pituitary adenoma pituitary adenoma pituitary adenomas are tumors that occur in the pituitary gland. most pituitary tumors are benign, approximately 35% are invasive and just 0.1% to 0.2% are carcinomas. pituitary adenomas represent from 10% to 25% of all intracranial neoplasms and the estimated prevalence rate in the general population is approximately 17%. pituitary adenomavisual field loss in bitemporal hemianopsia: peripheral vision loss affecting both eyes, resulting from a tumor – typically a pituitary adenoma – putting pressure on the optic chiasmspecialtyoncology, endocrinology 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 exceeding 10 mm (0.39 in) in size are defined as macroadenomas, with those smaller than 10 mm (0.39 in) 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. while pituitary adenomas are common, affecting approximately one in 6 of the general population, clinically active pituitary adenomas that require surgical treatment are more rare, affecting approximately one in 1,000 of the general population. signs and 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, which present as unexpected bone growth and unexpected lactation (in both men and women). a patient with 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 increased hormone level estrogen can increase 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 (sunct) – another type of stabbing headache characterized by short stabs of pain – cluster headache, and hemicrania continua (hs). compressive symptoms of pituitary adenomas (visual field deficits, decreased visual acuity, headaches) are more commonly seen with macroadenomas (which are greater than 10 mm in diameter) than with microadenomas (which are less than 10 mm in diameter). non-secreting adenomas can go undetected for an extended time because no obvious abnormalities are seen; the gradual reduction in normal activities due to decreased production of hormones is rather less evident. for example, insufficient adrenocorticotropic hormone means that the adrenal glands will not produce sufficient cortisol, resulting in slow recovery from illness, inflammation, and chronic fatigue; insufficient growth hormone in children and adolescents leads to diminished stature but which can have many other explanations. 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 morphological facial changes caused by acromegaly; frontal bossing, enlarged nose, prognathism and maxillary widening with separation of teeth and unseen, enlargement of the tongue, stuffy nose (macroglossia) 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 syndrome is a hormonal disorder that causes hypercortisolism, which is elevated levels of cortisol in the blood. cushing's disease (cd) 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 (acth) 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 (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. central diabetes insipidus is caused by diminished production of the antidiuretic hormone vasopressin that causes severe thirst and excessive production of very dilute urine (polyuria) 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. as the pituitary gland is in close proximity to the brain, invasive adenomas may invade the dura mater, cranial bone, or sphenoid bone. risk factors 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 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 is 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 (men-1), carney complex and with mutations in the aryl hydrocarbon receptor-interacting protein (aip) gene. fipa was first described in a limited cohort of families by albert beckers group in liège, belgium; later fipa was fully characterized in a multicenter international study of 64 families. fipa families are divided into those that are homogenous and have the same type of pituitary adenoma in all the affected family members (e.g. only acromegaly, only prolactinoma, etc.), while heterogeneous fipa families can have different pituitary adenomas in affected family members. genetics of fipa fipa has two known genetic causes, mutations in the ah receptor-interacting protein (aip) gene and duplications in chromosome xq26.3 that include the gpr101 gene that also causes x-linked acrogigantism (x-lag) syndrome. about 15–20% of fipa families carry a germline aip gene mutation or deletion, and the disease occurs as autosomal dominant with incomplete penetrance, meaning that about 20% of aip mutation carriers will develop a pituitary adenoma. aip mutation associated pituitary adenomas (either presenting as fipa or as individual, non familial cases) are usually growth hormone-secreting (acromegaly) or prolactin-secreting (prolactinoma) adenomas that are large (macroadenomas) and often occur in children, adolescents and young adults. daly and colleagues showed that acromegaly cases with aip mutations occurred about 20 years before acromegaly cases without aip mutations and these tumors are large and relatively treatment-resistant. due to their young age at onset, aip mutations are the most frequent genetic cause of pituitary gigantism (29% of cases). x-lag is a rare syndrome of very early childhood onset pituitary tumors/hyperplasia that leads to growth hormone excess and severe overgrowth and pituitary gigantism. three fipa families with x-lag have been reported to date all of which had transmission of a chromosome xq26.3 duplication from affected mother to affected son. the disease characteristics of very young onset pituitary gigantism leads to severe overgrowth if not treated adequately; many of the tallest humans in history (e.g. robert pershing wadlow; sandy allen, andré rousimoff (andre the giant), zeng jinlian) had a similar clinical history to patients with x-lag syndrome. the tallest historical individual with a known genetic cause was julius koch (geant constantin) who was found to have x-lag on genetic study of his skeleton. x-lag has 100% penetrance so far (all affected with the xq26.3 duplication have the disease and it affects predominantly females. isolated non familial cases of x-lag can either have a constitutional duplication of a chromosome xq26.3 including gpr101, or mosaicism for the duplication (present in a minority of cells) in the case of isolated male patients. x-lag causes about 10% of cases of pituitary gigantism. mechanism pituitary gland 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 (fossa) 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 (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. the posterior lobe (the neural lobe or neurohypophysis) 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 (dendrites) within the lobe.