Medical Info

What is the pituitary gland?
The pituitary gland sits near the base of the brain behind the nose and under part of the eye nerves in a bony hollow called the sella turcica, 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 bloodstream. Pituitary hormones are important for growth and development, metabolism (turning food into energy) and reproduction. The pituitary gland makes eight hormones and one of them is growth hormone.

What is growth hormone?

Growth hormone is produced in the pituitary gland and helps regulate height, bone length, and muscle growth. While we normally associate growth hormone with childhood, growth hormone is cruical throughout life to maintain healthy tissue and organs.

What is a pituitary tumor or pituitary adenoma and how does it affect the body?

A pituitary tumor or adenoma is a growth found on the pituitary gland. While the tumor can be quite small in comparison to other types of tumors, its affect on the body can be profound. The tumor can cause  excess growth hormone leading to the excess height normally associated with gigantism as well as other hormonal dysfunctions such as infertility found in both gigantism and acromegaly. The tumor also can press against the optic nerves which cross over just above the pituitary gland. This can lead to vision loss. Gigantism and acromegaly patients also report other difficult and life-altering symptoms such as severe headaches, altered facial features, visual field defects, joint pain, carpal tunnel syndrome, sleep disturbances, hypogonadiasm, and metabolic dysregulation. A pituitary adenoma is usually slow-growing and benign.  It is not usually cancerous. 

What is gigantism? Is that the same as acromegaly or acromegalic gigantism?

Gigantism is a medical condition caused by a tumor on the pituitary gland that leads to excessive growth hormone. Gigantism occurs in childhood before the person has gone through puberty.  Normally bones seal off at the ends at puberty which limits the person’s growth. With gigantism the bones do not seal off, and the person can continue to grow and may become extremely tall.

Acromegaly is also caused by a tumor on the pituitary gland that leads to excessive growth hormone. The difference is that the the condition occurs in adulthood after puberty. The excessive growth hormone does not cause the bones to grow length-wise so the person is not extemely tall,  but the excess growth hormone can still make the body grow in other ways. For example, internal organs continue to grow, causing an enlarged heart or spleen. Hands and feet grow much larger. Most notably, the face grows. The nose and jaw become enlarged, the brow becomes more prominent, and the face elongates causing the distinctive facial characteristics of someone with acromegaly or gigantism. 

Sometimes, the disease is referred to as acrogigantism, acromegalic gigantism, or pituitary gigantism, but they are all basically the same disease. 

How is gigantism and/or acromegaly treated?

Gigantism or acromegaly can be treated with medication, surgery, and/or radiotherapy. The course of treatment is dependent on how early the tumor is detected, the size of the tumor, and the exact effect the tumor is having on the body.  Early detection is key to  treating the tumor successfully.

Why aren’t all people diagnosed with gigantism extremely tall?

How tall someone who is diagnosed with gigantism becomes is dependent on other factors besides how much excess growth hormone is released in the body. One important factor is the age of the person when they go through puberty in relation to when the tumor begins to grow and cause excess growth hormone. Before puberty, long bones grow at the end of the bones in a layer of cartilage called the epiphyseal plate. At puberty, the epiphyseal plates begin to seal off and the long bones will no longer grow. This process of sealing off can take several years.

If a person develops a pituitary tumor at a young age and does not go through puberty, the body does not receive the signal to seal off the bones, so the bones will continue to grow and the person can become extremely tall.

On the other hand, if the person develops a tumor at the same young age but then goes through puberty, the bones will begin to seal off which will limit the person’s height. The person can still be quite tall but will not necessarily achieve the extreme height that another person may reach who developed the tumor at a different age and/or went through puberty at a different age.


What is Familial Isolated Pituitary Adenoma?
A pituitary tumor can occur sponataneously in about one person in every 1000. Only 5% (1 in 20) of these tumors are hereditary, meaning that they may be passed down through families. Familial Isolated Pituitary Adenoma (FIPA) is one of a small number of rare genetic disorders that can cause hereditary pituitary tumors.

What is an AIP gene mutation?

To understand a genetic mutation, we need to start with DNA. Most DNA is in the cell nucleus and contains a person’s hereditary information received from the parents. The information in the DNA is stored as a “code” using four chemical bases: adenine (A), guanine (G), cytosine (C), and thymine (T). There are about three billion bases in humans. The order of these bases tells the cells the information they need to function.

Genes are made up of DNA. Some of the genes use the DNA “code” as an instruction book to make proteins. Scientists give genes names to track where they are located and their function.  In the case of the AIP gene, the AIP gene is located on chromosome 11 and  provides instructions to make a protein called aryl hydrocarbon receptor-interacting protein. This protein helps regulate cell processes such as growth and division. It is also thought to be a tumor suppressor.

A gene mutation or variant is a change to the DNA “code” that makes up the gene. Someone can have a gene mutation that has occurred spontaneously, or the mutation can be inherited from a parent. Not all gene mutations cause disease, but in the case of the AIP gene, a mutation can cause gigantism. There are different ways that the AIP gene can be mutated.

What does the AIP ARG304STOP mutation mean?

Patients linked to Northern Ireland have the ARG304STOP mutation, which they inherited from a parent. This mutation causes the protein to stop forming before it is completed. The number 304 indicates exactly where the mutation occurs on the AIP gene. Scientists know that if the patient has this exact mutation, they are related to other patients with the ARG304STOP mutation, and at some point, their ancestors came from the genetic hotspot identified near Cookstown in Northern Ireland.

Other cohorts of patients with AIP mutations who have gigantism have been identified in other countries. These patients also have an AIP mutation but the exact location of the mutation on the AIP gene is different, so these patients are not related genetically to the Northern Ireland cohort.

Are there other genetic mutations that cause gigantism?

There are other genetic mutations that cause gigantism. For example,  there is an aggressive form of the disease called X-linked acrogigantism (X-LAG) which is caused by an inherited mutation on the GPR 101 gene on chromosome Xq26.3. This form is known to affect children who are very young and is more likely to cause the disease to occur in anyone  who has the defective gene.