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Gigantism

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Gigantism is a rare condition of accelerated growth and increased height as a result of too much growth hormone secretion during childhood or adolescence. It is almost always the result of a growth hormone secreting pituitary tumour.
Gigantism of the feet due to pituitary hyperfuncti

Enlargement of the feet due to pituitary hyperfunction (gigantism).

Alternative names for gigantism

Pituitary giant; acromegaly of childhood-onset.

What is gigantism?

Growth during childhood is controlled by the secretion of growth hormone into the bloodstream from the pituitary gland. Sex hormone secretion (oestrogen in females and testosterone in males) increases noticeably at puberty and causes the growth plates (epiphyses) found at the ends of long bones to slowly fuse together. Height growth stops at the end of puberty when the epiphyses have completely joined.

Gigantism is an endocrine disorder resulting from long-term secretion of too much growth hormone which accelerates the growth of muscle, bones and connective tissue in childhood or adolescence before the end of puberty. The consequence is an accelerated growth rate and increased height as well as a number of additional soft tissue changes. When left untreated or uncontrolled, some individuals suffering from gigantism have grown in excess of eight feet (2.43m) tall. The most famous example is that of Robert Wadlow, the tallest person in history at 8ft 11 in tall (2.71m).

Gigantism is very similar to acromegaly. Acromegaly is also caused by excess growth hormone secretion but during adulthood rather than childhood. This means that height is normal as the growth plates have fused before the excess growth hormone secretion occurs.

What causes gigantism?

Gigantism is almost always caused by a benign adenoma in the pituitary gland. An adenoma is a non-cancerous tumour and in the case of gigantism causes secretion of too much growth hormone.

Pituitary tumours can be small in size (micro-adenoma) or large (macro-adenoma). However, in gigantism they are frequently large and invade nearby brain tissue. The size of the adenoma directly affects the signs and symptoms experienced by the individual. Larger adenomas can damage the function of the normal pituitary gland causing failure of secretion of other hormones (hypopituitarism). In some cases, puberty may be delayed if pressure from the adenoma on the pituitary gland results in failure of sex hormone secretion and thus allows further growth of the skeleton.

Very rarely, growth hormone-secreting tumours can be found in unexpected places such as the liver, pancreas or lung.

What are the signs and symptoms of gigantism?

The signs and symptoms of gigantism are the accelerated growth leading to above-normal expected height for a child of their age. The effects of the growth hormone on bone, ligaments and soft tissue swelling can lead to coarse facial features, excessively large hands and feet with thick fingers and toes, prominent foreheads and jaws.

Headaches, visual disturbances and nausea can be caused by the tumour pressing on the brain and nerves to the eyes.

Gigantism can be complicated by diabetes, high blood pressure, carpal tunnel syndrome, and enlargement of the internal organs, especially the heart.

How common is gigantism?

Gigantism is an extremely rare condition which most endocrinologists may come across only a couple of times in their whole careers. Only approximately six new cases occur each year in the United Kingdom.

Is gigantism inherited?

Gigantism is generally not inherited. There are, however, a number of rare endocrine conditions associated with gigantism such as McCune Albright syndrome and multiple endocrine neoplasia type 1. A genetic mutation in the menin gene can be identified in affected families who have multiple endocrine neoplasia type 1. Gigantism seen in these conditions is still rare.

Recently, a new possible cause of pituitary tumours in families has been suggested, particularly tumours secreting growth hormone or prolactin. These often occur at a relatively young age. The cause may be a mutation in a protein called the aryl hydrocarbon receptor interacting protein.

How is gigantism diagnosed?  

Gigantism is diagnosed by taking blood tests to measure the levels of growth hormone and insulin-like growth factor 1 circulating in the blood. Insulin-like growth factor 1 is secreted into the blood primarily by the liver in response to growth hormone.

An oral glucose tolerance test is also performed.  This involves drinking a glucose solution and then having blood samples taken periodically over a few hours to estimate the growth hormone level.  Normally, the amount of growth hormone in the blood is reduced by the glucose solution. If a person suffers from pituitary gigantism, the growth hormone level may rise after the test, stay the same as the original level, ie, high, or be suppressed.  However, the degree of suppression is not enough to lower the growth hormone level down to the level seen after similar glucose suppression in people without this condition.

Raised levels of growth hormone and insulin-like growth factor 1 suggest a pituitary adenoma and would lead to further investigation such as a magnetic resonance imaging (MRI) scan.  A scan of the pituitary gland will identify any tumours.  If high levels of growth hormone are evident in the blood but no tumour is found in the pituitary gland, further MRI scans of the chest and liver will be performed to rule out growth hormone secreting tumours in the lungs and liver.  These investigations are all performed as an outpatient.

How is gigantism treated?  

Gigantism requires early diagnosis and aggressive treatment in order to prevent excess height and to improve life expectancy. Surgery is usually the first line of treatment with the aim of removing or reducing the size of the tumour to lower growth hormone levels. Surgery is normally performed as a planned hospital admission. The type of surgery will depend on the size of the tumour and how easily it can be reached.

Radiation therapy can be offered as an outpatient if surgery has not provided a complete cure. Radiation therapy can take several years to be completely effective. Around 50% of patients achieve control of growth hormone secretion within 7–10 years. Radiation therapy not only reduces growth hormone and insulin-like growth factor 1 levels, but is also effective in controlling tumour growth.

Drug therapy may also be used:

  • Before surgery to control symptoms and cause the tumour to shrink
     
  • Following surgery where growth hormone levels are not controlled
     
  • In patients while radiation treatment is taking effect
     
  • In some individuals where surgery cannot be performed

Depending on the drug used, several types of drug therapy may reduce the size of the tumour and prevent growth hormone and insulin-like growth factor 1 secretion. The classes of drugs used include dopamine agonists (cabergoline, bromocriptine and quinagolide), somatostatin analogues (octreotide and lanreotide), or growth hormone receptor antagonists (pegvisomant).

Are there any side-effects to the treatment?

Side-effects from surgery can include haemorrhage, infection, loss of sense of smell or damage to the pituitary gland resulting in pituitary hormone deficiencies (hypopituitarism). Hypopituitarism is treated by replacement with the necessary hormones, eg, hydrocortisone or thyroid hormone tablets.

Radiation therapy to the pituitary gland can also cause hypopituitarism. Vision is not worsened by radiation therapy. However, it may increase the risk of premature stroke or worsening memory but not all doctors are agreed on this.

Dopamine-based drugs can cause reduced appetite, nausea, vomiting and dizziness. Somatostatin analogues are given by injection and can cause skin and muscle irritation at the site of the injection. These drugs can also cause gut upset (most commonly diarrhoea and cramping abdominal pain) shortly after injections. About 20% of patients develop gallstones after long-term use but this does not usually cause symptoms. Pegvisomant can disturb the liver function and regular blood tests are used to monitor this.

Patients should consult their endocrinologist if they have any concerns about side-effects.

What are the longer-term implications of gigantism?

In the long-term, a diagnosis of gigantism means regular medical follow-up to monitor growth hormone and insulin-like growth factor 1 to ensure the tumour does not grow. Screening for complications of gigantism is required.

Height and overall size can affect mobility due to muscle weakness, osteoarthritis and peripheral nerve damage. Everyday activities can be affected such as buying homes, furniture, cars, clothes and shoes as they are made for "average-sized people". Some psychological problems may also be caused by this very rare condition.

Reduction of growth hormone levels to below 2.5 mcg per litre improves life expectancy to normal levels, significantly improves symptoms and prevents most of the associated complications. Left untreated, gigantism is associated with significant complications and an increased death rate of around twice the normal average for the population.

 

Written: March 2011