Lecture 2: Pituitary Pathology Flashcards
Histologically, typical pituitary adenomas are composed of what type of cells and how are they arranged?
Uniform, polygonal cells arrayed in sheets or cords
What 2 morphological features of pituitary adenomas distinguish them from non-neoplastic anterior pituitary parenchyma?
Cellular monomorphism and absence of a reticulin (CT) network
Atypical adenomas have a higher propensity for aggressive behavior and are associated with mutations in which gene?
TP53
Which genetic mutation is seen in many pituitary adenomas, especially somatotroph cell adenomas; leads to what signaling effects?
GNAS mutations —> α subunit of Gs loses GTPase activity—> ↑↑↑ cAMP
Peak age(s) of incidence for pituitary adenomas?
35 to 60 years of age
Sometimes rapid enlargement of a pituitary adenoma can lead to acute hemorrhage into an adenoma, a situation known as what?
Pituitary apoplexy
Some pituitary adenomas can secrete 2 hormones, what is the most common combination?
GH and prolactin = Bihormonal mammosomatotroph adenoma
Large pituitary adenomas, particularly nonfunctioning ones, may cause hypopituitarism how?
By encroaching on and destroying adjacent anterior pituitary parenchyma
What is the most common type of lactotroph adenoma based on morphology and what is the major type of cell/characteristics?
- Sparsely granulated lactotroph adenoma
- Comprised of chromophobic cells w/ juxtanuclear localization of the TF PIT-1
Lactotroph adenomas have a propensity to undergo what type of morphological change?
Dystrophic calcification, ranging from psammoma bodies to a “pituitary stone.”
Serum concentrations of what tend to correlate with the size of a lactotroph adenoma?
Prolactin
What are the most common presenting sx’s of lactotroph adenoma in women?
- Amenorrhea
- Galactorrhea
- Diminished libido
- Infertility
What are the most common presenting sx’s of lactotroph adenoma in men?
- Decreased libido
- Decreased sperm count
- Mass effect** –> Macroadenomas more common
What is another cause of pathologic hyperprolactinemia in the absence of a lactotroph adenoma?
Lactotroph hyperplasia due to loss of dopamine-mediated inhibition of prolactin secretion
Hyperprolactinemia in the absence of an adenoma may also be due to what other disease states?
Renal failure or hypothyroidism
Lactotroph adenomas can be treated with what drugs?
Dopamine agonists - Bromocriptine or Cabergoline
Which 2 serum markers are indicative of a GH-secreting somatotroph adenoma?
↑↑↑↑ GH and IGF-1 levels
What is one of the most sensitive tests for acromegaly?
Failure to suppress GH production in response to an oral glucose load
Explain the mechanism underlying the development of a large destructive pituitary adenoma aka Nelson Syndrome.
Develops folllowing surgical removal of adrenal glands for tx of Cushing Syndrome due to loss of the inhibitory effect of adrenal corticosteroids on a preexisting coritcotroph adenoma
What changes to the skin may be seen with Hypercortisolism?
Thinning of skin and striae
How can the high-dose dexamethasone suppression test help to distinguish corticotroph adenomas from ACTH-secreting tumors?
Corticotroph adenomas will show suppression of ACTH on high-dose dexamethasone suppression test
How will corticotroph adenomas respond to CRH stimulation test vs. ACTH-secreting tumors?
Corticotroph adenomas will have ↑↑↑ response to CRH stimulation test
Pharmacologic tx of corticotroph adenomas?
Somatostatin analogs or bromocriptine since some express dopamine receptors and somatostatin receptors
What is the most common form of clinically significant ischemic necrosis of the anterior pituitary?
Sheehan syndrome aka postpartum necrosis
What are Rathke cleft cysts lined with and how can they lead to hypopituitarism?
- Ciliated cuboidal epithelium w/ occasional goblet cells and anterior pituitary cells
- Can accumulate proteinaceous fluid and expand
What occurs in primary empty sella syndrome?
Defect in diaphragma sella causes arachnoid mater + CSF to herniate into the sella, expanding the sella and compressing the pituitary
What occurs in secondary empty sella syndrome?
Pituitary adenoma enlarges the sella and is then either surgically removed or undergoes infarction –> loss of pituitary function + empty space
Craniopharyngiomas may be seen in which 2 age groups; what is the most common type and dysfunction caused in each?
- Kids (5-15 y/o) = adamantinomatous craniophryngiomas; growth retardation from hypopituitarism
- Adults (>65 y/o) = papillary craniopharyngiomas; signs of ↑ ICP or hypopituitarism
What are 4 histological findings of adamantinomatous craniopharyngiomas?
- Squamous epithelium embedded in spongy “reticulum” w/ “palisading” at the periphery
- “Wet” keratin
- Calcified cyst aka dystrophic calcification
- Cholesterol-rich, thick brownish yellow fluid (“machine oil”)
