Pituitary Pathology - Martin- HYPER PITUITARISM Flashcards
what is an endocrine signal?
this is when a chemical/hormone is released by cells and travels in the blood stream to a distant site to activate a target tissue
what is the most common form of primary endocrine hyperfunction?
neoplasia (except in the thyroid)
endocrine disorders can be classified as a _ production or an _ production of hormones. Or when they develop as _ lesions.
overproduction
underproduction
mass lesions
a mass lesion is _ (functional/nonfunctional)
non functional
but they can compress other structures and lead to under production of other hormones
true hormones (endocrine secretions are) are released by _ glands
ductless
what is autocrine signaling and give an example
this is when signals released by a cell stimulate itself
** proliferation of a T lymphocyte is stimulated by cytokines relased from other T lymphocytes
what is paracrine signaling and give an example
when chemicals/hormones are relased and stimulate a neighboring cell
** stimulation of post-synaptic nuerons by neurotransmitters from a pre-synaptic neuron
the hypolamaus is responsible for maintaing what?
the bodys internal balance aka homeostasis by controlling HR, temperature, sleep cycles, body weight, blood pressure etc.
the hypolamaus is responsible for maintaing what?
the bodys internal balance aka homeostasis by controlling HR, temperature, sleep cycles, body weight, blood pressure etc.
regulatory hormones secreted by the hypothalamus are transported by the _ to the anterior and posterior pitutiary
hypophyseal-portal-system
what substances does the hypothalamus release?
TRH, CRF, VP, GnRH, Dopmaine(PIF), GHRH
the posterior pituitary is simulated _ control
neuroendocrine/electical signals
the anterior pituitary is stimulated through the _
hypophyseal portal
the posterior pituitary is dervved from the _ and is comproised of _
neurohypophysis
pituicytes (glial cells)
the anterior pituitary is derived from _ and has _ cavity origin
adenohypohysis
oral cavity origin
80% of the pituitary is anterior
axons from the hypothalamic nuceli extend into the posterior pituitary where _ and _ are stored until released into the systemic blood stream
oxytocin and vasopressin
hypothalmic axons that extend into the median eminence release hormones into the _ which then do to stimulate hormone release in the anterior pituitary
hypophyseal portal system
what are the portions of the pituitary histologically
- pars distalis (anterior)
- pars intermedia with colloid
- Pars Nervosa with pituicytes (posterior)
the anterior pituitary has epithelial cells that are derived from the
oral cavity
what cells are acidophils in the anterior pituitary
somatotrophs
mammosamatotrophs
lactotrophs
what cells are basophils in the anterior pituitary
corticotrophs
thyrotrophs
gonadotrophs
what do somatotrophs produce
GH (growth hormone)
what hormone do mammosomatoptrophs release
GH and PRL (growth hormone and prolactin)
what hormone do lactotrophs produce
PRL (prolactin)
what hormone do corticotrophs produce
ACTH, POMC, and MSH (melanocyte-stimulating hormone)
what do thyrotrophs produce
TSH (thyroid stimulating hormone)
what do gonadotrophs produce
FSH and LH
the posterior pituitary is a _ with modified _ cells called pituicytes and _ processes that extend from the hypothalamus thru the pituitary stalk to the posterior lobe
neurohypophysis
glial cells
axonal processes
while most hypothalamic factors promote pituitary release other are inhibitory, what are the 2 inhibitory hormones
somatostatin and dopamine (PIF)
what cell types within rathke pouch of the anterior pituitarty stem from the transcription factor precursor PIT-1
Somatotrophs, mammosomatotrophs, lactotrophs, thyrotrophs
lactotrophs also express the aplpa subuint of the estrogen receptor ERa
what cell in the anterior pituitary also expresses ERa (alpha subuint of the estrogen receptor)
lactotrophs
corticotrophs are derved from what transcription factor
TPIT
gonadotrphs are derived from what transcription factor precursors
steroidogenic factor 1 (SF1) and GATA-2
epression of lineages specific transcription factors are retained in _
pituitary adenomas to help classify tumors
TRH (thryotropin releasing hormone) acts on the AP to secrete _
Thyroid stimulating hormone
PIF/Dopamine is relased from the hypothamlamus and does what at the anterior pituitary?
it inhibits the release of prolactin at the anterior pituitary
corticotrophin releasing hormone is released from the hypothalamus and does what at the AP
cause ACTH release at the AP
adrenocrotiocotropic hormone
GHRH from the hypothalamus does what on the AP
increases growth hormone release
GH-RIH/Somatostatin (growth hormone release inhibiting hormone) does what on the AP
inhibits GH release from the AP
GnRH (gonadotropin releasing hormone) does what on the AP
it stimulates the release of FSH and LH
what hormones are released from the posterior pituitary what are their actions
oxytocin: contraction of the uterus, facilitates lactation, increases smooth muscle contraction like in the lacteriferous smooth muscle
Antidiurectic hormone/ AVP - increases blood pressure, conserve water in periods of hypovolemia and dehydration
preformed hormones that released directly into systemic circulation
what are the 3 clinical manifestatins of pituitary disease
hyperpituitarism, hypopituitarism, mass effect
what is hyperpituitarism?
excess secretion of trophic hormones
what is hyperpituitarism usually causes by?
hyperplasia, adenoma, carcinomas of the anterior pituitary
secretion of hormones by non-pituitary tumors, or hypothalamic disorders
what is hypopituitarism
def. of trophic hormones
what causes hypopituitarism
ischemic injury, surgery/radiation, inflammatory disorders, mass effects (nonfunctinal pituitary adenomas)
what is mass effect of the pituitary
when there is something so large that leads to compression of the decussating fibers of the optic chiasm that leads to bitermporal hemaniopsia and increased intracranail pressure (headache, nausea, vomiting)
what is a cause of mass effect in the pituitary
pituitary apoplexy which is rapid enlargement of the pituitary following acute hemorrhage into an adenoma (emergency!!)
clinical manifestations of posterior pituitary disease usually come to clinical attention due to?
differences in ADH secretion that alteral fluid and electrolyte balance
symptoms of increased intracranial pressure
headaches, N/V, hypertension, bradycardia, shallow breathing, papilledema
bilateral temporal hemianopsia is caused by?
compression of the optic chiasm
the optic chiasm lies above the _
diaphragma sellae
the most common sign that a pituitary tumor has extended beyond the confines of the sella turcica is a ?
visual defect caused by the gorwth pressing on the optic chiasm
what is bitemporal hemianopsia
when a tumor presses on the central fibers of the chiasm and spares the uncrossed lateral fibers which shows a blind spot in the upper-temporal quadrants which then gradually expands to occupy the lower temporal quadrant too
what is the most common cause of hyperpituitarusm?
adenoma (benign tumor) in the anterior lobe
they are classified on the basis of the hormoes and cell types they express
less common causes of hyperituitarism include pituitary _ or some _ disorders
carcinomas
hypothalamic disorders
large pituitary adenomas particularly nonfunctioning ones may cause hypopitutarism by ?
destroying adjacent normal tissue in the anterior pituitary by mass effect
common in gonadotrophs (typical for them to have mass effect)
what are null cell adenomas
a tumor that only presents as a mass effect
what are the associated syndromes of a somatotroph adenoma
gigantism and acromegaly
what are the associated syndromes with lactotroph adenomas?
galactorrhea, amenorrhea, sexual dysfunction and infertility
what is the associated syndrome with a thyrotroph adenoma
hyperthyroidism
what is the associated syndrome with a corticotroph adenoma
cushing syndrome, nelson syndrome, mass effect
what is the associated syndrome of a gonadotroph adenoma
mass effect, hypopituitarism
a microadenoma is how big?
how big is a macroadenoma?
Giant adenoma?
less than 1cm- micro
1-4cm- macro
>4- giant
lactoptrophs secrete?
somatotrophs secrete?
prolactin
growth hormone
peak age of a pituitary adenoma?
the majority of pituitary adenomas are?
35-60
majority are silent (incidentalomas)
size matters!!!
nonfunctional adenomas tend to be _ (smaller/larger) and come to attention due to _ _ not excess hromone production
larger
mass effect
what are the factors that aid in the pathogenesis of a pituitary adenoma
activating g proteins (GNAS) that allow for unchecked cell proliferation
Activating mutations like ubiquitin specific protease 8 which increases the activity of EGFR
and germline loss of function mutaitons like MEN1, CDKN1B, PRKAR1A, AIP etc.
GNAS activating mutation leads to _ adenoma
somatotroph
USP8 activating mutation leads to _ adenoma
corticotroph adenoma
PRKAR1A germline inactivating mutations results in a _ comples and what type of adenomas
carney complex
somatotroph or lactotroph adenoma
MEN1 germinle inactivating mutations are associated with what pituitary adenomas
somattrophs, lactotroph, and corticotroph
CDKN1B a germline inactivating mutation leads to what adenoma
corticotroph
(men-1-like)
AIP germline inactivating muation also known as _ _ _ _ syndrome causes what kind of adenomas
familial isolated pituitary adenoma syndrome
somatotroph and lactotrophs
usually younger than 35 y/o
HRAS is a somatic activating mutation causes what pituitary tumor?
pituitary carcinoma
germline inactivating mutation in DICER1 leads to what pituitary tumor
pituitary blastoma
what is a carney complex
a hereditary condition that caues spotty skin pigmentation- eyes, conjunctiva, genital area, myxomas (connective tissue tumors) - in the heart and other endocrine gland tumors
typical pituitary adeomas are soft well circumscribed and may or may not be confined to the _
sella (they can erode through or extend up through the diaphragma sella into the supresellar region and compress the optic chiasm and cranial nerves
if a pituitary adenoma is not _ it can infiltrate adjacent tissue and are termed aggressive
encapsulated
macroadenomas are more likely invasive with foci of?
hemorrhage and necrosis
what is the histology of a pituitary adenoma?
uniform monomorphic polygonal cells in sheets or cords with ABSENT supporting reticulin
soft gelatinous mass
IHC is used to idnetify subtypes of pituitary adenomas _ is low in normal pituitary adenomas and high in aggressive ones
Ki67
What is the most common secretory adenoma?
prolactinoma (lactotroph adenoma)
what are the presentations of a lactotroph adenoma/prolactinoma
prolactinemia (elevated prolactin levels) which can cause
girls: amenorrhea, galactorrhea, diminished libido, infertility, mass effect
men: decreased libido, decreased sperm count, mass effect
disrupts the mentrual cycle
older women have more subutle effects
a large majority of lactroph adenomas are composed of _ cells with _ localization of the transcription factor _ these are known as sparselt granulated lactotroph adenomas
much rarer are the _ densely granulated lactoptroph adenomas characterized by diffuse _ localization of _ transption factor
chromophobe cells
juxtanuclear
PIT-1
eosinophilic
cytoplasmic
PIT01
prolactin can be demonstrated within cytoplasmic secretory granules with _ stains and _
immunohistochemical stains and estrogen receptor alpha/PIT-1
lactotroph adenomas undergo _ _ ranging from isolated _ bodies to extensive _
dystrophic calcification
isolated psamomma bodies
extensive calcifications (pituitary stone)
serum prolactin levels correlate with the size of the prolactinoma
what can cause hyperprolactenemia without an adenoma
pregnancy, lactation/nipple stimulation, loss of dopamine, renal failure, hypothyroidism
loss of dopmaine leads to lactotroph _
hyperplasia
what causes a loss of dopamine
damage to the dopaminergic neurone, drugs , mass etc.
how does renal failre increase prolactin
it increases the production of prolactin and decreases the clearance of it
how does hypothyroidism cause hyperprolactinemia
high TRH can stumulate prolactin production
how can you treat a prolactinoma
with surgery: transphenoidal , craniotomy, radiation
or dopamine agonsitsL bromocriptine and cabergoline
a somatotroph adenoma causes?
gigantism in kids and acromegaly in adults
in a somatotroph adenoma there are persistantly elevated levels of _ which stimulate hepatic secretion of _
GH
insuling like growth factor (IGF-1)
what is the histology of somatotroph adenomas?
densely granulated somatotroph adeomas with esoinophilic cells with granular cytoplasm and large central nucleus
can have a sparsely granulate variant with chromophobe as well
bihormonal _ adenomas sythesize both GH and prolactin in the same cell
mammosomatotrophs
sparsely granulated somatotroph adenomas tend to be more _ than densely granulated adenomes and may be less responsive to _
aggressive
somatostain analogeus (growth hormone inhibitor)
if a somatotroph adenoma appears in children BEFORE the epiphyses have closed elevated levels of GH cause _
where there is a generlalized increase in body sixe with long arms and legs
gigantism
if levels of GH are increased AFTER the closure of the epiphysis _ develops
mostly effecting the skin, soft tissues, viscera, and bones of the hands, face, and feet
acromegaly
features of acromegaly
increased bone density (hyperostosis) in the spine and hips
prognathism (enlargement of the jow)
broadening of the lower face
fingers are thick and sausage like
GH excess can cause
gondal dysfunction, diabetes, generalized muscle weakness, HTN, arthritis, CHF and increased risk of GI cancer
how do you diagnose acromegaly/somatotroph adenoma
look at serum IGF-1 levels (secreted by the liver in predicatable amounts)
if this is high, do an oral glucose tolerance test and look for the GH reponse.
if GH production is not suprressed then this is indicative of acromegly (most sensitive test)
how do you treat acromegaly/somatotroph adenoma
surgical removal
somatostatin analaouge
GH receptor antagonsits
corticotroph adenomas are usually _ (microadenoma/macradenomas) and secrete _ which leads to?
microadenomas
ACTH
cushing syndrome
what is the histology of a corticotroph adenoma
basophilic meaning densely granulated or chromophobic meaning sparesely granulateld
both variants of a corticotroph adenoma stain positively for _ because they have the POMC precursor of ACTH. Nuclear _ is positive in neoplastic cells as well. There is an uncommon variant of corticotroph adenomas called _ cell adenoma that is characterized by ring like deposition of cytokeratin called crooke change. This variant is aggressive!
PAS
TPIT
crooke cell adenoma
how do you treat cortioctroph adenomas
somatostatin analogs or brombocriptine or surgery
how do you treat cushing syndrome
bromocriptine
what is cushing syndrome
hypercortisolism
it presents with central obesity, diabetes, hirsutism, adernal hyperplasia
what is the most common cause of cushing syndrome
iatrogenic, administration of glucocorticoids
what is cushing DISEASE
hypercortiloism from a pituitary ACTH adenoma (corticotroph adenoma)
signs of hypercortisolism
thin skin, stria, centripetal obesity, moon facies, hirutism
if it is conformed that a patient is making too much cortisol then a _ _ _ _ test is preformed.
low dose dexamethasone suppression test
given a 1mg dexamethasone steroid pill at 11pm
if levels of cortisol do not suppress cushing syndrome is confirmed
how can you check cortisol levels
24 hr urine cortisol level
salivary cortisol
in a pituitary adeoma causing cushing disease what are the following levels:
plasma/urinary cortisol levels:
corticotropin levels:
cortisol levels after low dose dexamethasone test:
cortisol levels after a high dose dexamthesone test:
plasma/urinary cortisol levels: elevated
corticotropin levels: elevated
cortisol levels after low dose dexamethasone test: not suppressed
cortisol levels after a high dose dexamthesone test: suppressed
for an ectopic source of corticotropin what are the following levels
plasma/urinary cortisol levels:
corticotropin levels:
cortisol levels after low dose dexamethasone test:
cortisol levels after a high dose dexamthesone test:
plasma/urinary cortisol levels: elevated
corticotropin levels: elevated
cortisol levels after low dose dexamethasone test: not suppressed
cortisol levels after a high dose dexamthesone test: not suppressed
for an adrenal tumor or hyperplasia producing cortisol what are the following levels
plasma/urinary cortisol levels:
corticotropin levels:
cortisol levels after low dose dexamethasone test:
cortisol levels after a high dose dexamthesone test:
plasma/urinary cortisol levels: elevated
corticotropin levels: suppressed
cortisol levels after low dose dexamethasone test: not suppressed
cortisol levels after a high dose dexamthesone test: not suppressed
how can an ectopic ACTH cause cushing syndrome
ectopic ACTH could be coming from a paraneoplastic syndrome: small cell carcinoma of the lung, pancres, or brain tumors
what is nelson syndrome
after removal of the adrenal glands to treat cushing syndrome, large pituitary adenomas form / get bigger
this occurs due to the loss of inhibitory effects from teh adrenal glands on the corticotroph microadenoma
have mass effects and hyperpigmentation
removal of adrenal- no more hypercortisolism
why does hyperpigmentation increase in nelson syndrome
ACTH is not broken down to cortisol because the adrenals are removed but POMC still breaks down into melaotropin ans ACTH which allows melanotropin to have tropic effects on melanocytes
gonadotroph adenomas produce _ and cause what?
LH and FSH
**need a larger amount to cause symptoms: low energy, decreased libido, amenorrhea
impaired vision, headache, diplopia on middle aged women
thyrotrope adenomas secrete and cause
TSH and they can cause hyperthyroidism
plurihormonal adenomas express _ and are aggressive
PIT-1
do null cell adenomas have hormonal markers?
they present with?
they can grow slowly or rapidly and cause _
no
mass effects (hypopituitarism)
rapid= pituitary apoplexy
pituitary carcinomas are usually functional and secrete _ and _, they have craniospinal or _ metz
prolactin and ACTH
systemic
pituitary blastomas occur in _ year olds and has a _ mutation, They have symptoms of _ disease and look like what on histology
2 y/o
DICER1
cushings disease
small round blue cells on histology
