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Panhypopituitarism

Hypopituitarism is a medical term describing deficiency (hypo) of one or more hormones of the pituitary gland. The pituitary produces a number of important regulating hormones, and its function is mainly regulated by the hypothalamus. In endocrinology, deficiency of multiple hormones of the anterior lobe is generally referred to as hypopituitarism, while deficiency of the posterior lobe generally only leads to diabetes insipidus. If both lobes malfunction, the term panhypopituitarism (generalised hypopituitarism) is used. more...

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Physiology

The primary hormones of the anterior pituitary are proteins and include

  • growth hormone (GH) - growth and glucose homeostasis
  • luteinizing hormone (LH) - menstrual cycle and reproduction
  • follicle stimulating hormone (FSH) - same
  • adrenocorticotropic hormone (ACTH) - stimulates glucocorticoid production in the adrenal gland
  • thyroid stimulating hormone (TSH) - stimulates thyroxine production in the thyroid
  • prolactin (PRL) - stimulates milk production in the breast

These hormones are secreted in individually characteristic pulsatile patterns, often with distinct circadian rhythm, rather than at steady rates throughout 24 hours.

The posterior pituitary produces antidiuretic hormone (ADH) and oxytocin, the former regulating plasma osmolarity and the latter regulating uterine contractions during childbirth.

Growth hormone is often the first hormone lost, so most people with hypopituitarism lack GH as well as one or more others. As for the posterior pituitary, ADH deficiency is the main problem, while oxytocin deficiency rarely causes clinically significant problems.

Causes

Hypopituitarism and panhypopituitarism can be congenital or acquired. A partial list of causes and forms:

  • Congenital hypopituitarism
    • Hypoplasia of the pituitary
      • Isolated idiopathic congenital hypopituitarism
      • Associated with other congenital syndromes and birth defects
        • Septo-optic dysplasia
        • Holoprosencephaly
        • Chromosome 22 deletion syndrome
        • Rapaport syndrome
    • Single gene defect forms of anterior pituitary hormone deficiency
  • Acquired hypopituitarism
    • trauma (e.g., skull base fracture)
    • surgery (e.g., removal of pituitary neoplasm)
    • tumor (secretory and non-secretory pituitary or hypothalamic neoplasms)
    • inflammation (e.g. sarcoidosis or autoimmune hypohysitis)
    • radiation (e.g., after cranial irradiation for childhood leukemia)
    • shock
      • (Sheehan's syndrome is hypopituitarism after heavy bleeding in childbirth)
    • hemochromatosis
  • other diseases.

Diagnosis

Hypopituitarism may come to medical attention by symptoms or features of pituitary hormone deficiency (e.g., poor growth, hypoglycemia, micropenis, delayed puberty, polyuria, impaired libido, fatigue, and many others), or because the physician has diagnosed one of the many disorders and conditions associated with hypopituitarism listed above and tests for it.

Replacement therapy

Hypopituitarism and panhypopituitarism are treated by replacement of appropriate hormones. Since the most of the anterior pituitary hormones are proteins released in pulsatile patterns, whose functions are to induce secretion of smaller molecule hormones (thyroid hormones and steroids), it is simpler and less expensive for most purposes to simply replace the target gland hormones. There are a few exceptions, such as fertility induction.

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Hypopituitarism
From Gale Encyclopedia of Medicine, 4/6/01 by Teresa G. Norris

Definition

Hypopituitarism is loss of function in an endocrine gland due to failure of the pituitary gland to secrete hormones which stimulate that gland's function. The pituitary gland is located at the base of the brain. Patients diagnosed with hypopituitarism may be deficient in one single hormone, several hormones, or have complete pituitary failure.

Description

The pituitary is a pea-sized gland located at the base of the brain, and surrounded by bone. The hypothalamus, another endocrine organ in the brain, controls the function of the pituitary gland by providing "hormonal orders." In turn, the pituitary gland regulates the many hormones that control various functions and organs within the body. The posterior pituitary acts as a sort of storage area for the hypothalamus and passes on hormones that control function of the muscles and kidneys. The anterior pituitary produces its own hormones which help to regulate several endocrine functions.

In hypopituitarism, something interferes with the production and release of these hormones, thus affecting the function of the target gland. Commonly affected hormones may include:

Gonadotropin deficiency

Gonadotropin deficiency involves two distinct hormones affecting the reproductive system. Luteinizing hormone (LH) stimulates the testes in men and the ovaries in women. This deficiency can affect fertility in men and women and menstruation in women. Follicle-stimulating hormone (FSH) has similar effects to LH.

Thyroid stimulating hormone deficiency

Thyroid stimulating hormone (TSH) is involved in stimulation of the thyroid gland. A lack of stimulation in the gland leads to hypothyroidism.

Adrenocorticotopic hormone deficiency

Also known as corticotropin, adrenocorticotopic hormone (ACTH) stimulates the adrenal gland to produce a hormone similar to cortisone, called cortisol. The loss of this hormone can lead to serious problems.

Growth hormone deficiency

Growth hormone (GH) regulates the body's growth. Patients who lose supply of this hormone before physical maturity will suffer impaired growth. Loss of the hormone can also affect adults.

Other hormone deficiencies

Prolactin stimulates the female breast to produce milk. A hormone produced by the posterior pituitary, antidiuretic hormone (ADH), controls the function of the kidneys. When this hormone is deficient, diabetes insipidus can result. However, patients with hypopituitarism rarely suffer ADH deficiency, unless the hypopituitarism is the result of hypothalamus disease.

Multiple hormone deficiencies

Deficiency of a single pituitary hormone occurs less commonly than deficiency of more than one hormone. Sometimes referred to as progressive pituitary hormone deficiency or partial hypopituitarism, there is usually a predictable order of hormone loss. Generally, growth hormone is lost first, then luteinizing hormone deficiency follows. The loss of follicle-stimulating hormone, thyroid stimulating hormone and adrenocorticotopic hormones follow much later. The progressive loss of pituitary hormone secretion is usually a slow process, which can occur over a period of months or years. Hypopituitarism does occasionally start suddenly with rapid onset of symptoms.

Panhypopituitarism

This condition represents the loss 0of all hormones released by the anterior pituitary gland. Panhypopituitarism is also known as complete pituitary failure.

Causes & symptoms

There are three major mechanisms which lead to the development of hypopituitarism. The first involves decreased release of hypothalamic hormones that stimulate pituitary function. The cause of decreased hypothalamic function may be congenital or acquired through interference such as tumors, inflammation, infection, mass lesions or interruption of blood supply. A second category of causes is any event or mass which interrupts the delivery of hormones from the hypothalamus. These may include particular tumors and aneurysms. Damage to the pituitary stalk from injury or surgery can also lead to hypopituitarism.

The third cause of hypopituitarism is damage to the pituitary gland cells. Destroyed cells can not produce the pituitary hormones that would normally be secreted by the gland. Cells may be destroyed by a number of tumors and diseases. Hypopituitarism is often caused by tumors, the most common of which is pituitary adenoma.

Symptoms of hypopituitarism vary with the affected hormones and severity of deficiency. Frequently, patients have had years of symptoms that were nonspecific until a major illness or stress occurred. Overall symptoms may include fatigue, sensitivity to cold, weakness, decreased appetite, weight loss and abdominal pain. Low blood pressure, headache and visual disturbances are other associated symptoms.

Gonadotropin deficiency

Symptoms specific to this hormone deficiency include decreased interest in sex for women and infertility in women and men. Women may also have premature cessation of menstruation, hot flashes, vaginal dryness and pain during intercourse. Women who are postmenopausal will not have obvious symptoms such as these and may first present with headache or loss of vision. Men may also suffer sexual dysfunction as a result of gonadotropin deficiency. In acquired gonadotropin deficiency, both men and women may notice loss of body hair.

Thyroid stimulating hormone deficiency

Intolerance to cold, fatigue, weight gain, constipation and pale, waxy and dry skin indicate thyroid hormone deficiency.

Adrenocorticotopic hormone deficiency

Symptoms of ACTH deficiency include fatigue, weakness, weight loss and low blood pressure. Nausea, pale skin and loss of pubic and armpit hair in women may also indicate deficiency of ACTH.

Growth hormone deficiency

In children, growth hormone deficiency will result in short stature and growth retardation. Symptoms such as obesity and skin wrinkling may or may not show in adults and normal release of growth hormone normally declines with age.

Other hormone deficiencies

Prolactin deficiency is rare and is the result of partial or generalized anterior pituitary failure. When present, the symptom is absence of milk production in women. There are no known symptoms for men. ADH deficiency may produce symptoms of diabetes insipidus, such as excessive thirst and frequent urination.

Multiple hormone deficiencies

Patients with multiple hormone deficiencies will show symptoms of one or more specific hormone deficiencies or some of the generalized symptoms listed above.

Panhypopituitarism

The absence of any pituitary function should show symptoms of one or all of the specific hormone deficiencies. In addition to those symptoms, patients may have dry, pale skin that is finely textured. The face may appear finely wrinkled and contain a disinterested expression.

Diagnosis

Once the diagnosis of a single hormone deficiency is made, it is strongly recommended that tests for other hormone deficiencies be conducted.

Gonadotropin deficiency

The detection of low levels of gonadotropin can be accomplished through simple blood tests which measure luteinizing hormone and follicle-stimulating hormone, simultaneously with gonadal steroid levels. The combination of results can indicate to a physician if the cause of decreased hormone levels or function belongs to hypopituitarism or some sort of primary gonadal failure. Diagnosis will vary among men and women.

Thyroid stimulating hormone deficiency

Laboratory tests measuring thyroid function can help determine a diagnosis of TSH deficiency. The commonly used tests are T4 and TSH measurement done simultaneously to determine the reserve, or pool, of thyroid-stimulating hormone.

Adrenocorticotopic hormone deficiency

An insulin tolerance test may be given to determine if cortisol levels rise when hypoglycemia is induced. If they do not rise, there is insufficient reserve of cortisol, indicating an ACTH deficiency. If the insulin tolerance test is not safe for a particular patient, a glucagon test offers similar results. A CRH (corticotropin-releasing hormone) test may also be given. It involves injection of CRH to measure, through regularly drawn blood samples, a resulting rise in ACTH and cortisol. Other tests which stimulate ACTH may be ordered.

Growth hormone deficiency

Growth hormone deficiency is measured through the use of insulin-like growth factor I tests, which measure growth factors that are dependent on growth hormones. Sleep and exercise studies may also be used to test for growth hormone deficiency, since these activities are known to stimulate growth hormone secretion. Several drugs also induce secretion of growth hormone and may be given to measure hormone response. The standard test for growth hormone deficiency is the insulin-induced hypoglycemia test. This test does carry some risk from the induced hypoglycemia. Other tests include an arginine infusion test, clonidine test and growth-hormone releasing hormone test.

Other hormone deficiencies

If a test calculates normal levels of prolactin, deficiency of the hormone is eliminated as a diagnosis. A TRH (thyrotropin-releasing hormone) simulation test can determine prolactin levels. A number of tests are available to detect ADH levels and to determine diagnosis of diabetes insipidus.

Multiple and general hypopituitarism tests

Physicians should be aware that nonspecific symptoms can indicate deficiency of one or more hormones and should conduct a thorough clinical history. In general, diagnosis of hypopituitarism can be accomplished with a combination of dynamic tests and simple blood tests, as well as imaging exams. Most of these tests can be conducted in an outpatient lab or radiology facility. Magnetic resonance imaging (MRI) exams with gadolinium contrast enhancement are preferred imaging exams to study the region of the hypothalamus and pituitary gland. When MRI is not available, a properly conducted computed tomography scan (CT scan) exam can take its place. These exams can demonstrate a tumor or other mass, which may be interfering with pituitary function.

Panhypopituitarism

The insulin-induced hypoglycemia, or insulin tolerance test, which is used to determine specific hormone deficiencies, is an excellent test to diagnose panhypopituitarism. This test can reveal levels of growth hormone, ACTH (cortisol) and prolactin deficiency. The presence of insufficient levels of all of these hormones is a good indication of complete pituitary failure. Imaging studies and clinical history are also important.

Treatment

Treatment differs widely, depending on the age and sex of the patient, severity of the deficiency, the number of hormones involved, and even the underlying cause of the hypopituitarism. Immediate hormone replacement is generally administered to replace the specific deficient hormone. Patient education is encouraged to help patients manage the impact of their hormone deficiency on daily life. For instance, certain illnesses, accidents or surgical procedures may have adverse complications due to hypopituitarism.

Gonadotropin deficiency

Replacement of gonadal steroids is common treatment for LH and FSH deficiency. Estrogen for women and testosterone for men will be prescribed in the lowest effective dosage possible, since there can be complications to this therapy. To correct women's loss of libido, small doses of androgens may be prescribed. To restore fertility in men, regular hormone injections may be required. Male and female patients whose hypopituitarism results from hypothalamic disease may be successfully treated with a hypothalamic releasing hormone (GnRH), which can restore gonadal function and fertility.

Thyroid stimulating hormone deficiency

In patients who have hypothyroidism, the function of the adrenal glands will be tested and treated with steroids before administering thyroid hormone replacement.

Adrenocorticotopic hormone deficiency

Hydrocortisone or cortisone in divided doses may be given to replace this hormone deficiency. Most patients require 20 mg or less of hydrocortisone per day.

Growth hormone deficiency

It is essential to treat children suffering from growth hormone deficiency. The effectiveness of growth hormone therapy in adults, particularly elderly adults, is not as well documented. It is thought to help restore normal muscle to fat ratios. Growth hormone is an expensive and cautiously prescribed treatment.

Treatment of multiple deficiencies and panhypopituitarism

The treatment of hypopituitarism is usually very straightforward, but must normally continue for the remainder of the patient's life. Some patients may receive treatment with GnRH, the hypothalamic hormone. In most cases, treatment will be based on the specific deficiency demonstrated. Patients with hypopituitarism should be followed regularly to measure treatment effectiveness and to avoid overtreatment with hormone therapy. If the cause of the disorder is a tumor or lesion, radiation or surgical removal are treatment options. Successful removal may reverse the hypopituitarism. However, even after removal of the mass, hormone replacement therapy may still be necessary.

Prognosis

The prognosis for most patients with hypopituitarism is excellent. As long as therapy is continued, many experience normal life spans. However, hypopituitarism is usually a permanent condition and prognosis depends on the primary cause of the disorder. It can be potentially life threatening, particularly when acute hypopituitarism occurs as a result of a large pituitary tumor. Morbidity from the disease has increased, although the cause is not known. It is possible that increased morbidity and death are due to overtreatment with hormones. Any time that recovery of pituitary function can occur is preferred to lifelong hormone therapy.

Prevention

There is no known prevention of hypopituitarism, except for prevention of damage to the pituitary/hypothalamic area from injury.

Key Terms

Adenoma
A benign (not threatening or cancerous) tumor that originates in a gland.
Androgen
A hormone that usually stimulates the sex hormones of the male.
Congenital
Present at birth.
Diabetes insipidus
A disorder originating in the pituitary gland which is characterized by excessive thirst and urination.
Endocrine
Refers to the system of internal secretion of substances into the body system from glands.
Hypoglycemia
Abnormal decrease of sugar in the blood.
Hypothyroidism
Deficient activity of the thyroid gland and resulting loss of energy.

Further Reading

For Your Information

    Books

  • Conn, R.B., Borer, W.Z., and Snyder, J.W. Current Diagnosis. Philadelphia, PA: WB Saunders Company, 1997.

    Organizations

  • Alliance for Genetic Support Groups. 35 Wisconsin Circle, Suite 440. Chevy Chase, MD 20815-7015. http://www.medhelp.org/geneticalliance/.
  • Human Growth Foundation. 7777 Leesburg Pike, Suite 202-South, Falls Church, VA 22043. 1-800-451-6434. http://www.genetic.org.

    Other

  • Health Answers. http://www.healthanswers.com.

Gale Encyclopedia of Medicine. Gale Research, 1999.

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