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- Symptoms and Complications
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(See also Overview of the Pituitary Gland.)
Hypopituitarism is an underactive pituitary gland that results in deficiency of one or more pituitary hormones.
Symptoms of hypopituitarism depend on what hormone is deficient and may include short height, infertility, intolerance to cold, fatigue, and an inability to produce breast milk.
The diagnosis is based on measuring the blood levels of hormones produced by the pituitary gland and on imaging tests done on the pituitary gland.
Treatment focuses on replacing deficient hormones with synthetic ones but sometimes includes surgical removal or irradiation of any pituitary tumors.
Hypopituitarism is an uncommon disorder. It can be caused by a number of factors, including certain inflammatory disorders, a pituitary tumor, or an insufficient blood supply to the pituitary gland.
Although symptoms sometimes begin suddenly and dramatically, they usually begin gradually and may go unrecognized for a long time. Symptoms depend on which pituitary hormones are deficient. In some cases, the pituitary gland's production of a single hormone decreases. More typically, the levels of several hormones decrease at the same time (panhypopituitarism). Production of growth hormone, luteinizing hormone, and follicle-stimulating hormone often decreases before that of thyroid-stimulating hormone and adrenocorticotropic hormone.
In children, a lack of growth hormone typically leads to poor overall growth and short height. In adults, growth hormone deficiency does not affect height, because the bones have finished growing. Adults usually have no symptoms other than sometimes reduced energy.
In premenopausal women, deficiencies of these hormones cause menstrual periods to stop (amenorrhea), infertility, vaginal dryness, and loss of some female sexual characteristics.
In men, deficiencies of these hormones result in wasting away (atrophy) of the testes, decreased sperm production and consequent infertility, erectile dysfunction, and loss of some male sexual characteristics.
In children, deficiencies of these hormones lead to delayed puberty. Deficiencies of luteinizing hormone and follicle-stimulating hormone can also occur in Kallmann syndrome, in which people may also have a cleft lip or palate, are color-blind, and are unable to sense smells.
Thyroid-stimulating hormone deficiency leads to an underactive thyroid gland (hypothyroidism), which results in such symptoms as confusion, intolerance to cold, weight gain, constipation, and dry skin. Most cases of hypothyroidism, however, are due to a problem originating in the thyroid gland itself, not to low levels of pituitary hormones.
Adrenocorticotropic hormone (ACTH) deficiency leads to an underactive adrenal gland (see Addison Disease), which results in fatigue, low blood pressure, low levels of sugar (glucose) in the blood, and low tolerance for stress. This is the most serious pituitary hormone deficiency. If the body is unable to make any ACTH, the person may die.
Prolactin deficiency reduces or eliminates a woman's ability to produce breast milk after childbirth. One cause of low prolactin levels and deficiency of other pituitary hormones is Sheehan syndrome, a rare complication of childbirth. Sheehan syndrome typically develops because of excessive blood loss and shock during childbirth, which results in partial destruction of the pituitary gland. Symptoms include fatigue, loss of pubic and underarm hair, and inability to produce breast milk. Prolactin deficiency has no known ill effects in men.
Pituitary apoplexy is a group of symptoms caused when blood flow to the pituitary is blocked, resulting in tissue destruction and bleeding. Most often, pituitary apoplexy occurs in a person who has a pituitary tumor. Symptoms include severe headache, stiff neck, fever, visual field defects, and problems with eye movements. The bleeding causes swelling of the pituitary, which presses on the hypothalamus, resulting in sleepiness or coma. The pituitary may suddenly stop producing hormones, especially ACTH, leading to low blood pressure and low levels of glucose in the blood. Doctors use magnetic resonance imaging to make the diagnosis.
Because the pituitary gland stimulates other glands, a deficiency in pituitary hormones often reduces the amount of hormones those other glands produce. Therefore, a doctor considers the possibility of pituitary malfunction when investigating a deficiency in another gland, such as the thyroid or adrenal gland. When symptoms suggest that several glands are underactive, a doctor may suspect hypopituitarism or polyglandular deficiency syndrome.
An evaluation usually begins by measuring blood levels of the hormones that the pituitary gland produces (typically, thyroid-stimulating hormone, prolactin, luteinizing hormone, and follicle-stimulating hormone) and at the same time measuring levels of the hormone produced by the target organs (typically, thyroid hormone, testosterone in men, and estrogen in women).
For example, a person with hypothyroidism due to failure of the pituitary gland has low levels of thyroid hormone and low or inappropriately normal levels of thyroid-stimulating hormone, which is produced by the pituitary gland. In contrast, a person with hypothyroidism due to failure of the thyroid gland itself has low levels of thyroid hormone and high levels of thyroid-stimulating hormone. Sometimes, doctors inject a synthetic version of a thyrotropin-releasing hormone, a hormone that stimulates release of thyroid-stimulating hormone and prolactin from the anterior part of the pituitary. The body's response to this injection may help doctors determine whether the pituitary or another gland is the cause of hormone deficiency.
Growth hormone production by the pituitary is difficult to evaluate because no test accurately measures it. The body produces growth hormone in several bursts each day, and the hormone is quickly used. Thus, the blood level at any given moment does not indicate whether production is normal over the course of a day. Instead, doctors measure the levels of insulin-like growth factor 1 (IGF-1) in the blood. Production of IGF-1 is controlled by growth hormone, and the level of IGF-1 tends to change slowly in proportion to the overall amount of growth hormone produced by the pituitary. In infants and young children, doctors may instead measure levels of a similar substance, IGF-binding protein type 3.
Because the levels of luteinizing hormone and follicle-stimulating hormone fluctuate with the menstrual cycle, their measurement in women may be difficult to interpret. However, in postmenopausal women who are not taking estrogen, luteinizing hormone and follicle-stimulating hormone levels normally are high.
Production of ACTH is usually assessed by measuring the levels of its target hormone (cortisol) in response to stimuli, such as an injection of synthetic ACTH (ACTH stimulation test) or a low level of sugar in the blood after an insulin injection (insulin tolerance test). If the level of cortisol does not change and the level of ACTH in the blood is normal or low, a deficiency of ACTH production is confirmed.
Once hypopituitarism is established by blood tests, the pituitary gland is usually evaluated with computed tomography (CT) or magnetic resonance imaging (MRI) to identify structural problems. CT or MRI helps reveal individual (localized) areas of abnormal tissue growth as well as general enlargement or shrinkage of the pituitary gland. The blood vessels that supply the pituitary can be examined with cerebral angiography.
Treatment is directed at the cause of pituitary underactivity (when possible) and at replacing deficient hormones.
When the cause of the pituitary hormone deficiency is a tumor, surgical removal of a tumor is often the most appropriate first treatment. Tumor removal also usually reduces any pressure symptoms and vision problems caused by the tumor. For all but the largest tumors, surgery can usually be done through the nose (transphenoidal).
Supervoltage or proton beam irradiation of the pituitary gland can be used to destroy a tumor. Large tumors and those that have extended beyond the bony structure at the base of the brain where the pituitary is located (sella turcica) may be impossible to remove with surgery alone. If so, doctors use supervoltage irradiation after surgery to kill the remaining tumor cells.
Irradiation of the pituitary gland tends to cause a slow loss of pituitary function. The loss may be partial or complete. Therefore, the function of the target glands is generally evaluated every 3 to 6 months for the first year and yearly thereafter for at least 10 years after treatment.
Tumors that produce prolactin can be treated with drugs that act like dopamine, such as bromocriptine or cabergoline. These drugs shrink the tumor while also lowering prolactin levels.
Treatment also focuses on replacing the deficient hormones, usually not by replacing pituitary hormones, but rather, by replacing their target hormones. For example, people deficient in thyroid-stimulating hormone are given thyroid hormone. Those deficient in ACTH are given adrenocortical hormones such as hydrocortisone. Those deficient in luteinizing hormone and follicle-stimulating hormone are given estrogen, progesterone, or testosterone.
Growth hormone is the only pituitary hormone that is replaced. Growth hormone treatment must be given by injection. When given to children who have growth hormone deficiency before the growth plates in their bones close, replacement growth hormone prevents them from being exceptionally short. Growth hormone is now also being used to treat some adults with growth hormone deficiency to improve body composition, increase bone density, and enhance quality of life.
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