The pituitary gland sits in a saddle shaped depression in the back of the skull below the hypothalamus. It is 3/8 inch or 1 cm in diameter.
The pituitary gland secretes hormones that stimulate other glands to produce their own hormones. It is often called the master gland because of its wide ranging influences, but the real master gland is a hypothalamus.
The pituitary gland consists of two anatomically and functionally different parts: the anterior lobe and the posterior lobe. The anterior lobe forms the bulk of the pituitary, and consists of glandular tissue that manufactures hormones. The posterior pituitary is really part of the brain and is derived from hypothalamic tissue. It does not make hormones itself, but stores and releases hormones produced by the hypothalamus.
Seven hormones are produced in the anterior pituitary. Four of these, known as tropic hormones, target other glands, prompting them to release their hormones. They are thyroid stimulating hormone (TSH) adrenocorticotropic hormone (ACTH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). The other hormones are: growth hormone (GH), prolactin and melanocyte-stimulating hormone (MSH) which act directly on target organs
Two hormones, oxytocin and vasopressin (ADH) are stored in the posterior lobe of the pituitary gland, but are produced in the hypothalamus.
TSH is secreted to stimulate the thyroid
ACTH is secreted to stimulate the adrenals glands
FSH is secreted to stimulate the ovaries and testes
LH is secreted to stimulate the ovaries and testes
Prolactin is secreted to stimulate milk production after giving birth
ADH is secreted to increase absorption of water into the blood by the kidneys
Oxytocin is secreted to contract the uterus during childbirth and stimulate the production
Hypopituitarism is a lack of one or more pituitary hormones. Lack of the hormones leads to a loss of function in the gland or organ that it controls.
To diagnose hypopituitarism, there must be low hormone levels due to a problem with the pituitary gland. The diagnosis must also rule out diseases of the organ that is affected by this hormone.
Levels of a pituitary hormone may be high in the bloodstream if you have a pituitary tumor that is producing too much of that hormone. The tumor may crush the rest of the cells of the pituitary leading to low levels of other hormones.
Hypopituitarism may be caused by:
- Brain surgery
- Brain tumor
- Head trauma
- Infections of the brain and the tissues that support the brain
- Subarachnoid hemorrhage (from a burst aneurysm)
- Tumors of the pituitary gland or hypothalamus
Occasionally, hypopituitarism is due to uncommon immune system or metabolic diseases such as:
- Lymphocytic hypophysitis
- Infiltrative diseases
- Sarcoidosis, an inflammatory disease occurring in various organs
- Histiocytosis X, in which abnormal cells cause scarring in numerous parts of the body such as the lungs and bones
- Hemochromatosis, which causes excess iron deposition in the liver and other tissues
- Sheehan syndrome: severe loss of blood during childbirth, which may cause damage to the front part of the pituitary gland (or postpartum hypopituitarism)
- Genetic mutations resulting in impaired pituitary hormone production
- Abdominal pain
- Hot flashes, irregular or no periods, loss of pubic hair, and inability to produce milk for breast-feeding in women
- Decreased appetite
- Decreased sexual interest
- Lack of sex drive
- Loss of armpit or pubic hair
- Loss of body or facial hair
- Low blood pressure
- Sensitivity to cold
- Short stature (less than 5 feet) if onset is during a growth period
- Slowed growth and sexual development (in children)
- Visual disturbances
- Weight loss
- Facial swelling
- Hair loss
- Hoarseness or changing voice
- Joint stiffness
- Weight gain (unintentional)
Note: Symptoms may develop slowly and may vary greatly, depending upon the number of lacking hormones and their target organs and the severity of the disorder.
- Brain CT scan
- Pituitary MRI
- Serum ACTH
- Serum cortisol
- Serum estradiol (estrogen)
- Serum follicle stimulating hormone (FSH)
- Serum insulin-like growth factor 1 (IGF-1)
- Serum luteinizing hormone (LH)
- Serum testosterone level
- Serum thyroid stimulating hormone (TSH)
If hypopituitarism is caused by a tumor, surgery may be needed to remove the tumor with or without radiation therapy. It is often necessary to replace hormones that are lacking even after successful treatment of a pituitary tumor.
Hypopituitarism is usually permanent and requires lifelong treatment. However, you can expect a normal life span. Many endocrinologists are NOT very good at treating and balancing these hormones, so self- monitoring and self-adjustments may be necessary.
Hormone therapy is needed to replace hormones that are no longer made by organs under the control of the pituitary gland.
These may include:
- Corticosteroids (cortisol)
- Growth hormone
- Sex hormones
- Thyroid hormones
Side effects of drug therapy can develop. In severe illness, failing to take extra corticosteroids can be life-threatening.
Many Endocrinologists are NOT very good are treating and balancing this many hormones, so self monitoring and self adjustments may be necessary.
Hyperprolactinemia is the most common endocrine disorder of the hypothalamic-pituitary axis. The diagnosis of hyperprolactinemia is made when serum prolactin levels are found on two separate occasions to be above the norm established for the testing laboratory.
A prolactinoma (tumor) is the most common cause of chronic hyperprolactinemia once pregnancy, primary hypothyroidism, and drugs that elevate serum prolactin levels have been excluded. Patients can present with hypogonadism, infertility, galactorrhea, osteopenia, and mass effects of the tumor. When hyperprolactinemia is confirmed, a cause for the disorder needs to be sought.
Prolactinomas account for 25 to 30% of functioning pituitary tumors and are the most frequent cause of chronic hyperprolactinemia. Occasionally, raised prolactin levels are caused by pituitary adenomas co-secreting prolactin and other anterior pituitary hormones. Lesions affecting the hypothalamus and pituitary stalk such as nonfunctioning adenomas, craniopharyngiomas, and gliomas rarely result in prolactin elevation of greater than 250 ng/mL (5000 mU/L).
Pathological hyperprolactinemia can be caused by nonhypothalamic-pituitary disease. Forty percent of patients with primary hypothyroidism have mild elevation of prolactin levels that can be normalized with a natural desiccated thyroid medication.
About 30% of patients with chronic renal failure and up to 80% of patients on hemodialysis have elevated prolactin levels. This is probably secondary to decreased clearance and increased production of prolactin as a result of disordered hypothalamic regulation of prolactin secretion. Correction of the renal failure by transplantation results in normalization of the prolactin level.
Hyperprolactinemia occurs more commonly in women. The prevalence of hyperprolactinemia ranges from 0.4% in an unselected normal adult population (10,000 normal Japanese adults working at a single factory) to as high as 9 to 17% in women with reproductive disorders. Its prevalence was found to be 5% in a family planning clinic population, 9% in a population of women with adult-onset amenorrhea, and 17% among women with polycystic ovary syndrome (see the page on PCOS)
Prolactin secretion is controlled by the predominantly inhibitory effect of the hypothalamus through one or more prolactin inhibitory factors (PIF) that reach the pituitary via the hypothalamic-pituitary portal vessels. Dopamine is the main physiological PIF, which acts on surface membrane dopamine D2 receptors on lactotroph cells. Disruption of the pituitary stalk and therefore the transport of dopamine to the lactotrophs, or blockade of endogenous dopamine receptors by a variety of drugs, leads to a moderate increase in prolactin secretion. Prolactin secretion is also influenced by prolactin-releasing factors such as vasoactive intestinal peptide and thyrotropin-releasing hormone, but their precise physiological roles are not clear.
Some of the drugs and supplements that will elevate prolactin are:
- MAOIs, SSRIs, TCAs
- Butyrophenones (e.g. haloperidol)
- Phenothiazines (e.g. thorazine)
- Thioxanthenes (e.g. thiothixene)
- Sumatriptan (Imitrex)
- Valproic acid (Depakote, Depakene)
- Dihydroergotamine (DHE 45)
- Methyldopa (Aldomet)
- Metoclopramine (Reglan)
- Medroxyprogesterone acetate
- Oral contraceptives
- Cimetidine (Tagamet)
- Famotidine (Pepcid)
- Ranitidine (Zantac)
- Blessed Thistle
- Red Clover
- Red Raspberry
- Nipple tenderness
- Nipple discharge
- Changes in nipple shape and appearance
- infrequent menstruation
- Loss of menstruation
- Heavy menstruation
- Decreased libido
- Habitual abortion
- Osteopenia – resulting from low estrogen
- Hirsutism – due to hyperandrogenism
- Acne – due to hyperandrogenism
- Infertility – due to low sperm production
- Nipple tenderness
- Nipple discharge
- Changes in nipple shape and appearance
- Enlarged breast
- Decreased libido
- Decreased potency
- Reduced muscle mass
Of a pituitary tumor
- Visual loss
- Discharge of cerebrospinal fluid from the nasal cavity
- Cranial neuropathies
Magnetic Resonance Imaging (MRI). Any patient who has hyperprolactinemia without an identified cause requires imaging of the hypothalamic-pituitary area. A mildly elevated serum prolactin level may be due to a nonfunctioning pituitary adenoma or craniopharyngioma compressing the pituitary stalk, although prolactin levels that are very high (>250 ng/mL) are almost always associated with a prolactinoma.
Magnetic resonance imaging (MRI) with gadolinium enhancement provides the best visualization of the sellar area, especially if there is a microadenoma, defined as a lesion ≤10 mm diameter. In cases where other causes of hyperprolactinemia have been excluded and no adenoma can be visualized with MRI, the hyperprolactinemia is referred to as “idiopathic.”
Dopamine agonists have become the treatment of choice for the majority of patients with hyperprolactinemic disorders although these drugs are not without some serious side effects. These dopamine agonists are bromocriptine, cabergoline and quinagolide. Dopamine agonist treatment may not be required indefinitely.
Estrogen therapy in the form of hormone replacement therapy or an oral contraceptive may be offered as an alternative to dopamine agonist therapy to women with IH or microprolactinoma who do not want to become pregnant and in whom estrogen deficiency is the major concern, particularly in those who are resistant to or intolerant of dopamine agonists. Patients receiving estrogens rather than a dopamine agonist should be monitored for symptoms or signs of tumor expansion, and therapy discontinued if there is radiological evidence of tumor enlargement.
Transsphenoidal surgery was the preferred therapy for prolactinomas before the availability of dopamine agonists in the early 1970s. Since then, surgery has gradually been used less frequently as the primary therapy and is now usually reserved for patients who are unresponsive to or intolerant of preferred medication therapy and for those rare patients who develop symptoms of mass effect despite treatment.Although dopamine agonists have the advantage of being a noninvasive treatment, transsphenoidal surgery offers the possibility of achieving complete cure in selected patients, although at the expense of significant risk in terms of morbidity, especially hypopituitarism, and a very low mortality rate.
Growth Hormone Deficiency
Growth hormone promotes linear growth by regulating the endocrine and paracrine production of insulin like growth factor 1 (IGF-1), which is produced by the liver and other target tissues, including the epiphyseal growth plate. Growth hormone’s diverse metabolic actions also include anabolic, lipolytic, and diabetogenic effects.
The incidence of short stature associated with severe childhood Growth Hormone deficiency (GHD) has been estimated in several studies to range between 1 per 4,000 to 1 per 10,000 live children. About 20,000 children per year receive growth hormone therapy, and approximately 4,000 new children are diagnosed annually as candidates for this treatment.
In children, the age of presentation varies with respect to the time of onset and the degree of GHD. Children with complete absence of growth hormone secretion usually present before reaching the age of 3 years, whereas those with lesser degrees of deficiency present at older ages. In adults, the age of presentation often coincides with the discovery of pituitary tumors, usually between the fourth and fifth decades of life.
Growth failure after a period of normal growth is a characteristic feature of GHD that presents during childhood.
Children present with short stature and low growth velocity for age and pubertal stage.
Consider the possibility of hypopituitarism in patients with neonatal hypoglycemia, prolonged jaundice, septo-optic dysplasia, midline facial defects (eg, cleft palate, solitary central incisor), male micropenis (not necessarily related to gonadotropin deficiency), histiocytosis X, previous cranial irradiation, and symptoms of a mass lesion in the hypothalamic-pituitary region (eg, headaches, visual disturbances).
The standing height standard deviation score is usually below -2.
Growth velocity is below the 10-25th percentile, which reflects growth deceleration.
Increased subcutaneous fat is present, especially around the trunk.
The face is immature, with a prominent forehead and depressed midfacial development
Dentition is delayed.
The average age of pubertal onset is delayed in males and females.
In males, the phallus may be small.
Causes of GHD in children can be divided into 3 categories.
Defective pituitary development that leads to pituitary aplasia
Genetic abnormalities, including autosomal-recessive, autosomal-dominant, or X-linked defects or a mutation or deletion in the growth hormone gene or in the GHRH.
Tumors of the hypothalamic-pituitary region – Craniopharyngioma is the most common tumor
Infiltrative diseases, including sarcoidosis, tuberculosis, histiocytosis X, hemochromatosis, and lymphocytic hypophysitis
Idiopathic – In many cases, no clear etiology can be identified.
Evaluation for GHD should be considered if the following conditions exist:
A child with a standing height of more than 3 standard deviation below the mean for chronological age, sex, and ethnic background
A child with a height velocity below the fifth to tenth percentile for age, with no clear etiology
A child with a standing height that is 2 SD to 3 SD below the mean for chronologic age, and with growth deceleration (growth velocity less than the twenty-fifth percentile) that cannot otherwise be explained.
Local laboratory assays and their cutoffs should be kept in mind when performing tests for GHD.
In newborns, a serum growth hormone level of less than 20 ng/mL is highly suggestive of GHD. After the newborn period, random serum growth hormone levels are of little value because of the pulsatile nature of growth hormone secretion. Measurement of growth hormone secretion through the night or for 24 hours is cumbersome, costly, and impractical.
Magnetic resonance imaging (MRI) of the hypothalamic-pituitary region to define the anatomy of this region and to identify tumors or congenital anomalies Bone age radiographs to assess chronologic age in children
The exact prevalence of adult-onset GHD is not known. Approximately 35,000 adults have GHD, and about 6,000 new adult patients are diagnosed annually.
Adult GHD is associated with the following problems:
Reduced bone mineral density and increased risk of osteoporotic bone fractures
Impaired cardiac function
Increased insulin sensitivity
Reduced exercise capacity
Decreased quality of life
Epidemiologic data suggest that adults with GHD have reduced life expectancy. This increased mortality is probably attributable to premature cardiovascular disease.
Adults with GHD usually have a history of pituitary tumors that may have been treated with surgery or radiation, or they may have previously suffered a head trauma.
Some patients will also have manifestations of deficiency of other pituitary hormones, such as thyroid, adrenal, and gonadal hormones.
The symptoms of GHD in adults are often nonspecific. Reported symptoms may include low energy level, decreased strength and exercise tolerance, increased weight or difficulty losing weight, emotional labiality, anxiety, social isolation, decreased libido, and impaired sleep. Some persons with GHD are entirely asymptomatic
Reduced lean body mass and increased weight, with body fat mass predominantly in the abdominal region
Thin and dry skin
Poor venous access
Reduced muscle mass and strength and reduced exercise performance
Causes of GHD in adults:
Pituitary disease – More than 90% of patients have pituitary disease, which is usually caused by a pituitary tumor, by surgery, or by radiation therapy for the tumor.
Other causes – These include trauma, tuberculosis, histiocytosis X, hemochromatosis, lymphocytic hypophysitis, and infiltrative diseases, such as sarcoidosis.
Idiopathic – In rare instances, no cause can be found.
Hypothalamic-pituitary dysfunction (eg, microphallus, septo-optic dysplasia, intracranial tumor, history of cranial irradiation) with decelerating growth.
Deficits in other hypothalamic-pituitary hormones, either congenital or acquired.
Adults with manifestations suggestive of GHD
Local laboratory assays and their cutoffs should be kept in mind when performing tests for GHD.
Growth hormone stimulation (provocative) tests play a critical role in the diagnosis of GHD.
The most frequently used tests include the insulin tolerance test (ITT); arginine; GHRH, with or without arginine; levodopa (L-dopa); glucagon, with or without a beta blocker, such as propranolol; and clonidine.
Most endocrinologists use a cutoff serum growth hormone concentration of more than 10 mcg/L in children and of more than 3 mcg/L (some authorities use 5 mcg/L) in adults to define normal response on provocative tests.
The Growth Hormone Research Society has recommended the ITT as the standard test for the diagnosis of GHD in adults.
In an ITT, insulin is administered intravenously to produce a nadir in the plasma glucose level of less than 40 mg/dL (2.2 mmol/L); serum (or blood) glucose and serum growth hormone levels are measured at times 0, 15, 30, 60, 90, and 120 minutes after administering insulin. An experienced staff under the direct supervision of a physician should perform the test. GHD is diagnosed when the growth hormone level is less than 5.1 mcg/L.
An ITT is contraindicated in patients with cardiovascular disease, cerebrovascular disease, or seizure disorders, or in patients older than 65 years.
The GHRH-arginine test is used by many centers as an alternative to the ITT. When the GHRH-arginine test is employed, a GHD is diagnosed when the growth hormone level is less than 4.1 mcg/L.
In patients with a GHD of hypothalamic origin (as a result, for example, of irradiation), GHRH can give falsely normal testing. In such patients, arginine without GHRH should be used.
Some clinicians require that these criteria occur on 2 provocative tests because of the high frequency of false-negative results for each single test.
Levels of insulin like growth factor 1 (IGF-1) or IGF–binding protein 3 (IGFBP-3) can provide presumptive evidence of reduced growth hormone secretion, but normal levels do not exclude the possibility of GHD. Patients who have a deficiency of 3 or more pituitary hormones and an IGF-1 level of < 84 ng/ml can be considered to have GHD and may not require provocative testing. However, some insurance bodies require the results of a growth hormone stimulation test before providing reimbursement for GH therapy.
Patients with GHD may have an increase in total cholesterol, low-density lipoprotein (LDL) cholesterol, and apolipoprotein B, as well as in triglyceride levels. The high-density lipoprotein (HDL) cholesterol level may be low.
Magnetic resonance imaging (MRI) of the hypothalamic-pituitary region to define the anatomy of this region and to identify tumors or congenital anomalies Bone mineral densitometry to look for reduced bone mineral density Cardiac echocardiogram to look for reduced ejection fraction at rest and during exercise
Acromegaly is a chronic metabolic disorder in which there is too much growth hormone and the body tissues gradually enlarge.
Acromegaly occurs in about 6 of every 100,000 adults. It is caused by abnormal production of growth hormone after the skeleton and other organs finish growing.
In more than 95 percent of people with acromegaly, a benign tumor of the pituitary gland, called an adenoma, produces excess GH. Most GH-secreting tumors are macro-adenomas, meaning they are larger than 1 centimeter. Depending on their location, these larger tumors may compress surrounding brain structures.
Compression of the surrounding normal pituitary tissue can alter production of other hormones. These hormonal shifts can lead to changes in menstruation and breast discharge in women and erectile dysfunction in men. If the tumor affects the part of the pituitary that controls the thyroid—another hormone-producing gland—then thyroid hormones may decrease. Too little thyroid hormone can cause weight gain, fatigue, and hair and skin changes. If the tumor affects the part of the pituitary that controls the adrenal gland, the hormone cortisol may decrease. Too little cortisol can cause weight loss, dizziness, fatigue, low blood pressure, and nausea.
Rarely, acromegaly is caused not by pituitary tumors but by tumors of the pancreas, lungs, and other parts of the brain. These tumors also lead to excess GH, either because they produce GH themselves or, more frequently, because they produce GHRH, the hormone that stimulates the pituitary to make GH. When these non-pituitary tumors are surgically removed, GH levels fall and the symptoms of acromegaly improve. In patients with GHRH-producing, non-pituitary tumors, the pituitary still may be enlarged and may be mistaken for a tumor. Physicians should carefully analyze all “pituitary tumors” removed from patients with acromegaly so they do not overlook the rare possibility that a tumor elsewhere in the body is causing the disorder.
Excessive production of growth hormone in children causes gigantism rather than acromegaly.
Carpal tunnel syndrome
Decreased muscle strength (weakness)
Enlarged bones of the face
Enlarged glands in the skin (sebaceous glands)
Enlarged jaw (prognathism) and tongue
Excessive height (when excess growth hormone production begins in childhood)
Limited joint movement
Abnormalities of the menstrual cycle and sometimes breast discharge in women
Erectile dysfunction in men
Deepening of the voice due to enlarged sinuses and vocal cords
Swelling of the bony areas around a joint
Thickening of the skin, skin tags
Widely spaced teeth
Widened fingers or toes due to skin overgrowth with swelling, redness, and pain
Other symptoms that may occur with this disease:
Excess hair growth in females
Weight gain (unintentional)
Signs and tests
High growth hormone level
High insulin-like growth factor 1 (IGF-1) level
Spine x-ray shows abnormal bone growth
Pituitary MRI may show a pituitary tumor
Echocardiogram may show an enlarged heart, leaky mitral valve, or leaky aortic valve
This disease may also change the results of the following tests:
Fasting plasma glucose
Glucose tolerance test
If acromegaly is suspected, a doctor must measure the GH level in a person’s blood to determine if it is elevated. However, a single measurement of an elevated blood GH level is not enough to diagnose acromegaly: Because GH is secreted by the pituitary in impulses, or spurts, its concentration in the blood can vary widely from minute to minute. At a given moment, a person with acromegaly may have a normal GH level, whereas a GH level in a healthy person may even be five times higher.
More accurate information is obtained when GH is measured under conditions that normally suppress GH secretion. Health care professionals often use the oral glucose tolerance test to diagnose acromegaly because drinking 75 to 100 grams of glucose solution lowers blood GH levels to less than 1 nanogram per milliliter (ng/ml) in healthy people. In people with GH overproduction, this suppression does not occur. The oral glucose tolerance test is a highly reliable method for confirming a diagnosis of acromegaly.
Physicians also can measure IGF-I levels, which increase as GH levels go up, in people with suspected acromegaly. Because IGF-I levels are much more stable than GH levels over the course of the day, they are often a more practical and reliable screening measure. Elevated IGF-I levels almost always indicate acromegaly. However, a pregnant woman’s IGF-I levels are two to three times higher than normal. In addition, physicians must be aware that IGF-I levels decline with age and may also be abnormally low in people with poorly controlled diabetes or liver or kidney disease.
Surgery to remove the pituitary tumor causing this condition corrects the abnormal growth hormone secretion in most patients. This surgery may not be available to patients in remote locations, so travel to a larger metropolitan area may be necessary for treatment.
Radiation of the pituitary gland is used for people who do not respond to the surgical treatment.
However, the reduction in growth hormone levels after radiation is very slow.
The following medications may be used to treat acromegaly:
Octreotide (Sandostatin) or bromocriptine (Parlodel) may control growth hormone release in some people.
Pegvisomant (Somavert) directly blocks the effects of growth hormone, and has been shown to improve symptoms of acromegaly.
These medications may be used before surgery, or when surgery is not possible. After treatment, periodic evaluation is necessary to ensure that the pituitary gland is working normally. Yearly evaluations are recommended.
Pituitary surgery is successful in most patients, depending on the size of the tumor and the experience of the surgeon.
Without treatment the symptoms will get worse, and the risk of cardiovascular disease and death.
Carpal tunnel syndrome
Glucose intolerance or diabetes
High blood pressure
Spinal cord compression