Acromegaly and gigantism

Definition

Acromegaly is a disease in which an abnormality in the pituitary gland leads to an oversecretion of growth hormone. In adults, this condition results in an enlargement of bones; in children, the abnormality results in excessive height and is called gigantism.

Description

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, i.e. in adults, the disorder is called acromegaly.

Demographics

Acromegaly is a relatively rare disorder, occurring in approximately 50 out of every 1 million people. Gigantism occurs even more rarely, with reported cases in the United States numbering only about 100 by 2004. Males and females are similarly affected. Onset of gigantism is usually at puberty , although some cases of toddlers and young children with gigantism have been reported.

Causes and symptoms

The pituitary is a small gland located at the base of the brain, which releases certain hormones that 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.

The most common cause of acromegaly and gigantism is the development of a noncancerous tumor within the pituitary, called a pituitary adenoma. In the case of pituitary adenomas, the tumor itself is 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 and abnormal production of breast milk in women or delayed development of reproductive organs. 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 can produce GHRH, which in turn triggers production of an abnormal quantity of GH.

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 coarse. 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 hollower, and patients may develop loud snoring. Children and adolescents with gigantism show a characteristic lengthening and enlargement of bones, principally of the limbs. Some symptoms caused by various hormonal changes are as follows:

• 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
• 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.

When to call the doctor

Because early diagnosis and treatment of acromegaly and gigantism can often lead to the avoidance of more serious symptoms, a healthcare professional should be contacted if a child develops any of the early symptoms of the disease, such as a marked increase in height or height that is excessive for his or her age.

Diagnosis

Because acromegaly produces slow changes, 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 periods often increases suspicion of the disease. By contrast, the effects of gigantism are typically dramatic, with remarkable changes over a short period of time.

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 (three to ten 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, is pubescent, is elderly, or is 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 gland and for identifying and locating an adenoma. When no adenoma can be located, the search for a GHRH-producing tumor in another location begins.

Treatment

The first step in treatment of acromegaly is removal of all or part of the pituitary adenoma. Removal usually 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.

Alternative treatment

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 ten years, however, and may also injure or destroy other normal parts of the pituitary.

Nutritional concerns

Individuals with acromegaly or gigantism who have diabetes or diabetes-like symptoms should maintain a diet that helps normalize blood sugar levels.

Prognosis

Without treatment, patients with acromegaly are likely to 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.

Prevention

The initial onset of acromegaly or gigantism cannot as of 2004 be prevented. Once a pituitary adenoma has been removed, radiotherapy and/or medication may be recommended to prevent a recurrence of the tumor.

Parental concerns

In the great majority of children of tall stature, genetics and nutrition are the cause of the greater-than-average height, and linear growth ceases with the end of puberty. In individuals with gigantism who are not treated, linear growth can continue unchecked for several decades. It is important that a child with the symptoms of gigantism be assessed medically so that treatment can be implemented and abnormal linear height as well as potentially serious symptoms such as heart disease or colon cancer be minimized or avoided.

Resources

BOOKS

Cohen, Pinchas. "Hyperpituitarism, Tall Stature, and Overgrowth Syndromes." In Nelson Textbook of Pediatrics , 17th ed. Edited by Richard E. Behrman et al. Philadelphia: Saunders, 2004.

Melmed, Shlomo, and David Kleinberg. "Acromegaly." In Williams Textbook of Endocrinology , 10th ed. Edited by P. Reed Larson et al. Philadelphia: Saunders, 2003.

PERIODICALS

Melmed, Shlomo, et al. "Consensus Guidelines for Acromegaly Management." Journal of Clinical Endocrinology and Metabolism 87, no. 9 (September 1, 2002): 87–95.

ORGANIZATIONS

Pituitary Network Association. PO Box 1958, Thousand Oaks, CA 91358. Web site: http://www.acromegaly.org.

WEB SITES

Shim, Melanie, and Pinchas Cohen. "Gigantism and Acromegaly." eMedicine , July 29, 2004. Available online at http://www.emedicine.com/ped/topic2634.htm (accessed December 23, 2004).

Rosalyn Carson-DeWitt, MD Stephanie Dionne Sherk