Endo-pituitary pathology Flashcards
A lactotroph is more commonly ____ granulated vs ___ granulated on histology
MC sparsely granulated vs densely granulated on histology
Northern Ireland has an large number of ____ gene carriers and therefore ___ patients
AIP gene carriers causing acromegaly patients (via somatotroph)
“Irish Giants”
is size important in terms of a corticotroph
size can be misleading, a very small corticotrophin adenoma can be very hyper functional and present with all sx of Cushings syndrome
USP8 somatic mutation seen in corticotrophs result in an upregulation of _____
EGFR
sign and sx of apoplexy into pituitary
sudden onset of excruciating HA, diplopia due to pressure on oculomotor nerves, and hypopituitarism
(can be a result of mass effect)
most common cause of cushing syndrome (not disease)
iatrogenic (healthcare associated)
-due to long term glucocorticoid administration (steroids)
how to dx somatotrophs by pathology
- Diffuse growth (sheet like: common in all adenomas)
- confirmation made with GH immunohistochemistry (immunostain for somatotroph)
- can be sparsely or densely granulated
- can be mixed with PRL-Secreting cells (mammosomatotroph)
define central diabetes insipidus ? sx? labs? how to dx? tx?
- insufficient ADH secretion due to posterior pituitary or hypothalamus pathology (tumor, trauma, infection, inflammation)
- results in decreased reclaimed free water from the renal collecting system
- sx: polyuria, polydipsia, life threatening dehydration
- Labs: hypernatremia, high serum osmolality, low urine osm and specific gravity
- dx: water deprivation test fails to increase urine osm. or desmopression tx shows increased urine sodium/osm
tx: desmopressin
tx of somatotrophs
somatostatin analogs
GH receptor antagonists
surgery
**SOMATOSTAIN inhibits GH
tx for corticotroph
somatostatin analog, bromocriptine (dopamine agonist), or surgery
**corticotrophs can express dopamine and somatostatin receptors
define Nelson Syndrome
- enlargement of of pituitary tumor (corticotroph adenoma) after surgical removal of both hyperplastic adrenal glands (used to tx hypercortisol secretion/Cushing syndrome from high ACTH)
- main sx: hyperpigmentation (ACTH affect on melanocyte stimulation)
how do gonadotrophs usually present
usually non-functioning or “silent”/”null cell” adenoma
-usually present with mass effect due to minimal function
presentation of lactotroph adenoma in women vs men
WOMEN
- present earlier due to menstrual irregularities, galactorrhea, decreased libido, infertility, and possible mass effect if large
- *responsible for >20% of cases of amenorrhea
MEN
-more present later with mass effect symptoms. early sx are decreased libido and decrease sperm count
what somatic genetic mutation are linked to pituitary adenomas? what familial mutations?
somatic:
1. GNAS - somatotrophs
2. USP8- corticotrophs
familial:
1. AIP - somatotrophs
(AIP gene causes FIPA- Familial isolated pituitary adenomas; via PAP- pituitary adenoma predisposition)
size of microadenoma vs macroadenoma vs giant adenoma of the Pituitary gland, and what are the implications?
micro- <1cm
macro- 1-4cm
giant- >4cm
*size is VERY important to determine how one presents clinically and extent of disease (i.e with mass effect, etc)
identify the nomenclature of the pituitary gland (anterior, posterior lobe, etc)
anterior lobe = adenohypophysis (vascular connections to hypothalamus)
posterior lobe = neurohypophysis (neuronal connection to the hypothalamus)
what is the most common secretory pituitary adenoma ?
Lactotroph adenoma (hyper secretion of prolactin)
what genetic mutation of the GPCR pathway is associated with pituitary adenoma ? what mechanism leads to the growth of the adenoma? what adenomas is it most common in?
GNAS mutation
- makes the alpha subunit of Gs lose its GTPase activity !
- GTPase activity is needed to convert GTP –> GDP which is an important regulatory step in turning off the Gs Cascade
- without GTPase activity the unregulated GTP will initiate uncontrollable cAMP driven cell proliferation
- very common in somatotrophs (40%) and more rare in corticotrophs
T/F
Thyrotrophs are rare and cause an increase in TSH levels
true
define SIADH ? sx? labs? tx?
- excess ADH secretion and increased reclaimed free water from the renal collecting system due to MOST COMMONLY Small cell carcinoma of the lung (also brain injury, subarachnoid hemorrhage, Drugs (SSRIs), or other malignancy)
- sx: increased thirst (due to ADH effects on brain). mental status changes, seizures (cerebral edema from hyponatremia), muscle weakness
- labs: hyponatremia, low serum osm, hypernaturia, high urine osm,
tx: free water restriction or demeclocycline
how do adenomas of the pituitary gland come to attention usually ?
either hyper function (hormonal excess) or nonfunctioning Mass effect
-Mass Effect: increased intracranial pressure (HA, N/V, Hypertension, papilledema, shallow breathing, bradycardia, confusion) and compression of optic chiasm (where nasal retinal fibers cross) is impeded causing loss of lateral temporal visual field (BILATERAL TEMPORAL HEMIANOPSIA) **can be seen in neoplasm and bleeds
response of corticotroph vs ACTH secreting tumor to a low and high dose dexamethasone test
corticotroph: no response to low dose (elevated ACTH) but response to high dose (suppressed ACTH levels)
ectopic: no response to low dose or high dose (continually elevated ACTH)
cushing syndrome vs cushing’s disease
Disease: refers to the specific etiology from the corticotroph pituitary adenoma (hyper secretion of ACTH and subsequent hypercortisolism)
syndrome: refers to the manifestations of hypercortisolism (does not have to a direct result of corticotroph adenoma, can be a primary adrenal dz)
- central obesity, DM, hirsutism (soft hair), adrenal hyperplasia, moon facies, very thick and dark striae, hypertension, think skin, menstrual changes
define primary empty sella syndrome (congenital defects of the sella)
(mechanical disturbance)
-CSF leaks into the sella turcica and compresses the pituitary
(the diaphragma sellae usually protects it, but with defects it allows CSF entry to squash the pituitary )
-results in hypopituitarism !!
define secondary empty sell syndrome (congenital defects of the sella)
the pituitary expands and infarcts within the sella turcica, leaving an empty space
(more likely to affect the anterior lobe)
-results in hypopituitarism!
as a lactotroph progresses, what histology features will likely be seen ? what may be seen on imaging?
stomal hyalinization (pink cloud deposits) and possible psammoma bodies (concentric calcifications due to increasing age)
-the dense calcifications can lead to pituitary stones seen on imaging !
describe the 4 main effects seen in Mass Effect of pituitary lesions (**can be seen in neoplasm and bleeds/apoplexy )
- increased intracranial pressure (HA, N/V, Hypertension, papilledema, shallow breathing, bradycardia, confusion)
- BILATERAL TEMPORAL HEMIANOPSIA: compression of optic chiasm (where nasal retinal fibers cross) is impeded causing loss of lateral temporal visual field
- Pituitary Apoplexy (hemorrhage into adenoma) can be deadly
- Hypopituitarism/ Hyperprolactinemia; underproduction of all Pituitary hormones expect overproduction of prolactin (only in nonfunctioning large mass showing mass effect!)
why is it important to check other hormone levels in the dx of somatotroph
bc it is common to be mixed with PRL-secreting cells (mammosomatotroph) therefore do not want to miss that
embryologic origin of the pituitary gland
- neuroectoderm - infundibular proves of brain tissue projects downward
- oral ectoderm- Rathke’s pouch from the stomodeum extends upward
define the two types of craniopharyngioma along with its origin and histologic features
(a neoplasm derived from anterior lobe/rathke’s pouch remnants, made of squamous cells with “wet” keratin pearls and is multiloculated and cystic)
- Kids (5-15yo)
- “adamantinomatous craniopharyngioma” that is calcified and hard (shows calcified cysts on histo)
- shows growth retardation and hypopituitarism - adults (>65yo)
- “papillary craniopharyngioma” that is softer with no calcifications
- shows signs of increased intracranial pressure or hypopituitarism
how to work up dx of Cushing syndrome (hypercortisolism)
- check ACTH levels (can also use CRH stimulation test to measure ACTH levels)
- If Low then is ACTH independent and use Cat scan/MRI of adrenals to dx
- if High then is ACTH dependent and need to distinguish between pituitary adenoma or ectopic ACTH producing tumor (via brain MRI or High dose dexamethasone test)
range of pituitary neoplasia
- adenomas
(well circumscribed, can erode bone, can bleed) - aggressive adenomas
(poor circumscribed, can invade brain, more likely as adenoma gets bigger) - pituitary carcinoma
(RARE, can metastasis or spread throughout brain) - others: Rahtke Cyst , craniopharyngioma
what is the tx for lactotrophs
dopamine agonists (bromocriptine, cabergoline)
Surgery (can go nasally through the sphenoid bone or resection via craniotomy)
radiation therapy
*Dopamine inhibits PRL (prolactin)
define Sheehan syndrome ? mechanism of defect? presentation?
pregnancy related postpartum infarction/necrosis of the anterior pituitary leading to hypopituitarism
- during gestation: gland doubles in size, but the blood supply does not increase leading to a vulnerable pituitary gland
- bloos loss during labor precipitate infarction
- sx can be acute or chronic, common first sign is failure to lactate (others: loss of pubic hair and fatigue)
define Rathke’s Cleft Cyst ? identify its histologic cells, and complications
-deirved from epithelium of anterior pituitary
*not a neoplasm, but a malformation
-a cystic mass that develops as a result of incomplete closure of the rathke’s pouch (oral ectoderm) outpouching during embryological development
(shows ciliated columnar cells)
-can expand and compress NL pituitary
-can rupture and result in inflammation of the pituitary or meningitis
mechanism of hypopituitarism
- squash cells (mass effect)
- killed off (ischemia, inflammation, surgery)
- bled into (apoplexy)
difference between gigantism and acromegaly
both are due to somatrotroph adenomas of the pituitary gland. (hyper secretion of GH)
gigantism - occurs in childhood before epiphyseal (growth) plates close; presents as very tall
acromegaly - occurs in adulthood after plate closure
*acromegaly will also present with enlarged thick fingers/hands, enlargement of face, protruding jaw, enlarged nose, thickened lips, joint pain, limited mobility, enlarged viscera (cardiomegaly), shortened lifespan usually due to cardiovascular complications
how to dx a somatotroph
- serum levels of IGF-1 secreted by the liver (GH itself is not stable)
- if it is elevated, f/u with OGTT (bc glucose is a natural inhibitor of GH; a NL OGTT would show decreased IGF-1, a OGTT of somatotroph will present with continually increased IGF-1 after glucose dose)
histology of the posterior vs anterior lobe
- posterior (neurohypophysis)
- brain tissue like, wispy neuroglial cells (supportive pituitcytes) and axonal neurons - anterior (adenohypophysis)
- glandular structure like, has red acidophils (secrete prolactin and GH) and blue basophils (secrete FH, LH, ACTH, TSH), and chromophobes (pale color)
sx of anterior hypopituitarism
- decreased GH (increased body fat, decreased muscle, reduced strength)
- decreased gonadotrophin (men: poor libido, impotence, infertility, reduced facial hair; women: amenorrhea, dyspareunia, infertility, breast atrophy)
- decreased TSH (decreased energy, constiplation, weight gain)
- decreased ACTH (weakness, tiredness, hypoglycemia)
- decreased prolactin (lactation failure)
