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107-412: Growth hormone therapy refers to the use of growth hormone (GH) as a prescription medication —it is one form of hormone therapy . 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. Growth hormone is now produced by recombinant DNA technology and is prescribed for

214-511: 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

321-513: A 15-year-old female with well-documented hypopituitarism secondary to a craniopharyngioma; a 53-year-old female with carcinoma of the breast and widespread skeletal metastases; a 68-year-old female with advanced postmenopausal osteoporosis; and a healthy 24-year-old medical student without any clinical or laboratory evidence of systemic disease. In 1985, unusual cases of Creutzfeldt–Jakob disease were found in individuals that had received cadaver-derived HGH ten to fifteen years previously. Based on

428-403: A GH antagonist such as pegvisomant may be employed to shrink the tumor or block function. Other drugs like octreotide (somatostatin agonist) and bromocriptine ( dopamine agonist ) can be used to block GH secretion because both somatostatin and dopamine negatively inhibit GHRH-mediated GH release from the anterior pituitary. The effects of growth hormone (GH) deficiency vary depending on

535-607: A banned sports doping agent and in this context is referred to as HGH. The term growth hormone has been incorrectly applied to refer to anabolic sex hormones in the European beef hormone controversy , which initially restricts the use of estradiol , progesterone , testosterone , zeranol , melengestrol acetate and trenbolone acetate . Genes for human growth hormone, known as growth hormone 1 (somatotropin; pituitary growth hormone) and growth hormone 2 (placental growth hormone; growth hormone variant), are localized in

642-405: A blood sample, testing for GH deficiency is constrained by the fact that levels are nearly undetectable for most of the day. This makes simple measurement of GH in a single blood sample useless for detecting deficiency. Physicians, therefore use a combination of indirect and direct criteria in assessing GHD, including: "Provocative tests" involve giving a dose of an agent that will normally provoke

749-405: A child who had fallen far behind in their height may grow into the normal height range. Excess adipose tissue may be reduced. GH treatment can confer a number of measurable benefits to severely GH-deficient adults, such as enhanced energy and strength, and improved bone density. Muscle mass may increase at the expense of adipose tissue. Although adults with hypopituitarism have been shown to have

856-406: A competing natural sequence growth hormone (Humatrope). Pharmacia (formerly Kabi, now Pfizer ) introduced Genotropin. Novo Nordisk introduced Norditropin. Serono (now EMD Serono) introduced Saizen and Serostim. Ferring has introduced Zomacton. Genentech eventually introduced another HGH product, Nutropin, and stopped making Protropin in 2004. Price competition had begun. Teva, which is primarily

963-625: 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. In 1997, Ronald Klatz of

1070-530: A generics company, has introduced Tev-tropin. Chinese companies have entered the market as well and have introduced more pricing competition: NeoGenica BioScience Ltd. introduced Hypertropin, GeneScience introduced Jintropin, Anhui Anke Biotechnology introduced Ansomone, Shanghai United Kefei Biotechnology introduced Kefei HGH, and Hygene BioPharm introduced Hygetropin. These are all recombinant human growth hormone products and they have competed with various marketing strategies. Most children with severe deficiency in

1177-488: 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

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1284-919: A month has been found to be as safe and effective as daily growth hormone injections. GH can be used to treat conditions that produce short stature but are not related to deficiencies in GH. However, results are not as dramatic when compared to short stature that is solely attributable to deficiency of GH. Examples of other causes of shortness often treated with GH are Turner syndrome , Growth failure secondary to chronic kidney disease in children, Prader–Willi syndrome , intrauterine growth restriction , and severe idiopathic short stature . Higher ("pharmacologic") doses are required to produce significant acceleration of growth in these conditions, producing blood levels well above normal ("physiologic"). One version of rHGH has also been FDA approved for maintaining muscle mass in wasting due to AIDS . Off-label prescription of HGH

1391-523: A multiple-step diagnostic process, usually culminating in GH stimulation tests to see if the patient's pituitary gland will release a pulse of GH when provoked by various stimuli. Several studies, primarily involving patients with GH deficiency , have suggested a crucial role of GH in both mental and emotional well-being and maintaining a high energy level. Adults with GH deficiency often have higher rates of depression than those without. While GH replacement therapy has been proposed to treat depression as

1498-546: A pituitary to release a burst of growth hormone. An intravenous line is established, the agent is given, and small amounts of blood are drawn at 15-minute intervals over the next hour to determine if a rise of GH was provoked. Agents which have been used clinically to stimulate and assess GH secretion are arginine , levodopa , clonidine , epinephrine and propranolol , glucagon , and insulin . An insulin tolerance test has been shown to be reproducible, age-independent, and able to distinguish between GHD and normal adults, and so

1605-430: A protein ( growth hormone-binding protein , GHBP), which is the truncated part of the growth hormone receptor , and an acid-labile subunit (ALS). Secretion of growth hormone (GH) in the pituitary is regulated by the neurosecretory nuclei of the hypothalamus . These cells release the peptides growth hormone-releasing hormone (GHRH or somatocrinin ) and growth hormone-inhibiting hormone (GHIH or somatostatin ) into

1712-426: A rare form of type 2 diabetes , and reduced sexual function. GH-secreting tumors are typically recognized in the fifth decade of life. It is extremely rare for such a tumor to occur in childhood, but, when it does, the excessive GH can cause excessive growth, traditionally referred to as pituitary gigantism . Surgical removal is the usual treatment for GH-producing tumors. In some circumstances, focused radiation or

1819-474: A rare growth defect in children and a handful of uncommon conditions like short bowel syndrome or Prader-Willi syndrome, a congenital disease that causes reduced muscle tone and a lack of hormones in sex glands." At the same time, anti-aging clinics where doctors prescribe, administer, and sell HGH to people are big business. In a 2012 article in Vanity Fair , when asked how HGH prescriptions far exceed

1926-590: A reduced life expectancy, and a cardiovascular mortality rate of more than double controls, treatment has not been shown to improve mortality, although blood lipid levels do improve. Similarly, although measurements of bone density improve with treatment, rates of fractures have not been shown to improve. Effects on quality of life are unproven, with a number of studies finding that adults with GHD had near-normal indicators of QoL at baseline (giving little scope for improvement), and many using outdated dosing strategies. However, it may be that those adults with poor QoL at

2033-563: 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

2140-455: A result of GH deficiency, the long-term effects of such therapy are unknown. GH has also been studied in the context of cognitive function , including learning and memory. GH in humans appears to improve cognitive function and may be useful in the treatment of patients with cognitive impairment that is a result of GH deficiency. GH is used as replacement therapy in adults with GH deficiency of either childhood-onset or adult-onset (usually as

2247-526: A result of an acquired pituitary tumor). In these patients, benefits have variably included reduced fat mass, increased lean mass, increased bone density, improved lipid profile, reduced cardiovascular risk factors, and improved psychosocial well-being. Long acting growth hormone (LAGH) analogues are now available for treating growth hormone deficiency both in children and adults. These are once weekly injections as compared to conventional growth hormone which has to be taken as daily injections. LAGH injection 4 times

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2354-401: A significant enhancement of nitrogen storage ... (and) there was a retention of potassium, phosphorus, calcium, and sodium. ... There was a gain in body weight during both periods. ... There was a significant increase in urinary excretion of aldosterone during both periods of administration of growth hormone. This was most marked with the human growth hormone. ... Impairment of

2461-621: 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 kidney failure were

2568-422: A term for someone with severe proportional shortness acquired pejorative connotations and is no longer used in a medical context. Notable modern pop cultural figures with growth hormone deficiency include actor and comedian Andy Milonakis , who has the appearance and voice of an adolescent boy despite being in his 40s. Argentine footballer Lionel Messi was diagnosed at age 10 with growth hormone deficiency and

2675-430: A third of cases no cause is apparent. The underlying mechanism generally involves problems with the pituitary gland . Some cases are associated with a lack of other pituitary hormones , in which case it is known as combined pituitary hormone deficiency . Diagnosis involves blood tests to measure growth hormone levels. Treatment is by growth hormone replacement using synthetic human growth hormone. The frequency of

2782-452: A variant of approximately 20 kDa originated by an alternative splicing is present in a rather constant 1:9 ratio, while recently an additional variant of ~ 23-24 kDa has also been reported in post-exercise states at higher proportions. This variant has not been identified, but it has been suggested to coincide with a 22 kDa glycosylated variant of 23 kDa identified in the pituitary gland. Furthermore, these variants circulate partially bound to

2889-457: 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 and the current uses and risks arising from GH use. Other articles describe GH physiology , diseases of GH excess ( acromegaly and pituitary gigantism ), deficiency , the recent phenomenon of HGH controversies , growth hormone in sports , and growth hormone for cows . Growth hormone deficiency

2996-539: A year in the US. GH supplementation is not recommended medically for the physiologic age-related decline in GH/IGF secretion. It may be appropriate in diagnosed adult-onset deficiency, where a weekly dose of approximately 25% of that given to children is given. Lower doses again are called for in the elderly to reduce the incidence of side effects and maintain age-dependent normal levels of IGF-1. In many countries, including

3103-695: Is a recombinant form of human GH produced by genetically engineered bacteria , manufactured by recombinant DNA technology . In both children and adults, costs of treatment in terms of money, effort, and the impact on day-to-day life, are substantial. GH treatment is not recommended for children who are not growing despite having normal levels of growth hormone, and in the UK it is not licensed for this use. Children requiring treatment usually receive daily injections of growth hormone. Most pediatric endocrinologists monitor growth and adjust dose every 3–6 months and many of these visits involve blood tests and x-rays. Treatment

3210-498: Is a drug. Also, under United States law, products sold as dietary supplements cannot have claims that the supplement treats or prevents any disease or condition, and the advertising material must contain a statement that the health claims are not approved by the FDA. The FTC and the FDA do enforce the law when they become aware of violations. In the United States, it is legal to give a bovine GH to dairy cows to increase milk production, and

3317-561: 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 the pituitary glands of human cadavers 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

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3424-406: Is associated with posterior pituitary hormone deficiency (usually diabetes insipidus ), the condition is termed panhypopituitarism . GH deficiency is treated by replacing GH with daily injections under the skin or into muscle. Until 1985, growth hormone for treatment was obtained by extraction from human pituitary glands collected at autopsy . Since 1985, recombinant human growth hormone ( rHGH )

3531-515: Is common (though GH deficiency alone rarely causes severe obesity). Some severely GH-deficient children have recognizable, cherubic facial features characterized by maxillary hypoplasia and forehead prominence. Other side effects in children include sparse hair growth and frontal recession, and pili torti and trichorrhexis nodosa are also sometimes present. Recognised effects include: Growth hormone deficiency in childhood commonly has no identifiable cause (idiopathic), and adult-onset GHD

3638-416: Is commonly due to pituitary tumours and their treatment or to cranial irradiation . A more complete list of causes includes: There are a variety of rare diseases that resemble GH deficiency, including the childhood growth failure, facial appearance, delayed bone age, and low insulin-like growth factor-1 (IGF-1) levels. However, GH testing elicits normal or high levels of GH in the blood, demonstrating that

3745-501: Is controversial and may be illegal. Claims for GH as an anti-aging treatment date back to 1990 when the New England Journal of Medicine published a study wherein GH was used to treat 12 men over 60. At the conclusion of the study, all the men showed statistically significant increases in lean body mass and bone mineral density, while the control group did not. The authors of the study noted that these improvements were

3852-407: Is known about the effects of GH on learning and memory." As of 2004, GH has been approved by the U.S. Food and Drug Administration for treatment of other conditions such as: 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

3959-467: Is legal to use GH in raising cows for beef; see article on Bovine somatotropin , cattle feeding , dairy farming and the beef hormone controversy . The use of GH in poultry farming is illegal in the United States. Similarly, no chicken meat for sale in Australia is administered hormones. Several companies have attempted to have a version of GH for use in pigs (porcine somatotropin) approved by

4066-610: 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 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

4173-602: Is normal for the pituitary to produce diminishing amounts of GH and many other hormones, particularly the sex steroids . Physicians, therefore, distinguish between the natural reduction in GH levels which comes with age, and the much lower levels of "true" deficiency. Such deficiency almost always has an identifiable cause, with adult-onset GHD without a definable cause ("idiopathic GH deficiency") extremely rare. GH does function in adulthood to maintain muscle and bone mass and strength, and has poorly understood effects on cognition and mood. Although GH can be readily measured in

4280-447: Is present from birth and never treated, adult heights can be as short as 48–65 inches (120–170 cm). Severe GH deficiency in early childhood also results in slower muscular development, so that gross motor milestones such as standing, walking, and jumping may be delayed. Body composition (i.e., the relative amounts of bone , muscle, and fat ) is affected in many children with severe deficiency, so that mild to moderate chubbiness

4387-418: Is rare in adults, with the most common cause being a pituitary adenoma . Other adult causes include a continuation of a childhood problem, other structural lesions or trauma , and very rarely idiopathic GHD. Adults with GHD "tend to have a relative increase in fat mass and a relative decrease in muscle mass and, in many instances, decreased energy and quality of life". Diagnosis of GH deficiency involves

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4494-399: Is the test of choice. Severe GH deficiency in childhood additionally has the following measurable characteristics: In childhood and adulthood, the diagnosing doctor will look for these features accompanied by corroboratory evidence of hypopituitarism such as deficiency of other pituitary hormones, a structurally abnormal pituitary, or a history of damage to the pituitary. This would confirm

4601-652: Is treated by replacing growth hormone. Lonapegsomatropin was approved for medical use in the United States in August 2021. The Endocrine Society has recommended that adult patients diagnosed with growth hormone deficiency (GHd) be administered an individualized GH treatment regimen. With respect to diagnosis, their guidelines state that "adults patients with structural hypothalamic/pituitary disease, surgery or irradiation in these areas, head trauma, or evidence of other pituitary hormone deficiencies be considered for evaluation for acquired GHd" and that "idiopathic GHd in adults

4708-433: Is usually extended as long as the child is growing, and lifelong continuation may be recommended for those most severely deficient. Nearly painless insulin syringes , pen injectors , or a needle-free delivery system reduce the discomfort. Injection sites include the biceps, thigh, buttocks, and stomach. Injection sites should be rotated daily to avoid lipoatrophy. Treatment is expensive, costing as much as US$ 10,000 to $ 40,000

4815-865: Is very rare, and stringent criteria are necessary to make this diagnosis. Because in the absence of suggestive clinical circumstances there is a significant false-positive error rate in the response to a single GH stimulation test, we suggest the use of two tests before making this diagnosis." GH replacement therapy can provide a number of measurable benefits to GH-deficient adults. These include improved bone density , 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. A peer-reviewed article published in 2010 indicates that "Growth hormone (GH) replacement unequivocally benefits growth, body composition, cardiovascular risk factors and quality of life. Less

4922-559: 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

5029-646: The FDA . GH has been studied for use in raising livestock more efficiently in industrial agriculture and several efforts have been made to obtain governmental approval to use GH in livestock production. These uses have been controversial. In the United States, the only FDA-approved use of GH for livestock is the use of a cow-specific form of GH called bovine somatotropin for increasing milk production in dairy cows. Retailers are permitted to label containers of milk as produced with or without bovine somatotropin. The names somatotropin ( STH ) or somatotropic hormone refer to

5136-523: The IOC and NCAA . Traditional urine analysis does not detect doping with HGH, so the ban was not enforced until the early 2000s, when blood tests that could distinguish between natural and artificial HGH were starting to be developed. Blood tests conducted by WADA at the 2004 Olympic Games in Athens, Greece , targeted primarily HGH. Use of the drug for performance enhancement is not currently approved by

5243-402: The growth hormone produced naturally in animals and extracted from carcasses. Hormone extracted from human cadavers is abbreviated hGH . The main growth hormone produced by recombinant DNA technology has the approved generic name ( INN ) somatropin and the brand name Humatrope and is properly abbreviated rhGH in the scientific literature. Since its introduction in 1992, Humatrope has been

5350-450: The hypophyseal portal venous blood surrounding the pituitary. GH release in the pituitary is primarily determined by the balance of these two peptides, which in turn is affected by many physiological stimulators (e.g., exercise, nutrition, sleep) and inhibitors (e.g., free fatty acids) of GH secretion. Somatotropic cells in the anterior pituitary gland then synthesize and secrete GH in a pulsatile manner, in response to these stimuli by

5457-509: 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. 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 genes were inserted into bacteria so that they could produce unlimited amounts of

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5564-422: The FDA but all applications have been withdrawn. Genentech pioneered the use of recombinant human growth hormone for human therapy, which was approved by the FDA in 1985. Prior to its production by recombinant DNA technology, growth hormone used to treat deficiencies was extracted from the pituitary glands of cadavers . Attempts to create a wholly synthetic HGH failed. Limited supplies of HGH resulted in

5671-437: The GH receptor. It appears that, in structure, GH is evolutionarily homologous to prolactin and chorionic somatomammotropin. Despite marked structural similarities between growth hormone from different species , only human and Old World monkey growth hormones have significant effects on the human growth hormone receptor . Several molecular isoforms of GH exist in the pituitary gland and are released to blood. In particular,

5778-501: The U.S. Food and Drug Administration (FDA) approved a version of rHGH called Omnitrope (Sandoz). A sustained-release form of growth hormone, Nutropin Depot (Genentech and Alkermes) was approved by the FDA in 1999, allowing for fewer injections (every 2 or 4 weeks instead of daily); however, the product was discontinued by Genentech/Alkermes in 2004 for financial reasons (Nutropin Depot required significantly more resources to produce than

5885-485: 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 1977, the NPA GH extraction and purification procedure

5992-478: The U.S., which would quickly undermine the NPA, which relied on a donation system like blood transfusion. The second offense was Kabi-Pharmacia's marketing campaign, which was directed at primary care physicians under the slogan, "Now, you determine the need," implying that the services of a specialist were not needed for growth hormone treatment anymore and that any short child might be a candidate for treatment. Although

6099-431: The UK is 3000-4000 GBP annually. When treated with GH, a severely deficient child will begin to grow faster within months. In the first year of treatment, the rate of growth may increase from half as fast as other children are growing to twice as fast (e.g., from 1 inch a year to 4 inches, or 2.5 cm to 10). Growth typically slows in subsequent years, but usually remains above normal so that over several years

6206-453: The UK, the majority view among endocrinologists is that the failure of treatment to provide any demonstrable, measurable benefits in terms of outcomes means treatment is not recommended for all adults with severe GHD, and national guidelines in the UK as set out by NICE suggest three criteria which all need to be met for treatment to be indicated: Where treatment is indicated, duration is dependent upon indication. Cost of adult treatment in

6313-521: The United States, it is only available legally from pharmacies by prescription from a licensed health care provider. In recent years in the United States, some health care providers are prescribing growth hormone in the elderly to increase vitality . While legal, the efficacy and safety of this use for HGH has not been tested in a clinical trial. Many of the functions of HGH remain unknown. In its role as an anabolic agent, HGH has been used by competitors in sports since at least 1982 and has been banned by

6420-404: The advertising text, with medical-sounding names described as "HGH Releasers". Typical ingredients include amino acids, minerals, vitamins, and/or herbal extracts, the combination of which are described as causing the body to make more GH with corresponding beneficial effects. In the United States, because these products are marketed as dietary supplements, it is illegal for them to contain GH, which

6527-559: The age at which they occur. Alterations in somatomedin can result in growth hormone deficiency with two known mechanisms; failure of tissues to respond to somatomedin , or failure of the liver to produce somatomedin. Major manifestations of GH deficiency in children are growth failure , the development of a short stature , and delayed sexual maturity. In adults, somatomedin alteration contributes to increased osteoclast activity, resulting in weaker bones that are more prone to pathologic fracture and osteoporosis . However, deficiency

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6634-537: The assumption that infectious prions causing the disease were transferred along with the cadaver-derived HGH, cadaver-derived HGH was removed from the market. In 1985, biosynthetic human growth hormone replaced pituitary-derived human growth hormone for therapeutic use in the U.S. and elsewhere. As of 2005, recombinant growth hormones available in the United States (and their manufacturers) included Nutropin ( Genentech ), Humatrope ( Lilly ), Genotropin ( Pfizer ), Norditropin ( Novo ), and Saizen ( Merck Serono ). In 2006,

6741-683: The authors of a commentary article published in the Journal of the American Medical Association in 2005, as meaning that prescribing HGH off-label may be considered illegal. And some articles in the popular press, such as those criticizing the pharmaceutical industry for marketing drugs for off-label use (with concern of ethics violations) have made strong statements about whether doctors can prescribe HGH off-label: "Unlike other prescription drugs, HGH may be prescribed only for specific uses. U.S. sales are limited by law to treat

6848-425: The body store more water in the muscles rather than increase muscle growth. This would explain the increase in lean body mass. GH has also been used experimentally to treat multiple sclerosis , to enhance weight loss in obesity , as well as in fibromyalgia , heart failure , Crohn's disease and ulcerative colitis , and burns. GH has also been used experimentally in patients with short bowel syndrome to lessen

6955-459: The body: GH has a short biological half-life of about 10 to 20 minutes. The most common disease of GH excess is a pituitary tumor composed of somatotroph cells of the anterior pituitary. These somatotroph adenomas are benign and grow slowly, gradually producing more and more GH. For years, the principal clinical problems are those of GH excess. Eventually, the adenoma may become large enough to cause headaches, impair vision by pressure on

7062-412: The condition is unclear. Most cases are initially noticed in children. The genetic forms of this disease are estimated to affect about 1 in 7,000 people. Most types occur equally in males and females though males are more often diagnosed. Severe prenatal deficiency of GH, as occurs in congenital hypopituitarism , has little effect on fetal growth. However, prenatal and congenital deficiency can reduce

7169-565: The day occur at 3- to 5-hour intervals. The plasma concentration of GH during these peaks may range from 5 to even 45 ng/mL. Between the peaks, basal GH levels are low, usually less than 5 ng/mL for most of the day and night. Additional analysis of the pulsatile profile of GH described in all cases less than 1 ng/ml for basal levels while maximum peaks were situated around 10-20 ng/mL. A number of factors are known to affect GH secretion, such as age, sex, diet, exercise, stress, and other hormones. Young adolescents secrete GH at

7276-416: 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

7383-616: The diagnosis; in the absence of pituitary pathology, further testing would be required. Growth hormone deficiency can be congenital or acquired in childhood or adult life. It can be partial or complete. It is usually permanent, but sometimes transient. It may be an isolated deficiency or occur in association with deficiencies of other pituitary hormones. The term hypopituitarism is often used interchangeably with GH deficiency but more often denotes GH deficiency plus deficiency of at least one other anterior pituitary hormone. When GH deficiency (usually with other anterior pituitary deficiencies)

7490-399: The end of the chain to facilitate the manufacturing process. It was discontinued in 2004. rBST refers to recombinant bovine somatotropin (cow growth hormone), or recombinant bovine GH (rbGH, RBGH). Growth hormone A recombinant form of HGH called somatropin ( INN ) is used as a prescription drug to treat children's growth disorders and adult growth hormone deficiency . In

7597-427: The evidence regarding recombinant human growth hormone and increased risk of death is inconclusive after reviewing sources including a French study which compared persons with certain kinds of short stature (idiopathic growth hormone deficiency and idiopathic or gestational short stature ) treated with recombinant human growth hormone during childhood and who were followed over a long period of time, with individuals in

7704-570: 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. Many of them stopped injections as they reached their final heights in

7811-408: The first year until mid-teens, poor growth and/or shortness is the hallmark of childhood GH deficiency. Growth is not as severely affected in GH deficiency as in untreated hypothyroidism , but growth at about half the usual velocity for age is typical. It tends to be accompanied by delayed physical maturation so that bone maturation and puberty may be several years delayed. When severe GH deficiency

7918-455: The formulations and delivery devices. Somapacitan-beco (Sogroya) is the first once-per week subcutaneous human growth hormone (hGH) therapy that was approved in the United States. It was approved for medical use in the United States in August 2020. 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,

8025-454: The general population of France. Perhaps the most famous person who exemplified the appearance of untreated congenital growth hormone deficiency was Charles Sherwood Stratton (1838–1883), who was exhibited by P. T. Barnum as General Tom Thumb , and married Lavinia Warren. Pictures of the couple show the typical adult features of untreated severe growth hormone deficiency. Despite the severe shortness, limbs and trunks are proportional. By

8132-475: The glucose tolerance curve was evident after 10 days of administration of the human growth hormone. No change in glucose tolerance was demonstrable on the fifth day of administration of monkey growth hormone." The other study, published in 1958, was conducted on six people: the same subject as the Science paper; an 18-year-old male with statural and sexual retardation and a skeletal age of between 13 and 14 years;

8239-451: The hypothalamus. The largest and most predictable of these GH peaks occurs about an hour after onset of sleep with plasma levels of 13 to 72 ng/mL. Maximal secretion of GH may occur within minutes of the onset of slow-wave (SW) sleep (stage III or IV). Otherwise there is wide variation between days and individuals. Nearly fifty percent of GH secretion occurs during the third and fourth NREM sleep stages. Surges of secretion during

8346-461: 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

8453-456: 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. Whole meetings were devoted to these questions; pediatric endocrinology had become

8560-481: The middle of the twentieth century, endocrinologists understood the clinical features of growth hormone deficiency. GH is a protein hormone, like insulin , which had been purified from pig and cow pancreases for treatment of type 1 diabetes since the 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). Extracted growth hormone

8667-741: 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 Recombinant growth hormone available in the U.S. (and their manufacturers) include 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

8774-446: The number of adult patients estimated to have HGH-deficiency, Dragos Roman, who leads a team at the FDA that reviews drugs in endocrinology, said "The F.D.A. doesn't regulate off-label uses of H.G.H. Sometimes it's used appropriately. Sometimes it's not." Injection site reactions are common. More rarely, patients can experience joint swelling, joint pain, carpal tunnel syndrome , and an increased risk of diabetes . In some cases,

8881-519: The opposite of the changes that would normally occur over a 10- to 20-year aging period. Despite the fact the authors at no time claimed that GH had reversed the aging process itself, their results were misinterpreted as indicating that GH is an effective anti-aging agent. This has led to organizations such as the controversial American Academy of Anti-Aging Medicine promoting the use of this hormone as an "anti-aging agent". A Stanford University School of Medicine meta-analysis of clinical studies on

8988-433: The optic nerves, or cause deficiency of other pituitary hormones by displacement. Prolonged GH excess thickens the bones of the jaw, fingers and toes, resulting in heaviness of the jaw and increased size of digits, referred to as acromegaly . Accompanying problems can include sweating, pressure on nerves (e.g., carpal tunnel syndrome ), muscle weakness, excess sex hormone-binding globulin (SHBG), insulin resistance or even

9095-417: The patient can produce an immune response against GH. GH may also be a risk factor for Hodgkin's lymphoma . One survey of adults that had been treated with replacement cadaver GH (which has not been used anywhere in the world since 1985) during childhood showed a mildly increased incidence of colon cancer and prostate cancer, but linkage with the GH treatment was not established. The first description of

9202-426: 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 more common and competitors entered the market. Eli Lilly launched

9309-524: The problem is not due to a deficiency of GH but rather to a reduced sensitivity to its action. Insensitivity to GH is traditionally termed Laron dwarfism , but over the last 15 years many different types of GH resistance have been identified, primarily involving mutations of the GH binding protein or receptors. Familial isolated growth hormone deficiency (IGHD) can be inherited as an autosomal recessive (type I), autosomal dominant (type II), or X-linked (type III) characteristic. As an adult ages, it

9416-522: 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 ( Creutzfeldt–Jakob disease ). 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

9523-562: 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

9630-492: The q22-24 region of chromosome 17 and are closely related to human chorionic somatomammotropin (also known as placental lactogen ) genes. GH, human chorionic somatomammotropin, and prolactin belong to a group of homologous hormones with growth-promoting and lactogenic activity. The major isoform of the human growth hormone is a protein of 191 amino acids and a molecular weight of 22,124 daltons . The structure includes four helices necessary for functional interaction with

9737-513: The rate of about 700 μg/day, while healthy adults secrete GH at the rate of about 400 μg/day. Sleep deprivation generally suppresses GH release, particularly after early adulthood. Stimulators of growth hormone (GH) secretion include: Inhibitors of GH secretion include: In addition to control by endogenous and stimulus processes, a number of foreign compounds ( xenobiotics such as drugs and endocrine disruptors ) are known to influence GH secretion and function. Effects of growth hormone on

9844-630: The requirement for intravenous total parenteral nutrition . In 1990, the US Congress passed an omnibus crime bill, the Crime Control Act of 1990 , that amended the Federal Food, Drug, and Cosmetic Act , that classified anabolic steroids as controlled substances and added a new section that stated that a person who "knowingly distributes, or possesses with intent to distribute, human growth hormone for any use in humans other than

9951-748: The rest of the Nutropin line ). Growth hormone deficiency Growth hormone deficiency ( GHD ), or human growth hormone deficiency, is a medical condition resulting from not enough growth hormone (GH). Generally the most noticeable symptom is that an individual attains a short height . Newborns may also present low blood sugar or a small penis size . In adults there may be decreased muscle mass , high cholesterol levels , or poor bone density . GHD can be present at birth or develop later in life. Causes may include genetics , trauma, infections, tumors , or radiation therapy . Genes that may be involved include GH1 , GHRHR , or BTK . In

10058-520: The restriction of HGH therapy to the treatment of idiopathic short stature. Very limited clinical studies of growth hormone derived from an Old World monkey, the rhesus macaque , were conducted by John C. Beck and colleagues in Montreal, in the late 1950s. The study published in 1957, which was conducted on "a 13-year-old male with well-documented hypopituitarism secondary to a crainiophyaryngioma," found that: "Human and monkey growth hormone resulted in

10165-430: The size of a male's penis , especially when gonadotropins are also deficient. Besides micropenis in males, additional consequences of severe deficiency in the first days of life can include hypoglycemia and exaggerated jaundice (both direct and indirect hyper­bili­rubi­nemia ). Even congenital GH deficiency does not usually impair length growth until after the first few months of life. From late in

10272-511: The start of treatment do benefit. The incidence of idiopathic GHD in infants is about 1 in every 3800 live births, and rates in older children are rising as more children survive childhood cancers which are treated with radiotherapy, although exact rates are hard to obtain. The incidence of genuine adult-onset GHD, normally due to pituitary tumours, is estimated at 10 per million. Like many other 19th century medical terms which lost precise meaning as they gained wider currency, " midget " as

10379-539: The subject published in early 2007 showed that the application of GH on healthy elderly patients increased muscle by about 2 kg and decreased body fat by the same amount. However, these were the only positive effects from taking GH. No other critical factors were affected, such as bone density, cholesterol levels, lipid measurements, maximal oxygen consumption, or any other factor that would indicate increased fitness. Researchers also did not discover any gain in muscle strength, which led them to believe that GH merely let

10486-430: The tissues of the body can generally be described as anabolic (building up). Like most other peptide hormones, GH acts by interacting with a specific receptor on the surface of cells. Increased height during childhood is the most widely known effect of GH. Height appears to be stimulated by at least two mechanisms: In addition to increasing height in children and adolescents, growth hormone has many other effects on

10593-546: The treatment of a disease or other recognized medical condition, where such use has been authorized by the Secretary of Health and Human Services" has committed a felony . The Drug Enforcement Administration of the US Department of Justice considers off-label prescribing of HGH to be illegal, and to be a key path for illicit distribution of HGH. This section has also been interpreted by some doctors, most notably

10700-420: The use of GH and will issue sanctions against athletes who are caught using it. However, because GH is a potent endogenous protein, it is very difficult to detect GH doping. In the United States, GH is legally available only by prescription from a medical doctor. To capitalize on the idea that GH might be useful to combat aging, companies selling dietary supplements have websites selling products linked to GH in

10807-479: The use of GH as a doping agent was Dan Duchaine's "Underground Steroid handbook" which emerged from California in 1982; it is not known where and when GH was first used this way. Athletes in many sports have used human growth hormone in order to attempt to enhance their athletic performance. Some recent studies have not been able to support claims that human growth hormone can improve the athletic performance of professional male athletes. Many athletic societies ban

10914-410: 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",

11021-420: Was associated with the development of Creutzfeldt–Jakob disease , and was withdrawn from use. RHGH (rHGH, rhGH) refers to recombinant human growth hormone, that is, somatropin ( INN ). Its amino acid sequence is identical with that of endogenous human GH. It is coincidental that RHGH also refers to rhesus monkey GH (RhGH), using the accepted naming convention of Rh for rhesus . Rhesus growth hormone

11128-499: 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." The FDA issued a Safety Communication in August 2011, stating that

11235-459: 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, that is, somatrem (INN). This was the first recombinant GH product marketed (trade name Protropin by Genentech). It had the same amino acid sequence as human GH with an extra methionine at

11342-625: 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 5 ft 0 in (1.52 m). 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

11449-442: Was used since the late 1950s until the late 1980s when its use was replaced by recombinant GH. In the late 1950s, Maurice Raben purified enough GH from human pituitary glands to successfully treat a GH-deficient boy. A few endocrinologists began to help parents of severely GH-deficient children to make arrangements with local pathologists to collect human pituitary glands after removal at autopsy . Parents would then contract with

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