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, and 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 (Fernández-Balsells, et al. 2011) 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 (0.39 in) 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% (14.4% in autopsy studies and 22.5% in radiologic studies). 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.
The pituitary gland is divided into two lobes, the anterior lobe (which accounts for two thirds of the volume of the gland), and the posterior lobe (one third of the volume) separated by the pars intermedia.
Anatomically pituitary tumors are classified by their size based on radiological findings; either microadenomas (less than <10 mm) or macroadenomas (equal or greater than ≥I0 mm).
Classification based on radioanatomical findings places adenomas into 1 of 4 grades (I–IV):
Stage I: microadenomas (<1 cm) without sella expansion.
Stage II: macroadenomas (≥1 cm) 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 ('non-functioning tumors') 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.
It has been recommended in the current Clinical Practice Guidelines (2011) 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.
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.
Multiple endocrine neoplasia
Adenomas of the anterior pituitary gland are a major clinical feature of multiple endocrine neoplasia type 1 (MEN1), 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 (CNC), also known as LAMB syndrome and NAME syndrome is an autosomal dominant condition comprising myxomas of the heart and skin, hyperpigmentation of the skin (lentiginosis), 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 (GH)-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 (FIPA) 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.
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.
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.
Acromegaly is a syndrome that results when the anterior pituitary gland produces excess growth hormone (GH). 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 disease may cause fatigue, weight gain, fatty deposits around the abdomen and lower back (truncal obesity) and face ("moon face"), stretch marks (striae) 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 (hirsutism) 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.
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 (for example, by CT scan or MRI).
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.
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