Hormones are chemicals that control important body functions such as metabolism, growth and development, and reproduction. Growth hormone, like a number of hormones, is produced by the pituitary gland. It is one in a series of hormones that control tissue growth.

• The hypothalamus, a part of the brain, produces growth hormone-releasing hormone (GHRH). GHRH stimulates the pituitary to produce growth hormone and release it into the bloodstream.
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• The hypothalamus produces another hormone called somatostatin that stops secretion of growth hormone.
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• Growth hormone in the bloodstream stimulates the liver to produce another hormone called insulin-like growth factor 1 (IGF-1).
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• IGF-1, in turn, promotes growth of bone and other tissues.
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• Normally, levels of GHRH, growth hormone, somatostatin, and IGF-1 are tightly controlled by each other in a natural “feedback loop.” This feedback loop regulates supply of these hormones in the body. For example, a high level of IGF-1 in the blood suppresses secretion of GHRH and growth hormone in healthy people. Disruption of this and other similar hormone feedback loops causes many different medical problems, referred to as endocrine disorders.
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• Levels of growth hormone and related hormones also are affected by sleep, exercise, stress, food intake, and blood sugar levels.

Excess growth hormone and IGF-1 in the blood cause most of the physical problems in acromegaly.

• Too much IGF-1 causes the bone growth that leads to changes in physical appearance and function.
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• It causes thickening of soft tissues such as skin, tongue, and muscles. Enlargement of the tongue can lead to breathing problems and sleep apnea. Overgrowth of muscles can entrap nerves, causing pain syndromes such as carpal tunnel syndrome.
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• Excess IGF-1 causes enlargement of organs such as the heart, which can result in heart failure and rhythm disorders.
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• Excess growth hormone changes the way the body processes sugar and fats. This can cause diabetes and high levels of fats such as triglycerides in the blood. This in turn can lead to atherosclerosis and heart disease.

In more than 95% of cases of acromegaly, the excess growth hormone is produced by a tumor of the pituitary gland called adenoma.

• Secretion of growth hormone by a pituitary tumor is not controlled by the feedback loop. The end result is an excess of IGF-1, which causes abnormal tissue growth.
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• Many adenomas are caused by a genetic defect, but we do not know what causes the defect. These tumors do not seem to run in families.
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• Adenomas are benign tumors, which means that they do not spread to other parts of the body.
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• They can, however, grow to considerable size and cause problems by pressing on and invading surrounding tissues.

The remaining cases of acromegaly are caused by other types of tumors that secrete growth hormone or GHRH.

• These other tumors may be in the pituitary gland or elsewhere in the body.
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• Acromegaly caused by excess growth hormone and acromegaly caused by excess GHRH have the same signs and symptoms.

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