Hypopituitarism

ByJohn D. Carmichael, MD, Keck School of Medicine of the University of Southern California
Reviewed/Revised Apr 2023
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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.

The pituitary is a pea-sized gland at the base of the brain. It secretes a number of hormones that control the function of most other endocrine glands. (See also Overview of the Pituitary Gland.)

Causes of Hypopituitarism

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.

Causes affecting primarily the pituitary

  • Pituitary tumors

  • Inadequate blood supply to the pituitary (due to severe bleeding, blood clots, anemia, or other conditions)

  • Infections

  • Inflammatory disorders (such as sarcoidosis)

  • Inflammation of the pituitary due to anticancer monoclonal antibody medications

  • Irradiation (as for a brain tumor)

  • Surgical removal of pituitary tissue

  • Autoimmune disorders

  • Surgical damage to the pituitary or to the blood vessels or nerves leading to it

Causes affecting primarily the hypothalamus

The hypothalamus is a region of the brain that lies just above the pituitary gland and controls pituitary function. Causes that affect the hypothalamus and therefore affect the pituitary include

  • Tumors of the hypothalamus

  • Inflammatory disorders

  • Head injuries

  • Deficiencies of hypothalamic hormones

Symptoms of Hypopituitarism

Symptoms depend on which pituitary hormones are deficient. Although symptoms sometimes begin suddenly and dramatically, they usually begin gradually and may go unrecognized for a long time.

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.

Growth hormone deficiency

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 may have symptoms that are not specific to growth hormone deficiency such as low energy, body composition changes such as more fat and less muscle, and changes in their cholesterol levels.

Deficiency of gonadotropins (follicle-stimulating hormone and luteinizing hormone)

In premenopausal women, deficiencies of gonadotropins 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

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 deficiency

Adrenocorticotropic hormone (ACTH) deficiency leads to an underactive adrenal gland (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

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.

Hypothalamus deficiencies

The hypothalamus is a small region of the brain near the pituitary gland. It produces hormones and nerve impulses that control the pituitary gland. Thus, tumors that affect the hypothalamus may cause deficiencies of pituitary hormones. They may also disturb the centers that control appetite, leading to obesity.

Pituitary apoplexy

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.

Diagnosis of Hypopituitarism

  • Blood tests to measure hormone levels

  • Imaging tests

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.

Growth hormone production by the pituitary is difficult to evaluate because no single blood level accurately reflects it. The body usually produces growth hormone in several bursts a night, 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. Measurement of IGF-1 is not sufficient to make the diagnosis of growth hormone deficiency in adults, because people with normal levels may still have growth hormone deficiency. In many cases, a stimulation test to try to make the pituitary secrete growth hormone is used.

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. When they are found to be low, this can be an indication of pituitary damage or insufficiency of other hormones.

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 of Hypopituitarism

  • Treatment of cause

  • Replacing deficient hormones

Treatment is directed at the cause of pituitary underactivity (when possible) and at replacing deficient hormones.

Treatment of cause

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 any remaining normal 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 medications that act like dopamine

Hormone replacement

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

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. In adults with growth hormone deficiency, treatment with growth hormone improves body composition, increases bone density, and improves quality of life.

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