Hypopituitarism
Hypopituitarism is an underactive pituitary gland that results in deficiency of one or more pituitary hormones.
Hypopituitarism, an uncommon disorder, can be caused by a number of factors, including a pituitary tumor or an insufficient blood supply to the pituitary gland.
 See the sidebar What Causes an Underactive Pituitary?
Symptoms and Complications
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 corticotropin.
Growth Hormone Deficiency: A lack of growth hormone typically leads to poor overall growth and short height (dwarfism) if it occurs in childhood. In adults, growth hormone deficiency does not affect height, because the bones have finished growing, but it can cause increased fat and reduced muscle tissue, thinning of bones, and reduced energy and quality of life.
Deficiency of Gonadotropins (follicle-stimulating hormone and luteinizing hormone): 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, and loss of some male sexual characteristics. Deficiencies of luteinizing hormone and follicle-stimulating hormone can also occur in Kallmann's syndrome, in which people may also have a cleft lip or palate (see Section 23, Chapter 265), are color-blind, and are unable to sense smells.
Thyroid-stimulating Hormone Deficiency: 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 (see Section 13, Chapter 163). Most cases of hypothyroidism, however, are due to a problem originating in the thyroid gland itself, not to low levels of pituitary hormones.
Corticotropin Deficiency: Corticotropin deficiency leads to an underactive adrenal gland (Addison's disease (see Section 13, Chapter 164)), which results in fatigue, low blood pressure, low levels of sugar in the blood, and low tolerance for stress. This is the most serious pituitary hormone deficiency; if the body is unable to make any corticotropin, it can be fatal.
Prolactin Deficiency: 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's syndrome, a rare complication of childbirth. Sheehan's 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.
Diagnosis
Because the pituitary gland stimulates other glands, a deficiency in pituitary hormones often reduces the amount of hormones the 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 a polyglandular deficiency syndrome.
An evaluation usually begins by measuring levels of the hormones that the pituitary gland produces and at the same time measuring levels of the hormone produced by the target organ. 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.
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 I (IGF-I) in the blood. Production of IGF-I is controlled by growth hormone, and the level of IGF-I tends to change slowly in proportion to the overall amount of growth hormone produced by the pituitary.
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 corticotropin is usually measured by assessing the response of its target hormone (cortisol) to stimuli, such as a low level of sugar in the blood after an insulin injection. If the level of cortisol does not change and the level of corticotropin in the blood is normal or low, a deficiency of corticotropin production is confirmed.
Once hypopituitarism is established by blood tests, the pituitary gland is usually evaluated with a computed tomography (CT) or magnetic resonance imaging (MRI) scan to identify structural problems. CT or MRI scans help 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 (see Section 6, Chapter 77).
See the sidebar Polyglandular Deficiency Syndromes.
Treatment
When possible, treatment is aimed at removing the cause of the pituitary hormone deficiency, such as a tumor. Surgical removal of a tumor is often the most appropriate first treatment, and 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 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. Tumors that produce prolactin can be treated with dopamine agonist drugs, such as bromocriptine or cabergoline. These drugs shrink the tumor while also lowering prolactin levels.
When it is not possible to remove the cause of the hormone deficiency, such as an insufficient blood supply to the pituitary gland, treatment focuses on replacing the deficient hormones, usually by replacing the target hormones. For example, people deficient in thyroid-stimulating hormone are given thyroid hormone, those deficient in corticotropin are given adrenocortical hormones such as hydrocortisone, and those deficient in luteinizing hormone and follicle-stimulating hormone are given estrogen, progesterone, or testosterone.
Growth hormone is the one 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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