Hypopituitarism
Encyclopedia
Hypopituitarism is the decreased (hypo) secretion of one or more of the eight hormone
s normally produced by the pituitary gland
at the base of the brain
. If there is decreased secretion of most pituitary hormones, the term panhypopituitarism (pan meaning "all") is used.
The signs and symptoms of hypopituitarism vary, depending on which hormones are undersecreted and on the underlying cause of the abnormality. The diagnosis of hypopituitarism is made by blood test
s, but often specific scans
and other investigations are needed to find the underlying cause, such as tumor
s of the pituitary, and the ideal treatment. Most hormones controlled by the secretions of the pituitary can be replaced by tablets or injections. Hypopituitarism is a rare disease
, but may be significantly underdiagnosed in people with previous traumatic brain injury
. The first description of the condition was made in 1914 by the German physician Dr Morris Simmonds
.
(FSH) and/or luteinizing hormone
(LH) leading to sex hormone
abnormalities. Growth hormone deficiency
is more common in people with an underlying tumor than those with other causes.
Sometimes, there are additional symptoms that arise from the underlying cause; for instance, if the hypopituitarism is due to a growth hormone-producing tumor, there may be symptoms of acromegaly
(enlargement of the hands and feet, coarse facial features), and if the tumor extends to the optic nerve
or optic chiasm
, there may be visual field defects. Headache
s may also accompany pituitary tumors, as well as pituitary apoplexy
(infarction or hemorrhage of a pituitary tumor) and lymphocytic hypophysitis
(autoimmune inflammation of the pituitary). Apoplexy, in addition to sudden headaches and rapidly worsening visual loss, may also be associated with double vision
that results from compression of the nerves in the adjacent cavernous sinus
that control the eye muscles
.
Pituitary failure results in many changes in the skin, hair and nails as a result of the absence of pituitary hormone action on these sites.
Deficiency of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), together referred to as the gonadotropin
s, leads to different symptoms in men and women. Women experience oligo-
or amenorrhea
(infrequent/light or absent menstrual periods respectively) and infertility
. Men lose facial, scrotal and trunk hair, as well as suffering decreased muscle mass and anemia
. Both sexes may experience a decrease in libido
and loss of sexual function
, and have an increased risk of osteoporosis
(bone fragility). Lack of LH/FSH in children is associated with delayed puberty.
Growth hormone
(GH) deficiency leads to a decrease in muscle mass, central obesity
(increase in body fat around the waist) and impaired attention and memory. Children experience growth retardation and short stature
.
Adrenocorticotropic hormone
(ACTH) deficiency leads to adrenal insufficiency
, a lack of production of glucocorticoid
s such as cortisol
by the adrenal gland
. If the problem is chronic, symptoms consist of fatigue, weight loss, failure to thrive
(in children), delayed puberty
(in adolescents), hypoglycemia
(low blood sugar levels), anemia
and hyponatremia
(low sodium levels). If the onset is abrupt, collapse
, shock and vomiting
may occur. ACTH deficiency is highly similar to primary Addison's disease
, which is cortisol deficiency as the result of direct damage to the adrenal glands; the latter form, however, often leads to hyperpigmentation
of the skin, which does not occur in ACTH deficiency.
Thyroid-stimulating hormone
(TSH) deficiency leads to hypothyroidism
(lack of production of thyroxine
(T4) and triiodothyronine
(T3) in the thyroid
). Typical symptoms are tiredness, intolerance to cold
, constipation
, weight gain
, hair loss
and slowed thinking, as well as a slowed heart rate
and low blood pressure
. In children, hypothyroidism leads to delayed growth and in extreme inborn forms to a syndrome called cretinism
.
Prolactin
plays a role in breastfeeding
, and inability to breastfeed may point at abnormally low prolactin levels.
(unrelated to diabetes mellitus
): inability to concentrate the urine
, leading to polyuria
(production of large amounts of clear urine) that is low in solutes, dehydration
and—in compensation—extreme thirst and constant need to drink (polydipsia
), as well as hypernatremia
(high sodium levels in the blood). ADH deficiency may be masked if there is ACTH deficiency, with symptoms only appearing when cortisol has been replaced.
Oxytocin
deficiency generally causes few symptoms, as it is only required at the time of childbirth
and breastfeeding.
. It consists of two lobes: the posterior pituitary, which consists of nervous tissue
branching out of the hypothalamus, and the anterior pituitary, which consists of hormone-producing epithelium
. The posterior pituitary secretes antidiuretic hormone, which regulates osmolarity of the blood, and oxytocin
, which causes contractions
of the uterus
in childbirth and participates in breastfeeding
.
The pituitary develops in the third week of embryogenesis
from interactions between the diencephalon
part of the brain and the nasal cavity. The brain cells secrete FGF-8
, Wnt5a
and BMP-4
, and the nasal cavity BMP-2
. Together, these cellular signals stimulate a group of cells from the nasal cavity to form Rathke's pouch
, which becomes independent of the nasal cavity and develops into the anterior pituitary; this process includes the suppression of production of a protein called Sonic hedgehog
by the cells of Rathke's pouch. The cells then differentiate
further into the various hormone-producing cells of the pituitary. This requires particular transcription factor
s that induce the expression of particular genes. Some of these transcription factors have been found to be deficient in some forms of rare combined pituitary hormone deficiencies (CPHD) in childhood. These are HESX1
, PROP1
, POU1F1
, LHX3
, LHX4
, TBX19
, SOX2
and SOX3
. Each transcription factor acts in particular groups of cells. Therefore, various genetic mutations are associated with specific hormone deficiencies. For instance, POU1F1 (also known as Pit-1) mutations cause specific deficiencies in growth hormone, prolactin and TSH. In addition to the pituitary, some of the transcription factors are also required for the development of other organs; some of these mutations are therefore also associated with specific birth defects.
Most of the hormones in the anterior pituitary are each part of an axis that is regulated by the hypothalamus
. The hypothalamus secretes a number of releasing hormone
s, often according to a circadian rhythm
, into blood vessels that supply the anterior pituitary
; most of these are stimulatory (thyrotropin-releasing hormone
, corticotropin-releasing hormone
, gonadotropin-releasing hormone
and growth hormone-releasing hormone), apart from dopamine
, which suppresses prolactin production. In response to the releasing hormone rate, the anterior pituitary produces its hormones (TSH, ACTH, LH, FSH, GH) that stimulate effector hormone glands in the body, although prolactin acts directly on the breast gland
. Once the effector glands produce sufficient hormones (thyroxine, cortisol, estradiol or testosterone and IGF-1), both the hypothalamus and the pituitary cells sense their abundance and reduce their secretion
of stimulating hormones. The hormones of the posterior pituitary are produced in the hypothalamus and are carried by nerve endings to the posterior lobe; their feedback system is therefore located in the hypothalamus, but damage to the nerve endings would still lead to a deficiency in hormone release.
Unless the pituitary damage is being caused by a tumor that overproduces a particular hormone, it is the lack of pituitary hormones that leads to the symptoms described above, and an excess of a particular hormone would indicate the presence of a tumor. The exception to this rule is prolactin: if a tumor compresses the pituitary stalk
, a decreased blood supply means that the lactotrope cells, which produce prolactin, are not receiving dopamine and therefore produce excess prolactin. Hence, mild elevations in prolactin are attributed to stalk compression. Very high prolactin levels, though, point more strongly towards a prolactinoma
(prolactin-secreting tumor).
The diagnosis of hypopituitarism is made on blood test
s. Two types of blood tests are used to confirm the presence of a hormone deficiency: basal levels, where blood samples are taken–usually in the morning–without any form of stimulation, and dynamic tests, where blood tests are taken after the injection of a stimulating substance. Measurement of ACTH and growth hormone usually requires dynamic testing, whereas the other hormones (LH/FSH, prolactin, TSH) can typically be tested with basal levels. There is no adequate direct test for ADH levels, but ADH deficiency can be confirmed indirectly; oxytocin levels are not routinely measured.
Generally, the finding of a combination of a low pituitary hormone together with a low hormone from the effector gland is indicative of hypopituitarism. Occasionally, the pituitary hormone may be normal but the effector gland hormone decreased; in this case, the pituitary is not responding appropriately, and the combination of findings is still suggestive of hypopituitarism.
level, and are therefore not interpretable unless prolactin is low or normal. In men, the combination of low LH and FSH in combination with a low testosterone
confirms LH/FSH deficiency; a high testosterone would indicate a source elsewhere in the body (such as a testosterone-secreting tumor). In women, the diagnosis of LH/FSH deficiency depends on whether the woman has been through the menopause
. Before the menopause, abnormal menstrual periods together with low estradiol
and LH/FSH levels confirm a pituitary problem; after the menopause (when LH/FSH levels are normally elevated and the ovaries produce less estradiol), inappropriately low LH/FSH alone is sufficient. Stimulation tests with GnRH are possible, but their use is not encouraged.
For TSH, basal measurements are usually sufficient, as well as measurements of thyroxine
to ensure that the pituitary is not simply suppressing TSH production in response to hyperthyroidism
(an overactive thyroid gland). A stimulation test with thyrotropin-releasing hormone
(TRH) is not regarded as useful. Prolactin can be measured by basal level, and is required for the interpretation of LH and FSH results in addition to the confirmation of hypopituitarism or diagnosis of a prolactin-secreting tumor.
(IGF-1) levels are decreased. If this is not the case, IGF-1 levels are poorly predictive of the presence of GH deficiency; stimulation testing with the insulin tolerance test
is then required. This is performed by administering insulin
to lower the blood sugar
to a level below 2.2 mmol/l
. Once this occurs, growth hormone levels are measured. If they are low despite the stimulatory effect of the low blood sugars, growth hormone deficiency is confirmed. The test is not without risks, especially in those prone to seizure
s or are known to have heart disease, and causes the unpleasant symptoms of hypoglycemia
. Alternative tests (such as the growth hormone releasing hormone
stimulation test) are less useful, although a stimulation test with arginine
may be used for diagnosis, especially in situations where an insulin tolerance test is thought to be too dangerous. If GH deficiency is suspected, and all other pituitary hormones are normal, two different stimulation tests are needed for confirmation.
If morning cortisol
levels are over 500 nmol/l
, ACTH deficiency is unlikely, whereas a level less than 100 is indicative. Levels between 100-500 require a stimulation test. This, too, is done with the insulin tolerance test. A cortisol level above 500 after achieving a low blood sugar rules out ACTH deficiency, while lower levels confirm the diagnosis. A similar stimulation test using corticotropin-releasing hormone
(CRH) is not sensitive enough for the purposes of the investigation. If the insulin tolerance test yields an abnormal result, a further test measuring the response of the adrenal glands to synthetic ACTH (the ACTH stimulation test
) can be performed to confirm the diagnosis. Stimulation testing with metyrapone
is an alternative. Some suggest that an ACTH stimulation test is sufficient as first-line investigation, and that an insulin torlerance test is only needed if the ACTH test is equivocal. The insulin tolerance test is discouraged in children. None of the tests for ACTH deficiency are perfect, and further tests after a period of time may be needed if initial results are not conclusive.
Symptoms of diabetes insipidus should prompt a formal fluid deprivation test
to assess the body's response to dehydration, which normally causes concentration of the urine and increasing osmolarity of the blood. If these parameters are unchanged, desmopressin
(an ADH analogue) is administered. If the urine then becomes concentrated and the blood osmolarity falls, there is a lack of ADH due to lack of pituitary function ("cranial diabetes insipidus"). In contrast, there is no change if the kidneys are unresponsive to ADH due to a different problem ("nephrogenic diabetes insipidus").
(MRI) scan of the pituitary is the first step in identifying an underlying cause. MRI may show various tumors and may assist in delineating other causes. Tumors smaller than 1 cm are referred to as microadenomas, and larger lesions are called macroadenomas. Computed tomography
with radiocontrast may be used if MRI is not available. Formal visual field test
ing by perimetry
is recommended, as this would show evidence of optic nerve compression by a tumor.
Other tests that may assist in the diagnosis of hypopituitarism, especially if no tumor is found on the MRI scan, are ferritin
(elevated in hemochromatosis), angiotensin converting enzyme (ACE) levels (often elevated in sarcoidosis), and human chorionic gonadotropin
(often elevated in tumor of germ cell origin
). If a genetic cause is suspected, genetic testing
may be performed.
(removal of the tumor by an operation through the nose and the sphenoidal sinuses
) may, apart from addressing symptoms related to the tumor, also improve pituitary function, although the gland is sometimes damaged further as a result of the surgery. When the tumor is removed by craniotomy
(opening the skull), recovery is less likely–but sometimes this is the only suitable way to approach the tumor. After surgery, it may take some time for hormone levels to change significantly. Retesting the pituitary hormone levels is therefore performed 2 to 3 months later.
Prolactinoma
s may respond to dopamine agonist
treatment–medication that mimics the action of dopamine on the lactrotrope cells, usually bromocriptine
or cabergoline
. This approach may improve pituitary hormone secretion in more than half the cases, and obviate the need for supplementary treatment.
Other specific underlying causes are treated as normally. For example, hemochromatosis is treated by venesection
, the regular removal of a fixed amount of blood. Eventually, this decreases the iron levels in the body and improves the function of the organs in which iron has accumulated.
for hypothyroidism, testosterone
for male hypogonadism, and estradiol
for female hypogonadism (usually with a progestagen
to inhibit unwanted effects on the uterus
). Growth hormone is available in synthetic form, but needs to be administered parenterally (by injection). Antidiuretic hormone can be replaced by desmopressin (DDAVP) tablets or nose spray
. Generally, the lowest dose of the replacement medication is used to restore wellbeing and correct the deranged results, as excessive doses would cause side-effects or complications. Those requiring hydrocortisone are usually instructed to increase their dose in physically stressful events such as injury, hospitalization and dental work as these are times when the normal supplementary dose may be inadequate, putting the patient at risk of adrenal crisis.
Long-term follow up by specialists in endocrinology
is generally needed for people with known hypopituitarism. Apart from ensuring the right treatment is being used and at the right doses, this also provides an opportunity to deal with new symptoms and to address complications of treatment.
Difficult situations arise in deficiencies of the hypothalamus-pituitary-gonadal axis in people (both men and women) who experience infertility
; infertility in hypopituitarism may be treated with subcutaneous infusions of FSH, human chorionic gonadotropin
–which mimics the action of LH–and occasionally GnRH.
and the metabolic syndrome
, and estradiol deficiency may lead to osteoporosis. While effective treatment of the underlying hormone deficiencies may improve these risks, it is often necessary to treat them directly.
and some also an increased risk of death of about 50% to 150% the normal population. It has been difficult to establish which hormone deficiency is responsible for this risk, as almost all patients studied had growth hormone deficiency. The studies also do not answer the question as to whether the hypopituitarism itself causes the increased mortality, or whether some of the risk is to be attributed to the treatments, some of which (such as sex hormone supplementation) have a recognized adverse effect on cardiovascular risk.
The largest study to date followed over a thousand people for eight years; it showed an 87% increased risk of death compared to the normal population
. Predictors of higher risk were: female sex, absence of treatment for sex hormone deficiency, younger age at the time of diagnosis, and a diagnosis of craniopharyngioma. Apart from cardiovascular disease, this study also showed an increased risk of death from lung disease.
Quality of life
may be significantly reduced, even in those people on optimum medical therapy. Many report both physical and psychological problems. It is likely that the commonly used replacement therapies still do not completely mimic the natural hormone levels in the body. Health costs remain about double those of the normal population.
(total number of cases in a population) and incidence
(annual number of new cases) of hypopituitarism. This study was conducted in Northern Spain and used hospital records in a well-defined population. The study showed that 45.5 people out of 100,000 had been diagnosed with hypopituitarism, with 4.2 new cases per year. 61% were due to tumors of the pituitary gland, 9% due to other types of lesions, and 19% due to other causes; in 11% no cause could be identified.
Recent studies have shown that people with a previous traumatic brain injury
, spontaneous subarachnoid hemorrhage
(a type of stroke) or radiation therapy
involving the head have a higher risk of hypopituitarism. After traumatic brain injury, as much as a quarter have persistent pituitary hormone deficiencies. Many of these people may have subtle or non-specific symptoms that are not linked to pituitary problems but attributed to their previous condition. It is therefore possible that many cases of hypopituitarism remain undiagnosed, and that the annual incidence would rise to 31 per 100,000 annually if people from these risk groups were to be tested.
, and various theories were proposed about its role in the body, but major clues as to the actual function of the gland were not advanced until the late 19th century, when acromegaly
due to pituitary tumors was described. The first known report of hypopituitarism was made by the German
physician and pathologist Dr Morris Simmonds
. He described the condition on autopsy
in a 46-year old woman who had suffered severe puerperal fever
eleven years earlier, and subsequently suffered amenorrhea, weakness, signs of rapid aging and anemia. The pituitary gland was very small and there were few remnants of both the anterior and the posterior pituitary. The eponym Simmonds' syndrome is used infrequently for acquired hypopituitarism, especially when cachexia
(general ill health and malnutrition) predominates. Most of the classic causes of hypopituitarism were described in the 20th century; the early 21st century saw the recognition of how common hypopituitarism could be in previous head injury victims.
Until the 1950s, the diagnosis of pituitary disease remained based on clinical features and visual field examination, sometimes aided by pneumoencephalography
and X-ray tomography
. Nevertheless, the field of pituitary surgery developed during this time. The major breakthrough in diagnosis came with the discovery of the radioimmunoassay
by Rosalyn Yalow and Solomon Berson
in the late 1950s. This allowed the direct measurement of the hormones of the pituitary, which as a result of their low concentrations in blood had previously been hard to measure. Stimulation tests were developed in the 1960s, and in 1973 the triple bolus test
was introduced, a test that combined stimulation testing with insulin, GnRH and TRH. Imaging of the pituitary, and therefore identification of tumors and other structural causes, improved radically with the introduction of computed tomography
in the late 1970s and magnetic resonance imaging in the 1980s.
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...
s normally produced by the pituitary gland
Pituitary gland
In vertebrate anatomy the pituitary gland, or hypophysis, is an endocrine gland about the size of a pea and weighing 0.5 g , in humans. It is a protrusion off the bottom of the hypothalamus at the base of the brain, and rests in a small, bony cavity covered by a dural fold...
at the base of the brain
Human brain
The human brain has the same general structure as the brains of other mammals, but is over three times larger than the brain of a typical mammal with an equivalent body size. Estimates for the number of neurons in the human brain range from 80 to 120 billion...
. If there is decreased secretion of most pituitary hormones, the term panhypopituitarism (pan meaning "all") is used.
The signs and symptoms of hypopituitarism vary, depending on which hormones are undersecreted and on the underlying cause of the abnormality. The diagnosis of hypopituitarism is made by blood test
Blood test
A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via fingerprick....
s, but often specific scans
Medical imaging
Medical imaging is the technique and process used to create images of the human body for clinical purposes or medical science...
and other investigations are needed to find the underlying cause, such as tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
s of the pituitary, and the ideal treatment. Most hormones controlled by the secretions of the pituitary can be replaced by tablets or injections. Hypopituitarism is a rare disease
Rare disease
A rare disease, also referred to as an orphan disease, is any disease that affects a small percentage of the population.Most rare diseases are genetic, and thus are present throughout the person's entire life, even if symptoms do not immediately appear...
, but may be significantly underdiagnosed in people with previous traumatic brain injury
Traumatic brain injury
Traumatic brain injury , also known as intracranial injury, occurs when an external force traumatically injures the brain. TBI can be classified based on severity, mechanism , or other features...
. The first description of the condition was made in 1914 by the German physician Dr Morris Simmonds
Morris Simmonds
Morris Simmonds was a German physician, pathologist, from a family originating in Hanau but born on the then Danish St. Thomas, US Virgin Islands in Caribbean Sea...
.
Signs and symptoms
The hormones of the pituitary have different actions in the body, and the symptoms of hypopituitarism therefore depend on which hormone is deficient. The symptoms may be subtle and are often initially attributed to other causes. In most of the cases, three or more hormones are deficient. The most common problem is insufficiency of follicle-stimulating hormoneFollicle-stimulating hormone
Follicle-stimulating hormone is a hormone found in humans and other animals. It is synthesized and secreted by gonadotrophs of the anterior pituitary gland. FSH regulates the development, growth, pubertal maturation, and reproductive processes of the body. FSH and Luteinizing hormone act...
(FSH) and/or luteinizing hormone
Luteinizing hormone
Luteinizing hormone is a hormone produced by the anterior pituitary gland. In females, an acute rise of LH called the LH surge triggers ovulation and development of the corpus luteum. In males, where LH had also been called interstitial cell-stimulating hormone , it stimulates Leydig cell...
(LH) leading to sex hormone
Sex steroid
Sex steroids, also known as gonadal steroids, are steroid hormones that interact with vertebrate androgen or estrogen receptors. Their effects are mediated by slow genomic mechanisms through nuclear receptors as well as by fast nongenomic mechanisms through membrane-associated receptors and...
abnormalities. Growth hormone deficiency
Growth hormone deficiency
Growth hormone deficiency is a medical condition in which the body does not produce enough growth hormone . Growth hormone, also called somatotropin, is a polypeptide hormone which stimulates growth and cell reproduction...
is more common in people with an underlying tumor than those with other causes.
Sometimes, there are additional symptoms that arise from the underlying cause; for instance, if the hypopituitarism is due to a growth hormone-producing tumor, there may be symptoms of acromegaly
Acromegaly
Acromegaly is a syndrome that results when the anterior pituitary gland produces excess growth hormone after epiphyseal plate closure at puberty...
(enlargement of the hands and feet, coarse facial features), and if the tumor extends to the optic nerve
Optic nerve
The optic nerve, also called cranial nerve 2, transmits visual information from the retina to the brain. Derived from the embryonic retinal ganglion cell, a diverticulum located in the diencephalon, the optic nerve doesn't regenerate after transection.-Anatomy:The optic nerve is the second of...
or optic chiasm
Optic chiasm
The optic chiasm or optic chiasma is the part of the brain where the optic nerves partially cross...
, there may be visual field defects. Headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...
s may also accompany pituitary tumors, as well as pituitary apoplexy
Pituitary apoplexy
Pituitary apoplexy or pituitary tumor apoplexy is bleeding into or impaired blood supply of the pituitary gland at the base of the brain. This usually occurs in the presence of a tumor of the pituitary, although in 80% of cases this has not been diagnosed previously...
(infarction or hemorrhage of a pituitary tumor) and lymphocytic hypophysitis
Autoimmune hypophysitis
Autoimmune hypophysitis or Lymphocytic hypophysitis is defined as below normal production of one or more hormones by the pituitary gland due to autoimmunity.-Signs and symptoms:...
(autoimmune inflammation of the pituitary). Apoplexy, in addition to sudden headaches and rapidly worsening visual loss, may also be associated with double vision
Diplopia
Diplopia, commonly known as double vision, is the simultaneous perception of two images of a single object that may be displaced horizontally, vertically, or diagonally in relation to each other...
that results from compression of the nerves in the adjacent cavernous sinus
Cavernous sinus
The cavernous sinus , within the human head, is a large collection of thin-walled veins creating a cavity bordered by the temporal bone of the skull and the sphenoid bone, lateral to the sella turcica.-Contents:...
that control the eye muscles
Muscles of orbit
The muscles of the orbit are a group of six muscles that control movement of the eye. Four of the muscles control the movement of the eye in the four cardinal directions: up, down, left and right...
.
Pituitary failure results in many changes in the skin, hair and nails as a result of the absence of pituitary hormone action on these sites.
Anterior pituitary
Deficiency of all anterior pituitary hormones is more common than individual hormone deficiency.Deficiency of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), together referred to as the gonadotropin
Gonadotropin
Gonadotropins are protein hormones secreted by gonadotrope cells of the pituitary gland of vertebrates. This is a family of proteins, which include the mammalian hormones follitropin , lutropin , placental chorionic gonadotropins hCG and eCG and chorionic gonadotropin , as well as at least two...
s, leads to different symptoms in men and women. Women experience oligo-
Oligomenorrhea
Oligomenorrhea is infrequent menstruation. More strictly, it is menstrual periods occurring at intervals of greater than 35 days, with only four to nine periods in a year. Also, menstrual periods should have been regularly established previously before the development of infrequent flow...
or amenorrhea
Amenorrhoea
Amenorrhoea , amenorrhea , or amenorrhœa, is the absence of a menstrual period in a woman of reproductive age. Physiological states of amenorrhoea are seen during pregnancy and lactation , the latter also forming the basis of a form of contraception known as the lactational amenorrhoea method...
(infrequent/light or absent menstrual periods respectively) and infertility
Infertility
Infertility primarily refers to the biological inability of a person to contribute to conception. Infertility may also refer to the state of a woman who is unable to carry a pregnancy to full term...
. Men lose facial, scrotal and trunk hair, as well as suffering decreased muscle mass and anemia
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
. Both sexes may experience a decrease in libido
Libido
Libido refers to a person's sex drive or desire for sexual activity. The desire for sex is an aspect of a person's sexuality, but varies enormously from one person to another, and it also varies depending on circumstances at a particular time. A person who has extremely frequent or a suddenly...
and loss of sexual function
Human sexual behavior
Human sexual activities or human sexual practices or human sexual behavior refers to the manner in which humans experience and express their sexuality. People engage in a variety of sexual acts from time to time, and for a wide variety of reasons...
, and have an increased risk of osteoporosis
Osteoporosis
Osteoporosis is a disease of bones that leads to an increased risk of fracture. In osteoporosis the bone mineral density is reduced, bone microarchitecture is deteriorating, and the amount and variety of proteins in bone is altered...
(bone fragility). Lack of LH/FSH in children is associated with delayed puberty.
Growth hormone
Growth hormone
Growth hormone is a peptide hormone that stimulates growth, cell reproduction and regeneration in humans and other animals. Growth hormone is a 191-amino acid, single-chain polypeptide that is synthesized, stored, and secreted by the somatotroph cells within the lateral wings of the anterior...
(GH) deficiency leads to a decrease in muscle mass, central obesity
Central obesity
Abdominal obesity, colloquially known as belly fat or clinically as central obesity, is the accumulation of abdominal fat resulting in an increase in waist size...
(increase in body fat around the waist) and impaired attention and memory. Children experience growth retardation and short stature
Short stature
Short stature refers to a height of a human being which is below expected. Shortness is a vague term without a precise definition and with significant relativity to context...
.
Adrenocorticotropic hormone
Adrenocorticotropic hormone
Adrenocorticotropic hormone , also known as 'corticotropin', 'Adrenocorticotrophic hormone', is a polypeptide tropic hormone produced and secreted by the anterior pituitary gland. It is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological...
(ACTH) deficiency leads to adrenal insufficiency
Adrenal insufficiency
Adrenal insufficiency is a condition in which the adrenal glands, located above the kidneys, do not produce adequate amounts of steroid hormones , primarily cortisol, but may also include impaired aldosterone production which regulates sodium, potassium and water retention...
, a lack of production of glucocorticoid
Glucocorticoid
Glucocorticoids are a class of steroid hormones that bind to the glucocorticoid receptor , which is present in almost every vertebrate animal cell...
s such as cortisol
Cortisol
Cortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,...
by the adrenal gland
Adrenal gland
In mammals, the adrenal glands are endocrine glands that sit atop the kidneys; in humans, the right suprarenal gland is triangular shaped, while the left suprarenal gland is semilunar shaped...
. If the problem is chronic, symptoms consist of fatigue, weight loss, failure to thrive
Failure to thrive
Failure to thrive is a medical term which is used in both pediatric and adult human medicine, as well as veterinary medicine ....
(in children), delayed puberty
Delayed puberty
Puberty is described as delayed puberty with exceptions when an organism has passed the usual age of onset of puberty with no physical or hormonal signs that it is beginning. Puberty may be delayed for several years and still occur normally, in which case it is considered constitutional delay, a...
(in adolescents), hypoglycemia
Hypoglycemia
Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...
(low blood sugar levels), anemia
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
and hyponatremia
Hyponatremia
Hyponatremia is an electrolyte disturbance in which the sodium concentration in the serum is lower than normal. In the vast majority of cases, hyponatremia occurs as a result of excess body water diluting the serum sodium and is not due to sodium deficiency. Sodium is the dominant extracellular...
(low sodium levels). If the onset is abrupt, collapse
Collapse (medical)
Collapse is a sudden and often unannounced loss of postural tone , often but not necessarily accompanied by loss of consciousness.If the episode was accompanied by a loss of consciousness, the term syncope is used. The main causes are cardiac , seizures or a psychological cause...
, shock and vomiting
Vomiting
Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
may occur. ACTH deficiency is highly similar to primary Addison's disease
Addison's disease
Addison’s disease is a rare, chronic endocrine disorder in which the adrenal glands do not produce sufficient steroid hormones...
, which is cortisol deficiency as the result of direct damage to the adrenal glands; the latter form, however, often leads to hyperpigmentation
Hyperpigmentation
In dermatology, hyperpigmentation is the darkening of an area of skin or nails caused by increased melanin.-Causes:Hyperpigmentation may be caused by sun damage, inflammation, or other skin injuries, including those related to acne vulgaris...
of the skin, which does not occur in ACTH deficiency.
Thyroid-stimulating hormone
Thyroid-stimulating hormone
Thyrotrophin-stimulating hormone is a peptide hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland, which regulates the endocrine function of the thyroid gland.- Physiology :...
(TSH) deficiency leads to hypothyroidism
Hypothyroidism
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...
(lack of production of thyroxine
Thyroxine
Thyroxine, or 3,5,3',5'-tetraiodothyronine , a form of thyroid hormones, is the major hormone secreted by the follicular cells of the thyroid gland.-Synthesis and regulation:...
(T4) and triiodothyronine
Triiodothyronine
Triiodothyronine, C15H12I3NO4, also known as T3, is a thyroid hormone. It affects almost every physiological process in the body, including growth and development, metabolism, body temperature, and heart rate....
(T3) in the thyroid
Thyroid
The thyroid gland or simply, the thyroid , in vertebrate anatomy, is one of the largest endocrine glands. The thyroid gland is found in the neck, below the thyroid cartilage...
). Typical symptoms are tiredness, intolerance to cold
Cold sensitivity
Cold sensitivity or cold intolerance is unusual discomfort felt by some people when in a cool environment.There is much variation in the sensitivity to cold experienced by different people, with some putting on many layers of clothing while others in the same environment feel comfortable in one...
, constipation
Constipation
Constipation refers to bowel movements that are infrequent or hard to pass. Constipation is a common cause of painful defecation...
, weight gain
Weight gain
Weight gain is an increase in body weight. This can be either an increase in muscle mass, fat deposits, or excess fluids such as water.-Description:...
, hair loss
Alopecia
Alopecia means loss of hair from the head or body. Alopecia can mean baldness, a term generally reserved for pattern alopecia or androgenic alopecia. Compulsive pulling of hair can also produce hair loss. Hairstyling routines such as tight ponytails or braids may induce Traction alopecia. Both...
and slowed thinking, as well as a slowed heart rate
Bradycardia
Bradycardia , in the context of adult medicine, is the resting heart rate of under 60 beats per minute, though it is seldom symptomatic until the rate drops below 50 beat/min. It may cause cardiac arrest in some patients, because those with bradycardia may not be pumping enough oxygen to their heart...
and low blood pressure
Hypotension
In physiology and medicine, hypotension is abnormally low blood pressure, especially in the arteries of the systemic circulation. It is best understood as a physiologic state, rather than a disease. It is often associated with shock, though not necessarily indicative of it. Hypotension is the...
. In children, hypothyroidism leads to delayed growth and in extreme inborn forms to a syndrome called cretinism
Cretinism
Cretinism is a condition of severely stunted physical and mental growth due to untreated congenital deficiency of thyroid hormones usually due to maternal hypothyroidism.-Etymology and use of cretin:...
.
Prolactin
Prolactin
Prolactin also known as luteotropic hormone is a protein that in humans is encoded by the PRL gene.Prolactin is a peptide hormone discovered by Henry Friesen...
plays a role in breastfeeding
Breastfeeding
Breastfeeding is the feeding of an infant or young child with breast milk directly from female human breasts rather than from a baby bottle or other container. Babies have a sucking reflex that enables them to suck and swallow milk. It is recommended that mothers breastfeed for six months or...
, and inability to breastfeed may point at abnormally low prolactin levels.
Posterior pituitary
Antidiuretic hormone (ADH) deficiency leads to the syndrome of diabetes insipidusDiabetes insipidus
Diabetes insipidus is a condition characterized by excessive thirst and excretion of large amounts of severely diluted urine, with reduction of fluid intake having no effect on the concentration of the urine. There are several different types of DI, each with a different cause...
(unrelated to diabetes mellitus
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
): inability to concentrate the urine
Urine
Urine is a typically sterile liquid by-product of the body that is secreted by the kidneys through a process called urination and excreted through the urethra. Cellular metabolism generates numerous by-products, many rich in nitrogen, that require elimination from the bloodstream...
, leading to polyuria
Polyuria
Polyuria is a condition usually defined as excessive or abnormally large production or passage of urine . Frequent urination is sometimes included by definition, but is nonetheless usually an accompanying symptom...
(production of large amounts of clear urine) that is low in solutes, dehydration
Dehydration
In physiology and medicine, dehydration is defined as the excessive loss of body fluid. It is literally the removal of water from an object; however, in physiological terms, it entails a deficiency of fluid within an organism...
and—in compensation—extreme thirst and constant need to drink (polydipsia
Polydipsia
Polydipsia is a medical symptom in which the patient displays excessive thirst. The word derives from the Greek πολυδιψία, which is derived from πολύς + δίψα...
), as well as hypernatremia
Hypernatremia
Hypernatremia or hypernatraemia is an electrolyte disturbance that is defined by an elevated sodium level in the blood. Hypernatremia is generally not caused by an excess of sodium, but rather by a relative deficit of free water in the body...
(high sodium levels in the blood). ADH deficiency may be masked if there is ACTH deficiency, with symptoms only appearing when cortisol has been replaced.
Oxytocin
Oxytocin
Oxytocin is a mammalian hormone that acts primarily as a neuromodulator in the brain.Oxytocin is best known for its roles in sexual reproduction, in particular during and after childbirth...
deficiency generally causes few symptoms, as it is only required at the time of childbirth
Childbirth
Childbirth is the culmination of a human pregnancy or gestation period with the birth of one or more newborn infants from a woman's uterus...
and breastfeeding.
Causes
| Type | Causes | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Tumors | Most cases of hypopituitarism are due to pituitary adenoma Pituitary adenoma Pituitary adenomas are tumors that occur in the pituitary gland, and account for about 15% of intracranial neoplasms. Tumors which exceed 10 mm in size are defined as macroadenomas, and those smaller than 10 mm are referred to as microadenomas... s compressing the normal tissue in the gland, and rarely other brain tumor Brain tumor A brain tumor is an intracranial solid neoplasm, a tumor within the brain or the central spinal canal.Brain tumors include all tumors inside the cranium or in the central spinal canal... s outside the gland—craniopharyngioma Craniopharyngioma Craniopharyngioma is a type of brain tumor derived from pituitary gland embryonic tissue, that occurs most commonly in children but also in men and women in their 50s and 60s.... , meningioma Meningioma The word meningioma was first used by Harvey Cushing in 1922 to describe a tumor originating from the meninges, the membranous layers surrounding the CNS .... , chordoma Chordoma Chordoma is a rare slow-growing malignant neoplasm thought to arise from cellular remnants of the notochord. The evidence for this is the location of the tumors , the similar immunohistochemical staining patterns, and the demonstration that notochordal cells are preferentially left behind in the... , ependymoma Ependymoma Ependymoma is a tumor that arises from the ependyma, a tissue of the central nervous system. Usually, in pediatric cases the location is intracranial, while in adults it is spinal. The common location of intracranial ependymoma is the fourth ventricle... , glioma Glioma A glioma is a type of tumor that starts in the brain or spine. It is called a glioma because it arises from glial cells. The most common site of gliomas is the brain.-By type of cell:... or metastasis Metastasis Metastasis, or metastatic disease , is the spread of a disease from one organ or part to another non-adjacent organ or part. It was previously thought that only malignant tumor cells and infections have the capacity to metastasize; however, this is being reconsidered due to new research... from cancer Cancer Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the... elsewhere in the body. |
||||||||||||||||||
| Infection, inflammation and infiltration |
The pituitary may also be affected by infection Infection An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease... s of the brain (brain abscess Brain abscess Brain abscess is an abscess caused by inflammation and collection of infected material, coming from local or remote infectious sources, within the brain tissue... , meningitis Meningitis Meningitis is inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges. The inflammation may be caused by infection with viruses, bacteria, or other microorganisms, and less commonly by certain drugs... , encephalitis Encephalitis Encephalitis is an acute inflammation of the brain. Encephalitis with meningitis is known as meningoencephalitis. Symptoms include headache, fever, confusion, drowsiness, and fatigue... ) or of the gland itself, or it may be infiltrated by abnormal cells (neurosarcoidosis Neurosarcoidosis Neurosarcoidosis refers to sarcoidosis, a condition of unknown cause featuring granulomas in various tissues, involving the central nervous system . It can have many manifestations, but abnormalities of the cranial nerves are the most common... , histiocytosis Histiocytosis In medicine, histiocytosis refers to an excessive number of histiocytes, , and is typically used to refer to a group of rare diseases which share this as a characteristic... ) or excessive iron (hemochromatosis). Empty sella syndrome Empty sella syndrome Empty sella syndrome is a disorder that involves the sella turcica, a bony structure at the base of the brain that surrounds and protects the pituitary gland... is unexplained disappearance of pituitary tissue, probably due to outside pressure. Autoimmune or lymphocytic hypophysitis Autoimmune hypophysitis Autoimmune hypophysitis or Lymphocytic hypophysitis is defined as below normal production of one or more hormones by the pituitary gland due to autoimmunity.-Signs and symptoms:... occurs when the immune system directly attacks the pituitary. |
||||||||||||||||||
| Vascular | As a pregnancy Pregnancy Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets... comes to term, a pregnant woman's pituitary gland is vulnerable to low blood pressure, such as may result form hemorrhage; pituitary damage due to bleeding after childbirth Postpartum hemorrhage Hemorrhage after delivery, or postpartum hemorrhage, is the loss of greater than 500 ml of blood following vaginal delivery, or 1000 ml of blood following cesarean section... is called Sheehan's syndrome Sheehan's syndrome Sheehan syndrome, also known as Simmonds' syndrome or postpartum hypopituitarism or postpartum pituitary necrosis, is hypopituitarism , caused by necrosis due to blood loss and hypovolemic shock during and after childbirth... . Pituitary apoplexy Pituitary apoplexy Pituitary apoplexy or pituitary tumor apoplexy is bleeding into or impaired blood supply of the pituitary gland at the base of the brain. This usually occurs in the presence of a tumor of the pituitary, although in 80% of cases this has not been diagnosed previously... is hemorrhage or infarction Infarction In medicine, infarction refers to tissue death that is caused by a local lack of oxygen due to obstruction of the tissue's blood supply. The resulting lesion is referred to as an infarct.-Causes:... (loss of blood supply) of the pituitary. Other forms of stroke are increasingly recognized as a cause for hypopituitarism. |
||||||||||||||||||
| Physical | External physical causes for hypopituitarism include traumatic brain injury Traumatic brain injury Traumatic brain injury , also known as intracranial injury, occurs when an external force traumatically injures the brain. TBI can be classified based on severity, mechanism , or other features... , subarachnoid hemorrhage Subarachnoid hemorrhage A subarachnoid hemorrhage , or subarachnoid haemorrhage in British English, is bleeding into the subarachnoid space—the area between the arachnoid membrane and the pia mater surrounding the brain... , neurosurgery Neurosurgery Neurosurgery is the medical specialty concerned with the prevention, diagnosis, treatment, and rehabilitation of disorders which affect any portion of the nervous system including the brain, spine, spinal cord, peripheral nerves, and extra-cranial cerebrovascular system.-In the United States:In... and ionizing radiation Ionizing radiation Ionizing radiation is radiation composed of particles that individually have sufficient energy to remove an electron from an atom or molecule. This ionization produces free radicals, which are atoms or molecules containing unpaired electrons... (e.g. radiation therapy Radiation therapy Radiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control... for a previous brain tumor). |
||||||||||||||||||
| Congenital | Congenital hypopituitarism (present at birth) may be the result of complications around delivery, or may be the result of insufficient development (hypoplasia Hypoplasia Hypoplasia is underdevelopment or incomplete development of a tissue or organ. Although the term is not always used precisely, it properly refers to an inadequate or below-normal number of cells. Hypoplasia is similar to aplasia, but less severe. It is technically not the opposite of hyperplasia... ) of the gland, sometimes in the context of specific genetic abnormalities. Mutations may cause either insufficient development of the gland or decreased function. Forms of combined pituitary hormone deficiency ("CPHD") include:
Kallmann syndrome Kallmann syndrome Kallmann syndrome is a genetic disorder marked by anosmia and hypogonadism - the decreased functioning of the glands that produce sex hormones. Abnormalities in various genes may cause a defect in the hypothalamus, causing a deficiency of gonadotropin-releasing hormone ; this in turn causes... causes deficiency of the gonadotropins only. Bardet-Biedl syndrome Bardet-Biedl syndrome The Bardet–Biedl syndrome is a ciliopathic human genetic disorder that produces many effects and affects many body systems. It is characterized principally by obesity, retinitis pigmentosa, polydactyly, mental retardation, hypogonadism, and renal failure in some cases.-Summary of the... and Prader-Willi syndrome Prader-Willi syndrome Prader–Willi syndrome is a rare genetic disorder in which seven genes on chromosome 15 are deleted or unexpressed on the paternal chromosome... have been associated with pituitary hormone deficiencies. |
Pathophysiology
The pituitary gland is located at the base of the brain, and intimately connected with the hypothalamusHypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
. It consists of two lobes: the posterior pituitary, which consists of nervous tissue
Nervous tissue
Nervous tissue is one of four major classes of vertebrate tissue.Nervous tissue is the main component of the nervous system - the brain, spinal cord, and nerves-which regulates and controls body functions...
branching out of the hypothalamus, and the anterior pituitary, which consists of hormone-producing epithelium
Epithelium
Epithelium is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. Epithelial tissues line the cavities and surfaces of structures throughout the body, and also form many glands. Functions of epithelial cells include secretion, selective...
. The posterior pituitary secretes antidiuretic hormone, which regulates osmolarity of the blood, and oxytocin
Oxytocin
Oxytocin is a mammalian hormone that acts primarily as a neuromodulator in the brain.Oxytocin is best known for its roles in sexual reproduction, in particular during and after childbirth...
, which causes contractions
Contraction (childbirth)
-Throughout menstrual cycle:The uterus frequently contracts throughout the entire menstrual cycle, and these contractions have been termed endometrial waves or contractile waves. These appear to involve only the sub-endometrial layer of the myometrium...
of the uterus
Uterus
The uterus or womb is a major female hormone-responsive reproductive sex organ of most mammals including humans. One end, the cervix, opens into the vagina, while the other is connected to one or both fallopian tubes, depending on the species...
in childbirth and participates in breastfeeding
Lactation
Lactation describes the secretion of milk from the mammary glands and the period of time that a mother lactates to feed her young. The process occurs in all female mammals, however it predates mammals. In humans the process of feeding milk is called breastfeeding or nursing...
.
The pituitary develops in the third week of embryogenesis
Embryogenesis
Embryogenesis is the process by which the embryo is formed and develops, until it develops into a fetus.Embryogenesis starts with the fertilization of the ovum by sperm. The fertilized ovum is referred to as a zygote...
from interactions between the diencephalon
Diencephalon
The diencephalon is the region of the vertebrate neural tube which gives rise to posterior forebrain structures. In development, the forebrain develops from the prosencephalon, the most anterior vesicle of the neural tube which later forms both the diencephalon and the...
part of the brain and the nasal cavity. The brain cells secrete FGF-8
FGF8
Fibroblast growth factor 8 is a protein that in humans is encoded by the FGF8 gene.-External links:*...
, Wnt5a
WNT5A
Protein Wnt-5a is a protein that in humans is encoded by the WNT5A gene.-Further reading:...
and BMP-4
Bone morphogenetic protein 4
Bone morphogenetic protein 4 is a protein that in humans is encoded by` BMP4 gene.BMP4 is a member of the bone morphogenetic protein family which is part of the transforming growth factor-beta superfamily...
, and the nasal cavity BMP-2
Bone morphogenetic protein 2
Bone morphogenetic protein 2 or BMP-2 belongs to the TGF-β superfamily of proteins.-Function:BMP-2 like other bone morphogenetic proteins, plays an important role in the development of bone and cartilage. It is involved in the hedgehog pathway, TGF beta signaling pathway, and in cytokine-cytokine...
. Together, these cellular signals stimulate a group of cells from the nasal cavity to form Rathke's pouch
Rathke's pouch
In embryogenesis, Rathke's pouch is a depression in the roof of the developing mouth in front of the buccopharyngeal membrane. It gives rise to the anterior pituitary , a part of the endocrine system.-Development:...
, which becomes independent of the nasal cavity and develops into the anterior pituitary; this process includes the suppression of production of a protein called Sonic hedgehog
Sonic hedgehog
Sonic hedgehog homolog is one of three proteins in the mammalian signaling pathway family called hedgehog, the others being desert hedgehog and Indian hedgehog . SHH is the best studied ligand of the hedgehog signaling pathway. It plays a key role in regulating vertebrate organogenesis, such as...
by the cells of Rathke's pouch. The cells then differentiate
Cellular differentiation
In developmental biology, cellular differentiation is the process by which a less specialized cell becomes a more specialized cell type. Differentiation occurs numerous times during the development of a multicellular organism as the organism changes from a simple zygote to a complex system of...
further into the various hormone-producing cells of the pituitary. This requires particular transcription factor
Transcription factor
In molecular biology and genetics, a transcription factor is a protein that binds to specific DNA sequences, thereby controlling the flow of genetic information from DNA to mRNA...
s that induce the expression of particular genes. Some of these transcription factors have been found to be deficient in some forms of rare combined pituitary hormone deficiencies (CPHD) in childhood. These are HESX1
HESX1
Homeobox expressed in ES cells 1, also known as homeobox protein ANF, is a homeobox protein that in humans is encoded by the HESX1 gene.Expression of HEX1 and HESX1 marks the anterior visceral endoderm of the embryo...
, PROP1
PROP1
Homeobox protein prophet of Pit-1 is a protein that in humans is encoded by the PROP1 gene.- External links :*...
, POU1F1
Pituitary-specific positive transcription factor 1
POU domain, class 1, transcription factor 1 , also known as POU1F1, is a transcription factor for growth hormone.-Interactions:...
, LHX3
LHX3
LIM/homeobox protein Lhx3 is a protein that in humans is encoded by the LHX3 gene.- Function :LHX3 encodes a protein of a large protein family, members of which carry the LIM domain, a unique cysteine-rich zinc-binding domain. The encoded protein is a transcription factor that is required for...
, LHX4
LHX4
LIM/homeobox protein Lhx4 is a protein that in humans is encoded by the LHX4 gene.-Further reading:...
, TBX19
TBX19
T-box transcription factor TBX19 is a protein that in humans is encoded by the TBX19 gene....
, SOX2
SOX2
SRY -box 2, also known as SOX2, is a transcription factor that is essential to maintain self-renewal of undifferentiated embryonic stem cells....
and SOX3
SOX3
Transcription factor SOX-3 is a protein that in humans is encoded by the SOX3 gene.This gene encodes a member of the SOX family of transcription factors involved in the regulation of embryonic brain development and in determination of cell fate. The encoded protein acts as a transcriptional...
. Each transcription factor acts in particular groups of cells. Therefore, various genetic mutations are associated with specific hormone deficiencies. For instance, POU1F1 (also known as Pit-1) mutations cause specific deficiencies in growth hormone, prolactin and TSH. In addition to the pituitary, some of the transcription factors are also required for the development of other organs; some of these mutations are therefore also associated with specific birth defects.
| Thyroid Hypothalamic-pituitary-thyroid axis The hypothalamic-pituitary-thyroid axis is part of the endocrine system responsible for the regulation of metabolism.As its name suggests, it depends upon the hypothalamus, the pituitary gland, and the thyroid gland.... | Adrenal Hypothalamic-pituitary-adrenal axis The hypothalamic-pituitary-adrenal axis , also known as thelimbic-hypothalamic-pituitary-adrenal axis and, occasionally, as the hypothalamic-pituitary-adrenal-gonadotropic axis, is a complex set of direct influences and feedback interactions among the hypothalamus, the pituitary gland ,... | Gonads Hypothalamic-pituitary-gonadal axis The hypothalamic–pituitary–gonadal axis refers to the effects of the hypothalamus, pituitary gland, and gonads as if these individual endocrine glands were a single entity as a whole... | Growth | Thyrotrope Thyrotrope Thyrotropes are endocrine cells in the anterior pituitary which produce thyroid stimulating hormone in response to thyrotropin releasing hormone .Thyrotropes appear basophilic in histological preparations.... | Corticotrope Corticotrope Corticotropes are basophilic cells in the anterior pituitary that produce adrenocorticotropic hormone, melanocyte-stimulating hormone and lipotropin. These cells respond to corticotropin releasing hormone and make up about 20% of the cells in the anterior pituitary.... |
Gonadotrope Gonadotrope Gonadotropes are endocrine cells in the anterior pituitary that produce the gonadotropins, follicle-stimulating hormone and luteinizing hormone... |
Somatotrope Somatotrope Somatotropes are cells in the anterior pituitary that produce growth hormone.-Description:Somatotropic cells constitute 30-40% of anterior pituitary cells... |
Lactotrope |
|---|---|---|---|---|---|
| Pituitary hormone | TSH | ACTH | LH/FSH | GH | Prolactin |
| End organ | Thyroid | Adrenal | Testes or ovaries | Liver | Breast gland |
| Product | Thyroxine | Cortisol | Testosterone or estradiol | IGF-1 | Milk (no feedback) |
Most of the hormones in the anterior pituitary are each part of an axis that is regulated by the hypothalamus
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...
. The hypothalamus secretes a number of releasing hormone
Releasing hormone
A releasing hormone or releasing factor is a hormone whose main purpose is to control the release of another hormone. The main releasing hormones secreted by the hypothalamus are:*Thyrotropin-releasing hormone ,...
s, often according to a circadian rhythm
Circadian rhythm
A circadian rhythm, popularly referred to as body clock, is an endogenously driven , roughly 24-hour cycle in biochemical, physiological, or behavioural processes. Circadian rhythms have been widely observed in plants, animals, fungi and cyanobacteria...
, into blood vessels that supply the anterior pituitary
Hypophyseal portal system
The hypophyseal portal system is the system of blood vessels that link the hypothalamus and the anterior pituitary in the brain.It allows endocrine communication between the two structures. It is part of the hypothalamic-pituitary-adrenal axis. The anterior pituitary receives releasing and...
; most of these are stimulatory (thyrotropin-releasing hormone
Thyrotropin-releasing hormone
Thyrotropin-releasing hormone , also called thyrotropin-releasing factor , thyroliberin or protirelin, is a tropic tripeptide hormone that stimulates the release of thyroid-stimulating hormone and prolactin by the anterior pituitary...
, corticotropin-releasing hormone
Corticotropin-releasing hormone
Corticotropin-releasing hormone , originally named corticotropin-releasing factor , and also called corticoliberin, is a polypeptide hormone and neurotransmitter involved in the stress response...
, gonadotropin-releasing hormone
Gonadotropin-releasing hormone
Gonadotropin-releasing hormone , also known as Luteinizing-hormone-releasing hormone and luliberin, is a tropic peptide hormone responsible for the release of follicle-stimulating hormone and luteinizing hormone from the anterior pituitary. GnRH is synthesized and released from neurons within...
and growth hormone-releasing hormone), apart from dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
, which suppresses prolactin production. In response to the releasing hormone rate, the anterior pituitary produces its hormones (TSH, ACTH, LH, FSH, GH) that stimulate effector hormone glands in the body, although prolactin acts directly on the breast gland
Mammary gland
A mammary gland is an organ in mammals that produces milk to feed young offspring. Mammals get their name from the word "mammary". In ruminants such as cows, goats, and deer, the mammary glands are contained in their udders...
. Once the effector glands produce sufficient hormones (thyroxine, cortisol, estradiol or testosterone and IGF-1), both the hypothalamus and the pituitary cells sense their abundance and reduce their secretion
Negative feedback
Negative feedback occurs when the output of a system acts to oppose changes to the input of the system, with the result that the changes are attenuated. If the overall feedback of the system is negative, then the system will tend to be stable.- Overview :...
of stimulating hormones. The hormones of the posterior pituitary are produced in the hypothalamus and are carried by nerve endings to the posterior lobe; their feedback system is therefore located in the hypothalamus, but damage to the nerve endings would still lead to a deficiency in hormone release.
Unless the pituitary damage is being caused by a tumor that overproduces a particular hormone, it is the lack of pituitary hormones that leads to the symptoms described above, and an excess of a particular hormone would indicate the presence of a tumor. The exception to this rule is prolactin: if a tumor compresses the pituitary stalk
Pituitary stalk
The pituitary stalk is the connection between the hypothalamus and the posterior pituitary....
, a decreased blood supply means that the lactotrope cells, which produce prolactin, are not receiving dopamine and therefore produce excess prolactin. Hence, mild elevations in prolactin are attributed to stalk compression. Very high prolactin levels, though, point more strongly towards a prolactinoma
Prolactinoma
A prolactinoma is a benign tumor of the pituitary gland that produces a hormone called prolactin. It is the most common type of pituitary tumor...
(prolactin-secreting tumor).
Diagnosis
Blood test
A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via fingerprick....
s. Two types of blood tests are used to confirm the presence of a hormone deficiency: basal levels, where blood samples are taken–usually in the morning–without any form of stimulation, and dynamic tests, where blood tests are taken after the injection of a stimulating substance. Measurement of ACTH and growth hormone usually requires dynamic testing, whereas the other hormones (LH/FSH, prolactin, TSH) can typically be tested with basal levels. There is no adequate direct test for ADH levels, but ADH deficiency can be confirmed indirectly; oxytocin levels are not routinely measured.
Generally, the finding of a combination of a low pituitary hormone together with a low hormone from the effector gland is indicative of hypopituitarism. Occasionally, the pituitary hormone may be normal but the effector gland hormone decreased; in this case, the pituitary is not responding appropriately, and the combination of findings is still suggestive of hypopituitarism.
Basal tests
Levels of LH/FSH may be suppressed by a raised prolactinProlactin
Prolactin also known as luteotropic hormone is a protein that in humans is encoded by the PRL gene.Prolactin is a peptide hormone discovered by Henry Friesen...
level, and are therefore not interpretable unless prolactin is low or normal. In men, the combination of low LH and FSH in combination with a low testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
confirms LH/FSH deficiency; a high testosterone would indicate a source elsewhere in the body (such as a testosterone-secreting tumor). In women, the diagnosis of LH/FSH deficiency depends on whether the woman has been through the menopause
Menopause
Menopause is a term used to describe the permanent cessation of the primary functions of the human ovaries: the ripening and release of ova and the release of hormones that cause both the creation of the uterine lining and the subsequent shedding of the uterine lining...
. Before the menopause, abnormal menstrual periods together with low estradiol
Estradiol
Estradiol is a sex hormone. Estradiol is abbreviated E2 as it has 2 hydroxyl groups in its molecular structure. Estrone has 1 and estriol has 3 . Estradiol is about 10 times as potent as estrone and about 80 times as potent as estriol in its estrogenic effect...
and LH/FSH levels confirm a pituitary problem; after the menopause (when LH/FSH levels are normally elevated and the ovaries produce less estradiol), inappropriately low LH/FSH alone is sufficient. Stimulation tests with GnRH are possible, but their use is not encouraged.
For TSH, basal measurements are usually sufficient, as well as measurements of thyroxine
Thyroxine
Thyroxine, or 3,5,3',5'-tetraiodothyronine , a form of thyroid hormones, is the major hormone secreted by the follicular cells of the thyroid gland.-Synthesis and regulation:...
to ensure that the pituitary is not simply suppressing TSH production in response to hyperthyroidism
Hyperthyroidism
Hyperthyroidism is the term for overactive tissue within the thyroid gland causing an overproduction of thyroid hormones . Hyperthyroidism is thus a cause of thyrotoxicosis, the clinical condition of increased thyroid hormones in the blood. Hyperthyroidism and thyrotoxicosis are not synonymous...
(an overactive thyroid gland). A stimulation test with thyrotropin-releasing hormone
Thyrotropin-releasing hormone
Thyrotropin-releasing hormone , also called thyrotropin-releasing factor , thyroliberin or protirelin, is a tropic tripeptide hormone that stimulates the release of thyroid-stimulating hormone and prolactin by the anterior pituitary...
(TRH) is not regarded as useful. Prolactin can be measured by basal level, and is required for the interpretation of LH and FSH results in addition to the confirmation of hypopituitarism or diagnosis of a prolactin-secreting tumor.
Stimulation tests
Growth hormone deficiency is almost certain if all other pituitary tests are also abnormal, and insulin-like growth factor 1Insulin-like growth factor 1
Insulin-like growth factor 1 also known as somatomedin C is a protein that in humans is encoded by the IGF1 gene. IGF-1 has also been referred to as a "sulfation factor" and its effects were termed "nonsuppressible insulin-like activity" in the 1970s.IGF-1 is a hormone similar in molecular...
(IGF-1) levels are decreased. If this is not the case, IGF-1 levels are poorly predictive of the presence of GH deficiency; stimulation testing with the insulin tolerance test
Insulin tolerance test
An insulin tolerance test is a medical diagnostic procedure during which insulin is injected into a patient's vein to assess pituitary function, adrenal function, and sometimes for other purposes. An ITT is usually ordered and interpreted by endocrinologists.Insulin injections are intended to...
is then required. This is performed by administering insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
to lower the blood sugar
Blood sugar
The blood sugar concentration or blood glucose level is the amount of glucose present in the blood of a human or animal. Normally in mammals, the body maintains the blood glucose level at a reference range between about 3.6 and 5.8 mM , or 64.8 and 104.4 mg/dL...
to a level below 2.2 mmol/l
Hypoglycemia
Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...
. Once this occurs, growth hormone levels are measured. If they are low despite the stimulatory effect of the low blood sugars, growth hormone deficiency is confirmed. The test is not without risks, especially in those prone to seizure
Seizure
An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...
s or are known to have heart disease, and causes the unpleasant symptoms of hypoglycemia
Hypoglycemia
Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...
. Alternative tests (such as the growth hormone releasing hormone
Growth hormone releasing hormone
Growth-hormone-releasing hormone , also known as growth-hormone-releasing factor , somatoliberin or somatocrinin, is a releasing hormone for growth hormone...
stimulation test) are less useful, although a stimulation test with arginine
Arginine
Arginine is an α-amino acid. The L-form is one of the 20 most common natural amino acids. At the level of molecular genetics, in the structure of the messenger ribonucleic acid mRNA, CGU, CGC, CGA, CGG, AGA, and AGG, are the triplets of nucleotide bases or codons that codify for arginine during...
may be used for diagnosis, especially in situations where an insulin tolerance test is thought to be too dangerous. If GH deficiency is suspected, and all other pituitary hormones are normal, two different stimulation tests are needed for confirmation.
If morning cortisol
Cortisol
Cortisol is a steroid hormone, more specifically a glucocorticoid, produced by the adrenal gland. It is released in response to stress and a low level of blood glucocorticoids. Its primary functions are to increase blood sugar through gluconeogenesis; suppress the immune system; and aid in fat,...
levels are over 500 nmol/l
Mole (unit)
The mole is a unit of measurement used in chemistry to express amounts of a chemical substance, defined as an amount of a substance that contains as many elementary entities as there are atoms in 12 grams of pure carbon-12 , the isotope of carbon with atomic weight 12. This corresponds to a value...
, ACTH deficiency is unlikely, whereas a level less than 100 is indicative. Levels between 100-500 require a stimulation test. This, too, is done with the insulin tolerance test. A cortisol level above 500 after achieving a low blood sugar rules out ACTH deficiency, while lower levels confirm the diagnosis. A similar stimulation test using corticotropin-releasing hormone
Corticotropin-releasing hormone
Corticotropin-releasing hormone , originally named corticotropin-releasing factor , and also called corticoliberin, is a polypeptide hormone and neurotransmitter involved in the stress response...
(CRH) is not sensitive enough for the purposes of the investigation. If the insulin tolerance test yields an abnormal result, a further test measuring the response of the adrenal glands to synthetic ACTH (the ACTH stimulation test
ACTH stimulation test
The ACTH stimulation test is a medical test usually ordered and interpreted by endocrinologists to assess the functioning of the adrenal glands stress response by measuring the adrenal response to adrenocorticotropic hormone...
) can be performed to confirm the diagnosis. Stimulation testing with metyrapone
Metyrapone
Metyrapone is a drug used in the diagnosis of adrenal insufficiency and occasionally in the treatment of Cushing's syndrome .-Mechanism:...
is an alternative. Some suggest that an ACTH stimulation test is sufficient as first-line investigation, and that an insulin torlerance test is only needed if the ACTH test is equivocal. The insulin tolerance test is discouraged in children. None of the tests for ACTH deficiency are perfect, and further tests after a period of time may be needed if initial results are not conclusive.
Symptoms of diabetes insipidus should prompt a formal fluid deprivation test
Fluid deprivation test
A fluid or water deprivation test is a medical test which can be used to determine whether the patient has diabetes insipidus as opposed to other causes of polydipsia...
to assess the body's response to dehydration, which normally causes concentration of the urine and increasing osmolarity of the blood. If these parameters are unchanged, desmopressin
Desmopressin
Desmopressin is a synthetic replacement for vasopressin, the hormone that reduces urine production. It may be taken nasally, intravenously, or as a tablet...
(an ADH analogue) is administered. If the urine then becomes concentrated and the blood osmolarity falls, there is a lack of ADH due to lack of pituitary function ("cranial diabetes insipidus"). In contrast, there is no change if the kidneys are unresponsive to ADH due to a different problem ("nephrogenic diabetes insipidus").
Further investigations
If one of these tests shows a deficiency of hormones produced by the pituitary, magnetic resonance imagingMagnetic resonance imaging
Magnetic resonance imaging , nuclear magnetic resonance imaging , or magnetic resonance tomography is a medical imaging technique used in radiology to visualize detailed internal structures...
(MRI) scan of the pituitary is the first step in identifying an underlying cause. MRI may show various tumors and may assist in delineating other causes. Tumors smaller than 1 cm are referred to as microadenomas, and larger lesions are called macroadenomas. Computed tomography
Computed tomography
X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...
with radiocontrast may be used if MRI is not available. Formal visual field test
Visual field test
A visual field test is an examination that may be performed to analyze a patient's visual field. The exam may be performed by a technician in one of several ways. The test may be performed by a technician directly, with the assistance of a machine, or completely by an automated machine...
ing by perimetry
Perimetry
Perimetry or campimetry is the systematic measurement of differential light sensitivity in the visual field by the detection of the presence of test targets on a defined background. Visual field testing can be performed clinically with confrontational field testing keeping the subject's gaze fixed...
is recommended, as this would show evidence of optic nerve compression by a tumor.
Other tests that may assist in the diagnosis of hypopituitarism, especially if no tumor is found on the MRI scan, are ferritin
Ferritin
Ferritin is a ubiquitous intracellular protein that stores iron and releases it in a controlled fashion. The amount of ferritin stored reflects the amount of iron stored. The protein is produced by almost all living organisms, including bacteria, algae and higher plants, and animals...
(elevated in hemochromatosis), angiotensin converting enzyme (ACE) levels (often elevated in sarcoidosis), and human chorionic gonadotropin
Human chorionic gonadotropin
Human chorionic gonadotropin or human chorionic gonadotrophin is a glycoprotein hormone produced during pregnancy that is made by the developing embryo after conception and later by the syncytiotrophoblast .. Some tumors make this hormone; measured elevated levels when the patient is not...
(often elevated in tumor of germ cell origin
Germ cell tumor
A germ cell tumor is a neoplasm derived from germ cells. Germ cell tumors can be cancerous or non-cancerous tumors. Germ cells normally occur inside the gonads...
). If a genetic cause is suspected, genetic testing
Genetic testing
Genetic testing is among the newest and most sophisticated of techniques used to test for genetic disorders which involves direct examination of the DNA molecule itself. Other genetic tests include biochemical tests for such gene products as enzymes and other proteins and for microscopic...
may be performed.
Treatment
Treatment of hypopituitarism is threefold: removing the underlying cause, treating the hormone deficiencies, and addressing any other repercussions that arise from the hormone deficiencies.Underlying cause
Pituitary tumors require treatment when they are causing specific symptoms, such as headaches, visual field defects or excessive hormone secretion. Transsphenoidal surgeryTranssphenoidal surgery
Transsphenoidal surgery is a type of surgery in which surgical instruments are inserted into part of the brain by going through the nose and the sphenoid bone . Transsphenoidal surgery is used to remove tumors of the pituitary gland.- External links :* entry in the public domain NCI Dictionary of...
(removal of the tumor by an operation through the nose and the sphenoidal sinuses
Sphenoidal sinuses
The two sphenoidal sinuses contained within the body of the sphenoid vary in size and shape; owing to the lateral displacement of the intervening septum they are rarely symmetrical....
) may, apart from addressing symptoms related to the tumor, also improve pituitary function, although the gland is sometimes damaged further as a result of the surgery. When the tumor is removed by craniotomy
Craniotomy
A craniotomy is a surgical operation in which a bone flap is temporarily removed from the skull to access the brain. Craniotomies are often a critical operation performed on patients recording, brain imaging, and for neurological manipulations such as electrical stimulation and chemical...
(opening the skull), recovery is less likely–but sometimes this is the only suitable way to approach the tumor. After surgery, it may take some time for hormone levels to change significantly. Retesting the pituitary hormone levels is therefore performed 2 to 3 months later.
Prolactinoma
Prolactinoma
A prolactinoma is a benign tumor of the pituitary gland that produces a hormone called prolactin. It is the most common type of pituitary tumor...
s may respond to dopamine agonist
Dopamine agonist
A dopamine agonist is a compound that activates dopamine receptors in the absence of dopamine. Dopamine agonists activate signaling pathways through the dopamine receptor and trimeric G-proteins, ultimately leading to changes in gene transcription.-Uses:...
treatment–medication that mimics the action of dopamine on the lactrotrope cells, usually bromocriptine
Bromocriptine
Bromocriptine , an ergoline derivative, is a dopamine agonist that is used in the treatment of pituitary tumors, Parkinson's disease , hyperprolactinaemia, neuroleptic malignant syndrome, and type 2 diabetes.- Indications :Amenorrhea, female infertility, galactorrhea, hypogonadism, and acromegaly...
or cabergoline
Cabergoline
Cabergoline , an ergot derivative, is a potent dopamine receptor agonist on D2 receptors. In vitro, rat studies show cabergoline has a direct inhibitory effect on pituitary lactotroph cells...
. This approach may improve pituitary hormone secretion in more than half the cases, and obviate the need for supplementary treatment.
Other specific underlying causes are treated as normally. For example, hemochromatosis is treated by venesection
Venipuncture
In medicine, venepuncture, venopuncture or venipuncture is the process of obtaining intravenous access for the purpose of intravenous therapy or for blood sampling of venous blood. This procedure is performed by medical laboratory scientists, medical practitioners, some EMTs, paramedics,...
, the regular removal of a fixed amount of blood. Eventually, this decreases the iron levels in the body and improves the function of the organs in which iron has accumulated.
Hormone replacement
Most pituitary hormones can be replaced indirectly by administering the products of the effector glands: hydrocortisone (cortisol) for adrenal insufficiency, levothyroxineLevothyroxine
Levothyroxine, also L-thyroxine, synthetic T4, or 3,5,3',5'-tetraiodo-L-thyronine, is a synthetic form of thyroxine , used as a hormone replacement for patients with thyroid problems. The natural hormone is chemically in the chiral L-form, as is the pharmaceutical agent...
for hypothyroidism, testosterone
Testosterone
Testosterone is a steroid hormone from the androgen group and is found in mammals, reptiles, birds, and other vertebrates. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands...
for male hypogonadism, and estradiol
Estradiol
Estradiol is a sex hormone. Estradiol is abbreviated E2 as it has 2 hydroxyl groups in its molecular structure. Estrone has 1 and estriol has 3 . Estradiol is about 10 times as potent as estrone and about 80 times as potent as estriol in its estrogenic effect...
for female hypogonadism (usually with a progestagen
Progestagen
Progestogens are a group of hormones including progesterone.The progestogens are one of the five major classes of steroid hormones, in addition to the estrogens, androgens, mineralocorticoids, and glucocorticoids. All progestogens are characterized by their basic 21-carbon skeleton, called a...
to inhibit unwanted effects on the uterus
Uterus
The uterus or womb is a major female hormone-responsive reproductive sex organ of most mammals including humans. One end, the cervix, opens into the vagina, while the other is connected to one or both fallopian tubes, depending on the species...
). Growth hormone is available in synthetic form, but needs to be administered parenterally (by injection). Antidiuretic hormone can be replaced by desmopressin (DDAVP) tablets or nose spray
Nasal spray
Nasal sprays come in a variety of forms. Medicated such as Astelin, Afrin and Nasonex and natural such as Sinusoothe and Sterimar. Although delivery methods vary, most nasal sprays function by instilling a fine mist into the nostril by action of a hand-operated pump mechanism.-Antihistamine nasal...
. Generally, the lowest dose of the replacement medication is used to restore wellbeing and correct the deranged results, as excessive doses would cause side-effects or complications. Those requiring hydrocortisone are usually instructed to increase their dose in physically stressful events such as injury, hospitalization and dental work as these are times when the normal supplementary dose may be inadequate, putting the patient at risk of adrenal crisis.
Long-term follow up by specialists in endocrinology
Endocrinology
Endocrinology is a branch of biology and medicine dealing with the endocrine system, its diseases, and its specific secretions called hormones, the integration of developmental events such as proliferation, growth, and differentiation and the coordination of...
is generally needed for people with known hypopituitarism. Apart from ensuring the right treatment is being used and at the right doses, this also provides an opportunity to deal with new symptoms and to address complications of treatment.
Difficult situations arise in deficiencies of the hypothalamus-pituitary-gonadal axis in people (both men and women) who experience infertility
Infertility
Infertility primarily refers to the biological inability of a person to contribute to conception. Infertility may also refer to the state of a woman who is unable to carry a pregnancy to full term...
; infertility in hypopituitarism may be treated with subcutaneous infusions of FSH, human chorionic gonadotropin
Human chorionic gonadotropin
Human chorionic gonadotropin or human chorionic gonadotrophin is a glycoprotein hormone produced during pregnancy that is made by the developing embryo after conception and later by the syncytiotrophoblast .. Some tumors make this hormone; measured elevated levels when the patient is not...
–which mimics the action of LH–and occasionally GnRH.
Complications
Several hormone deficiencies associated with hypopituitarism may lead to secondary diseases. For instance, growth hormone deficiency is associated with obesity, raised cholesterolCholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...
and the metabolic syndrome
Metabolic syndrome
Metabolic syndrome is a combination of medical disorders that, when occurring together, increase the risk of developing cardiovascular disease and diabetes. It affects one in five people in the United States and prevalence increases with age...
, and estradiol deficiency may lead to osteoporosis. While effective treatment of the underlying hormone deficiencies may improve these risks, it is often necessary to treat them directly.
Prognosis
Several studies have shown that hypopituitarism is associated with an increased risk of cardiovascular diseaseCardiovascular disease
Heart disease or cardiovascular disease are the class of diseases that involve the heart or blood vessels . While the term technically refers to any disease that affects the cardiovascular system , it is usually used to refer to those related to atherosclerosis...
and some also an increased risk of death of about 50% to 150% the normal population. It has been difficult to establish which hormone deficiency is responsible for this risk, as almost all patients studied had growth hormone deficiency. The studies also do not answer the question as to whether the hypopituitarism itself causes the increased mortality, or whether some of the risk is to be attributed to the treatments, some of which (such as sex hormone supplementation) have a recognized adverse effect on cardiovascular risk.
The largest study to date followed over a thousand people for eight years; it showed an 87% increased risk of death compared to the normal population
Standardized mortality ratio
The standardized mortality ratio or SMR in epidemiology is the ratio of observed deaths to expected deaths, where expected deaths are calculated for a typical area with the same age and gender mix by looking at the death rates for different ages and genders in the larger population.The SMR may be...
. Predictors of higher risk were: female sex, absence of treatment for sex hormone deficiency, younger age at the time of diagnosis, and a diagnosis of craniopharyngioma. Apart from cardiovascular disease, this study also showed an increased risk of death from lung disease.
Quality of life
Quality of life
The term quality of life is used to evaluate the general well-being of individuals and societies. The term is used in a wide range of contexts, including the fields of international development, healthcare, and politics. Quality of life should not be confused with the concept of standard of...
may be significantly reduced, even in those people on optimum medical therapy. Many report both physical and psychological problems. It is likely that the commonly used replacement therapies still do not completely mimic the natural hormone levels in the body. Health costs remain about double those of the normal population.
Epidemiology
There is only one study that has measured the prevalencePrevalence
In epidemiology, the prevalence of a health-related state in a statistical population is defined as the total number of cases of the risk factor in the population at a given time, or the total number of cases in the population, divided by the number of individuals in the population...
(total number of cases in a population) and incidence
Incidence (epidemiology)
Incidence is a measure of the risk of developing some new condition within a specified period of time. Although sometimes loosely expressed simply as the number of new cases during some time period, it is better expressed as a proportion or a rate with a denominator.Incidence proportion is the...
(annual number of new cases) of hypopituitarism. This study was conducted in Northern Spain and used hospital records in a well-defined population. The study showed that 45.5 people out of 100,000 had been diagnosed with hypopituitarism, with 4.2 new cases per year. 61% were due to tumors of the pituitary gland, 9% due to other types of lesions, and 19% due to other causes; in 11% no cause could be identified.
Recent studies have shown that people with a previous traumatic brain injury
Traumatic brain injury
Traumatic brain injury , also known as intracranial injury, occurs when an external force traumatically injures the brain. TBI can be classified based on severity, mechanism , or other features...
, spontaneous subarachnoid hemorrhage
Subarachnoid hemorrhage
A subarachnoid hemorrhage , or subarachnoid haemorrhage in British English, is bleeding into the subarachnoid space—the area between the arachnoid membrane and the pia mater surrounding the brain...
(a type of stroke) or radiation therapy
Radiation therapy
Radiation therapy , radiation oncology, or radiotherapy , sometimes abbreviated to XRT or DXT, is the medical use of ionizing radiation, generally as part of cancer treatment to control malignant cells.Radiation therapy is commonly applied to the cancerous tumor because of its ability to control...
involving the head have a higher risk of hypopituitarism. After traumatic brain injury, as much as a quarter have persistent pituitary hormone deficiencies. Many of these people may have subtle or non-specific symptoms that are not linked to pituitary problems but attributed to their previous condition. It is therefore possible that many cases of hypopituitarism remain undiagnosed, and that the annual incidence would rise to 31 per 100,000 annually if people from these risk groups were to be tested.
History
The pituitary was known to the ancients, such as GalenGalen
Aelius Galenus or Claudius Galenus , better known as Galen of Pergamon , was a prominent Roman physician, surgeon and philosopher...
, and various theories were proposed about its role in the body, but major clues as to the actual function of the gland were not advanced until the late 19th century, when acromegaly
Acromegaly
Acromegaly is a syndrome that results when the anterior pituitary gland produces excess growth hormone after epiphyseal plate closure at puberty...
due to pituitary tumors was described. The first known report of hypopituitarism was made by the German
Germany
Germany , officially the Federal Republic of Germany , is a federal parliamentary republic in Europe. The country consists of 16 states while the capital and largest city is Berlin. Germany covers an area of 357,021 km2 and has a largely temperate seasonal climate...
physician and pathologist Dr Morris Simmonds
Morris Simmonds
Morris Simmonds was a German physician, pathologist, from a family originating in Hanau but born on the then Danish St. Thomas, US Virgin Islands in Caribbean Sea...
. He described the condition on autopsy
Autopsy
An autopsy—also known as a post-mortem examination, necropsy , autopsia cadaverum, or obduction—is a highly specialized surgical procedure that consists of a thorough examination of a corpse to determine the cause and manner of death and to evaluate any disease or injury that may be present...
in a 46-year old woman who had suffered severe puerperal fever
Puerperal fever
Puerperal fever or childbed fever, is a bacterial infection contracted by women during childbirth or miscarriage. It can develop into puerperal sepsis, which is a serious form of septicaemia. If untreated, it is often fatal....
eleven years earlier, and subsequently suffered amenorrhea, weakness, signs of rapid aging and anemia. The pituitary gland was very small and there were few remnants of both the anterior and the posterior pituitary. The eponym Simmonds' syndrome is used infrequently for acquired hypopituitarism, especially when cachexia
Cachexia
Cachexia or wasting syndrome is loss of weight, muscle atrophy, fatigue, weakness, and significant loss of appetite in someone who is not actively trying to lose weight...
(general ill health and malnutrition) predominates. Most of the classic causes of hypopituitarism were described in the 20th century; the early 21st century saw the recognition of how common hypopituitarism could be in previous head injury victims.
Until the 1950s, the diagnosis of pituitary disease remained based on clinical features and visual field examination, sometimes aided by pneumoencephalography
Pneumoencephalography
Pneumoencephalography is a medical procedure in which most of the cerebrospinal fluid is drained from around the brain and replaced with air, oxygen, or helium to allow the structure of the brain to show up more clearly on an X-ray image...
and X-ray tomography
Tomography
Tomography refers to imaging by sections or sectioning, through the use of any kind of penetrating wave. A device used in tomography is called a tomograph, while the image produced is a tomogram. The method is used in radiology, archaeology, biology, geophysics, oceanography, materials science,...
. Nevertheless, the field of pituitary surgery developed during this time. The major breakthrough in diagnosis came with the discovery of the radioimmunoassay
Radioimmunoassay
Radioimmunoassay is a very sensitive in vitro assay technique used to measure concentrations of antigens by use of antibodies...
by Rosalyn Yalow and Solomon Berson
Solomon Berson
Solomon Aaron Berson was an American physician and scientist whose discoveries, mostly together with Rosalyn Yalow, caused major advances in clinical biochemistry....
in the late 1950s. This allowed the direct measurement of the hormones of the pituitary, which as a result of their low concentrations in blood had previously been hard to measure. Stimulation tests were developed in the 1960s, and in 1973 the triple bolus test
Triple bolus test
A triple bolus test or a dynamic pituitary function test is a medical diagnostic procedure used to assess a patient's pituitary function.A triple bolus test is usually ordered and interpreted by endocrinologists....
was introduced, a test that combined stimulation testing with insulin, GnRH and TRH. Imaging of the pituitary, and therefore identification of tumors and other structural causes, improved radically with the introduction of computed tomography
Computed tomography
X-ray computed tomography or Computer tomography , is a medical imaging method employing tomography created by computer processing...
in the late 1970s and magnetic resonance imaging in the 1980s.
External links
- Hypopituitarism at the Pituitary Foundation (UK)