Pendred Syndrome Health Article

Definition

Pendred syndrome is an inherited condition that causes hearing loss typically beginning at birth and usually leads to the development of an enlarged thyroid, called a goiter. The thyroid is a gland responsible for normal body growth and metabolism. People with Pendred syndrome often have altered development of certain bones in the inner ear and/or balance problems as well. Vaughan Pendred first described the presence of hearing loss and goiter in two sisters in 1896, and thus the condition became known as Pendred syndrome. Genetic research has identified a gene on chromosome number seven that is usually altered in people with Pendred syndrome.

Description

Pendred syndrome is sometimes called goiter-sensorineural deafness, due to the common existence of both goiter and a form of hearing loss called sensorineural hearing loss in affected individuals. In order to understand how goiter occurs, it is helpful to first understand how the thyroid gland normally works. The thyroid is located underneath the larynx (voice box), in the front of the neck. The main role of the thyroid is to trap iodine, an essential nutrient found in various foods as well as salt, and to use it to make two important hormones: T3 and T4. These thyroid hormones allow the body to grow normally and to increase the speed of metabolism (breakdown) of nutrients. The thyroid is able to create these hormones because of a series of chemical reactions. A portion of the brain called the hypothalamus is responsible for controlling many body functions. One of its functions is to make a chemical called thyroid releasing hormone (TRH). This hormone travels to another gland, called the anterior pituitary gland, which is located underneath the brain. The TRH stimulates the anterior pituitary gland, which makes a chemical called thyroid stimulating hormone (TSH). This hormone travels to the thyroid, and activates the release of T3 and T4 into the body.

The word goiter is used to describe an enlargement of the thyroid gland. People with goiter may have hypothyroidism (they make too little T3/T4), hyperthyroidism (they make too much T3/T4), or they may have thyroid glands that work normally. Approximately 44–50% of people with Pendred syndrome have hypothyroidism, while the remaining 50–56% have thyroid glands that create a normal amount of thyroid hormones. However, approximately 75% develop goiter at some point in time, although it is rarely present at birth. Thirty to 40% of individuals develop an enlarged thyroid in late childhood or during their early teen-age years. The remaining 60–70% show symptoms during their early adult years. The enlargement of the thyroid gland happens because the mechanisms that control iodine transfer within the cells of the thyroid do not work well. This transfer is necessary to allow the iodine to bind to (and in doing so, help generate) thyroid hormones stored inside the thyroid. Since the iodine is not moved to the correct area of the thyroid, it becomes "pooled," rather than attaching itself to thyroid hormones. This faulty processing of iodine among people with Pendred syndrome can often be confirmed by the use of a perchlorate discharge test. Perchlorate is a chemical that causes the pooled iodine to be pushed out of the thyroid into the bloodstream where it can be measured. Since people with Pendred syndrome usually have more pooled iodine than normal, they will push out or discharge a larger amount of iodine when they are exposed to perchlorate. However, not all affected individuals show abnormal results, so the test is not perfect.

Pendred syndrome causes a specific type of hearing impairment called sensorineural hearing loss (SNHL). The ear can be divided into three main parts: the outer ear, the middle ear, and the inner ear. The parts of the outer ear include the pinna (the visible portion of the ear), the ear canal and the eardrum. The pinna directs sound waves from the environment through the ear canal, toward the eardrum. The eardrum vibrates, and causes tiny bones (called ossicles), which are located in the middle ear, to move. This movement causes pressure changes in fluids surrounding the parts that make up the inner ear. The main structures of the inner ear are the cochlea and the vestibular system. These structures send information regarding hearing and balance to the brain. The cochlea is shaped like a snail shell, and it contains specialized sensory cells (called hair cells) that change the sound waves into electrical messages. These messages are then sent to the brain through a nerve (called the auditory nerve) that allows the brain to "hear" sounds from the environment. The vestibular system is a specialized organ that helps people maintain their balance. The vestibular system contains three structures called semi-circular canals, which send electrical messages to the brain about movement and body position. This allows people to maintain their balance when moving by sensing changes in their direction and speed.

Sensorineural hearing loss occurs when parts of the inner ear (including the cochlea and/or auditory nerve) do not work correctly. The amount (or degree) of hearing loss can be described by measuring the hearing threshold (the sound level that a person can just barely hear) in decibels (dB). The greater a person's dB hearing level, the louder the sound must be to just barely be heard. Hearing loss is often defined as mild, moderate, severe, or profound. For people with mild hearing loss (26–45 dB), understanding conversations in a noisy environment, at a distance, or with a soft-spoken person is difficult. Moderate hearing loss (46–65 dB) causes people to have difficulty understanding conversations, even if the environment is quiet. People with severe hearing loss (66–85 dB) have difficulty hearing conversation unless the speaker is standing nearby or is talking loudly. Profound hearing loss (>85 dB) may prevent people from hearing sounds from their environment or even loud conversation. People with Pendred syndrome generally have severe to profound SNHL that is congenital (i.e. present at birth) in both ears. However, some affected individuals develop SNHL during childhood, after they have learned to speak.

People with SNHL often undergo specialized imaging tests, such as computed tomography (CT) and/or magnetic resonance imaging (MRI) scans, which create detailed images of the tissue and bone structures of the inner ear. Approximately 85% of people affected with Pendred syndrome have physical changes in the inner ear that can be seen with these tests. A common finding is a visible change in the snail-shaped cochlea called a Mondini malformation, in which the cochlea is underdeveloped and has too few coils compared to a normal cochlea. Another visible change sometimes seen in the inner ear is called enlarged vestibular aqueduct. The vestibular aqueduct is a narrow canal that allows fluid to move within the inner ear. Enlarged vestibular aqueduct (EVA) is the most common form of inner ear abnormality that is seen with CT or MRI scans. As the name implies, the vestibular aqueduct (canal) is larger than normal in people with EVA. Although EVA is seen in approximately 10–12% of people who are born with SNHL, some people with EVA can have SNHL that fluctuates (comes and goes) or is progressive (gradually worsening) as well as balance problems. In spite of the fact that Pendred syndrome has typically been diagnosed among people with both SNHL and goiter/thyroid problems, as of 2000, preliminary studies support the finding that some people with EVA and SNHL have a form of Pendred syndrome, even if they do not have goiter or thyroid problems.

Pendred syndrome also causes vestibular dysfunction in approximately 66% of affected individuals, which means they have abnormalities in their vestibular (balance) system. This may cause problems such as dizziness because they cannot sense changes in direction or speed when they are moving.