Term
| what is another name for the anterior pituitary gland? how much of the entire gland does it comprise? |
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Definition
| the anterior pituitary gland, also called the adenohypophysis comprises 80% of the total pituitary gland |
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Term
| what is another name for the posterior pituitary gland? |
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Definition
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Term
| what are the cell types and their main product found in the anterior pituitary gland? |
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Definition
| somatotrophs (GH ~50% of hormone-producing cells in pituitary), lactotrophs (prolactin), corticotrophs (ACTH, pro-opiomelanocortin/POMC, melanocyte-stimulating hormone/MSH, endorphins, and lipotrophin), thyrotrophs (TSH), and gonadotrophs (FSH, LH). |
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Term
| how might a tumor of a particular cell type cause hypopituitarism? |
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Definition
| if it encroaches on that of another set of cell types |
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Term
| what characterizes the posterior pituitary gland? |
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Definition
| oxytocin and antidiuretic hormone (ADH) are synthesized in the hypothalamus and stored in the posterior pituitary. modified glial cells and axonal processes extend from the hypothalamus through the pituitary stalk and into the posterior lobe. |
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Term
| what is hyperpituitarism? |
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Definition
| excess secretion of hormones - caused by *adenomas, hyperplasia, and CA of the anterior pituitary |
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Term
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Definition
| deficiency of hormones - may be due to destruction of tissue such as sx, radiation, inflammation, and nonfunctional pituitary adenomas |
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Term
| what characterizes localized mass effects due to pituitary disease? |
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Definition
| these may be monitored as radiographic changes of the sella turcica, and may compress the optic chiasm (causing visual disturbances), cause increased intracranial pressure, and if acute hemorrhage is associated - pituitary apoplexy (rapid enlargement, sudden death) can occur. |
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Term
| what is the most common cause of hyperpituitarism? |
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Definition
| anterior pituitary adenoma, some of which may produce 2 hormones (w/1 dominant). |
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Term
| what demographics are usually affected by pituitary adenomas? |
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Definition
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Term
| what is the size range for pituitary adenomas? |
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Definition
| microadenomas are < 1 cm and macroadenomas are > 1 cm. large pituitary adenomas may cause hypopituitarism if they destroy the adjacent pituitary. |
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Term
| what genetics are associated w/pituitary adenomas? |
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Definition
| G protein mutations, which disrupt signaling and can result in continual stimulation of 2nd messengers (cAMP). the G alpha protein, encoded by the GNAS gene on chr 20, if mutated has decreased GTPase activity. GTP is stimulatory for endocrine cell production (mitogenic), and its prolonged presence as a result of the G alpha protein mutation = *40% of somatotroph cell adenomas. |
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Term
| what are the 4 genes which familial pituitary adenomas are associated with? |
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Definition
| MEN1 (mutations of menin tumor suppressor gene/TSG leads to *multiple endocrine neoplasia syndrome type 1), CDKN1B (produces cell cycle checkpoint regulator *p27/KIP1, which when mutated = MEN1-like syndrome), PRKAR1A (if function is lost = inappropriate cAMP activation and neoplasm formation, seen in *carney's syndrome), and AIP (aryl hydrocarbon receptor interacting protein, mutations of which may cause *GH adenomas/acromegaly) |
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Term
| what molecular abnormalities are commonly seen in aggressive pituitary tumors? |
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Definition
| overexpression of cyclin D, mutations of p53, epigenetic silencing of the rb gene, and activation of the HRAS oncogene (more seen in rare pituitary CA) |
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Term
| what mutation type/tumor types are associated w/G alpha protein mutations? |
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Definition
| activating mutations (gain of function) leading to GH adenomas |
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Term
| what mutation type/tumor types are associated w/PRKAR1A mutations? |
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Definition
| inactivating mutations of PKA regulators leading (gain of function) to GH/prolactin adenomas |
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Term
| what mutation type/tumor types are associated w/HRAS mutations? |
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Definition
| activating mutations (gain of function) leading to pituitary CA |
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Term
| what mutation type/tumor types are associated w/MEN1 mutations? |
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Definition
| inactivating mutations of MEN1 TSG (loss of function) leading to GH, prolactin, and ACTH adenomas |
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Term
| what mutation type/tumor types are associated w/CDKN1B? |
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Definition
| mutations of CDKN1B (p27/KIP1 - loss of function) lead to ACTH adenomas and a MEN1-like syndrome. |
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Term
| what mutation type/tumor types are associated w/AIP? |
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Definition
| mutations of AIP (loss of function) lead to GH adenomas |
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Term
| what mutation type/tumor types are associated w/rb mutations? |
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Definition
| methylation of rb genes (loss of function) leads to aggressive adenomas |
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Term
| what is the general gross morphology of pituitary adenomas? |
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Definition
| most are soft, gelatinous and limited to the sella turcica - though they manifest in a wide range of sizes, and the larger macroadenomas may compress the optic chiasm or some cranial nerves. if the sphenoid sinuses/dura/brain become involved: invasive adenoma (different from metastasis) |
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Term
| what is the general histology of pituitary adenomas? |
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Definition
| most consist of uniform, polygonal cells in sheets/cords *w/little supporting connective tissue. *cellular monomorphism and *absence of a reticulin network distinguish pituitary adenomas from normal cells. |
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Term
| what characterizes atypical adenomas? |
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Definition
| this subset has significant mitotic activity and tends to invade/recur. Ki-67/p53 are associated w/atypical adenomas. |
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Term
| what is the *most common type of functional or hyperfunctional adenoma? |
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Definition
| prolactinomas - which range from small to larger. |
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Term
| what characterizes prolactinomas histologically? |
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Definition
| prolactinomas are mostly composed of weakly acidophilic/chromophobic cells and may undergo *dystrophic calcification w/psammoma bodies (concentric, laminated bodies). prolactin can be demonstrated in the perinuclear secretory granules of the cytoplasm via immunohistological staining (*crescent shaped pattern). *amyloid deposition is also present (apple-green birefringence). |
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Term
| what is the clinical presentation of a prolactinoma? |
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Definition
| prolactinemia secondary to a prolactinoma can cause amenorrhea, galactorrhea (nipple discharge), loss of libido, and infertility. it is more common in women 20-40, and symptoms are more apparent in younger pts. prolactinomas may be treated w/bromocriptine or sx. |
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Term
| what is the *second most common type of functional or hyperfunctional adenoma? |
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Definition
| a somatotrophic GH adenoma, which may become large and is classified as 1 of 2 types: densely/sparsely granulated |
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Term
| what characterizes the densely granulated type of somatotrophic GH adenoma? |
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Definition
| monomorphic cells, strong GH staining, and perinuclear staining for *cytokeratin |
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Term
| what characterizes the sparsely granulated type of somatotrophic GH adenoma? |
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Definition
| nuclear/cytologic pleomorphism, weak staining for GH |
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Term
| what is a common kind of bihormonal adenoma? |
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Definition
| one which secretes both GH and prolactin |
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Term
| what is the clinical manifestation of somatotrophic GH adenomas? |
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Definition
| elevated levels of GH stimulate hepatic secretion of IGF-1 (insulin-like growth factor). if this occurs in children whose epiphysial plates have not closed = gigantism. if this occurs in pts whose epiphysial plates have closed = acromegaly (bigger feet, hands, hips, and lantern-like jaw change). GH excess can lead to gonadal disturbances, *DM, weakness, HTN, arthritis, CHF, and *increased risk of GI CA. |
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Term
| how are somatotrophic GH adenomas diagnosed? |
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Definition
| documentation of increased GH/IGF-1 levels. failure to suppress GH levels after an oral glucose load = sensitive test for acromegaly. |
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Term
| how are somatotrophic GH adenomas treated? |
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Definition
| surgical removal of tumor or GH-binding medication |
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Term
| what characterizes ACTH-secreting corticotroph adenomas? |
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Definition
| excess ACTH = adrenal hypersecretion of cortisol/hypercortisolism/cushing disease (hypercortisolism from other causes = cushing syndrome). most are *microadenomas and *densely granulated (some are sparsely granulated). |
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Term
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Definition
| the result if the adrenals are removed to treat cushing syndrome - due to lack of feedback of adrenal corticoids on a preexisting microadenoma |
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Term
| why might a pt w/a ACTH-secreting corticotroph adenoma look "bronze"? |
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Definition
| this is due to the stimulatory effect of ACTH precursor products on melanocytes |
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Term
| what characterizes gonadotroph adenomas? |
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Definition
| these secrete LH/FSH and are most common in middle-aged men/women. they *often do not cause clinical symptoms, but can produce headaches, diplopia, pituitary apoplexy, or paradoxically: gonadal hypofunction (in men, decreased LH may lead to decreased libido and in women amenorrhea may occur). |
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Term
| what characterizes thyrotroph adenomas? |
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Definition
| these are *rare, but produce TSH and can cause hyperthyroidism |
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Term
| what is a non-functioning adenoma? |
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Definition
| these, also called null-cell adenomas, make up about 25-30% of all pituitary adenomas. most pts present w/mass effects rather than hormonal and may compress the anterior pituitary and cause *hypopituitarism. |
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Term
| what characterizes pituitary CA? |
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Definition
| pituitary CA is rare (<1% of pituitary tumors) and most are functional tumors producing prolactin/ACTH. these may have cranial, spinal, or systemic metastases. |
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Term
| why is hypopituitarism a less common result of a pituitary tumor? what is the etiology of hypopituitarism? |
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Definition
| a significant amount, 75% if the anterior pituitary needs to be destroyed for hypofunction to occur. often hypopituitarism is accompanied by posterior dysfunction, which is then usually due to a hypothalamic disorder. other etiologies: traumatic brain injury/subarachnoid hemorrhage, pituitary necrosis, empty sella syndrome, sx, radiation, pituitary apoplexy (sudden hemorrhage), *rathke cell cyst (cysts lined by ciliated cuboidal epithelium that expands/compresses the pituitary), sheehan syndrome, hypothalamic lesions, and inflammatory disorders/infections (TB, sarcoidosis) |
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Term
| what is sheehan syndrome? |
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Definition
| an important cause of hypopituitarism where postpartum necrosis occurs in the anterior pituitary due to *obstetric hemorrhage (which infarcts an already enlarged pituitary). the posterior is usually not as affected as it receives its blood supply from arterial branches. |
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Term
| what are other possible causes of pituitary necrosis? |
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Definition
| DIC, sickle cell, and increased intracranial pressure |
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Term
| what are the 2 types of empty sella syndrome? |
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Definition
| *primary type: defect in the diaphragma sella, allowing the arachnoid mater CSF to herniate into the sella, expanding it and compressing the pituitary = visual defects and endocrine abnormalities. *secondary type: a mass enlarges the sella - but is surgically removed/undergoes spontaneous necrosis, leading to loss of pituitary function. |
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Term
| what characterizes hypothalamic lesions as a cause of hypopituitarism? |
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Definition
| hypothalamic lesions interfere w/delivery of pituitary hormone releasing factors and can lead to DM insipidus (reduced ADH) |
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Term
| what are some of the clinical effects of hypopituitarism? |
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Definition
| lack of GH: pituitary dwarfism, lack of FSH/LH: amenorrhea/loss of libido/infertility/impotence, lack of TSH/ACTH: hypothyroidism/hypogonadism, and lack of prolactin: failure of postpartum lactation |
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Term
| what are the posterior pituitary syndromes? |
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Definition
| diabetes insipidus (DI) and SIADH |
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Term
| what is diabetes insipidus (DI)? |
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Definition
| excessive urination due to kidneys being unable to resorb water. etiologies of *central DI: head trauma, tumors, inflammation of the hypothalamus or pituitary, surgical intervention, or idiopathic - all leading to damage to the posterior pituitary (site of ADH production). etiologies of *nephrogenic DI: inability of renal tubules to respond to ADH. either will result in very dilute urine w/low specific gravity, increased serum osmolality/Na+ (due to a lack of free water), and thirst/polydipsia. |
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Term
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Definition
| excessive resorption of free water, resulting in *dilutional-type hyponatremia*. etiologies: malignant tumors, drugs inducing ADH secretion, trauma, and infection. SIADH can be lethal, leading to cerebral edema w/neurogenic dysfunction. |
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Term
| what is a craniopharyngioma? |
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Definition
| these slow growing tumors arise from the remnants of rathke pouch cysts in the suprasellar region. they appear in bimodal age distribution (kids and pts 65 y/o). pts present w/headaches, visual problems, and children may present w/growth retardation from pituitary hypofunction/GH deficiency. |
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Term
| how do craniopharyngiomas appear grossly? histologically? |
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Definition
| 3-4 cm, either encapsulated+solid or cystic+multiloculated, craniopharyngiomas encroach on the optic chiasm and cranial nerves. they may also bulge into the 3rd ventricle and base of brain. histologically, there are 2 types: adamantinomatous and papillary. *adamantinomatous craniopharyngiomas are seen in children, often have calcifications (fibrosis, cyst formation, chronic inflammation), and consist of nests/cords of stratified squamous in a reticular background w/palisading squamous at the periphery. compact laminar keratin is usually seen and the cysts contain cholesterol (rich thick brown fluid). these tumors often have fingerlets which can extend into adjacent brain. *papillary craniopharyngiomas contain solid sheets and papillae lined by well differentiated squamous epithelium and usually lack keratin/calcifications/peripheral palisading. |
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Term
| what characterizes tumors which metastasize to the pituitary? |
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Definition
| this is somewhat common, esp from the breast, lung, and GI. most are asymptomatic initially (anterior requires 75% destruction to start losing function). |
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