encodes tumor suppressor gene merlin

responsible for familial pituitary adenoma syndrome

on chromosome 11q13

gene responsible for "MEN1-like" syndrome

located on chr 12p13

mutation causes Carney complex

on chr 17q24

autosomal dominant disorder of pituitary adenomas

loss of functional protein leads to inappropriate activation of cAMP cellular targets

mutation responsible for familial pituitary adenomas

incomplete penetrance

on chr 11q

pts often present with acromegaly due to an underlying GH-secreting adenoma

typically affects pts <35 yrs

soft, well-circumscribed lesion that may be confined to the sella turcica; larger growths compress the optic chiasm --> bitemporal hemianopia

relatively uniform, polygonal cells arrayed in sheets or cords

supporting connective tissue is sparse = soft gelatinous consistency

cellular monomorphism and absence of reticulin network

symptoms are related to endocrine abnormalities and mass effects

lesion of the pituitary that invades neighboring tissues

usually macroadenomas

foci of hemorrhage and necrosis are more common

adenoma with brisk mitotic activity and staining greater than 3% of nuclei with Ki-67

extensive nuclear p53 immunoreactivity

invasive, aggressive behavior is more common

acute hemorrhage in an adenoma

may cause sudden onset of excruciating headache, diplopia, and hypopituitarism

may even cause cardiovascular collapse, loss of consciousness, sudden death

most frequent type of hyperfunctioning pituitary adenoma

acidophilic or chromophobic cells

tend to undergo dystrophic calcification: psammoma bodies, extensive calcification ("pituitary stone")

amenorrhea, galactorrhea, loss of libido, infertility

tx with bromocriptine

Somatotroph adenomas

(GH cell adenomas)

densely (monomorphic, acidophilic) or sparsely (pleomorphhic, chromophobic) granulated pituitary adenoma w/ persistently elevated IFG-1/somatomedin C

presents as gigantism (pre-epiphyseal closure) or acromegaly (post-epiphyseal closure)

gonadal dysfunction, DM, hypertension, arthritis, congestive heart failure, increased risk of GI cancers

failure to suppress GH production after oral gluclose load = acromegaly (hyperostosis, prognathism)

adenoma composed of monomorphic, acidophilic cells

retain strong cytoplasmic GH reactivity on immunostain

cytokeratin staining in a perinuclear distribution

pure GH-cell containing adenoma composed of chromophobe cells with considerable nuclear and cytologic pleomorphism

focal, weak staining for GH

Corticotroph Adenomas 

(ACTH cell adenomas)

most often basophilic (densely granulated), occasionally chromophobic (sparsely granulated)

positive stain with PAS due to POMC presence

hypercortisolism (Cushing syndrome)

occurs after surgical removal of the adrenals, often for tx of Cushing syndrome

loss of inhibitory effect of adrenal corticosteroids on a preexisting corticotroph microadenoma

present with mass effects of pituitary tumor; may also be hyperpigmentation

Gonadotroph adenoma

(LH and FSH producing)

*may actually impair LH secretion, FSH is primary secretion

secrete hormones inefficiently and variably

usually identified when increasing size causes neurologic symptoms (impaired vision, headaches, diplopia, pituitary apoplexy)

can also cause decreased energy, libido, amenorrhea due to secondary gonadal hypofunction

Thyrotroph adenomas

(TSH producing)

adenomas that do not secrete hormone

typical presentation is due to mass effects

may cause hypopituitarism

can be caused by tumors, injury, hemorrhage, surgery, radiation, pituitary apoplexy, necrosis, Rathke cleft cyst, empty sella syndrome, genetic defects, hypothalamic lesions, or inflammatory disorders

usually accompanied by diabetes insipidus

occurs when 75% of the parenchyma is lost

hypopituitarism caused by postpartum necrosis of the anterior pituitary

ischemic, necrotic tissue is replaced by fibrous tissue attached to the wall of an empty sella

cysts lined by ciliated cuboidal epithelium with occasional goblet cells and anterior pituitary cells

compromises pituitary function

presence of an enlarged, empty sella tucica

defect in the diaphragm sella that allows arachnoid mater and CSF to herniate into the sella, resulting in expansion of the sella and pituitary compression

usually obese women with a history of multiple pregnancies

visual field defects, hyperprolactinemia, hypopituitarism

presence of an enlarged, empty sella tucica

caused by a mass that enlarges the sella but is either removed by surgery or undergoes spontaneous necrosis

leads to hypopituitarism

ADH deficiency

polyuria, polydipsia

caused by trauma or spontaneous

increased serum sodium and osmolality

result of renal tubular unresponsiveness to ADH

polyuria, polydipsia

caused by trauma or spontaneous

increased serum sodium and osmolality

hyponatremia caused by ADH excess

usually caused by secretion of ectopic ADH by malignant neoplasms (esp. small-cell carcinomas of the lung), drug-induced ADH secretion, and various CNS disorders

hyponatremia, cerebral edema, neurologic dysfunction

hypothalamic suprasellar tumor most often observed in children; thought to be vestigial Rathke's pouch

radiologically demonstrable dystrophic calcifications

nests or cord of stratified squamous epithelium in a spongy reticulum that becomes increasingly prominent in internal layers; palisading pattern

cysts with cholesterol-rich, thick brownish-yellow, machine oil-like fluid

hypothalamic suprasellar tumor most often observed in adults > 65; thought to be vestigial Rathke's pouch

contain both solid sheets and papillae lined by well-differentiated squamous epithelium

usually lack keratin, calcification, and cysts

no palisading epithelium or spongy reticulum

best characterized abnormality in pituitary adenomas

leads to constitutive receptor activity and increased cAMP levels