Pituitary News, Issue 24 - Summer 2002.

Acromegaly is a disabling condition that can dominate the lives of patients and even with the best care currently available the disease cannot be adequately controlled in a significant minority of patients. However, these are exciting times as new forms of treatment offer the prospect of better control of symptoms and avoidance of the long-term complications of the disease.

Surgical techniques are improving, new forms of Radiotherapy are being developed, and advances in medical treatment are being made. New forms of already established classes of drugs and a completely new type of drug offer the prospect of previously unachievable levels of control of the disease. The progress in surgical and radiotherapy techniques are pertinent to patients with other pituitary conditions.

Endoscopes are fibre-optic cameras that allow doctors 'to look round corners' and have been used for many years to examine the stomach and bowels (colonoscopy) and are the basis of 'key-hole' surgery. Small endoscopes have been developed to enable surgeons to get a better view of the more inaccessible areas of the pituitary during pituitary operations, such as the cavernous sinuses. Endoscopy, although not suitable for all operations, along with other new techniques, for example the ability to scan the Pituitary gland during surgery, should, in the future, result in better removal of tumour with fewer complications.

Radiotherapy

Radiotherapy is evolving as scientific expertise at imaging the pituitary gland has allowed more focussed radiotherapy to be delivered to pituitary tumours with the surrounding brain receiving very little. For forty years radiotherapy has relied on three beams directed at the Pituitary tumour with inevitably some radiation falling on surrounding tissues. The dose of radiotherapy has been limited by the risk of damaging those surrounding tissues, namely the optic nerves and surrounding brain. To reduce the potential for harm the 'three field' radiotherapy is divided up into small doses (fractions). The new stereotactic (focussed) forms of radiotherapy rely on very precise scans (usually MRI) to safely aim a much larger dose of radiation at the tumour. Rather than using three beams, either a moving beam or nearly three hundred fixed beams are used to ensure very little radiation strikes the surrounding brain. Stereotactic radiotherapy (or radiosurgery) can be safely given in a single session and is faster acting which in the case of acromegaly means GH levels should fall faster. The most widely available form of stereotactic radiotherapy is the 'Gamma Knife' while stereotactic Linac is becoming available. Stereotactic radiotherapy was the subject of a more detailed article in Issue 23 of Pituitary News.

Somatostatin analogues

Somatostatin analogues are the most powerful drugs currently available for treating acromegaly, with the original analogue, Octreotide, having been available for approximately 10 years. Octreotide (Sandostatin®) controls GH levels in approximately 60% of patients and in some may cause the tumour to shrink. Octreotide can be taken as a three times per day subcutaneous (under the skin) injection or as a once a month Intramuscular injection. The alternative somatostatin analogue, Lanreotide (Somatuline®) comes as a two weekly intramuscular injection or in a recently released once monthly, easy-to-give preparation (Lanreotide Autogel®) administered by deep Subcutaneous injection. New and hopefully more powerful somatostatin analogues are being developed that will be effective in a greater proportion of patients but it will be several years before they are widely available.

Pegvisomant

Even with the best available surgery, radiotherapy and medical treatment there remains a significant minority of patients whose acromegaly remains uncontrolled and who need additional treatment.

Pegvisomant is a new type of drug treatment that is completely different from existing medical therapies. Unlike the dopamine agonists (Bromocriptine, cabergoline) or the somatostatin analogues (octreotide, lanreotide), it has no effect on the pituitary tumour. The medications mentioned above, work by 'sitting' (on receptors) on the tumour surface to block the release of Growth hormone (GH). Pegvisomant makes no attempt to inhibit GH release but rather it works throughout the body to block the action of GH. Pegvisomant is a modified (genetically engineered) GH that attaches to specific parts (receptors) of the cells surface throughout the body and inhibits normal GH from binding and stimulating the cells. GH receptors are situated all over the body, in organs such as the liver and heart, and tissue like muscle and bone. This means that GH released from the pituitary tumour cannot activate these receptors, and therefore the undesirable effects of too much GH are controlled. It is GH binding to cells that stimulates cells to make IGF-1 (Insulin-like Growth Factor-1), which in turn is responsible for most of the actions of GH. Pegvisomant does not attempt to lower levels of GH in the blood and therefore GH cannot be used to measure the severity of acromegaly in patients on pegvisomant. Instead, IGF-1 levels are used as the best means of assessing acromegaly in patients on pegvisomant. In a study of patients with acromegaly 97% of patients treated with pegvisomant achieved a normal IGF-1 level. The improvement in IGF-1 is accompanied by an improvement in well-being and energy levels and a reduction in swelling of the fingers and other tissues. Pegvisomant is self-administered as a once daily subcutaneous injection.