Growth Problems

Growth problems manifest as excessive or insuficient growth, caused by incorrect hormone levels and can have a major impact on a person's life. Research by the pharmaceutical industry has led to synthetic hormones and other medicines which can help correct the imbalance. Thus, patients are able to take part in all activities of their age.

What is growth abnormality? Top

Growth abnormalities can manifest in either growth retardation or excessive growth. First and foremost, there are many factors which may affect a child’s growth without meaning the child has a growth disorder. Causes can be environmental factors as well as hereditary factors and prolonged periods of poor health.

Growth retardation or failure is mostly caused by inadequate secretion of human growth hormone or somatotrophin. Without treatment, children with growth hormone deficiency remain small for their age and reach a final height of about 40cm below what would otherwise be expected.

The deficiency may be present at birth, or it may begin at any time during infancy or childhood. Cases also include children with Turner syndrome, with chronic renal failure and Prader-Willi syndrome.

Most often, it is the result of a disorder of the pituitary gland, which lies just beneath the brain failing to produce adequate levels of the hormone, caused by partial deficiency of growth hormone releasing hormone. The deficiency does not always continue into adulthood, possibly due to maturation of the structures in the brain. Children therefore need to be reviewed and retested once their final height has been reached.

For many patients, the cause of the deficiency remains unknown. However, there are also several known causes, including a tumour of the pituitary region, the treatment of a brain tumour or another form of cancer, a genetic disorder or a severe injury to the head. Growth hormone continues to play an important role throughout adulthood, regulating metabolism and body composition, and improving general quality of life.

Over-production of growth hormone leads to the clinical feature of acromegaly. The term is derived from the Greek nouns “akron” (meaning high, top, or extremity) and “mega” (meaning large), which refer to the clinical picture of the coarsening of facial features and the enlargement of the hands, feet and jaw. Acromegaly is triggered by over-secretion of growth hormone, often caused by a tumour of the pituitary gland, and leads in turn to the over-production of insulin-like growth-factor (IGF-1).

Who does growth abnormality affect? Top

The prevalence of growth hormone deficiency in childhood is around three in 10,000 of the population. For the European Union, this would mean about 150,000 people. Some children with the disorder produce enough growth hormone on their own that they may stop the treatment once growth has finished. However, some remain growth hormone deficient as adults and may need to continue treatment throughout their lives.

Growth hormone deficiency in adults may also result from decreased production of growth hormone from the anterior pituitary gland. It usually occurs as a consequence of a structural pituitary disease or peripituitary lesion, eg. pituitary adenoma, or as a result of treatment e.g. cranial irradiation or surgery.

It is estimated that the prevalence of adult onset growth hormone deficiency is one in 10,000 of the population. Reported symptoms include low energy levels, decreased exercise tolerance, increased weight, mood swing, anxiety, social isolation, and impaired sleep.

Acromegaly has an incidence of four to six cases per million inhabitants and affects around three thousand people in Europe. European countries have started to set up national data banks to register all detected cases. The UK data bank started in 1997 and has since then collected data of some 1.600 people. Apart from the symptoms mentioned above, patients with the condition suffer from headaches, excessive sweating, soft-tissue swelling and joint disorders.

Present treatments Top

Growth hormone was first isolated and used in treatment in 1956, and its structure was first identified in 1972. However, until the mid-1980s, the only source of growth hormone was pituitary glands extracted from human cadavers.

Synthetic growth hormone was first manufactured using genetic engineering techniques in 1985. The synthetic growth hormone produced today is 100 per cent identical to the natural growth hormone produced by the body.

In Europe, several human recombinant growth hormone preparations from different manufacturers are available for the long-term treatment of short stature of children and adults caused by a decreased or absent secretion of pituitary growth hormone. In order to improve their growth rate, children require injections daily or several times weekly over many years. Preparations for once a month application are also available.

To ease application, needle-free delivery systems have been developed and received EU authorisation in June 2002. There are also compounds approved for the extended indication of treating growth disturbance in short children born small for their gestational age who fail to catch up growth by four years of age or later.

Current therapies for acromegaly include surgery to remove the pituitary tumour, radiation therapy and medicines including dopamine agonists and somatostatin analogues. Since November 2002, a new class of medicines – growth hormone receptor antagonists – to treat the disorder is available in Europe.

As growth hormone hypersecretion has been known to be the cause of insulin resistance, the new medicine which is applied via injections, works by blocking the effects of growth hormone and normalising insulin-like growth factor-1 (IGF-1) levels. It is used in acromegaly patients who have responded inadequately to surgery or radiation or other medical therapies or for whom other therapies are not appropriate.

What’s in the development pipeline? Top

Pegylated molecules of somatotrophin have been synthesized to prolong the half-life of recombinant growth hormone in the human body. They are in Phase 3 clinical trials.

Research is also going on to develop further easy-to-use application systems to facilitate application for children and carers and to improve compliance.

The longer-term future Top

Researchers aim to understand better the phenomenon of growth on the cellular and genomic levels. Special attention is paid to the IGF-1 system which signals to cells to grow, differentiate, and survive. One central player is the IGF-1 receptor. Transduction of signals through this molecule leads to multiple series of intracellular events and the activation of pathways.

Gene therapy is also considered to offer new avenues for better treatment options in growth abnormalities.