Pituitary adenomas are tumors that occur in the pituitary gland. Pituitary adenomas are
generally divided into three categories dependent upon their biological functioning: benign
adenoma, invasive adenoma, or carcinomas, with carcinomas accounting for 0.1% to 0.2%,
approximately 35% being invasive adenomas and most being benign adenomas. Pituitary
adenomas represent from 10% to 25% of all intracranial neoplasms and the estimated prevalence
rate in the general population is approximately 17%.
Non-invasive and non-secreting pituitary adenomas are considered to be benign in the literal
as well as the clinical sense; however a recent meta-analysis of available research has shown
there are to date scant studies - of poor quality - to either support or refute this
assumption. Adenomas which exceed 10 millimetres in size
are defined as macroadenomas, with those smaller than 10 mm referred to as microadenomas.
Most pituitary adenomas are microadenomas, and have an estimated prevalence of 16.7%.
A majority of pituitary microadenomas often remain undiagnosed and those that are diagnosed
are often found as an incidental finding, and are referred to as incidentalomas.
Pituitary macroadenomas are the most common cause of hypopituitarism, and in the majority
of cases they are non-secreting adenomas. Invasive adenomas may invade the dura mater,
cranial bone, or sphenoid bone. Although previously believed that clinically active pituitary
adenomas were rare, recent studies have suggested that they may affect approximately one in
1000 of the general population.
Overview
The pituitary gland or hypophysis is often referred to as the "master gland" of the human
body. Part of the hypothalamic-pituitary axis, it controls most of the body's endocrine functions
via the secretion of various hormones into the circulatory system. The pituitary gland
is located below the brain in a depression of the sphenoid bone known as the sella turcica.
Although anatomically and functionally connected to the brain, the pituitary gland sits outside
the blood–brain barrier. It is separated from the subarachnoid space by the diaphragma
sella, therefore the arachnoid mater and thus cerebral spinal fluid cannot enter the sella
turcica. The pituitary gland is divided into two lobes,
the anterior lobe, and the posterior lobe separated by the pars intermedia.
The posterior lobe of the pituitary gland is not, despite its name, a true gland. The
posterior lobe contains axons of neurons that extend from the hypothalamus to which it is
connected via the pituitary stalk. The hormones vasopressin and oxytocin, produced by the
neurons of the supraoptic and paraventricular nuclei of the hypothalamus, are stored in
the posterior lobe and released from axon endings within the lobe.
The pituitary gland's anterior lobe is a true gland which produces and secretes six different
hormones: thyroid-stimulating hormone, adrenocorticotropic hormone, follicle-stimulating hormone, luteinizing
hormone, growth hormone, and prolactin. Classification
Pituitary adenomas are classified based on upon anatomical, histological and functional
criteria. Anatomically pituitary tumors are classified
by their size based on radiological findings; either microadenomas or macroadenomas.
Classification based on radioanatomical findings places adenomas into 1 of 4 grades:
Stage I: microadenomas without sella expansion. Stage II: macroadenomas and may extend above
the sella. Stage III: macroadenomas with enlargement
and invasion of the floor or suprasellar extension. Stage IV is destruction of the sella.
Histological classification utilizes an immunohistological characterization of the tumors in terms of
their hormone production. Historically they were classed as either basophilic, acidophilic,
or chromophobic on the basis of whether or not they took up the tinctorial stains hematoxylin
and eosin. This classification has fallen into disuse, in favor of a classification
based on what type of hormone is secreted by the tumor. Approximately 20-25% of adenomas
do not secrete any readily identifiable active hormones yet they are still sometimes referred
to as 'chromophobic'. Functional classification is based upon the
tumors endocrine activity as determined by serum hormone levels and pituitary tissue
cellular hormone secretion detected via immunohistochemical staining. The "Percentage of hormone production
cases" values are the fractions of adenomas producing each related hormone of each tumor
type as compared to all cases of pituitary tumors, and does not directly correlate to
the percentages of each tumor type because of smaller or greater incidences of absence
of secretion of the expected hormone. Thus, nonsecretive adenomas may be either null cell
adenomas or a more specific adenoma that, however, remains nonsecretive.
Pituitary incidentalomas Pituitary incidentalomas are pituitary tumors
that are characterized as an incidental finding. They are often discovered by computed tomography
or magnetic resonance imaging, performed in the evaluation of unrelated medical conditions
such as suspected head trauma, in cancer staging or in the evaluation of nonspecific symptoms
such as dizziness and headache. It is not uncommon for them to be discovered at autopsy.
In a meta-analysis, adenomas were found in an average of 16.7% in postmortem studies,
with most being microadenomas; macrodenomas accounted for only 0.16% to 0.2% of the decedents.
While non-secreting, noninvasive pituitary microadenomas are generally considered to
be literally as well as clinically benign, there are to date scant studies of low quality
to support this assertion. It has been recommended in the current Clinical
Practice Guidelines by the Endocrine Society - a professional, international medical organization
in the field of endocrinology and metabolism - that all patients with pituitary incidentalomas
undergo a complete medical history and physical examination, laboratory evaluations to screen
for hormone hypersecretion and for hypopituitarism. If the lesion is in close proximity to the
optic nerves or optic chiasm, a visual field examination should be performed. For those
with incidentalomas which do not require surgical removal, follow up clinical assessments and
neuroimaging should be performed as well follow-up visual field examinations for incidentalomas
that abut or compress the optic nerve and chiasm and follow-up endocrine testing for
macroincidentalomas. Ectopic pituitary adenoma
An ectopic pituitary adenoma is a rare type of tumor which occurs outside of the sella
turcica, most often in the sphenoid sinus, suprasellar region, nasopharynx and the cavernous
sinuses. Metastases to the pituitary gland
Carcinomas that metastasize into the pituitary gland are uncommon and typically seen in the
elderly, with lung and breast cancers being the most prevalent, In breast cancer patients,
metastases to the pituitary gland occur in approximately 6-8% of cases.
Symptomatic pituitary metastases account for only 7% of reported cases. In those who are
symptomatic Diabetes insipidus often occurs with rates approximately 29-71%. Other commonly
reported symptoms include anterior pituitary dysfunction, visual field defects, headache/pain,
and ophthalmoplegia. Risk factors
Multiple endocrine neoplasia Adenomas of the anterior pituitary gland are
a major clinical feature of multiple endocrine neoplasia type 1, a rare inherited endocrine
syndrome that affects 1 person in every 30,000. MEN causes various combinations of benign
or malignant tumors in various glands in the endocrine system or may cause the glands to
become enlarged without forming tumors. It often affects the parathyroid glands, pancreatic
islet cells, and anterior lobe of the pituitary gland. MEN1 may also cause non-endocrine tumors
such as facial angiofibromas, collagenomas, lipomas, meningiomas, ependymomas, and leiomyomas.
Approximately 25 percent of patients with MEN1 develop pituitary adenomas.
Carney complex Carney complex, also known as LAMB syndrome
and NAME syndrome is an autosomal dominant condition comprising myxomas of the heart
and skin, hyperpigmentation of the skin, and endocrine overactivity and is distinct from
Carney's triad. Approximately 7% of all cardiac myxomas are associated with Carney complex.
Patients with CNC develop growth hormone-producing pituitary tumors and in some instances these
same tumors also secrete prolactin. There are however no isolated prolactinomas or any
other type of pituitary tumor. In some patients with CNC, the pituitary gland is characterized
by hyperplastic areas with the hyperplasia most likely preceding the formation of GH-producing
adenomas. Familial isolated pituitary adenoma
Familial isolated pituitary adenoma is a term that used to identify a condition that displays
an autosomal dominant inheritance and is characterised by the presence of two or more related patients
affected by adenomas of the pituitary gland only, with no other associated symptoms that
occur in Multiple endocrine neoplasia Type 1 or Carney complex.
Symptoms Physical
Hormone secreting pituitary adenomas cause one of several forms of hyperpituitarism.
The specifics depend on the type of hormone. Some tumors secrete more than one hormone,
the most common combination being GH and prolactin. A pituitary adenoma may present with visual
field defects, classically bitemporal hemianopsia. It arises from the compression of the optic
nerve by the tumor. The specific area of the visual pathway at which compression by these
tumours occurs is at the optic chiasma. The anatomy of this structure causes pressure
on it to produce a defect in the temporal visual field on both sides, a condition called
bitemporal hemianopsia. If originating superior to the optic chiasm, more commonly in a craniopharyngioma
of the pituitary stalk, the visual field defect will first appear as bitemporal inferior quadrantanopia,
if originating inferior to the optic chiasm the visual field defect will first appear
as bitemporal superior quadrantanopia. Lateral expansion of a pituitary adenoma can also
compress the abducens nerve, causing a lateral rectus palsy.
Also, a pituitary adenoma can cause symptoms of increased intracranial pressure.
Prolactinomas often start to give symptoms especially during pregnancy, when the hormone
progesterone increases the tumor's growth rate.
Various types of headaches are common in patients with pituitary adenomas. The adenoma may be
the prime causative factor behind the headache or may serve to exacerbate a headache caused
by other factors. Amongst the types of headaches experienced are both chronic and episodic
migraine, and more uncommonly various unilateral headaches; primary stabbing headache, short-lasting
unilateral neuralgiform headache attacks with conjunctival injection and tearing - another
type of stabbing headache characterized by short stabs of pain -, cluster headache, and
hemicrania continua. Psychiatric
Various psychiatric manifestations have been associated with pituitary disorders including
pituitary adenomas. Psychiatric symptoms such as depression, anxiety apathy, emotional instability,
easy irritability and hostility have been noted.
Complications
Acromegaly is a syndrome that results when the anterior pituitary gland produces excess
growth hormone. Approximately 90-95% of acromegaly cases are caused by a pituitary adenoma and
it most commonly affects middle aged adults, Acromegly can result in severe disfigurement,
serious complicating conditions, and premature death if unchecked. The disease which is often
also associated with gigantism, is difficult to diagnose in the early stages and is frequently
missed for many years, until changes in external features, especially of the face, become noticeable
with the median time from the development of initial symptoms to diagnosis being twelve
years. Cushing's syndrome is a hormonal disorder
that causes hypercortisolism, which is elevated levels of cortisol in the blood. Cushing's
disease is the most frequent cause of Cushing's syndrome, responsible for approximately 70%
of cases. CD results when a pituitary adenoma causes excessive secretion of adrenocorticotropic
hormone that stimulates the adrenal glands to produce excessive amounts of cortisol.
Cushing's disease may cause fatigue, weight gain, fatty deposits around the abdomen and
lower back and face, stretch marks on the skin of the abdomen, thighs, breasts and arms,
hypertension, glucose intolerance and various infections. In women it may cause excessive
growth of facial hair and in men erectile dysfunction. Psychiatric manifestations may
include depression, anxiety, easy irritability and emotional instability. It may also result
in various cognitive difficulties. Hyperpituitarism is a disease of the anterior
lobe of the pituitary gland which is usually caused by a functional pituitary adenoma and
results in hypersecretion of adenohypophyseal hormones such as growth hormone; prolactin;
thyrotropin; luteinizing hormone; follicle stimulating hormone; and adrenocorticotropic
hormone. Pituitary apoplexy is a condition that occurs
when pituitary adenomas suddenly hemorrhage internally, causing a rapid increase in size
or when the tumor outgrows its blood supply which causes tissue necrosis and subsequent
swelling of the dead tissue. Pituitary apoplexy often presents with visual loss and sudden
onset headache and requires timely treatment often with corticosteroids and if necessary
surgical intervention. Central diabetes insipidus is caused by diminished
production of the antidiuretic hormone vasopressin that causes severe thirst and excessive production
of very dilute urine which can lead to dehydration. Vasopressin is produced in the hypothalamus
and is then transported down the pituitary stalk and stored in the posterior lobe of
the pituitary gland which then secretes it into the bloodstream.
The diagnosis of CDI is based on the results of urine and blood tests, and a water deprivation
test which tests the body's ability to concentrate urine. CDI is often treated with desmopressin
acetate a synthetic vasopressin known as DDAVP administered via nasal spray.
Diagnosis and workup Diagnosis of pituitary adenoma can be made,
or at least suspected, by a constellation of related symptoms presented above.
Tumors which cause visual difficulty are likely to be a macroadenoma greater than 10 mm in
diameter; tumors less than 10 mm are microadenoma. The differential diagnosis includes pituitary
tuberculoma, especially in developing countries and in immumocompromised patients. The diagnosis
is confirmed by testing hormone levels, and by radiographic imaging of the pituitary.
Treatment Treatment options depend on the type of tumor
and on its size: Prolactinomas are most often treated with
bromocriptine or more recently, cabergoline or quinagolide which decrease tumor size as
well as alleviates symptoms, both dopamine agonists, and followed by serial imaging to
detect any increase in size. Treatment where the tumor is large can be with radiation therapy
or surgery, and patients generally respond well. Efforts have been made to use a progesterone
antagonist for the treatment of prolactinomas, but so far have not proved successful.
Somatotrophic adenomas respond to octreotide, a long-acting somatostatin analog, in many
but not all cases according to a review of the medical literature. Unlike prolactinomas,
thyrotrophic adenomas characteristically respond poorly to dopamine agonist treatment.
Surgery is a common treatment for pituitary tumors. Trans-sphenoidal adenectomy surgery
can often remove the tumor without affecting other parts of the brain. Endoscopic surgery
has become common recently. See also
Pituitary disease Pituitary tumour
References
External links Cancer.gov: pituitary tumors
Cleveland Clinic: Evaluation and management of pituitary incidentalomas [3]
The Pituitary Foundation