The Consequences of Chronically Elevated Growth Hormone Levels

Cardiovascular complications and cancer are the leading causes of death in patients with acromegaly

There are several medical conditions where growth hormone (GH) or GH secretagogues might be prescribed to manage a disease or deficiency. These peptides are capable of increasing GH levels and the doses that are given are intended to normalise levels. But what happens if a person’s GH levels chronically exceed normal levels? This article will cover the most common reasons human GH (hGH) or GH secretagogues are prescribed, instances where we can observe the effects of chronically elevated GH and how it can impact health.

GH and GH Secretagogues as Medicine

Since GH stimulates growth, its most well-established use is as a treatment for growth hormone deficiency (GHD). Children with GHD or other conditions that result in stunted growth can attain a greater final adult height with GH treatment,1 while adults with GHD who receive GH treatment benefit from improved body composition, blood lipid profiles, bone health and quality of life.2–4

GH secretagogues such as sermorelin and tesamorelin increase GH levels, as these are both analogues of growth hormone-releasing hormone (GHRH), a hormone that stimulates the release of GH from the pituitary. Sermorelin is used in the diagnosis and treatment of GHD in children,5 while tesamorelin is used to reduce abdominal adiposity in adults with HIV associated lipodystrophy.6 Other GH secretagogues such as ipamorelin and hexarelin, which are currently unapproved for human use, work by agonising ghrelin receptors, also leading to an increase in GH release. Ghrelin is a hormone known to stimulate hunger, so promoting GH release by activating the ghrelin/growth hormone secretagogue receptor (GHSR-1a) also increases appetite.7

GH and GHRH analogues have established uses in medicine, however, research has uncovered other possible benefits to stimulating GH secretion.

Experimental Uses

More experimental uses include the use of HGH or GH secretagogues to counter certain aspects of ageing and improve body composition.

One study found that giving men over 50 the same dose of GH that is administered to those of the same age with GHD improved leg strength without altering body composition.8 Most other studies have not reported such positive improvements in strength but have reported a change in body composition.9,10 A reduction in body fat and increase in lean mass has been observed in multiple studies, however, because many of these studies do not report an improvement in physical strength or athletic performance and instead find a measurably higher body water mass, this increase in lean mass is likely due to water retention rather than myofibrillar protein synthesis.11

Many of the advantages conferred by drugs that increase GH are of greatest benefit to those in recovery, the elderly and obese, as GH can prevent loss of muscle mass and retention of strength after surgery, improve skin thickness, cognition, bone density, body composition and sleep in the elderly and reduce visceral adiposity in obese patients.12–15

When GH or GH secretagogues are prescribed, doses given are carefully controlled and patients are monitored by medical professionals. We are still in the process of learning about the effects of GH when administered for more experimental uses, but this research has attracted much attention due to the appeal of its potential. Exogenous GH supplementation carries risks when not carefully controlled and monitored, especially when higher than physiological doses are administered over long periods of time. Disorders that lead to an excess of GH secretion have given us the earliest ideas of the potential health problems chronically elevated GH can result in, and we see the same problems in cases of GH and GH secretagogue abuse.

Abnormal GH Secretion and Prolonged Supraphysiological Exogenous Administration

Tumours of the pituitary, non-pituitary tumours that secrete GH or GHRH and pituitary hyperplasia can all lead to a high level of GH being secreted. If this occurs in childhood, it can lead to gigantism and comes with the development of features and symptoms such as:

  • Tall stature: When elevated GH secretion begins as a child, before bone plates fuse, it causes a significant increase in height.
  • Coarsening and elongation of the face with prominent forehead and/or jaw: Elongation of the face is seen in cases of gigantism but less so in adult-onset acromegaly.
  • Insulin resistance and increased risk of type 2 diabetes: GH breaks down stored fat in the body, hence its use to treat abdominal adiposity in those with HIV associated lipodystrophy. However, the liberated free fatty acids can prevent tissues such as the muscle and liver from responding normally to insulin, resulting in elevated blood sugar levels.16
  • Large hands and feet: GH stimulates the production of IGF-1, which promotes bone and tissue growth.
  • Organomegaly: This includes enlargement of the heart, which can lead to cardiomyopathy.17
  • Excessive sweating: The increase in IGF-1 can enlarge and overstimulate sweat glands.18
  • Vision problems: A pituitary tumour can press on the optic chiasm, where the optic nerves from each eye cross, disrupting nerve signals and leading to vision difficulties. In addition to this, excessive GH can, in rare cases, cause intracranial hypertension and swelling of the optic nerve, which can affect vision.19
  • Joint pain: High GH levels can cause cartilage to grow abnormally thick and absorb an excess of water, becoming weaker and less able to protect joints. This can lead to inflammation in the joints and remodelling of the bone beneath the cartilage, resulting in pain and acromegalic arthropathy.20,21
  • Delayed puberty: Approximately one third of children with pituitary gigantism experience delayed puberty.22 In some cases, this may be due to high levels of prolactin, which suppress reproductive hormones.23
  • Sleep problems: Physical changes occur in the airways, such as enlargement of the tongue, leading to obstructive sleep apnoea.24
  • Muscle weakness: Muscle tissue structure is altered, increasing muscle size but reducing muscle quality. The metabolic changes that occur as a result of elevated GH mean that muscle tissue is less able to utilise glucose.25–27
  • Oedema: GH promotes sodium retention and thus water retention. This water retention contributes to joint pain, carpal tunnel syndrome and high blood pressure.28,29

In adults, excess GH leads to acromegaly, which carries with it most of the same health risks as gigantism. An increase in height is not seen when acromegaly develops in adulthood, due to bone plates having fused. The delay in puberty and elongation of the face also only develop in children.

Mitigation of Risk

The prolonged elevation of GH can lead to many unfavourable effects on health. In those with pituitary tumours, surgery can be performed to remove the tumour, radiation therapy can reduce tumour size and somatostatin analogues can be administered to counter the effect of GH.

When used for the treatment of disorders such as GHD, the aim of treatment is to normalise GH levels, as such, GH treatment allows these patients to lead more normal lives. When administered to the elderly, who are experiencing a natural decline in GH levels, we may also see some modest benefits. However, in those with pituitary tumours or who are administered higher than physiological doses of GH over the course of several months or years, GH can increase the risk of disease and induce permanent physical changes.30

This array of medical problems that comes with chronically elevated GH levels stresses the importance of correctly monitoring and managing GH levels.

Conclusion

HGH is a valuable medicine, but only when used in the appropriate doses. Those who receive GH as part of their treatment require careful monitoring by a medical professional so that their dosing and treatment strategy can be adapted to offer the greatest benefit. When GH levels are chronically elevated, whether due to disease or inappropriate administration, this can increase the risk of disease, emphasising the importance of medical intervention and guidance to normalise GH levels.

References

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