulatory effect of GH, it can enhance immunorecevory after radiation in mice and nonhuman primates.
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 sometimes offered in these circumstances.
GH replacement (i.e. adding it to the body when it is missing) unequivocally significantly improve health increasing muscle
and bone
mass, improving cardiocirculatory parameters.
In GH deficient children and adults, improvement of cognitive functions (memory
, attention) have been observed in small studies after the administration of GH.
Neurodegenerative diseases (i.e. Alzheimer's disease
) are connected with the decline of growth hormone levels, therefore some authors suggest that it is necessary to evaluate the use GH as future antinuerodegenerative strategy.
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.
Children with inflammatory bowel disease
and Crohn's disease
have often GH and IGF-I deficiency and /or GH resistance.
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, but it is unknown whether this actually leads to an increased adult height.
Children with Crohn's disease
can often have growth reduction, it was seen that growth hormone treatment can increase height. However further studies are necessary to better evaluate the efficacy of this therapy.
Poor growth is a part of Noonan syndrome
and many other genetic syndrome
s. 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 in (2.5–5.1 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.
Coeliac Disease
can prevent children from reaching their expected growth potential, if it begins before growth is complete. Stunted growth can be a result of Coeliac Disease damaging the intestines and preventing proper nutrient absorption. Treatment involves a gluten-free diet. HGH treatment has been used in an attempt to recover lost growth due to this effect.
On occasion, GH has 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 exclusive list.
Other scientists have explored whether hGH treatment could be useful in adults that are not severely deficient in GH. Treatment of healthy, normally aging individuals found the only benefit to be a slight increase in muscle mass, with frequent side-effects and no evidence that it is safe to use long-term.
GH has been given to attempt 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 caloric restriction to attempt to treat 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 potential benefit, but this has not been widely adopted for a variety of reasons (cost, injections, potential aggravation of insulin resistance
, etc.). Recent studies suggest that side-effects, in particular, insulin resistance, may outweigh the potential benefits of such therapy.
A study in the New England Journal of Medicine suggested that HGH might be a beneficial treatment for patients with Crohn's disease.
Fibromyalgia
and chronic fatigue syndrome
are poorly understood and vaguely defined conditions with overlapping features. After demonstration of disordered GH secretion and higher rates of tissue breakdown in patients with these conditions, a few people tried growth hormone treatment to see whether 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 given to patients to attempt 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 may possibly be improved with GH treatment.
Some recent clinical studies have shown that low-dose GH treatment for adults with GH deficiency changes the body composition by increasing muscle
mass, decreasing fat mass, increasing bone
density and muscle strength, effect cardiovascular parameters (i.e. decrease of LDL cholesterol), affects the quality of life and, if properly used, without significant side effects.
GH has been taken by athletes wanting to increase recovery, strength, and power. 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.
In GH deficient children and adults, improvement of cognitive functions (memory
, attention) have been observed in small studies after the administration of GH.
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 having received GH. The reason is unknown, but GH is now rarely used in ICU patients unless they have severe growth hormone deficiency.
GH treatment usually decreases insulin sensitivity, but some studies showed no evidence for increased diabetes
incidence in GH-treated adult hypopituitary patients.
In past it was believed that GH treatment could increase the cancer
risk; a large study recently concluded that "With relatively short follow-up, the overall primary cancer risk in 6840 patients receiving GH as adults was not increased. Elevated SIRs (which is risk of getting cancer) were found for subgroups in the USA cohort defined by age <35 years or childhood onset GH 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.
Like many other nineteenth-century medical terms that 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.
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 pancreas
es for treatment of type 1 diabetes since the 1920s. However, pig and cow GH did not work at all 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 1950s, Maurice Raben purified enough GH from human pituitary gland
s 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.
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.
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 1960s 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 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”.
In 1977, the NPA GH extraction and purification procedure was refined and improved.
A shortage of available cadaver GH worsened in the late 1970s 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 . Children who were short for reasons other than severe GH deficiency were lied to and told that they would not benefit from treatment. Only those pediatric endocrinologists that remained at university medical centers with departments able to support a research program had access to NPA growth hormone.
In the late 1970s, 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 physician
s 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.
s were inserted into bacteria so that they 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.
In 1985, four young adults in the U.S. having received NPA growth hormone in the 1960s 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 having 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 recombinant human 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 (National Cooperative Growth Study
).
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 Nordisk
, and Serono
marketed nearly identical recombinant 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.
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.
The major scientific arguments dated back to the days of GH scarcity:
It was the ethical
questions that were new. Is GH not a wise use of finite healthcare 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” 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.
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 pharmaceutical companies that were making growth hormone to achieve approval to market for those specific indications. Turner syndrome
and chronic renal failure
were the first of these “nonGH-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.
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 having been treated with GH in childhood for severe deficiency. Although the injections are painless, many of them had been happy to leave injections behind as they reached final heights in the low-normal range. However, as adults in their 30s and 40s, these people, who had been children with growth hormone deficiency, were now adults with growth hormone deficiency and 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.
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. 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.
There are always entrepreneurs who do not need much evidence to see a business opportunity. In 1997, Ronald Klatz of the American Academy of Anti-Aging Medicine
published Grow Young With HGH: The Amazing Medically Proven Plan To Reverse the Effects Of Aging, an uncritical touting of GH as the answer to aging. This time, the internet amplified the proposition and spawned a hundred frauds and scams. However, their adoption of the "HGH" term has provided an easy way to distinguish the hype from the evidence.
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.
As of 2004, GH use continues to rise, though it is no longer the most expensive prescription drug in the formulary. Recombinant growth hormone available in the U.S. (and their manufacturers) included Nutropin (Genentech
), Humatrope (Eli Lilly and Company
), Genotropin (Pfizer
), Norditropin (Novo Nordisk
), Tev-Tropin (Teva
) and Saizen
(Merck Serono
). The products are nearly identical in composition, efficacy, and cost, varying primarily in the formulations and delivery devices.
Due to the immunostimulatory effect of GH, it can enhance immunorecevory after radiation in mice and nonhuman primates.
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 sometimes offered in these circumstances.
GH replacement (i.e. adding it to the body when it is missing) unequivocally significantly improve health increasing muscle
and bone
mass, improving cardiocirculatory parameters.
In GH deficient children and adults, improvement of cognitive functions (memory
, attention) have been observed in small studies after the administration of GH.
Neurodegenerative diseases (i.e. Alzheimer's disease
) are connected with the decline of growth hormone levels, therefore some authors suggest that it is necessary to evaluate the use GH as future antinuerodegenerative strategy.
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.
Children with inflammatory bowel disease
and Crohn's disease
have often GH and IGF-I deficiency and /or GH resistance.
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, but it is unknown whether this actually leads to an increased adult height.
Children with Crohn's disease
can often have growth reduction, it was seen that growth hormone treatment can increase height. However further studies are necessary to better evaluate the efficacy of this therapy.
Poor growth is a part of Noonan syndrome
and many other genetic syndrome
s. 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 in (2.5–5.1 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.
Coeliac Disease
can prevent children from reaching their expected growth potential, if it begins before growth is complete. Stunted growth can be a result of Coeliac Disease damaging the intestines and preventing proper nutrient absorption. Treatment involves a gluten-free diet. HGH treatment has been used in an attempt to recover lost growth due to this effect.
On occasion, GH has 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 exclusive list.
Other scientists have explored whether hGH treatment could be useful in adults that are not severely deficient in GH. Treatment of healthy, normally aging individuals found the only benefit to be a slight increase in muscle mass, with frequent side-effects and no evidence that it is safe to use long-term.
GH has been given to attempt 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 caloric restriction to attempt to treat 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 potential benefit, but this has not been widely adopted for a variety of reasons (cost, injections, potential aggravation of insulin resistance
, etc.). Recent studies suggest that side-effects, in particular, insulin resistance, may outweigh the potential benefits of such therapy.
A study in the New England Journal of Medicine suggested that HGH might be a beneficial treatment for patients with Crohn's disease.
Fibromyalgia
and chronic fatigue syndrome
are poorly understood and vaguely defined conditions with overlapping features. After demonstration of disordered GH secretion and higher rates of tissue breakdown in patients with these conditions, a few people tried growth hormone treatment to see whether 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 given to patients to attempt 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 may possibly be improved with GH treatment.
Some recent clinical studies have shown that low-dose GH treatment for adults with GH deficiency changes the body composition by increasing muscle
mass, decreasing fat mass, increasing bone
density and muscle strength, effect cardiovascular parameters (i.e. decrease of LDL cholesterol), affects the quality of life and, if properly used, without significant side effects.
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.
rHGH refers to recombinant human growth hormone (somatropin). It contains the identical amino acid sequence of human GH and is "natural sequence" GH. In chemical structure, it is 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 pharmaceutical companies in the US.
It is coincidental that 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.
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.
rBST refers to recombinant bovine somatropin (cow growth hormone), or recombinant bovine GH (rbGH).
Growth hormone
Growth hormone is a peptide hormone that stimulates growth, cell reproduction and regeneration in humans and other animals. Growth hormone is a 191-amino acid, single-chain polypeptide that is synthesized, stored, and secreted by the somatotroph cells within the lateral wings of the anterior...
(GH) in medical treatment. Growth hormone is a peptide hormone
Peptide hormone
Peptide hormones are a class of peptides that are secreted into the blood stream and have endocrine functions in living animals.Like other proteins, peptide hormones are synthesized in cells from amino acids according to an mRNA template, which is itself synthesized from a DNA template inside the...
secreted by the pituitary gland that stimulates growth
Cell growth
The term cell growth is used in the contexts of cell development and cell division . When used in the context of cell division, it refers to growth of cell populations, where one cell grows and divides to produce two "daughter cells"...
and cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
reproduction. In the past, growth hormone was extracted from human pituitary glands. GH is now produced by recombinant DNA technology and is prescribed for a variety of reasons. GH therapy has been a focus of social and ethical controversies for 50 years.
This article describes the history of GH treatment, current uses, risks, and social controversies arising from GH use. Other articles describe GH physiology
Growth hormone
Growth hormone is a peptide hormone that stimulates growth, cell reproduction and regeneration in humans and other animals. Growth hormone is a 191-amino acid, single-chain polypeptide that is synthesized, stored, and secreted by the somatotroph cells within the lateral wings of the anterior...
, diseases of GH excess (acromegaly
Acromegaly
Acromegaly is a syndrome that results when the anterior pituitary gland produces excess growth hormone after epiphyseal plate closure at puberty...
and pituitary gigantism
Gigantism
Gigantism, also known as giantism , is a condition characterized by excessive growth and height significantly above average...
), deficiency
Growth hormone deficiency
Growth hormone deficiency is a medical condition in which the body does not produce enough growth hormone . Growth hormone, also called somatotropin, is a polypeptide hormone which stimulates growth and cell reproduction...
, the recent phenomenon of HGH controversies
HGH controversies
Controversies regarding the use of human growth hormone as treatment method have centered around the claims, products, and businesses related to the use of growth hormone as an anti-aging therapy...
, and growth hormone for cows
Bovine somatotropin
Bovine somatotropin , or BGH, is a chain of amino acids produced by the cow's pituitary gland. Like other hormones, it is produced in small quantities and is used in regulating metabolic processes...
.
HGH deficiency in children
Growth hormone deficiencyGrowth hormone deficiency
Growth hormone deficiency is a medical condition in which the body does not produce enough growth hormone . Growth hormone, also called somatotropin, is a polypeptide hormone which stimulates growth and cell reproduction...
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 peptide molecule, it must be injected into subcutaneous tissue or muscle to get it into the blood. Nearly painless insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
syringe
Syringe
A syringe is a simple pump consisting of a plunger that fits tightly in a tube. The plunger can be pulled and pushed along inside a cylindrical tube , allowing the syringe to take in and expel a liquid or gas through an orifice at the open end of the tube...
s make this less trying than is usually anticipated, but perceived discomfort is a subjective value.
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
Adipose tissue
In histology, adipose tissue or body fat or fat depot or just fat is loose connective tissue composed of adipocytes. It is technically composed of roughly only 80% fat; fat in its solitary state exists in the liver and muscles. Adipose tissue is derived from lipoblasts...
. 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. .
Still, costs of treatment in terms of money, effort, and perhaps quality of life
Quality of life
The term quality of life is used to evaluate the general well-being of individuals and societies. The term is used in a wide range of contexts, including the fields of international development, healthcare, and politics. Quality of life should not be confused with the concept of standard of...
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.
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.
HGH deficiency in adults
GH replacement therapy can provide a number of measurable benefits to GH-deficient adults. These include improved bone densityBone density
Bone density is a medical term normally referring to the amount of mineral matter per square centimeter of bones. Bone density is used in clinical medicine as an indirect indicator of osteoporosis and fracture risk.This medical bone density is not the true physical "density" of the bone, which...
. Increased Muscle
Muscle
Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...
mass, decrease of adipose tissue
Adipose tissue
In histology, adipose tissue or body fat or fat depot or just fat is loose connective tissue composed of adipocytes. It is technically composed of roughly only 80% fat; fat in its solitary state exists in the liver and muscles. Adipose tissue is derived from lipoblasts...
, faster hair
Hair
Hair is a filamentous biomaterial, that grows from follicles found in the dermis. Found exclusively in mammals, hair is one of the defining characteristics of the mammalian class....
and nail growth, strengthened immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
, increased circulatory system
Circulatory system
The circulatory system is an organ system that passes nutrients , gases, hormones, blood cells, etc...
, and improved blood lipid
Lipid
Lipids constitute a broad group of naturally occurring molecules that include fats, waxes, sterols, fat-soluble vitamins , monoglycerides, diglycerides, triglycerides, phospholipids, and others...
levels, but long term mortality benefit has not yet been demonstrated.
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 some adults to seek medical care, unacceptability of injections, inadequate insurance coverage, and significantly lower rates of diagnosis and treatment offered by internist endocrinologists
Endocrinology
Endocrinology is a branch of biology and medicine dealing with the endocrine system, its diseases, and its specific secretions called hormones, the integration of developmental events such as proliferation, growth, and differentiation and the coordination of...
.
A peer-review article published in 2010 indicates that "Growth hormone (GH) replacement unequivocally benefits growth, body composition, cardiovascular risk factors and quality of life. Less is known about the effects of GH on learning and memory."
Other
As of 2004, GH has been approved by the U.S. Food and Drug AdministrationFood and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
for treatment of five other conditions in children and one other indication in adults:
- In adults, wasting (or cachexiaCachexiaCachexia or wasting syndrome is loss of weight, muscle atrophy, fatigue, weakness, and significant loss of appetite in someone who is not actively trying to lose weight...
) caused by AIDS.
- Turner syndromeTurner syndromeTurner syndrome or Ullrich-Turner syndrome encompasses several conditions in human females, of which monosomy X is most common. It is a chromosomal abnormality in which all or part of one of the sex chromosomes is absent...
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 in (5.1–7.6 cm) on this dose. The gains appear to be dose-dependent. It has been used successfully in toddlers with Turner syndrome, as well as in older girls.
- Chronic renal failureChronic renal failureChronic kidney disease , also known as chronic renal disease, is a progressive loss in renal function over a period of months or years. The symptoms of worsening kidney function are unspecific, and might include feeling generally unwell and experiencing a reduced appetite...
results in many problems, including growth failure. GH treatment for several years both before and after transplantationOrgan transplantOrgan transplantation is the moving of an organ from one body to another or from a donor site on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative medicine is allowing scientists and engineers to create organs to be...
may prevent further deceleration of growth and may narrow the height deficit, though even with treatment net adult height loss may be about 4 in (10.2 cm).
- Prader-Willi syndromePrader-Willi syndromePrader–Willi syndrome is a rare genetic disorder in which seven genes on chromosome 15 are deleted or unexpressed on the paternal chromosome...
, a generally non-hereditary genetic condition, is a case where GH is prescribed for benefits in addition to height. GH is now standard care for children with PWS in the United States, when prescribed with appropriate precautions by an experienced endocrinologist. GH can help children with PWS in height, weight, body mass, strength, and agility. . Reports have indicated increase of growth rate (especially in the first year of treatment) and a variety of other positive effects, including improved body composition (higher muscle mass, lower fat mass); improved weight management; increased energy and physical activity; improved strength, agility, and endurance; and improved respiratory function. The Prader-Willi Syndrome Association (USA) recommends that a sleep study be conducted before initiating GH treatment in a child with PWS. At this time there is no direct evidence of a causative link between growth hormone and the respiratory problems seen in PWS (among both those receiving and those not receiving GH treatment), including sudden death. A follow-up sleep study after one year of GH treatment may also be indicated. GH (specifically Pfizer's version, Genotropin) is the only treatment that has received an FDA indication for children with PWS. The FDA indication only applies to children.
- 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 are limited.
- Idiopathic short statureIdiopathic short statureIdiopathic short stature refers to extreme short stature that does not have a diagnostic explanation after an ordinary growth evaluation...
(ISS) is one of the most controversial indications for GH as pediatric endocrinologists do not agree on its definition, diagnostic criteriaMedical diagnosisMedical diagnosis refers both to the process of attempting to determine or identify a possible disease or disorder , and to the opinion reached by this process...
, 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 1990s, the pharmaceutical manufacturer Eli Lilly and CompanyEli Lilly and CompanyEli Lilly and Company is a global pharmaceutical company. Eli Lilly's global headquarters is located in Indianapolis, Indiana, in the United States...
sponsored trials of HumatropeHumatropeHumatrope is a polypeptide hormone of rDNA origin. Manufactured by Eli Lilly and Company, it is used to stimulate linear growth in pediatric patients who lack adequate normal human growth hormone...
(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 – in adult height. Controversy has arisen as to whether all of these children were truly "short normal" children, since the average IGF1 was low. It was not surprising that 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.
Research
Everything discussed in this section involves either studies to see if GH could be useful for other diseases or conditions, or off-label uses that doctors have developed in the course of their daily work. None of the uses described below have been approved by the FDA.Due to the immunostimulatory effect of GH, it can enhance immunorecevory after radiation in mice and nonhuman primates.
Post-transplant growth failure sometimes improves with GH. Many children who suffer from chronic renal, liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
, and heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
disease grow poorly for years before a transplant
Organ transplant
Organ transplantation is the moving of an organ from one body to another or from a donor site on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative medicine is allowing scientists and engineers to create organs to be...
is required (or available). While growth may improve after correction of organ function by successful transplantation, the immunosuppressive
Immunosuppression
Immunosuppression involves an act that reduces the activation or efficacy of the immune system. Some portions of the immune system itself have immuno-suppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other...
drugs taken to protect the transplanted organ may continue to interfere with growth. Growth hormone may help offset these effects and is sometimes offered in these circumstances.
GH replacement (i.e. adding it to the body when it is missing) unequivocally significantly improve health increasing muscle
Muscle
Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...
and bone
Bone
Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...
mass, improving cardiocirculatory parameters.
In GH deficient children and adults, improvement of cognitive functions (memory
Memory
In psychology, memory is an organism's ability to store, retain, and recall information and experiences. Traditional studies of memory began in the fields of philosophy, including techniques of artificially enhancing memory....
, attention) have been observed in small studies after the administration of GH.
Neurodegenerative diseases (i.e. Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
) are connected with the decline of growth hormone levels, therefore some authors suggest that it is necessary to evaluate the use GH as future antinuerodegenerative strategy.
X-linked hypophosphatemic rickets is an inherited disorder of phosphorus
Phosphorus
Phosphorus is the chemical element that has the symbol P and atomic number 15. A multivalent nonmetal of the nitrogen group, phosphorus as a mineral is almost always present in its maximally oxidized state, as inorganic phosphate rocks...
metabolism that results in growth failure and rickets
Rickets
Rickets is a softening of bones in children due to deficiency or impaired metabolism of vitamin D, magnesium , phosphorus or calcium, potentially leading to fractures and deformity. Rickets is among the most frequent childhood diseases in many developing countries...
. GH has been shown to accelerate growth modestly.
Children with inflammatory bowel disease
Inflammatory bowel disease
In medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...
and Crohn's disease
Crohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...
have often GH and IGF-I deficiency and /or GH resistance.
Inflammatory bowel disease
Inflammatory bowel disease
In medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...
(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, but it is unknown whether this actually leads to an increased adult height.
Children with Crohn's disease
Crohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...
can often have growth reduction, it was seen that growth hormone treatment can increase height. However further studies are necessary to better evaluate the efficacy of this therapy.
Poor growth is a part of Noonan syndrome
Noonan syndrome
Noonan Syndrome is a relatively common autosomal dominant congenital disorder considered to be a type of dwarfism, that affects both males and females equally. It used to be referred to as the male version of Turner's syndrome ; however, the genetic causes of Noonan syndrome and Turner syndrome...
and many other genetic syndrome
Syndrome
In medicine and psychology, a syndrome is the association of several clinically recognizable features, signs , symptoms , phenomena or characteristics that often occur together, so that the presence of one or more features alerts the physician to the possible presence of the others...
s. 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 in (2.5–5.1 cm) of extra adult height.
Small numbers of children with various forms of bone dysplasia (dwarfism
Dwarfism
Dwarfism is short stature resulting from a medical condition. It is sometimes defined as an adult height of less than 4 feet 10 inches , although this definition is problematic because short stature in itself is not a disorder....
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.
Coeliac Disease
Coeliac disease
Coeliac disease , is an autoimmune disorder of the small intestine that occurs in genetically predisposed people of all ages from middle infancy onward...
can prevent children from reaching their expected growth potential, if it begins before growth is complete. Stunted growth can be a result of Coeliac Disease damaging the intestines and preventing proper nutrient absorption. Treatment involves a gluten-free diet. HGH treatment has been used in an attempt to recover lost growth due to this effect.
On occasion, GH has 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 exclusive list.
Other scientists have explored whether hGH treatment could be useful in adults that are not severely deficient in GH. Treatment of healthy, normally aging individuals found the only benefit to be a slight increase in muscle mass, with frequent side-effects and no evidence that it is safe to use long-term.
GH has been given to attempt to promote healing of large burns
Burn (injury)
A burn is a type of injury to flesh caused by heat, electricity, chemicals, light, radiation or friction. Most burns affect only the skin . Rarely, deeper tissues, such as muscle, bone, and blood vessels can also be injured...
by reducing the amount of protein breakdown during the early post-injury period.
GH has been used as an adjunct to caloric restriction to attempt to treat obesity
Obesity
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
. GH promotes lipolysis
Lipolysis
Lipolysis is the breakdown of lipids and involves the hydrolysis of triglycerides into free fatty acids followed by further degradation into acetyl units by beta oxidation. The process produces Ketones, which are found in large quantities in ketosis, a metabolic state that occurs when the liver...
and reduces proteolysis
Proteolysis
Proteolysis is the directed degradation of proteins by cellular enzymes called proteases or by intramolecular digestion.-Purposes:Proteolysis is used by the cell for several purposes...
. 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
Starvation
Starvation is a severe deficiency in caloric energy, nutrient and vitamin intake. It is the most extreme form of malnutrition. In humans, prolonged starvation can cause permanent organ damage and eventually, death...
economy. Results showed potential benefit, but this has not been widely adopted for a variety of reasons (cost, injections, potential aggravation of insulin resistance
Insulin resistance
Insulin resistance is a physiological condition where the natural hormone insulin becomes less effective at lowering blood sugars. The resulting increase in blood glucose may raise levels outside the normal range and cause adverse health effects, depending on dietary conditions. Certain cell types...
, etc.). Recent studies suggest that side-effects, in particular, insulin resistance, may outweigh the potential benefits of such therapy.
A study in the New England Journal of Medicine suggested that HGH might be a beneficial treatment for patients with Crohn's disease.
Fibromyalgia
Fibromyalgia
Fibromyalgia is a medical disorder characterized by chronic widespread pain and allodynia, a heightened and painful response to pressure. It is an example of a diagnosis of exclusion...
and chronic fatigue syndrome
Chronic fatigue syndrome
Chronic fatigue syndrome is the most common name used to designate a significantly debilitating medical disorder or group of disorders generally defined by persistent fatigue accompanied by other specific symptoms for a minimum of six months, not due to ongoing exertion, not substantially...
are poorly understood and vaguely defined conditions with overlapping features. After demonstration of disordered GH secretion and higher rates of tissue breakdown in patients with these conditions, a few people tried growth hormone treatment to see whether 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 given to patients to attempt 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
Growth hormone deficiency
Growth hormone deficiency is a medical condition in which the body does not produce enough growth hormone . Growth hormone, also called somatotropin, is a polypeptide hormone which stimulates growth and cell reproduction...
and may possibly be improved with GH treatment.
Some recent clinical studies have shown that low-dose GH treatment for adults with GH deficiency changes the body composition by increasing muscle
Muscle
Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...
mass, decreasing fat mass, increasing bone
Bone
Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...
density and muscle strength, effect cardiovascular parameters (i.e. decrease of LDL cholesterol), affects the quality of life and, if properly used, without significant side effects.
GH has been taken by athletes wanting to increase recovery, strength, and power. 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.
In GH deficient children and adults, improvement of cognitive functions (memory
Memory
In psychology, memory is an organism's ability to store, retain, and recall information and experiences. Traditional studies of memory began in the fields of philosophy, including techniques of artificially enhancing memory....
, attention) have been observed in small studies after the administration of GH.
Adverse effects
The New England Journal of Medicine published two editorials in 2003 expressing concern about off-label uses of HGH and the proliferation of advertisements for "HGH-Releasing" dietary supplements, and emphasized that there is no evidence that use of HGH in healthy adults or in geriatric patients is safe and effective - and especially emphasized that risks of long-term HGH treatment are unknown. One editorial was by Jeffrey M. Drazen, M.D., the editor-in-chief of the journal; the other one was by Dr. Mary Lee Vance, who provided the NEJM's editorial original, cautious comment on a much cited 1990 study on the use of HGH in geriatric patients with low growth hormone levels.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 having received GH. The reason is unknown, but GH is now rarely used in ICU patients unless they have severe growth hormone deficiency.
GH treatment usually decreases insulin sensitivity, but some studies showed no evidence for increased diabetes
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
incidence in GH-treated adult hypopituitary patients.
In past it was believed that GH treatment could increase the cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
risk; a large study recently concluded that "With relatively short follow-up, the overall primary cancer risk in 6840 patients receiving GH as adults was not increased. Elevated SIRs (which is risk of getting cancer) were found for subgroups in the USA cohort defined by age <35 years or childhood onset GH deficiency."
History
Perhaps the most famous person who exemplified the appearance of untreated congenital growth hormone deficiencyGrowth hormone deficiency
Growth hormone deficiency is a medical condition in which the body does not produce enough growth hormone . Growth hormone, also called somatotropin, is a polypeptide hormone which stimulates growth and cell reproduction...
was Charles Sherwood Stratton
General Tom Thumb
General Tom Thumb was the stage name of Charles Sherwood Stratton , a dwarf who achieved great fame under circus pioneer P.T. Barnum.-Early life:...
(1838–1883), who was exhibited by P.T. Barnum as General Tom Thumb
General Tom Thumb
General Tom Thumb was the stage name of Charles Sherwood Stratton , a dwarf who achieved great fame under circus pioneer P.T. Barnum.-Early life:...
, 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.
Like many other nineteenth-century medical terms that lost precise meaning as they gained wider currency, “midget
Midget
A midget is a short person with relatively average bodily proportions in comparison with other human beings. The term is often improperly used to describe a person with the medical condition dwarfism. The two terms are often used synonymously because both terms originate as words defining small...
,” as a term for someone with extreme proportional shortness, acquired pejorative connotations and is no longer used in medical contexts.
By the middle of the twentieth century, endocrinologists understood the clinical features of growth hormone deficiency. GH is a protein hormone, like insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
, which had been purified from pig and cow pancreas
Pancreas
The pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...
es for treatment of type 1 diabetes since the 1920s. However, pig and cow GH did not work at all in humans, due to greater species-to-species variation of molecular structure (i.e., insulin is considered more "evolutionarily conserved" than GH).
Extraction for treatment
Extracted growth hormone was used since late 1950s until late 1980s when its use was replaced by recombinant GH.In the late 1950s, Maurice Raben purified enough GH from human pituitary gland
Pituitary gland
In vertebrate anatomy the pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g , in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity covered by a dural fold...
s 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
Autopsy
An autopsy—also known as a post-mortem examination, necropsy , autopsia cadaverum, or obduction—is a highly specialized surgical procedure that consists of a thorough examination of a corpse to determine the cause and manner of death and to evaluate any disease or injury that may be present...
. Parents would then contract with a biochemist
Biochemistry
Biochemistry, sometimes called biological chemistry, is the study of chemical processes in living organisms, including, but not limited to, living matter. Biochemistry governs all living organisms and living processes...
to purify enough growth hormone to treat their child. Few families could manage such a complicated undertaking.
In 1960, the National Pituitary Agency was formed as a branch of the U.S. National Institutes of Health
National Institutes of Health
The National Institutes of Health are an agency of the United States Department of Health and Human Services and are the primary agency of the United States government responsible for biomedical and health-related research. Its science and engineering counterpart is the National Science Foundation...
. 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.
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
Pediatric endocrinology
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....
provided most of this care, but in the late 1960s 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 that Creutzfeldt-Jacob disease could be transmitted by neurosurgical
Neurosurgery
Neurosurgery is the medical specialty concerned with the prevention, diagnosis, treatment, and rehabilitation of disorders which affect any portion of the nervous system including the brain, spine, spinal cord, peripheral nerves, and extra-cranial cerebrovascular system.-In the United States:In...
procedures and cornea transplantation. CJD is a rapidly fatal dementing disease
Dementia
Dementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging...
of the brain also known as spongiform encephalopathy, related to “mad cow disease”.
In 1977, the NPA GH extraction and purification procedure was refined and improved.
A shortage of available cadaver GH worsened in the late 1970s 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 . Children who were short for reasons other than severe GH deficiency were lied to and told that they would not benefit from treatment. Only those pediatric endocrinologists that remained at university medical centers with departments able to support a research program had access to NPA growth hormone.
In the late 1970s, 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 physician
Primary care physician
A primary care physician, or PCP, is a physician/medical doctor 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....
s 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.
Recombinant human growth hormone (rHGH)
In 1981, the new American corporation Genentech, after collaboration with Kabi, developed and started trials of recombinant human growth hormone (rHGH) made by a new technology (recombinant DNA) in which human geneGene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
s were inserted into bacteria so that they 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.
In 1985, four young adults in the U.S. having received NPA growth hormone in the 1960s 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 having 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 recombinant human 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
Orphan drug
An orphan drug is a pharmaceutical agent that has been developed specifically to treat a rare medical condition, the condition itself being referred to as an orphan disease...
status, and a pioneering post-marketing surveillance
Postmarketing surveillance
Postmarketing surveillance is the practice of monitoring the safety of a pharmaceutical drug or device after it has been released on the market and is an important part of the science of pharmacovigilance...
registry for tracking safety and effectiveness (National Cooperative Growth Study
National Cooperative Growth Study
National Cooperative Growth Study is the largest observational database in the U.S. of children with growth disorders. Started in 1985, NCGS was a long term longitudinal study following patients undergoing growth hormone treatment in North America . The study was closed in 2010. At that time it...
).
Within a few years, GH treatment had become “big business” in more than one sense. In the United States, Eli Lilly
Eli Lilly and Company
Eli Lilly and Company is a global pharmaceutical company. Eli Lilly's global headquarters is located in Indianapolis, Indiana, in the United States...
launched a competing natural sequence growth hormone, and, in Europe, Pharmacia (formerly Kabi, now Pfizer
Pfizer
Pfizer, Inc. is an American multinational pharmaceutical corporation. The company is based in New York City, New York with its research headquarters in Groton, Connecticut, United States...
), Novo Nordisk
Novo Nordisk
Novo Nordisk manufactures and markets pharmaceutical products and services. Created in 1989 through a merger of two Danish companies dating back to the 1920s, it has become one of the world's leading companies in diabetes care, where Novo Nordisk pursues research into pulmonary delivery systems;...
, and Serono
Serono
Serono is a biotechnology company headquartered in Geneva, Switzerland. The company was founded as the Serono Pharmacolodgical Institute by Cesare Serono in 1906 in Italy. A key step in its development was the discovery of a method of extracting urinary gonadotropins by Dr Piero Donini allowing...
marketed nearly identical recombinant 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.
Pediatric endocrinology
Pediatric endocrinology
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....
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.
The major scientific arguments dated back to the days of GH scarcity:
- Everyone agrees on the nature and diagnosis of severe GH deficiencyGrowth hormone deficiencyGrowth hormone deficiency is a medical condition in which the body does not produce enough growth hormone . Growth hormone, also called somatotropin, is a polypeptide hormone which stimulates growth and cell reproduction...
, but what are the edges and variations? - How should marked constitutional delayDelayed pubertyPuberty is described as delayed puberty with exceptions when an organism has passed the usual age of onset of puberty with no physical or hormonal signs that it is beginning. Puberty may be delayed for several years and still occur normally, in which case it is considered constitutional delay, a...
be distinguished from partial GH deficiency? - To what extent is “normal shortnessShort statureShort stature refers to a height of a human being which is below expected. Shortness is a vague term without a precise definition and with significant relativity to context...
” 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
Bioethics
Bioethics is the study of controversial ethics brought about by advances in biology and medicine. Bioethicists are concerned with the ethical questions that arise in the relationships among life sciences, biotechnology, medicine, politics, law, and philosophy....
questions that were new. Is GH not a wise use of finite healthcare 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” 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
Bioethics
Bioethics is the study of controversial ethics brought about by advances in biology and medicine. Bioethicists are concerned with the ethical questions that arise in the relationships among life sciences, biotechnology, medicine, politics, law, and philosophy....
issues.
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 pharmaceutical companies that were making growth hormone to achieve approval to market for those specific indications. Turner syndrome
Turner syndrome
Turner syndrome or Ullrich-Turner syndrome encompasses several conditions in human females, of which monosomy X is most common. It is a chromosomal abnormality in which all or part of one of the sex chromosomes is absent...
and chronic renal failure
Chronic renal failure
Chronic kidney disease , also known as chronic renal disease, is a progressive loss in renal function over a period of months or years. The symptoms of worsening kidney function are unspecific, and might include feeling generally unwell and experiencing a reduced appetite...
were the first of these “nonGH-deficient causes of shortness” to receive FDA
Food and Drug Administration
The Food and Drug Administration is an agency of the United States Department of Health and Human Services, one of the United States federal executive departments...
approval for GH treatment, and Prader-Willi syndrome
Prader-Willi syndrome
Prader–Willi syndrome is a rare genetic disorder in which seven genes on chromosome 15 are deleted or unexpressed on the paternal chromosome...
and intrauterine growth retardation followed. Similar expansion of use occurred in Europe.
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
Quality of life
The term quality of life is used to evaluate the general well-being of individuals and societies. The term is used in a wide range of contexts, including the fields of international development, healthcare, and politics. Quality of life should not be confused with the concept of standard of...
of adults with severe GH deficiency. Most were people having been treated with GH in childhood for severe deficiency. Although the injections are painless, many of them had been happy to leave injections behind as they reached final heights in the low-normal range. However, as adults in their 30s and 40s, these people, who had been children with growth hormone deficiency, were now adults with growth hormone deficiency and 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.
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. As with other types of hormone supplementation for aging (testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
, estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...
, DHEA
Dehydroepiandrosterone
5-Dehydroepiandrosterone is a 19-carbon endogenous steroid hormone. It is the major secretory steroidal product of the adrenal glands and is also produced by the gonads and the brain. DHEA is the most abundant circulating steroid in humans....
), confirmation of benefit and accurate understanding of risks has been only slowly evolving.
There are always entrepreneurs who do not need much evidence to see a business opportunity. In 1997, Ronald Klatz of the American Academy of Anti-Aging Medicine
American Academy of Anti-Aging Medicine
The American Academy of Anti-Aging Medicine is a United States registered 501 nonprofit organization that promotes the field of anti-aging medicine and trains and certifies physicians in this specialty. As of 2011, approximately 26,000 practitioners had been given certificates...
published Grow Young With HGH: The Amazing Medically Proven Plan To Reverse the Effects Of Aging, an uncritical touting of GH as the answer to aging. This time, the internet amplified the proposition and spawned a hundred frauds and scams. However, their adoption of the "HGH" term has provided an easy way to distinguish the hype from the evidence.
In 2003, growth hormone hit the news again, when the US FDA granted Eli Lilly
Eli Lilly and Company
Eli Lilly and Company is a global pharmaceutical company. Eli Lilly's global headquarters is located in Indianapolis, Indiana, in the United States...
approval to market Humatrope for the treatment of idiopathic short stature
Idiopathic short stature
Idiopathic short stature refers to extreme short stature that does not have a diagnostic explanation after an ordinary growth evaluation...
. 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.
As of 2004, GH use continues to rise, though it is no longer the most expensive prescription drug in the formulary. Recombinant growth hormone available in the U.S. (and their manufacturers) included Nutropin (Genentech
Genentech
Genentech Inc., or Genetic Engineering Technology, Inc., is a biotechnology corporation, founded in 1976 by venture capitalist Robert A. Swanson and biochemist Dr. Herbert Boyer. Trailing the founding of Cetus by five years, it was an important step in the evolution of the biotechnology industry...
), Humatrope (Eli Lilly and Company
Eli Lilly and Company
Eli Lilly and Company is a global pharmaceutical company. Eli Lilly's global headquarters is located in Indianapolis, Indiana, in the United States...
), Genotropin (Pfizer
Pfizer
Pfizer, Inc. is an American multinational pharmaceutical corporation. The company is based in New York City, New York with its research headquarters in Groton, Connecticut, United States...
), Norditropin (Novo Nordisk
Novo Nordisk
Novo Nordisk manufactures and markets pharmaceutical products and services. Created in 1989 through a merger of two Danish companies dating back to the 1920s, it has become one of the world's leading companies in diabetes care, where Novo Nordisk pursues research into pulmonary delivery systems;...
), Tev-Tropin (Teva
Teva Pharmaceutical Industries
Teva Pharmaceutical Industries Ltd. , is an international pharmaceutical company headquartered in Petah Tikva, Israel. It specializes in generic and proprietary pharmaceuticals and active pharmaceutical ingredients...
) and Saizen
Saizen
Saizen is a commercial preparation of synthetic somatropin . Manufactured by Merck Serono, Saizen is produced by recombinant DNA technology from a mammalian cell line that was modified by the addition of the human GH gene, resulting in an identical 191-amino acid sequence and structure.-Usage: ...
(Merck Serono
Merck Serono
Merck Serono is a pharmaceutical company headquartered in Geneva, Switzerland. In September 2006, Merck KGaA announced its intent to purchase the majority of Serono shares from Ernesto Bertarelli and the Bertarelli family. The Merck-Serono merger was announced on September 21, 2006...
). The products are nearly identical in composition, efficacy, and cost, varying primarily in the formulations and delivery devices.
Society and culture
GH has been taken illegally by athletes wanting to increase recovery, strength, and power. 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.Research
Everything discussed in this section involves either studies to see if GH could be useful for other diseases or conditions, or off-label uses that doctors have developed in the course of their daily work. None of the uses described below have been approved by the FDA.Due to the immunostimulatory effect of GH, it can enhance immunorecevory after radiation in mice and nonhuman primates.
Post-transplant growth failure sometimes improves with GH. Many children who suffer from chronic renal, liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
, and heart
Heart
The heart is a myogenic muscular organ found in all animals with a circulatory system , that is responsible for pumping blood throughout the blood vessels by repeated, rhythmic contractions...
disease grow poorly for years before a transplant
Organ transplant
Organ transplantation is the moving of an organ from one body to another or from a donor site on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative medicine is allowing scientists and engineers to create organs to be...
is required (or available). While growth may improve after correction of organ function by successful transplantation, the immunosuppressive
Immunosuppression
Immunosuppression involves an act that reduces the activation or efficacy of the immune system. Some portions of the immune system itself have immuno-suppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other...
drugs taken to protect the transplanted organ may continue to interfere with growth. Growth hormone may help offset these effects and is sometimes offered in these circumstances.
GH replacement (i.e. adding it to the body when it is missing) unequivocally significantly improve health increasing muscle
Muscle
Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...
and bone
Bone
Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...
mass, improving cardiocirculatory parameters.
In GH deficient children and adults, improvement of cognitive functions (memory
Memory
In psychology, memory is an organism's ability to store, retain, and recall information and experiences. Traditional studies of memory began in the fields of philosophy, including techniques of artificially enhancing memory....
, attention) have been observed in small studies after the administration of GH.
Neurodegenerative diseases (i.e. Alzheimer's disease
Alzheimer's disease
Alzheimer's disease also known in medical literature as Alzheimer disease is the most common form of dementia. There is no cure for the disease, which worsens as it progresses, and eventually leads to death...
) are connected with the decline of growth hormone levels, therefore some authors suggest that it is necessary to evaluate the use GH as future antinuerodegenerative strategy.
X-linked hypophosphatemic rickets is an inherited disorder of phosphorus
Phosphorus
Phosphorus is the chemical element that has the symbol P and atomic number 15. A multivalent nonmetal of the nitrogen group, phosphorus as a mineral is almost always present in its maximally oxidized state, as inorganic phosphate rocks...
metabolism that results in growth failure and rickets
Rickets
Rickets is a softening of bones in children due to deficiency or impaired metabolism of vitamin D, magnesium , phosphorus or calcium, potentially leading to fractures and deformity. Rickets is among the most frequent childhood diseases in many developing countries...
. GH has been shown to accelerate growth modestly.
Children with inflammatory bowel disease
Inflammatory bowel disease
In medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...
and Crohn's disease
Crohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...
have often GH and IGF-I deficiency and /or GH resistance.
Inflammatory bowel disease
Inflammatory bowel disease
In medicine, inflammatory bowel disease is a group of inflammatory conditions of the colon and small intestine. The major types of IBD are Crohn's disease and ulcerative colitis.-Classification:...
(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, but it is unknown whether this actually leads to an increased adult height.
Children with Crohn's disease
Crohn's disease
Crohn's disease, also known as regional enteritis, is a type of inflammatory bowel disease that may affect any part of the gastrointestinal tract from mouth to anus, causing a wide variety of symptoms...
can often have growth reduction, it was seen that growth hormone treatment can increase height. However further studies are necessary to better evaluate the efficacy of this therapy.
Poor growth is a part of Noonan syndrome
Noonan syndrome
Noonan Syndrome is a relatively common autosomal dominant congenital disorder considered to be a type of dwarfism, that affects both males and females equally. It used to be referred to as the male version of Turner's syndrome ; however, the genetic causes of Noonan syndrome and Turner syndrome...
and many other genetic syndrome
Syndrome
In medicine and psychology, a syndrome is the association of several clinically recognizable features, signs , symptoms , phenomena or characteristics that often occur together, so that the presence of one or more features alerts the physician to the possible presence of the others...
s. 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 in (2.5–5.1 cm) of extra adult height.
Small numbers of children with various forms of bone dysplasia (dwarfism
Dwarfism
Dwarfism is short stature resulting from a medical condition. It is sometimes defined as an adult height of less than 4 feet 10 inches , although this definition is problematic because short stature in itself is not a disorder....
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.
Coeliac Disease
Coeliac disease
Coeliac disease , is an autoimmune disorder of the small intestine that occurs in genetically predisposed people of all ages from middle infancy onward...
can prevent children from reaching their expected growth potential, if it begins before growth is complete. Stunted growth can be a result of Coeliac Disease damaging the intestines and preventing proper nutrient absorption. Treatment involves a gluten-free diet. HGH treatment has been used in an attempt to recover lost growth due to this effect.
On occasion, GH has 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 exclusive list.
Other scientists have explored whether hGH treatment could be useful in adults that are not severely deficient in GH. Treatment of healthy, normally aging individuals found the only benefit to be a slight increase in muscle mass, with frequent side-effects and no evidence that it is safe to use long-term.
GH has been given to attempt to promote healing of large burns
Burn (injury)
A burn is a type of injury to flesh caused by heat, electricity, chemicals, light, radiation or friction. Most burns affect only the skin . Rarely, deeper tissues, such as muscle, bone, and blood vessels can also be injured...
by reducing the amount of protein breakdown during the early post-injury period.
GH has been used as an adjunct to caloric restriction to attempt to treat obesity
Obesity
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
. GH promotes lipolysis
Lipolysis
Lipolysis is the breakdown of lipids and involves the hydrolysis of triglycerides into free fatty acids followed by further degradation into acetyl units by beta oxidation. The process produces Ketones, which are found in large quantities in ketosis, a metabolic state that occurs when the liver...
and reduces proteolysis
Proteolysis
Proteolysis is the directed degradation of proteins by cellular enzymes called proteases or by intramolecular digestion.-Purposes:Proteolysis is used by the cell for several purposes...
. 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
Starvation
Starvation is a severe deficiency in caloric energy, nutrient and vitamin intake. It is the most extreme form of malnutrition. In humans, prolonged starvation can cause permanent organ damage and eventually, death...
economy. Results showed potential benefit, but this has not been widely adopted for a variety of reasons (cost, injections, potential aggravation of insulin resistance
Insulin resistance
Insulin resistance is a physiological condition where the natural hormone insulin becomes less effective at lowering blood sugars. The resulting increase in blood glucose may raise levels outside the normal range and cause adverse health effects, depending on dietary conditions. Certain cell types...
, etc.). Recent studies suggest that side-effects, in particular, insulin resistance, may outweigh the potential benefits of such therapy.
A study in the New England Journal of Medicine suggested that HGH might be a beneficial treatment for patients with Crohn's disease.
Fibromyalgia
Fibromyalgia
Fibromyalgia is a medical disorder characterized by chronic widespread pain and allodynia, a heightened and painful response to pressure. It is an example of a diagnosis of exclusion...
and chronic fatigue syndrome
Chronic fatigue syndrome
Chronic fatigue syndrome is the most common name used to designate a significantly debilitating medical disorder or group of disorders generally defined by persistent fatigue accompanied by other specific symptoms for a minimum of six months, not due to ongoing exertion, not substantially...
are poorly understood and vaguely defined conditions with overlapping features. After demonstration of disordered GH secretion and higher rates of tissue breakdown in patients with these conditions, a few people tried growth hormone treatment to see whether 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 given to patients to attempt 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
Growth hormone deficiency
Growth hormone deficiency is a medical condition in which the body does not produce enough growth hormone . Growth hormone, also called somatotropin, is a polypeptide hormone which stimulates growth and cell reproduction...
and may possibly be improved with GH treatment.
Some recent clinical studies have shown that low-dose GH treatment for adults with GH deficiency changes the body composition by increasing muscle
Muscle
Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...
mass, decreasing fat mass, increasing bone
Bone
Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...
density and muscle strength, effect cardiovascular parameters (i.e. decrease of LDL cholesterol), affects the quality of life and, if properly used, without significant side effects.
Terminology
Growth hormone (GH l) is also called somatotropin (British: somatotrophin). The human form of growth hormone is known as human growth hormone, or hGH (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.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
Creutzfeldt-Jakob disease
Creutzfeldt–Jakob disease or CJD is a degenerative neurological disorder that is incurable and invariably fatal. CJD is at times called a human form of mad cow disease, given that bovine spongiform encephalopathy is believed to be the cause of variant Creutzfeldt–Jakob disease in humans.CJD...
, and was withdrawn from use.
rHGH refers to recombinant human growth hormone (somatropin). It contains the identical amino acid sequence of human GH and is "natural sequence" GH. In chemical structure, it is 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 pharmaceutical companies in the US.
It is coincidental that rHGH also refers to rhesus monkey GH, using the accepted naming convention. Rhesus
Rhesus
Rhesus can refer to any of the following:* Rhesus of Thrace, a king in Greek mythology* S. Vivianus Rhesus, a Roman governor of Thrace* In Greek mythology, a river-god, son of Oceanus and Tethys...
growth hormone
Growth hormone
Growth hormone is a peptide hormone that stimulates growth, cell reproduction and regeneration in humans and other animals. Growth hormone is a 191-amino acid, single-chain polypeptide that is synthesized, stored, and secreted by the somatotroph cells within the lateral wings of the anterior...
was never used by physicians to treat human patients, but rhesus GH was part of the lore of the underground anabolic steroid
Anabolic steroid
Anabolic steroids, technically known as anabolic-androgen steroids or colloquially simply as "steroids", are drugs that mimic the effects of testosterone and dihydrotestosterone in the body. They increase protein synthesis within cells, which results in the buildup of cellular tissue ,...
community in those years, and fraudulent versions may have been bought and sold in gyms.
met-GH refers to methionyl-growth hormone. This was the first recombinant GH product marketed (Protropin by Genentech). It had the same amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
sequence as human GH with an extra methionine
Methionine
Methionine is an α-amino acid with the chemical formula HO2CCHCH2CH2SCH3. This essential amino acid is classified as nonpolar. This amino-acid is coded by the codon AUG, also known as the initiation codon, since it indicates mRNA's coding region where translation into protein...
at the end of the chain to facilitate the manufacturing process. It was discontinued in the late 1990s.
rBST refers to recombinant bovine somatropin (cow growth hormone), or recombinant bovine GH (rbGH).
Support organizations
- The Most Frequently Asked Questions when Beginning GH Treatment-The MAGIC Foundation for Children's Growth
- http://pwsausa.org Prader-Willi Syndrome Association (USA)