Pituitary Hormone Tests

Definition

Pituitary hormones include growth hormone, adrenocorticotropic hormone, thyroid stimulating hormone, follicle stimulating hormone, luteinizing hormone, prolactin, antidiuretic hormone, and oxytocin. The first six of these are made in the anterior pituitary gland, under the control of the hypothalamus. The last two are made during transport to the posterior pituitary from precursor peptides produced by the hypothalamus. This cluster of hormones has a vast and complex impact on the growth, fertility, and function of the human body via the effect of the hormones on their target organs.

Growth hormone (hGH), or somatotropin, is responsible for normal body growth and development, and regulates carbohydrate and protein metabolism. Adrenocorticotropic hormone (ACTH) regulates cortisol release from the adrenal glands. Thyroid stimulating hormone (TSH) regulates the synthesis and release of thyroid hormones. Follicle stimulating hormone (FSH) controls the maturation of the ovarian follicle in females and the development of the seminiferous tubules and sperm production in males. In females, luteinizing hormone (LH) causes release of the ovum from the ovary and supports the corpus luteum after ovulation. In males, LH supports testosterone production. Both FSH and LH are found at highest concentrations in plasma immediately before a woman ovulates. Prolactin promotes lactation, or milk production, after childbirth. Antidiuretic hormone (ADH), also called vasopressin, acts on the kidneys (collecting tubules) to increase the reabsorption of water. Oxytocin is released during labor and breastfeeding. It causes smooth muscle contractions needed for delivery and promotes the release of breast milk.

Purpose

Measurement of several pituitary hormones may be requested to investigate pituitary dysfunction in general. The entire gland may cease to function normally due to a hypothalamic disease, surgery, pituitary tumor, or trauma (e.g., Sheehan's syndrome, pituitary failure caused by hemorrhage into the gland after obstetric delivery). Alternatively, one or more specific hormones may be measured to investigate dysfunction of a target organ. For example, LH, FSH, and prolactin are commonly measured along with estrogen (estradiol) and progesterone to investigate ovarian failure. ACTH is needed to investigate the cause of adrenocortical excess or insufficiency. TSH is specifically used to diagnose thyroid under- or over-activity. Growth hormone is used to test for growth impairment or acromegaly. ADH testing is used to investigate disturbances in electrolytes (sodium and potassium) that will be abnormal when either too much or too little water is reabsorbed by the kidneys. Oxytocin is rarely measured, but may be used to identify ectopic production by tumor cells (e.g., lung carcinoma) that secrete the hormone.

Precautions

Each of these hormones is involved in intricate relationships with other organ systems. Levels may vary markedly depending on time of sampling (hGH, ACTH, prolactin), phase of the menstrual or reproductive cycle (FSH, LH), age, sex, physical activity, and a variety of psychological and nutritional factors. A thorough history of the patient's physical activities and medications is very helpful in interpreting blood test results. Pituitary hormones may be measured on plasma or urine. The nurse or phlebotomist collecting the sample should observe universal precautions for the prevention of transmission of bloodborne pathogens.

Many drugs are known to affect the level of pituitary hormones. For example, TSH test results may be influenced by such medications as lithium, potassium iodide, aspirin, dopamine, heparin, and corticosteroids. In addition, small fibrin clots and heterophile antibodies (HAMA) have been known to cause erroneous results with some immunoassays.

Growth hormone

Human growth hormone (hGH), or somatotropin, is a protein made up of 191 amino acids. It is secreted by the anterior pituitary gland and coordinates normal growth and development. Human growth is characterized by two spurts, one at birth and the other at puberty. hGH plays an important role at both of these times. Receptors that respond to hGH exist on cells and tissues throughout the body. The most pronounced effect of hGH is on linear skeletal development, but hGH also greatly increases lean muscle mass. Humans have two forms of hGH, and the functional difference between the two is unclear. hGH is produced in the anterior portion of the pituitary gland by somatotrophs under the control of hormonal peptides from the hypothalamus. The primary hypothalamic hormone regulating hGH is growth hormone-releasing hormone (GHRH). When blood glucose levels fall, GHRH triggers the secretion of stored hGH. As blood glucose levels rise, GHRH release is turned off. Increases in blood protein levels trigger a similar response. GHRH is opposed by growth hormone-inhibiting hormone (GHIH), which is a neuropeptide causing decreased release of hGH and TSH and which inhibits gastrin, secretin, and insulin. As a result of this hypothalamic feedback loop, hGH levels fluctuate throughout the day.

Because of its critical role in producing hGH and other hormones, an aberrant pituitary gland will often yield altered growth. Dwarfism (very small stature) can be caused by underproduction of hGH or insulin-like growth factor I (IGF-I), or by a flaw in the target tissue response to either of these. Overproduction of hGH or IGF-I, or an exaggerated response to these hormones, can lead to gigantism or acromegaly, both of which are characterized by a very large stature. Gigantism is the result of hGH overproduction in early childhood, leading to a skeletal height up to 8 feet (2.4 m) or more. In this condition, the epiphyseal plates of the long bones do not close, and they remain responsive to hGH. Acromegaly results when hGH is overproduced after the onset of puberty. This disorder is characterized by an enlarged skull, hands and feet, nose, neck, and tongue owing to proliferation of connective tissue.

Growth hormone in plasma or urine is usually measured by radioimmunoassay (RIA). Some fluorescent and chemiluminescent enzyme immunoassays are available, as well. In children, hGH in plasma is often too low to detect or permit differentiation of normal and deficient levels. A child below average in height who has normal pituitary function may have a low level of growth hormone as a result of normal physiological variation. Diagnosis is made either by a provocative test or measurement of IGF-I. A deficiency of IGF-I occurs in both hGH deficiency and protein malnutrition. Provocative testing for hGH deficiency involves administration of a drug known to stimulate release of growth hormone, or vigorous exercise, which does the same. Drugs used include arginine, insulin, glucagon, and propranolol. In the exercise test, a blood sample is measured for hGH immediately following exercise performed vigorously for 20 minutes. A level greater than 6 nanograms per mL rules out growth hormone deficiency. A lower response is suggestive and is followed by a drug stimulation test. Growth hormone is increased in approximately 90% of persons with acromegaly. Acromegaly is caused by an adenoma in the pituitary that produces hGH. For suspected cases that do not demonstrate an elevated plasma level, a glucose suppression test is needed for diagnosis. The test is performed by giving 100 grams of glucose orally, and collecting a blood sample one hour later. The gluocse should suppress hGH to below 1 ng/mL. Failure to do so is evidence of acromegaly.

Adrenocorticotropic hormone

ACTH production is controlled by the production of corticotropin-releasing hormone (CRH) by the hypothalamus. The release of this neuropeptide is inhibited by plasma cortisol via negative feedback. When plasma cortisol is elevated, CRH is inhibited and less ACTH is produced. As a result the adrenal cortex produces less cortisol and ACTH levels return to normal. Conversely, if cortisol levels fall, CRH is released, causing increased secretion of ACTH by the pituitary. ACTH levels rise in response to stress, emotions, injury, infection, burns, surgery, and decreased blood pressure.

Cushing's disease is caused by an abnormally high level of circulating cortisol (hydrocortisone). The high level may be the result of an adrenal gland tumor; enlargement of both adrenal glands due to a pituitary tumor; production of ACTH by a tumor outside the pituitary gland (ectopic production); or excessive administration of corticosteroid drugs. Corticosteroid drugs are widely used for reducing inflammation in such disorders as rheumatoid arthritis, inflammatory bowel disease, and asthma.

Addison's disease is a rare disorder in which symptoms are caused by a deficiency of cortisol and aldosterone. The most common cause of this disease is an autoimmune disorder. Addison's disease generally progresses slowly, with symptoms developing gradually over months or years. However, acute episodes, called Addisonian crises, are brought on by infection, injury, or other stresses.

ACTH is measured by RIA or fluorescent and chemiluminescent enzyme immunoassay. ACTH in plasma is measured in order to help differentiate the cause of Cushing's disease. Approximately half of persons with Cushing's disease (pituitary Cushing's) have a normal ACTH level and half will have an elevated level. Most persons with adrenal tumors will have low (less than 10 picograms/L) or undetectable ACTH in the plasma owing to suppression by cortisol. Most persons with ectopic ACTH secreting tumors will have elevated levels in excess of 200 pg/L. Persons with primary Addison's disease will usually have high ACTH levels (greater than 150 picrograms/L) caused by negative feedback (low cortisol) while those with secondary Addison's disease will have low or normal ACTH levels owing to pituitary failure or hypothalmic suppression.

Thyroid stimulating hormone

Thyroid stimulating hormone is released by the anterior pituitary in response to thyroid releasing hormone (TRH) from the hypothalamus. It results in synthesis, storage, and release of T3 and T4, the thyroid hormones.

Elevated levels of free T3 and T4 exert negative feedback on the hypothalamus inhibiting the release of TRH which reduces TSH. Thyroid hormones have pronounced effects on the body's rate of metabolism. Decreased levels are responsible for myxedema, which produces a constellation of such symptoms as edema, low heart rate, intolerance to cold, hyperlipidemia, and anemia. The most common cause of myxedema is Hashimoto's disease, an autoimmune condition causing chronic hypothyroidism. Increased levels of the thyroid hormones (hyperthyroidism) causes a condition called thyrotoxicosis. It is characterized by exophthalmia (protruding eyeballs), tachycardia, insomnia, and weight loss. The most common cause of hyperthyroidism is Graves' disease.

TSH is commonly measured by enzyme immunoassay, and is the best screening test for diagnosis of both hypothyroidism and hyperthyroidism. In primary hypothyroidism, the plasma level of free T4 will be low and TSH will be elevated. In primary hyperthyroidism, the plasma level of free T3 will be high and TSH will be low. In thyroid disease caused by pituitary failure, the TSH and thyroid hormones will move in the same direction. For example, in secondary hypothyroidism, both free T4 and TSH will be low.

Follicle stimulating hormone and luteinizing hormone

Both FSH and LH are regulated by the hypothalamic release of gonadotropin-releasing hormone. In males, both hormones are inhibited via negative feedback by testosterone. In females, both hormones are inhibited via negative feedback by estrogen and progesterone. Levels of these hormones show pulse variation; this is especially true of LH and for this reason, 24-hour urine levels are preferred by some clinicans over plasma measurements. FSH and LH are performed when a person exhibits abnormal reproductive function. In women such conditions as precocious puberty, polycystic ovaries, failure to ovulate, dysmenorrhea, and the onset of menopause are the primary reasons for measuring these hormones. In males, these hormones are measured along with testosterone to diagnose and differentiate the cause of gonadal failure.

Levels of FSH and LH are somewhat constant prior to puberty. At puberty, both hormone levels increase significantly. In women the levels of both hormones varies with the phase of the menstrual cycle. Both FSH and LH peak in the midcycle just prior to ovulation. Prior to this peak levels are somewhat higher than they are after ovulation. The midcycle peak has been used to identify the best opportunity to conceive. A urine LH detection kit is available for use at home. This test is sometimes called an "ovulation test" and is similar to a home pregnancy test. A sample of the woman's first morning urine is tested with the materials provided in the kit. These home tests may be used by women who want to become pregnant. By monitoring levels of LH and watching for the surge signaling ovulation, a couple can time sexual intercourse to increase the chance that the egg will be fertilized.

LH and FSH are measured mainly by enzyme or chemiluminescent immunoassays. In males, testosterone RIA is used along with FSH and LH to differentiate the cause of gonadal failure. A low testosterone with low LH or FSH points to a hypothalmic-pituitary cause. A low testosterone with an increased LH and/or FSH indicates primary testicular failure. In females, LH and FSH are measured along with estrogen, progesterone, and prolactin to investigate the cause of abnormal gonadal function. In menopause, the midcycle peaks for both LH and FSH are usually higher than in normal menstruating females. Prior to menopause, the LH peak is greater in magnitude than FSH. However, in menopause, this pattern reverses. In females, low plasma estrogen and progesterone seen with elevated serum or urinary levels of LH and FSH signal primary ovarian failure. Conversely, low estrogen and progesterone in association with low levels of LH and FSH indicate pituitary (secondary) hypogonadism. Prolactin levels should also be performed when evaluating hypogonadism in females. High plasma prolactin caused by pituitary adenoma causes inhibition of LH and FSH by negative feedback. Therefore, prolactinoma may be responsible for ovarian failure.

Prolactin

Prolactin is also known as the lactogenic hormone or lactogen. It is essential for enlargement of the mammary glands during pregnancy, and for stimulating and maintaining lactation after childbirth. Like hGH, prolactin acts directly on tissues, and levels rise in response to sleep and to physical or emotional stress. During sleep, prolactin levels in nonpregnant females can reach as high as those seen in pregnant women (as high as ten to twenty times the normal level). Prolactin secretion is controlled by prolactin-releasing and prolactin-inhibiting factors secreted by the hypothalamus. In addition, TRH can also stimulate prolactin secretion.

Prolactin deficiency is rare, and like hGH it cannot be diagnosed without a provocative test because low and normal levels overlap. As with hGH, a normal or elevated level will rule out a deficiency. Documentation of prolactin deficiency requires the use of the TRH stimulation test and demonstration of a subnormal response. Elevated prolactin is the most common pituitary abnormality. Microadenomas of the pituitary that produce prolactin are the most common pituitary tumors. Depending on the type of cell involved, these tumors are also called prolactin-secreting pituitary acidophilic or chromophobic adenomas. However, there are several other conditions that increase plasma prolactin including pregnancy, drugs, hypothyroidism, and renal failure. Prolactinoma is typically associated with a plasma prolactin level greater than 200 nanograms per mL. Because about half of microadenomas are too small to see by imaging tests such as CT scans, plasma prolactin levels above 200 ng/mL, together with the absence of other known causes, are used to diagnose prolactinoma.

Pituitary neoplasia

Pituitary tumors are often responsible for increases in one or more pituitary hormones. About 30% of pituitary adenomas produce prolactin and about 20% of produce FSH. Ectopic hormones may also be produced, for example, ACTH by squamous cell carcinoma of the lung. In addition, the pituitary gland is often involved in multiple endocrine neoplasia, type 1 (MEN-1). This condition is inherited as an autosomal dominant disorder. It involves enlargement of at least two endocrine glands, which may be the result of hyperplasia, adenoma, or adenocarcinoma. One or more pituitary hormones will be secreted when the gland is involved. Therefore, plasma levels of pituitary hormones are sometimes measured to diagnose and to monitor various malignant diseases.

Posterior pituitary hormones

The purpose of ADH is to control the amount of water reabsorbed by the kidneys. Water is continually being taken into the body in food and drink, as well as being produced by chemical reactions in cells. Water is also continually lost in urine, sweat, feces, and in the breath as water vapor. ADH acts to keep blood and extracellular fluid volumes constant under conditions of constantly changing water and solute intake. Under normal conditions, the blood volume expands when excess water is absorbed. This reduces the plasma osmolality, which inhibits the release of ADH, causing water to be lost in the urine. Under conditions of water deprivation, plasma osmolality increases. This stimulates the osmoreceptors in the carotid sinus and ADH is released. The distal collecting tubule of the kidney reabsorbs more water, causing the osmolality to fall until blood volume is restored. Various factors can affect ADH production, thereby disturbing the body's water balance. Physical stress, surgery, and high levels of anxiety can stimulate ADH release. Alcohol consumption reduces ADH production by direct action on the brain, resulting in a temporarily increased production of urine. Abnormal water balance occurs in diabetes insipidus, when the pituitary gland produces insufficient ADH; and in chronic renal disease, when the kidneys fail to respond to ADH. The reverse effect, water retention, can result from temporarily increased ADH production after a major operation or accident. Water retention may also be caused by the secretion of ADH by some tumors, especially of the brain and lung. Any condition other than the thirst response that causes increased release of ADH is referred to as the syndrome of inappropriate ADH release (SIADH). Ectopic ADH production by tumors is the most common cause.

Antidiuretic hormone is measured by RIA. It is used in conjunction with serum and urine osmolality or sodium measurements to differentiate SIADH from psychogenic polydipsia and other causes of low electrolytes and to differentiate neurogenic (pituitary) diabetes insipidus from nephrogenic (renal) diabetes insipidus.

Oxytocin is released by the posterior pituitary to cause strong uterine contractions in labor and delivery, and it also acts on muscle cells in lactating breast tissue to aid in the release of milk. Oxytocin levels are rarely measured, but oxytocin is often used in the hospital setting to induce or reinforce uterine contractions in labor. It is also useful in its natural or commercial form for helping the uterus to stay small and contracted after delivery, minimizing blood loss. Oxytocin is produced by males as well, and its function is thought to be related to sperm transportation.

Preparation

Pituitary hormones demonstrate both diurnal and pulse variation, and it is important to note the time of day that the sample is collected. Samples for both ACTH and ADH should be drawn in the fasting state. Blood for ACTH is usually drawn early in the morning, when ACTH is anticipated to be at its peak; and is also assessed in the evening, when it is expected to be at its lowest level. ACTH is very labile and should be collected in EDTA, using plastic tubes. The blood should be centrifuged immediately (preferably in the cold) and the plasma removed and frozen until the time of assay. FSH and LH vary greatly depending upon the time of collection. For this reason, results should be evaluated with regard to the time of sampling. Since levels vary greatly during the menstrual cycle, the levels must be evaluated with regard to the menstrual phase. Some clinicians prefer to pool plasma specimens collected across the menstrual cycle for a single measurement, or to use 24-hour urine samples for measurement. Growth hormone specimens should be collected using heparin or EDTA from a fasting patient. The various tests used to investigate human growth hormone are highly influenced by the fasting or non-fasting state, as well as the presence or absence of recent exercise. Prolactin levels should be drawn in the morning at least two hours after the patient wakes (samples drawn earlier may show sleep-induced peak levels). No specific preparation is necessary for drawing TSH levels, but illness and stress can affect results significantly.

Aftercare

No special care is necessary after collection of blood or urine for pituitary hormone assessment. Patients should return to normal eating and exercise, and resume routine medications. Following venipuncture for blood plasma hormone tests, the laboratory technologist, nurse, or phlebotomist drawing the sample should inspect the venipuncture site to make sure that the wound has closed and no bleeding is present. The site should be covered with an adhesive bandage. There is no notable aftercare for patients undergoing 24-hour urine hormone tests. Patients should be reminded to resume foods and medications that were restricted prior to testing.

Complications

Complications from drawing blood are minimal and may include slight bleeding from the venipuncture site, fainting, or lightheadedness after the blood sample is drawn. Blood may accumulate under the puncture site (hematoma) if pressure is not applied to the site immediately after drawing blood. There are no complications for the urine test. Some of the test protocols for growth hormone assessment involve administering drugs, such that nausea, sleepiness, sweating and/or nervousness may occur. Severe hypoglycemia could theoretically occur with insulin, but this is unlikely if the patient is closely monitored and treated appropriately.

Results

The normal ranges for pituitary hormone tests are highly method-dependent, resulting in significant laboratory variation. Also, age, sex, and sampling time must be taken into consideration when interpreting results.

Generally, hGH ranges from undetectable to 5ng/mL for adult men, up to 10 ng/mL for adult women, and as high as 16 ng/mL in children over six years. Arginine (an amino acid), insulin, and other substances are sometimes used to try to elicit higher levels of hGH to investigate a possible deficiency. Decreased levels are seen in hGH deficiency, dwarfism, hyperglycemia, failure to thrive, and delayed sexual maturity. Excess hGH is responsible for the syndromes of gigantism and acromegaly. Excess secretion is stimulated by anorexia nervosa, stress, hypoglycemia, and exercise.

Representative normal values for ACTH range from 8-100 pg/mL between 4 and 8 AM, and less than 50 pg/mL between 8 and 10 PM. High levels of ACTH may be caused by ACTH-producing tumors. These tumors may be either in the pituitary or in another area (such as tumors from lung cancer or ovarian cancer). In Addison's disease, the adrenal glands fail, and the pituitary gland secretes very high levels of ACTH in an attempt to restore normal adrenal hormone. Low levels of ACTH may occur because of decreased pituitary function. Low ACTH levels may result from adrenal adenoma which causes high levels of cortisol. The cortisol causes negative feedback to the pituitary.

Representative adult normal values for TSH are 0.2 to 4.7 microunits per mL (uU/mL). Higher values may by caused by congenital hypothyroidism (cretinism) or primary hypothyroidism (thyroid gland failure). Low values may be due to hyperthyroidism such as in Graves' disease or thyroiditis, or secondary hypothyroidism (hypothalamic or pituitary failure).

FSH test results vary according to age and sexual maturity. The phase of a woman's menstrual cycle or use of birth-control pills also affects test results. For an adult male, normal results range from 4-25 U/L. For a premenopausal woman, normal values range from 4-30 U/L. In a pregnant woman, FSH levels are too low to measure. After menopause, normal values range from 40-250 U/L. FSH levels fluctuate during premenopause. If no other symptoms are present, an elevated FSH level should not be interpreted as proof that menopause has begun. Anorexia nervosa and disorders of the hypothalamus or pituitary gland can result in abnormally low FSH levels. Abnormal levels can also indicate precocious puberty, hypopituitarism (diffuse failure of the pituitary to make hormones), Klinefelter's syndrome (in men), Turner syndrome, testicular failure, and polycystic ovarian syndrome.

The normal range for LH in males is 1-8 mU/mL and in children is 1-5 mU/mL. Levels in females vary dramatically based upon the phase of the menstrual cycle. In the follicular phase, levels are normally in the range of1.7-15 mU/mL; in the midcycle peak they are normally between 16-104 mU/mL; and in the luteal phase they normally range from 0.6-16 mU/mL. LH in postmenopausal women is normally in the range of 16-66 mU/mL. Abnormally high levels may be found in primary gonadal dysfunction, polycystic ovarian syndrome, and pituitary adenoma. Abnormally low levels can be seen with delayed puberty, congenital adrenal hyperplasia, stress, malnutrition and diffuse pituitary or hypothalamic problems.

Reference ranges for prolactin vary from laboratory to laboratory, but are generally between 3-15 ng/mL for adult males and 3.8-23 ng/mL for nonpregnant adult females. Prolactin levels in pregnancy vary greatly with the time of gestation. Normal values in the third trimester are 95-475 ng/mL. Increased prolactin levels are found in galactorrhea, amenorrhea, hypothyroidism, prolactinsecreting pituitary tumors, infiltrative diseases of the hypothalamus, and metastatic cancer of the pituitary gland. Higher levels than normal are also seen in stress, which may be produced by anorexia nervosa, surgery, strenuous exercise, trauma, and in renal (kidney) failure. Decreased prolactin levels are seen in pituitary failure.

ADH normal ranges are also laboratory-specific but can range from 1-5 pg/mL or 1-5 ng/L (SI units). Patients who are dehydrated; who have a decreased amount of blood in the body (hypovolemia); or who are undergoing severe physical stress (e.g., trauma, pain or prolonged mechanical ventilation) may exhibit increased ADH levels as a normal response to the needs of the body. Similarly, patients who are overly hydrated may have decreased ADH levels. Abnormal conditions that cause increased levels (SIADH) include central nervous system tumors, ectopic tumors, and infection. ADH deficiency is called diabetes insipidus, and results in severe water losses from the body. It is easily treated with nasally administered vasopressin.

Health care team roles

A physician will order pituitary tests and will interpret the results often with the aid of an endocrinologist. A nurse or phlebotomist will draw blood samples and give instructions for 24-hour urine collection if needed. Nurses are also responsible for accurate history-taking in order to document medications, stressors, or exercise that may influence test results. Clinical laboratory scientists/medical technologists perform the various hormone assays. Tests for hGH, ACTH, and ADH are usually performed by reference laboratories.

KEY TERMS

Adrenal glands—A pair of endocrine glands that lie on top of the kidneys, which produce natural steroid-based hormones.

Anovulatory bleeding—Bleeding without release of an egg from an ovary.

Klinefelter's syndrome—Inheritance of an extra X chromosome that results in small testes and male infertility.

Polycystic ovarian syndrome—A condition in which a woman has little or no menstruation, is infertile, has excessive body hair, and is usually obese. The ovaries may contain several cysts.

BOOKS

Malarkey, Louise M., and Mary Ellen McMorrow. Nurse's Manual of Laboratory Tests and Diagnostic Procedures, 2nd ed. Philadelphia: W.B. Saunders Company, 2000. pp. 580-584, 552-555, 683-696.

Pagana, Kathleen Deska, and Timothy James Pagana. Mosby's DIagnostic and Laboratory Test Reference, 4th ed. St. Louis, MO: Mosby, 1998. pp. 23-28

Tierney, Lawrence M., Stephen J. McPhee and Maxine A. Papadakis. Current Medical Diagnosis and Treatment 2001. New York: Lange Medical Books/McGraw-Hill, 2001. p. 1092-1102.

OTHER

National Library of Medicine. Medline. <http://www.nlm.nih.gov/medlineplus/ency/article/003684.htm>.

National Library of Medicine. Medline. <http://www.nlm.nih.gov/medlineplus/ency/article/000343.htm>.

University of Toledo. <http://www.neurosci.pharm.utoledo.edu/MBC3320/vasopressin.htm>.

Erika J. Norris