Familial (inherited) Isolated Pituitary Adenoma (FIPA)

What is the pituitary gland?

Photo capture: Pituitary gland

The pituitary gland sits in a bony hollow near the base of the brain behind the nose and under part of the eye nerves, and is roughly the size and shape of a bean. It is the master gland of the body’s endocrine system, which is made up of a number of glands that release hormones (the body’s chemical messengers) into the blood. Pituitary hormones are important for growth and development, metabolism (turning food into energy) and reproduction.

What is Familial Isolated Pituitary Adenoma?

A pituitary adenoma is usually a slow-growing and benign (not cancer) tumor of the pituitary gland, which occurs in about 1 person in every 1000. About 5% (1 in 20) of these tumors may be passed down through families. Familial Isolated Pituitary Adenoma (FIPA) is one of a small number of rare genetic disorders that can cause pituitary tumors that run in families.

Patients with FIPA are said to have ‘isolated’ pituitary tumors because, unlike in some other endocrine disorders that run in families, they do not have a raised risk of tumors growing in any other glands in the body.

Some pituitary gland tumors may make too much or too little in the way of hormones, both of which can cause a range of symptoms. We look at these symptoms further on.

If a pituitary tumor is very large, it can cause headaches and problems with vision as it is close to the eye nerves.

It is very important to stress that pituitary tumors are not ‘tumors of the brain’.

How is FIPA diagnosed?

In order to rule out other disorders that can cause hereditary pituitary tumors, a diagnosis of FIPA is generally made when:

• The pituitary is the only gland affected
AND
• The patient has a family history of pituitary gland tumors
AND/OR
• The patient has a gene change (mutation) associated with FIPA.

If the patient or their family members have had tumors in other glands (especially other endocrine glands, such as the parathyroids, pancreas, adrenals, thyroid and testes), testing for other genetic conditions will be offered.

Families with FIPA

Currently there are 3 groups of patients with FIPA and two known gene changes:
1. Patients with a change in the AIP gene
2. Patients with a change in the GPR101 gene
3. Patients who have FIPA but no gene change can be found

Patients with an AIP gene change
In about 20% (1 in 5) of families with FIPA, a gene change can be found in a protein called aryl hydrocarbon receptor interacting protein (AIP). About 20% (1 in 5) patients with an AIP gene change will develop pituitary tumors in their lifetime, usually by the age of 30. We do not know why some people with the gene change develop the disease while others not. In about half of these patients the disease may begin in childhood or teenage years, and both males and females can be affected. The most common tumor type makes growth hormone which can cause a condition called acromegaly. If this tumor is active before puberty, the extra growth hormone can cause someone to grow taller than expected based on the height of their parents (gigantism). The second most common tumor type is called a prolactinoma. The different types of tumor and their effects are looked at later in this booklet. Patients with an AIP gene change may have tumors that grow quickly and that respond less well to medicines. Both types of tumor, or sometimes mixed tumors can be seen in different members of the same family. It is important to note that sometimes an AIP mutation is found without a known family history of pituitary tumors. This is because not all patients with the gene change will develop the disease (around 1 in 5 do). Family members of a patient with an AIP gene change will need to be tested in case they also have the gene change . If these family members are found to have the AIP gene change, they can be tested (screened) for early signs of the disease. The earlier we find the pituitary tumor in a patient, the better the expected outcome. Very rarely a new gene change can be present in a patient but not in their parents. This is called a ‘de novo mutation’ but has only ever been found in a few patients.

Patients with a GPR101 gene change (XLAG)
A change in the X chromosome gene GPR101 is very rare. This is a special type of gene change where there are two copies of the same gene next to each other on the same chromosome (gene duplication). Patients with GPR101 duplication are very young children (almost always under 2 years old) when rapid growth starts with high levels of growth hormone and a protein called insulin-like growth factor (IGF-1) in the blood. The disease caused by GPR101 gene duplication is also known as X-linked acrogigantism, or XLAG. You can find out more about how it is passed down in families later in this booklet. Most of the patients are girls and patients with a GPR101 gene change usually do not have a family history of the disease.

Patients without a known gene change
In 80% (8 in 10) of families with FIPA, the gene change that causes the disorder is not yet known. In these cases, the disorder most often starts in adults. Males and females are equally affected. The two most common tumor types are those that make growth hormone and prolactin, followed by tumors that appear to make no hormones (non-functioning). Within a particular family the types of tumors can be the same or different.

For more information, visit the AMEND website