Professor Stephen Shalet
Christie Hospital, Manchester

In reality, adult Growth hormone replacement treatment started in 1989, when adult growth hormone deficiency (AGHD) was recognised by researchers in London and Denmark.

Clinical symptoms of AGHD include impairment of quality of life, change in body composition (decrease in lean muscle mass and an increase in fat mass especially in the trunk), decrease in bone mass, dehydration and decrease in exercise tolerance. There is also an increased risk of heart attack due to an adverse cardiovascular risk factor profile, atherosclerosis of large blood vessels and elevated cholesterol levels.

Patients with hypopituitarism have a two-fold mortality rate when compared to the general population, but it is not certain why the risk is higher. It is difficult to prove that it is due to low growth hormone levels as other factors are also involved, especially inappropriate replacement of other low or missing hormones and previous Radiotherapy.

It is partly this 'unknown' that leads to prescribing variations. In Sweden the potential benefit of growth hormone replacement in reducing cardiovascular risk and death is used as the reason for treatment and almost 100% of those diagnosed are treated. In the UK quality of life (QOL) issues are generally the reason for prescribing. Research in Manchester, by research fellow Sarah Holmes, estimated that 40% of adults with severe GHD have a reduced quality of life. However, researchers in Scandinavia would put this figure higher and those in Scotland lower. In one study on the effects of GH, of 100 people selected, one-third chose not to enter the study. Of those who participated in the study 50% did not feel any benefit and 50% found it life transforming. Other findings show that around 60% of people who have AGHD are depressed.

Possible reasons for these differences include issues related to rehydration, changes in muscle strength, cardiac function and brain functioning. The characteristics of those who most feel a benefit from GH treatment are uncertain, but it is those with initial lower quality of life scores who have had the best reactions. There tends to be no gender variation in QOL. Those with childhood onset GHD tend to report less impairment of QOL. This is possibly because adults appreciate more what they have lost, although people often accept the changes in their lives as normal and accommodate them accordingly.

Due to the non-specific symptoms associated with GH deficiency, such as exhaustion and weight gain, the condition is not usually diagnosed quickly. The majority of people in the general population with these symptoms will not be GHD so it is unrealistic to expect a GP to think of GHD straightaway. GPs are also unlikely to be expert in GH treatment.

GH works with another hormone called Insulin-like Growth Factor-1 (IGF-1). As GH levels cannot be measured directly the hormone IGF-1 is measured instead. It is not yet known exactly what levels IGF-1 should be at, but the aim is for it to be not too high or too low. It is also uncertain where an individual's level should be within the normal range. This is also true for other hormone replacement such as Thyroxine. Women normally produce more GH than men and there is a natural 14% drop in production every decade of life.

The downside to GH treatment is dose-related side-effects. These are now less of a problem as it has been realised that adults need a lower dose than children. Symptoms of too much GH include oedema (increase in fluid), Carpal Tunnel Syndrome and muscle and joint pain. Long-term effects are not yet known as GH treatment has only been used since the late 1980s. There has been concern that GH treatment may possibly cause tumour recurrence, but there is no evidence to support this. If GH treatment is stopped there is evidence in children of reduced IGF-1 levels within three months and possibly as early as one month. Bone mineral density is affected more in childhood onset than in adult onset GHD.

Endocrinologists have different views and beliefs with regard to the benefits of GH treatment, though a position statement produced by the Society of Endocrinology is in favour of treatment. Scientists like random controlled studies. Initial trials were placebo controlled but used too high a GH dose and there is a need to repeat these trials with correct dose. NICE is currently examining GH use and will hopefully support its use, with a view to it becoming more widely available.