Professor Peter Clayton
Manchester Children's Hospital

Professor Julian Davis
Manchester Royal Infirmary

The embryonic Pituitary gland forms during the first 10 to 12 weeks of pregnancy. The anterior pituitary is derived from Rathke's pouch in the roof of the mouth, which grows upwards. Cells from part of the brain grow downwards to form the posterior pituitary. It is thought that craniopharyngiomas and Rathke's Cleft Cysts occur when something goes wrong in this process.

Craniopharyngiomas and Rathke's Cleft Cysts are both rare benign tumours, which are derived from the remnants of Rathke's pouch. A Craniopharyngioma is made of solid tissue, cysts and calcified nodules and occupies the space within and above the pituitary gland. Rathke's Cleft Cysts are cysts filled with either a fine or thick fluid and arise within the pituitary gland.

Lesions in the area of the pituitary gland have a confined space in which to grow. As a result of this they tend to squash the existing structures. The direction of growth of lesions within or near the pituitary gland has a direct bearing on how they present.

Pressure effects can be caused by the tumour exerting pressure on either the pituitary or the optic nerve, leading to headache and visual difficulty, or on other parts of the brain, resulting in hydrocephalus (build up of the Cerebrospinal fluid within the brain). Headaches are persistent and are usually worse in the morning. These are often accompanied by nausea and vomiting.

Hormonal effects can be caused either by damage to the pituitary gland itself or to the Hypothalamus, which controls the pituitary. This leads to pituitary hormone deficiency. About half of children with craniopharyngiomas present with endocrine deficiency, primarily growth deficiency. A simple way to identify growth deficiency is by taking regular measurements of height. Another important sign is when a child begins to go through puberty but then stops. On hormone testing the child is most likely to be deficient in all the pituitary hormones (panhypopituitarism).

Hypothalamic effects can occur when the tumour damages the hypothalamus, leading to problems with appetite regulation, temperature control and memory.

As Rathke's Cleft Cysts occur within the pituitary gland they can easily be confused with pituitary tumours. Typical symptoms include headache, visual loss and endocrine deficiency. However, it is less common for a patient with a Rathke's Cleft Cyst to be suffering from panhypopituitarism.

Diagnosis of craniopharyngioma or Rathke's Cleft Cyst usually occurs as a result of clinical suspicion due to a patient presenting with headache, visual loss and hypopituitarism and an abnormal CT or MRI scan. On a MRI scan different shades can often be seen highlighting the solid and cystic areas of the tumour. Craniopharyngiomas can also be diagnosed by chance on skull X-rays, due to the visible calcium deposits.

Craniopharyngiomas are treated using a combination of surgery, Radiotherapy and hormone replacement.

Surgery can be performed to remove all or part of the lesion or to insert a shunt to drain fluid from the cyst and should be performed by an experienced neurosurgeon. If it is felt that surgery could cause significant damage to the structures surrounding the pituitary then surgery may be avoided.

Radiotherapy treatment usually follows on from surgery. This can be used to reduce any tumour residue after surgery and has been shown to reduce the chance of regrowth of the tumour. In some cases, where surgery is not advisable initially, it may be possible to use radiotherapy to shrink the lesion and then surgery can be reconsidered. Radiotherapy is most commonly used for childhood craniopharyngiomas, but is never used in children of less than two years of age, due to the possibility of causing brain damage. In this situation, radiotherapy is deferred to a later date.

Hormone replacement is used to replace one or more of the hormones under the control of the pituitary, which may be deficient as a result of damage caused by the tumour, surgery or radiotherapy.

After surgery there is a 10-20% possibility of recurrence or regrowth of a craniopharyngioma. If regrowth does occur, further surgery, to remove the tumour or drain cysts, or radiotherapy may be performed.

Treatment of Rathke's Cleft Cysts, with regard to surgery and hormone replacement, is similar to that for craniopharyngiomas. Radiotherapy is generally not used, as its role in treating Rathke's Cleft Cysts is uncertain.

In the immediate post-operative period, tests on pituitary function should be performed, in particular with respect to steroid replacement and Diabetes Insipidus, which may be transient or permanent.

In the long-term, pituitary function should continue to be assessed and scans should be performed to check on any residual tissue and shunt function. It may also be necessary to assess hypothalamic function with respect to fluid balance, appetite regulation, somnolence and temperature.

Craniopharyngiomas can cause hypothalamic damage by disrupting the appetite centres, which are found in the hypothalamus, leading to hyperphagia (overeating) and/or a lack of vagus nerve function in the pancreas. The latter increases the amount of insulin produced by the body, leading to fat storage and obesity. Diet and exercise continue to be the preferred method of trying to control the problem, although studies using antiobesity drugs, such as orlistat, are ongoing.