Joyce, a 38-year-old schoolteacher with type-2 diabetes, was 75 pounds overweight at her last physical exam. Today she comes in looking somewhat thinner, but complaining of severe pain in both wrists that began over a month ago and steadily became worse. She denies trauma or new activities involving use of her hands. However, Joyce reveals that about six months ago, she started taking “the most wonderful pills to lose weight,” consequently shedding about 27 pounds. She takes the pills at night to cause her body to release HGH, a process to which she credits her weight loss. She reports unusually good blood sugar control and more restful sleep. Could Joyce’s wrist complaints be associated with her new “diet pill?” Are you aware of research associating HGH release and blood sugar levels or insomnia?

Your uncle Timothy has been acting strangely. After his last myocardial infarction, he was diagnosed with adult HGH deficiency and prescribed injections twice daily. An endocrinologist carefully monitors him and his expensive therapy. Once sedentary for a 53-year-old man, he is now not only quite active, but both his blood pressure and cholesterol levels have improved. He even joined a gym! Your father Richard, Timothy’s younger brother, asked his physician to prescribe injections for him, also. However, testing revealed that Richard did not have HGH deficiency. Determined to experience the same benefits as his brother, Richard purchases HGH injections from an Internet site and begins self-administration. Would you be able to explain the difference in indications for HGH use by the two brothers? Could you recognize adverse effects of HGH use?

Water, sunlight, and fertilizer control the growth process in plants. Nurses learn in their basic education programs that humans, however, have an elaborate hormonal feedback system that regulates their growth process. Growth hormone-releasing hormone (GHRH), manufactured in the hypothalamus, stimulates the pituitary gland to produce HGH. Also known as somatotropin, HGH is produced primarily during slow-wave sleep.¹ This master hormone stimulates or modulates cell activities. When released, HGH also causes the liver to create insulin-like growth factor (IGF-1 or somatomedin C), a substance that causes bone and tissue growth and mediates many actions of HGH. Via a feedback mechanism, this growth process signals the reduced need for HGH production.

In youth, HGH is responsible for normal growth processes. Underproduction results in dwarfism, overproduction in giantism. Children periodically secrete HGH in large amounts followed by minimal secretion, resulting in “growth spurts.” Cyclical patterns of growth and rest periods occur. As children grow, their cells rest, regroup, and then grow again. This process typically continues until the bone ends (epiphyses) seal up and prevent further increases in height. In adults, cells are repaired and replaced, the cells then rest and regroup, and then the cycle of repairing and replacing cells begins again, but with the cycle occurring at a much slower pace and less often than in childhood.

With increasing age, the rate of production of HGH declines sharply. In fact, circulating levels fall by as much as 50% from puberty to the mid-30s.² About 500 mcg of HGH are released daily at age 20, diminishing to 200 mcg by age 40 and about 25 mcg by age 80.² Circulating HGH raises blood glucose levels by antagonizing insulin in anticipation of stress. This process leads to glucose intolerance, lipolysis (the breakdown of fat cells and a reduction of fat stores), and protein anabolism (build-up of lean body mass).^1,3

In adults, HGH is responsible for tissue repair and maintenance, not for height-associated growth. As HGH levels diminish with age, tissue integrity and function decline. Sleep disturbances become more common, especially among men.^1,3 About two-thirds of HGH secretion in men occurs at night, while only one-third occurs at night in women.¹ As the quality and duration of sleep diminishes, so does the ability of the pituitary to secrete more HGH. The aging process is now believed to be the result of declining HGH secretion, not a cause.²

Why do we grow old?

In modern society, very few people seem to be interested in growing old gracefully. Nurses need only consider the multitude of antiaging lotions and gels, and expensive plastic surgery procedures that patients already use or undergo to reverse the exterior signs of aging. However, with age, all humans experience somatopause — changes associated with the normal aging process, which include muscle atrophy, a diminished bone density that increases the risk of fractures, an increased body fat mass, and sleep disturbances.

As the production and release of HGH declines, there is an increase in the production of somatostatin, a hormone produced in the anterior pituitary that stops HGH from being distributed in the body. To mediate HGH actions, IGF-1 seeks out receptors on cell surfaces that signal changes, such as increases in muscle size. A long-term deficiency of IGF-1 results in increased insulin resistance.

Other changes with the aging process include —

• Fragility/weakness
• Osteopenia/osteoporosis
• Lack of energy
• Loss of muscle mass
• Reduced exercise capacity
• Decreased T4 (thyroxine) to T3 (triiodothyronine) conversion
• Diminished hair and nail growth
• Reduction in internal organ size
• Thinning skin due to collagen reduction
• Impaired temperature regulation and sweat excretion
• Diminished extracellular fluid volume
• Reduced basal metabolic rate
• Obesity, particularly increased abdominal and visceral fat
• Reduced sex drive
• Unfavorable lipid profile (reduced high-density lipids, increased low-density lipids, and apolipoprotein-B)

A diminished HGH level is not the only factor in the aging process. Some things, including exercise and oral estradiol hormone replacement therapy, seem to have an antiaging effect, by indirectly increasing endogenous levels of HGH.⁴

The war on aging has recently shifted from rejuvenating exterior signs of aging to understanding the biochemical mechanisms of the aging process. Attempts to reverse the interior process on a biochemical level are taking center stage. While aging has been the normal, expected progression from birth to death, the process may occur at a much faster rate as a result of HGH deficiency. Biomedical enhancement, including off-label HGH use, is aimed at improving mind, body, and performance despite inconclusive data on long-term efficacy and risks.^4,5 Deficiency remains the only approved indication for HGH replacement therapy use among adults. However, the use of HGH for antiaging, weight reduction, and other conditions has gained widespread attention through online direct-to-consumer marketing, despite this practice being deemed illegal by the U.S. Food and Drug Administration (FDA).⁶

The off-label use of HGH for antiaging has brought much attention to the minimally addressed problem of true HGH deficiency in adults. In the U.S., routine screening and treatment for adult HGH deficiency is not common, due in part to lack of provider awareness, third-party coverage limitations, and attribution of symptoms to other disease processes.⁷ Very few adults with HGH deficiency are diagnosed and treated in the U.S., compared to Germany and Sweden where the diagnosis and treatment of HGH deficiency is viewed as a treatment priority to reduce cardiovascular risks.⁸

Keeping tabs on HGH

HGH deficiency is defined differently in adults than in children because height, growth rate, and bone age are not diagnostic factors. Causes for acquired HGH deficiency among adults include breast and lung cancer, tuberculosis, syphilis, head injury, surgery, radiotherapy, and sarcoidosis. Benign tumors of the pituitary that do not secrete hormones (adenomas) are quite common in older adults, and more than 90% of adults with true HGH deficiency have pituitary or hypothalamic disease.¹

Fibromyalgia is associated with diminished HGH levels.^9,10 Symptoms of fibromyalgia, in which IGF-1 levels are also diminished, closely resemble those of HGH deficiency syndrome. Individuals with HGH deficiency and those with fibromyalgia exhibit sleep pattern and quality abnormalities.^9,10

GH deficiencies have also been implicated as a cause of the inflammation and pain in adult rheumatoid arthritis and juvenile chronic arthritis. Among patients with these disorders, not only are the levels of GH diminished, but defects in the GH receptors have been identified. These abnormalities are responsible for abnormal changes in the synovial lining leading to joint destruction.¹¹

GH deficiency not only contributes to disease incidence, it can also be the result of diseases and trauma. Take, for example, the incidence of GH deficiency associated with traumatic brain injury. Patients are just as likely to experience GH deficiency after a traumatic brain injury as they are to show diminished levels after discovery of a pituitary adenoma.¹²

Catabolic states, such as AIDS wasting, can result in HGH resistance, a state in which a sufficient quantity of HGH is unable to properly mediate activity at the cellular level. Also, lipodystrophy, an abnormal distribution of fat, often ensues.¹³

Diagnosing adult HGH deficiency

True levels of HGH are difficult to obtain because of a short half-life of 20 minutes. Instead, IGF-1, with a half-life of 20 hours, can be measured to indirectly assess HGH levels and monitor responses to treatment. However, IGF-1 levels are not reliable enough to diagnose HGH deficiency.

For approved drug use, the FDA requires clinical diagnosis based on a subnormal HGH response to a single stimulation test in adults and two subnormal test results in children. The insulin tolerance test (ITT) is considered the “gold standard” for HGH deficiency diagnosis. Because patients are subjected to induced hypoglycemia, the ITT is contraindicated for patients with seizure disorders, coronary artery disease, angina, and cortisol deficiency. The test is expensive and time consuming, often requiring supervision by a specialist during the procedure.

Other reliable challenge tests for adults, which include administration of certain medications or hormones to stimulate HGH release under supervision, are listed in the sidebar.

Get younger? Get slimmer?

The process of using HGH to treat diagnosed deficiency may slow, stop, or reverse the aging process. While the former has been widely accepted as beneficial, the latter still remains investigational. Although claims that HGH extends age are currently unsupported, reliable controlled clinical trials are producing data that demonstrates an improvement of health status for longer periods of time with HGH use in the absence of deficiency.¹⁴ Some providers now focus on “stopping or setting back the clock,” and antiaging clinics that provide extensive assessment and treatments are springing up all over the country and abroad. An Internet search revealed over 330,000 “hits” offering antiaging HGH information as well as opportunities to purchase HGH and HGH-stimulating products.

Some research suggests that low-dose HGH administration combined with caloric restriction may have a therapeutic role in treating obesity. Weight loss using HGH occurs without loss of lean body mass. It also takes place in a desired state of positive nitrogen balance as an anabolic state is maintained both during exercise and at rest.¹⁵ However, HGH use has not been approved as a weight-loss intervention, and it has been clinically associated with increased insulin resistance.¹⁵

Nurses should be cautious when discussing investigational or off-label use of medications. They need to gather in a nonjudgmental way as much information as possible about patients’ use of all medications, as well as any unusual or unexpected adverse effects. This information should also include substances that patients consume without the guidance of their prescribing healthcare provider.

What other benefits may HGH use have?

Recent studies have also evaluated the use of HGH in the treatment of dilated cardiomyopathy.^16,17 In one study, eight pediatric patients receiving HGH for six months had improved left ventricular function and ejection fractions.¹⁶ HGH may also have a role in treating the atherogenesis, hypertension, and insulin resistance found in Syndrome X, a disorder of lipid and glucose metabolism.¹⁸

Clinicians are exploring the use of HGH in the treatment of Crohn’s disease in conjunction with increased protein intake.¹⁹ A problem associated with impaired gastric absorptive function and inflammation is an increased risk for osteoporosis and metabolic bone disorders. One study explored the use of HGH among patients with severe short bowel syndrome and found that they had increased markers of bone turnover and strengthening of the femoral neck bone mass because of the anabolic effects on bone cells.²⁰

HGH may help with the treatment and prevention of osteoporosis. Research demonstrated a pronounced increase in bone mineral density and bone turnover, particularly in the lumbar spine and femoral neck, with the use of HGH.^21,22 However, men seem to be more sensitive than women to the effects of HGH on bone, and women would need higher doses to achieve the same benefit.²² One explanation for this gender difference is the impact of estrogen on sleep and, in turn, nighttime HGH production.¹ The correlation between use of HGH and fracture risk remains inconclusive, because of the lack of long-term studies.²¹

Individuals with HIV have also found HGH supplementation beneficial, for both HIV-associated lypodystrophy and weight loss, especially with the wasting experienced by individuals receiving highly active antiretroviral therapy (HAART).^23,24

Severely burned children have been shown to benefit tremendously when given long-term GH therapy. The children were followed for a year after burn injury, and their progress was compared to children who did not receive GH therapy. Children given GH therapy were taller, heavier, and had more lean body mass than children who did not receive GH therapy. Those receiving GH therapy also appeared to have a cardiac benefit, as their left ventricular ejection fractions were significantly improved as well.²⁵

Patients on chronic hemodialysis have also shown to benefit from GH therapy by maintaining protein homeostasis and experiencing less muscle mass wasting during GH therapy.²⁶

Multiple benefits of HGH use have been demonstrated for individuals with cystic fibrosis. The benefits of HGH use include increased exercise tolerance; improved muscular, cardiovascular, and pulmonary function; and improved quality of life.²⁷

Yet research has indicated that when GH is used as an adjunct to improve the efficiency of parenteral nutrition after major GI surgery, it was not effective and was associated with major risks, and it did not prevent nitrogen loss or provide a metabolic advantage.²⁸

Finally, a relationship between HGH levels and cognitive ability is emerging from recent data.^3,29 In one study, Mini Mental Status Exam scores directly correlated with circulating levels of IGF-1. People with low levels scored lower than those with adequate levels.³ The potential for a detrimental cycle that accelerates cognitive decline exists. As cognitive function declines, nutritional status often declines, resulting in protein calorie malnutrition. Physical activity also declines, and can impair IGF-1 function and diminish HGH secretion.²⁹

Another study examined the impact of daily GH releasing hormone therapy treatment among healthy older adults ages 60 to 85. The study found significant improvement in cognitive functions after six months of continuous use.³⁰

Approved uses for HGH

HGH has been approved as a treatment for children with growth hormone deficiency for many years. In 1996, the FDA approved HGH for use in adults with identified GH deficiency. This approval was fueled by evidence that GH deficiency increases the risk of death from cardiovascular disease, lowers cardiac output, lowers bone density, and increases serum lipid concentrations. Additional indications include the use of HGH for short stature associated with Turner syndrome, achondroplasia (short-limb dwarfism), chronic renal disease, intrauterine growth retardation as a result of maternal deficiency, short-small for gestational age children, and anterior pituitary dysfunction after traumatic brain injury.^13,31 However, the routine use of GH for any other purpose among healthy adults without diagnosed deficiency has not been approved and is considered an “experimental” or “off-label” use.³²

Supplementing or stimulating HGH production

HGH therapy usually involves two injections a day of recombinant (r)HGH (Humatropin, Norditropin, Nutropin AQ, Genotropin). The replacement of cadaver-derived HGH with synthetic preparations from genetic engineering is reducing the price of therapy, which can still cost more than $2,100 per month. New slow-releasing solutions, such as Nutropin depot, require less frequent administration. Doses of HGH injections are typically adjusted depending on serum IGF-1 levels.

Other chemical compounds — releasers (or secretagogues) — stimulate the pituitary to release more endogenous HGH and inhibit somatostatin production/release from the hypothalamus. These substances typically contain amino acids, not actual HGH. Intranasal secretagogue sprays are being tested in clinical trials.

Sublingual sprays containing either small doses of rHGH (up to 2,000 nanograms) or secretagogues are available as dietary supplements without a prescription. Sprays, such as Somatotropin, 21st Century HGH, Maximum Result, and Ultimate HGH, are inhaled two or three times a day. Even homeopathic sprays, including Full Spectrum and Regenesis, are now available. However, their effectiveness has not been clinically demonstrated in large-scale trials. Because so many different sprays are available online and in health food stores, nurses can have a hard time keeping up with their patients’ products. It is best to have patients bring the sprays they are using to health visits so nurses can tell if they contain rHGH or a secretagogue.

Oral secretagogues are also available as pills, dissolvable tablets, and powders, which can be obtained without a prescription. They are less potent than injectable HGH and have erratic absorption rates of only about 5% to 10% of the ingested substance because of the influence of gastric pH levels. While carbonated delivery (like taking Alka-Seltzer) of oral secretogogues improves absorption, the tablets may aggravate patients with citric acid allergies or sensitivities.² Oral secretagogues may be used alone or as an adjunct to rHGH injections. They are less expensive at about $65 to $250 per month. Like the sprays, oral secretagogues are marketed under dozens of names, including Longevity, Symbiotropin, and GHT Stack. They are taken at bedtime, at least four hours after the last meal. A typical dosing schedule involves repeated cycles of five days of therapy and two days with none. Cyclic dosing reduces overstimulation and reduced efficacy.

Concerns and complications

The off-label use of HGH and the use of secretagogues, which do not require a prescription, concerns medical professionals. Concerns over legal liability are emerging, especially if complications occur with off-label use.⁷ Chronic, excessive use of these substances can produce many complications, which are usually dose-dependent, regardless of whether or not they are used by healthy individuals or as a potential treatment during chronic or acute illness. In fact, use during critical illness has been associated with an increased incidence of death.³²

With less than 24 years of evaluative data, much needs to be learned about the long-term effects and risks of even approved GH supplementation. Some effects seem to persist after the GH or secretogogue therapy has been stopped. For example, musculoskeletal and collagen changes — favorable in the treatment of osteoporosis and reduction of fracture risk, unfavorable for those left with the adverse effect of carpal tunnel syndrome or acromegaly — may continue long after therapy is discontinued.33 On the other hand, some effects, such as improved cognition, fade away without continued GH supplementation.

Some recommendations and cautions have emerged. For example, pregnant or lactating women should not take GH supplements or secretagogues unless prescribed and monitored by the prescribing professional. GH is not advised for people with cancer because of the potential of enhanced cancer-cell growth. And the use of HGH to enhance athletic performance is considered abuse, unless an athlete has a proven deficiency.³⁴

Even so, abuse is not uncommon despite the lack of research on the long-term effects of GH supplementation among athletes. One study revealed that one-forth of athletes using anabolic steroids were also using growth hormones.³⁵ While testing for abuse during training is difficult because HGH naturally occurs in the body with extreme fluctuations, newer immunoassay tests are available to more accurately determine recombinant HGH misuse.³⁴

Although the FDA has not approved the use of HGH for anything beyond documented GH deficiency and short for stature/small for gestational age children, patients who seek treatment for other medical problems need screening for the use of GH replacement medications, supplements, or secretagogues. Clinicians need to evaluate the impact of these substances on their treatment plan. As always, nurses need to fully evaluate every substance that patients use to determine potential contributions to problems; risk for interactions with other medications, foods, or disease states; and the need for patient education.