Acromegaly and Gigantism
Acromegaly and Gigantism
Acromegaly is a disorder in which the abnormal release of a particular chemical from the pituitary gland in the brain causes increased growth in bone and soft tissue, as well as a variety of other disturbances throughout the body. This chemical released from the pituitary gland is called growth hormone (GH). The body's ability to process and use nutrients like fats and sugars is also altered. In children whose bony growth plates have not closed, the chemical changes of acromegaly result in exceptional growth of long bones. This variant is called gigantism, with the additional bone growth causing unusual height. When the abnormality occurs after bone growth stops, the disorder is called acromegaly.
Acromegaly is a relatively rare disorder, occurring in approximately 50 out of every one million people (50/1,000,000). Both men and women are affected. Because the symptoms of acromegaly occur so gradually, diagnosis is often delayed. The majority of patients are not identified until they are middle aged.
Causes and symptoms
The pituitary is a small gland located at the base of the brain. A gland is a collection of cells that releases certain chemicals, or hormones, which are important to the functioning of other organs or body systems. The pituitary hormones travel throughout the body and are involved in a large number of activities, including the regulation of growth and reproductive functions. The cause of acromegaly can be traced to the pituitary's production of GH.
Under normal conditions, the pituitary receives input from another brain structure, the hypothalamus, located at the base of the brain. This input from the hypothalamus regulates the pituitary's release of hormones. For example, the hypothalamus produces growth hormone-releasing hormone (GHRH), which directs the pituitary to release GH. Input from the hypothalamus should also direct the pituitary to stop releasing hormones.
In acromegaly, the pituitary continues to release GH and ignores signals from the hypothalamus. In the liver, GH causes production of a hormone called insulin-like growth factor 1 (IGF-1), which is responsible for growth throughout the body. When the pituitary refuses to stop producing GH, the levels of IGF-1 also reach abnormal peaks. Bones, soft tissue, and organs throughout the body begin to enlarge, and the body changes its ability to process and use nutrients like sugars and fats.
Adenoma — A type of noncancerous (benign) tumor that often involves the overgrowth of certain cells found in glands.
Gland — A collection of cells that releases certain chemicals, or hormones, that are important to the functioning of other organs or body systems.
Hormone — A chemical produced in one part of the body that travels to another part of the body in order to exert an effect.
Hypothalamus — A structure within the brain responsible for a large number of normal functions throughout the body, including regulating sleep, temperature, eating, and sexual development. The hypothalamus also regulates the functions of the pituitary gland by directing the pituitary to stop or start production of its hormones.
Pituitary — A gland located at the base of the brain that produces a number of hormones, including those that regulate growth and reproductive functions. Overproduction of the pituitary hormone called growth hormone (GH) is responsible for the condition known as acromegaly.
In acromegaly, an individual's hands and feet begin to grow, becoming thick and doughy. The jaw line, nose, and forehead also grow, and facial features are described as "coarsening". The tongue grows larger, and because the jaw is larger, the teeth become more widely spaced. Due to swelling within the structures of the throat and sinuses, the voice becomes deeper and sounds more hollow, and patients may develop loud snoring. Various hormonal changes cause symptoms such as:
- heavy sweating
- oily skin
- increased coarse body hair
- improper processing of sugars in the diet (and sometimes actual diabetes)
- high blood pressure
- increased calcium in the urine (sometimes leading to kidney stones)
- increased risk of gallstones; and
- swelling of the thyroid gland
People with acromegaly have more skin tags, or outgrowths of tissue, than normal. This increase in skin tags is also associated with the development of growths, called polyps, within the large intestine that may eventually become cancerous. Patients with acromegaly often suffer from headaches and arthritis. The various swellings and enlargements throughout the body may press on nerves, causing sensations of local tingling or burning, and sometimes result in muscle weakness.
The most common cause of this disorder (in 90% of patients) is the development of a noncancerous tumor within the pituitary, called a pituitary adenoma. These tumors are the source of the abnormal release of GH. As these tumors grow, they may press on nearby structures within the brain, causing headaches and changes in vision. As the adenoma grows, it may disrupt other pituitary tissue, interfering with the release of other hormones. These disruptions may be responsible for changes in the menstrual cycle of women, decreases in the sexual drive in men and women, and the abnormal production of breast milk in women. In rare cases, acromegaly is caused by the abnormal production of GHRH, which leads to the increased production of GH. Certain tumors in the pancreas, lungs, adrenal glands, thyroid, and intestine produce GHRH, which in turn triggers production of an abnormal quantity of GH.
Because acromegaly produces slow changes over time, diagnosis is often significantly delayed. In fact, the characteristic coarsening of the facial features is often not recognized by family members, friends, or long-time family physicians. Often, the diagnosis is suspected by a new physician who sees the patient for the first time and is struck by the patient's characteristic facial appearance. Comparing old photographs from a number of different time periods will often increase suspicion of the disease.
Because the quantity of GH produced varies widely under normal conditions, demonstrating high levels of GH in the blood is not sufficient to merit a diagnosis of acromegaly. Instead, laboratory tests measuring an increase of IGF-1 (3-10 times above the normal level) are useful. These results, however, must be carefully interpreted because normal laboratory values for IGF-1 vary when the patient is pregnant, undergoing puberty, elderly, or severely malnourished. Normal patients will show a decrease in GH production when given a large dose of sugar (glucose). Patients with acromegaly will not show this decrease, and will often show an increase in GH production. Magnetic resonance imaging (MRI) is useful for viewing the pituitary, and for identifying and locating an adenoma. When no adenoma can be located, the search for a GHRH-producing tumor in another location begins.
The first step in treatment of acromegaly is removal of all or part of the pituitary adenoma. Removal requires surgery, usually performed by entering the skull through the nose. While this surgery can cause rapid improvement of many acromegaly symptoms, most patients will also require additional treatment with medication. Bromocriptine (Parlodel) is a medication that can be taken by mouth, while octreotide (Sandostatin) must be injected every eight hours. Both of these medications are helpful in reducing GH production, but must often be taken for life and produce their own unique side effects. Some patients who cannot undergo surgery are treated with radiation therapy to the pituitary in an attempt to shrink the adenoma. Radiating the pituitary may take up to 10 years, however, and may also injure/destroy other normal parts of the pituitary.
Without treatment, patients with acromegaly will most likely die early because of the disease's effects on the heart, lungs, brain, or due to the development of cancer in the large intestine. With treatment, however, a patient with acromegaly may be able to live a normal lifespan.
Biller, Beverly M. K., and Gilbert H. Daniels. "Growth Hormone Excess: Acromegaly and Gigantism." In Harrison's Principles of Internal Medicine, edited by Anthony S. Fauci, et al. New York: McGraw-Hill, 1997.
Pituitary Tumor Network Association. 16350 Ventura Blvd., #231, Encino, CA 91436. (805) 499-9973.