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Growth hormone is produced and released by the pituitary gland. This is a pea-sized gland just below the brain. Normal release of growth hormone before attainment of puberty allows for normal growth of humans.
Growth hormone release is stimulated by the hypothalamus of the brain. The hypothalamus makes hormones that regulate the pituitary. One of the hormones that regulates the growth hormone is the growth hormone-releasing hormone (GHRH), which stimulates the pituitary gland to produce GH.
When growth hormone is released into the blood, it stimulates the liver to produce another hormone – insulin-like growth factor 1 (IGF-1). This IGF-1 causes growth of muscle, bones and cartilage throughout the body. In adults this process is required for growth and repair of body tissues.
The hypothalamus makes another hormone called somatostatin. This inhibits GH production and release. Normally the levels of each of the four hormones – GHRH, Somatostatin, Growth Hormone and IGF-1 are tightly regulated by each other and by other factors such as sleep, exercise, blood sugar levels, stress etc.
Acromegaly is caused by prolonged overproduction of GH by the pituitary gland. This leads to excessive rise of IGF-1 as well leading to bone overgrowth and organ enlargement. Rise in levels of IGF-1 changes glucose and fat metabolism leading to an increased risk of heart disease and diabetes.
Causes of acromegaly may be due to pituitary tumors or non-pituitary tumors.
This is the cause of acromegaly in more than 95 percent of people with the condition. Acromegaly results from a benign or non cancerous tumor of the pituitary gland, called an adenoma. This tumor produces excess GH.
Pituitary tumors may be micro- or macro-adenomas determined by their size. Acromegaly is commonly caused by macro-adenomas. This means they are over 1cm in size.
These larger tumors may also press upon the nearby structures of the brain. If the tumor grows upwards, it presses on the optic chiasm. At this site the optic nerves that carry information about vision from the eyes to the brain from either eye cross each other. If the tumor presses on the optic chiasm, there may be vision problems and loss of vision.
Similarly if the tumor grows to its sides an area of the brain called the cavernous sinus may be encroached. This site contains several nerves that may be damaged.
Growth of the tumor also causes a derangement of other hormones produced by the pituitary gland. This can lead to problems like sexual dysfunction, loss of libido, abnormal menstruation and breast discharge in women. Thyroid hormone production may also be altered leading to underactive thyroids or hypothyroidism.
The adrenal gland functions of releasing hormone cortisol may also be affected if the pituitary gland functioning is altered. Decline in cortisol levels can cause weight loss, fatigue, low blood pressure etc. Excess secretion of other pituitary hormones like prolactin may be seen from the pituitary adenomas. Prolactin stimulates the breast to produce milk.
Most pituitary tumors develop on their own and are usually not linked to genes and are not inherited. The DNA of the pituitary cell may be altered to give rise to the tumor. This is called a mutation and is not present since birth. The mutation occurs in a gene that regulates the transmission of chemical signals and permanently switches on the signal that asks the cells to continue dividing uncontrolled.
Acromegaly in very rare cases may also be caused by non-pituitary tumors. The other tumors include those of the lungs, pancreas, and other parts of the brain. These tumors also lead to excess GH, either because they produce GH themselves or because they produce GHRH that stimulates the pituitary to release GH.
If there is excess production of GHRH from these secondary tumors, the size of the pituitary may be increased leading to mistaken suspicion of a pituitary tumor.