ACROMEGALY AND GIGANTISM CAUSES

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.

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.