Adult Growth Hormone Deficiency

Dr Paul Lee, Dept of Diabetes and Endocrinology,
Princess Alexandra Hospital, Brisbane, Queensland.

Contents

It is well-known that growth hormone (GH) stimulates growth in children. However research in the last few decades has shown that GH also plays a critical role in metabolism and in the maintenance of physical fitness and health in adults. GH is the most abundant hormone in the pituitary gland and continues to be produced throughout adult life. The effects of GH are widespread and it plays a general role in maintaining the metabolic process and the integrity of many tissues in the body in adults.

What causes growth hormone deficiency in adults?

The most common cause of GH deficiency in adults is a tumour of the pituitary gland. The tumour may compress the pituitary gland resulting in the damage of cells which produce GH. The treatment of the pituitary tumour itself, either by surgery or by radiation, can also damage these GH-producing cells. Traumatic brain injury such as from a motor vehicle accident is a common but poorly appreciated cause.

What are the symptoms of growth hormone deficiency in adults?

Adults with GH deficiency, whether dating from childhood or acquired in later adult life, develop abnormalities in metabolism and a loss of physical fitness. These patients have a recognizable “clinical syndrome”, associated with a characteristic history, symptoms, signs, as summarized in Table 1.

Table 1 Symptoms and signs of growth hormone deficiency

Symptoms

Signs

Weakness

Increased fat mass

Impaired sense of well-being

Reduced muscle mass

Low mood and motivation

Reduced bone density

Lack of energy and vitality

Thin, dry skin with reduced sweating

Decreased exercise capacity

High blood fats


GH is important in controlling metabolism, especially with regards to how the body uses different nutrient fuels to meet energy requirements. GH stimulates the burning of fat and building of muscle. Adults with GH deficiency therefore develop excessive body fat and a loss in muscle mass. The gain in fat mass increases the levels of blood lipids (cholesterol and triglycerides), increasing the risk of developing diabetes. The reduction in muscle mass also results in an impairment of physical performance and muscle strength.

The combined metabolic and functional abnormities in adult GH deficiency are accompanied by significant impairment of psychological well-being and reduced quality of life. Patients with GH deficiency experience fatigue, easy exhaustion, and lack of vitality. Recent studies have revealed marked impairment in quality of life regardless of country and cultural background [1].

Thus, the collective evidence indicates that adults who lack GH suffer from metabolic abnormalities, reduced physical fitness, impaired psychological well being and reduced quality of life.

How is growth hormone deficiency diagnosed in adults?

Although the features of GH deficiency are recognizable, they are not particularly distinct and mimic changes of the aging process and a sedentary life. Thus, clinical suspicion of GH deficiency must be confirmed by laboratory diagnosis.

To confirm the diagnosis of GH deficiency in adults, the following are required:

  • A GH stimulation test: this is the most reliable test. It is performed in a specialized centre under supervision. Different types of stimulation tests are available, the best known being the insulin-induced hypoglycaemia test.
  • Measurement of insulin-like growth factor I (IGF-I): this is a helpful test based on a single blood sample. It is usually low but may be in normal in GH deficiency.


IMPORTANT:

A single measurement of GH has no value. Random testing of IGF1 level outside the context of pituitary condition is unlikely to yield meaningful information as its level is affected by many conditions.

WHO TO TREAT

GH deficiency should be diagnosed by laboratory testing within an appropriate clinical context. Testing for GH deficiency should be considered in patients with a high probability of pituitary disease and manifest clinical features of the syndrome. This includes patients with a history of pituitary disease, radiation to the head, known childhood onset GH deficiency and previous head injury.

Growth Hormone Replacement

The benefit effects of GH replacement in adults with GH deficiency were first reported in 1989. Since then, the impact of GH replacement has been extensively studied, with long-term experience of up to 10 years indicating sustained benefits.

BENEFITS

GH treatment induces profound effects on protein and fat metabolism. It stimulates the growth of muscle and the burning of fat. Patients who received GH treatment lost fat mass and gained muscle mass. One of the first studies of adult replacement reported a significant reduction of 18% body fat and a corresponding increase of lean body mass of 10% over a 6-month treatment period [2]. These metabolic changes are accompanied by an improvement in cholesterol profile.

The increase in muscle mass during GH treatment is accompanied by an improvement in muscle strength, exercise capacity and performance. Patients on GH treatment have reported improvement in mood, energy, sleep, and vitality. According to the partner, the patients were more alert, active, and industrious, and had greater vitality and endurance during GH treatment [3]. A large survey in 304 patients showed not only an improvement in quality of life, but also significant reduction in the numbers of sick days and doctor visits during 12 months of GH therapy [4].

SAFETY

The experience from several large clinical trials indicates that GH treatment is safe and well tolerated. The most common side effect is tissue swelling caused by the retention of fluid. It is usually mild and resolve in the majority of patients either spontaneously or with reducing the dose of GH.

Conclusions

Based on the global evidence of efficacy and safety, adults with GH deficiency should be replacement with GH, a principle consistent with the tenet of hormone replacement for hormone deficiency in the practice of endocrinology. This is recommendation is endorsed by the Endocrine Society of Australia that adults with GH deficiency should be considered for GH replacement therapy. The Endocrine Society of Australia recommends the therapeutic guidelines of the Growth Hormone Research Society, the US and British Endocrine Societies for the treatment and monitoring of GH deficient patients on GH therapy [5].

 

References:

  • Blum WF, Shavrikova EP, Edwards DJ, et al: Decreased quality of life in adult patients with growth hormone deficiency compared with general populations using the new, validated, self-weighted questionnaire, questions on life satisfaction hypopituitarism module. J Clin Endocrinol Metab 88:4158–4167, 2003.
  • Bengtsson B-A, Eden S, Lonn L, et al: Treatment of adults with growth hormone (GH) deficiency with recombinant human GH. J Clin Endocrinol Metab 76:309–317, 1993.
  • Burman P, Broman JE, Hetta J, et al: Quality of life in adults with growth hormone (GH) deficiency: Response to treatment with recombinant GH in a placebo-controlled 21 month trial. J Clin Endocrinol Metab 80:3585–3590, 1995.
  • Hernberg-Stahl E, Luger A, Abs R, et al: Healthcare consumption decreases in parallel with improvements in quality of life during GH replacement in hypopituitary adults with GH deficiency. J Clin Endocrinol Metab 86:5277–5281, 2001.
  • Ho KK; 2007 GH Deficiency Consensus Workshop Participants. Consensus guidelines for the diagnosis and treatment of adults with GH deficiency II: a statement of the GH Research Society in association with the European Society for Pediatric Endocrinology, Lawson Wilkins Society, European Society of Endocrinology, Japan Endocrine Society, and Endocrine Society of Australia. Eur J Endocrinol. 2007; 157:695-700.
 
 The Endocrine Society of Australia

Position Statement on Growth Hormone Replacement of Growth Hormone Deficiency in Adults

The Endocrine Society of Australia (ESA) holds the view that adults with growth hormone (GH) deficiency are not normal and have impaired health. Such patients have a characteristic clinical syndrome which include abnormal body composition, reduced physical fitness, increased cardiovascular risk factors, osteopaenia and impaired psychological function. Based on evidence that GH replacement is beneficial, the ESA endorses the principle that adults with GH deficiency should be considered for GH replacement therapy. Such patients must be accurately diagnosed. Patients with a history of organic hypothalamic-pituitary disease exhibiting characteristics of the GH deficient syndrome and who fulfil the diagnostic criteria defined by the Growth Hormone Research Society should be considered eligible for treatment. The ESA recommends the therapeutic guidelines of the Growth Hormone Research Society* for the treatment and monitoring of GH deficient patients on GH therapy.

*Consensus guidelines for the diagnosis and treatment of adults with growth hormone deficiency: summary statement of the Growth Hormone Research Society Workshop on Adult Growth Hormone Deficiency. J Clin Endocrinol Metab 83:379-381, 1998.

 

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