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ENRP Exam 2 > Pituitary Pathology - Martin- HYPER PITUITARISM > Flashcards

Pituitary Pathology - Martin- HYPER PITUITARISM Flashcards

1
Q

what is an endocrine signal?

A

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

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2
Q

what is the most common form of primary endocrine hyperfunction?

A

neoplasia (except in the thyroid)

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3
Q

endocrine disorders can be classified as a _ production or an _ production of hormones. Or when they develop as _ lesions.

A

overproduction

underproduction

mass lesions

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4
Q

a mass lesion is _ (functional/nonfunctional)

A

non functional

but they can compress other structures and lead to under production of other hormones

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5
Q

true hormones (endocrine secretions are) are released by _ glands

A

ductless

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6
Q

what is autocrine signaling and give an example

A

this is when signals released by a cell stimulate itself

** proliferation of a T lymphocyte is stimulated by cytokines relased from other T lymphocytes

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7
Q

what is paracrine signaling and give an example

A

when chemicals/hormones are relased and stimulate a neighboring cell

** stimulation of post-synaptic nuerons by neurotransmitters from a pre-synaptic neuron

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8
Q

the hypolamaus is responsible for maintaing what?

A

the bodys internal balance aka homeostasis by controlling HR, temperature, sleep cycles, body weight, blood pressure etc.

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9
Q

the hypolamaus is responsible for maintaing what?

A

the bodys internal balance aka homeostasis by controlling HR, temperature, sleep cycles, body weight, blood pressure etc.

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10
Q

regulatory hormones secreted by the hypothalamus are transported by the _ to the anterior and posterior pitutiary

A

hypophyseal-portal-system

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11
Q

what substances does the hypothalamus release?

A

TRH, CRF, VP, GnRH, Dopmaine(PIF), GHRH

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12
Q

the posterior pituitary is simulated _ control

A

neuroendocrine/electical signals

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13
Q

the anterior pituitary is stimulated through the _

A

hypophyseal portal

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14
Q

the posterior pituitary is dervved from the _ and is comproised of _

A

neurohypophysis

pituicytes (glial cells)

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15
Q

the anterior pituitary is derived from _ and has _ cavity origin

A

adenohypohysis

oral cavity origin

80% of the pituitary is anterior

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16
Q

axons from the hypothalamic nuceli extend into the posterior pituitary where _ and _ are stored until released into the systemic blood stream

A

oxytocin and vasopressin

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17
Q

hypothalmic axons that extend into the median eminence release hormones into the _ which then do to stimulate hormone release in the anterior pituitary

A

hypophyseal portal system

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18
Q

what are the portions of the pituitary histologically

A
  1. pars distalis (anterior)
  2. pars intermedia with colloid
  3. Pars Nervosa with pituicytes (posterior)
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19
Q

the anterior pituitary has epithelial cells that are derived from the

A

oral cavity

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20
Q

what cells are acidophils in the anterior pituitary

A

somatotrophs

mammosamatotrophs

lactotrophs

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21
Q

what cells are basophils in the anterior pituitary

A

corticotrophs

thyrotrophs

gonadotrophs

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22
Q

what do somatotrophs produce

A

GH (growth hormone)

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23
Q

what hormone do mammosomatoptrophs release

A

GH and PRL (growth hormone and prolactin)

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24
Q

what hormone do lactotrophs produce

A

PRL (prolactin)

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25
Q

what hormone do corticotrophs produce

A

ACTH, POMC, and MSH (melanocyte-stimulating hormone)

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26
Q

what do thyrotrophs produce

A

TSH (thyroid stimulating hormone)

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27
Q

what do gonadotrophs produce

A

FSH and LH

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28
Q

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

A

neurohypophysis

glial cells

axonal processes

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29
Q

while most hypothalamic factors promote pituitary release other are inhibitory, what are the 2 inhibitory hormones

A

somatostatin and dopamine (PIF)

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30
Q

what cell types within rathke pouch of the anterior pituitarty stem from the transcription factor precursor PIT-1

A

Somatotrophs, mammosomatotrophs, lactotrophs, thyrotrophs

lactotrophs also express the aplpa subuint of the estrogen receptor ERa

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31
Q

what cell in the anterior pituitary also expresses ERa (alpha subuint of the estrogen receptor)

A

lactotrophs

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32
Q

corticotrophs are derved from what transcription factor

A

TPIT

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33
Q

gonadotrphs are derived from what transcription factor precursors

A

steroidogenic factor 1 (SF1) and GATA-2

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34
Q

epression of lineages specific transcription factors are retained in _

A

pituitary adenomas to help classify tumors

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35
Q

TRH (thryotropin releasing hormone) acts on the AP to secrete _

A

Thyroid stimulating hormone

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36
Q

PIF/Dopamine is relased from the hypothamlamus and does what at the anterior pituitary?

A

it inhibits the release of prolactin at the anterior pituitary

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37
Q

corticotrophin releasing hormone is released from the hypothalamus and does what at the AP

A

cause ACTH release at the AP

adrenocrotiocotropic hormone

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38
Q

GHRH from the hypothalamus does what on the AP

A

increases growth hormone release

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39
Q

GH-RIH/Somatostatin (growth hormone release inhibiting hormone) does what on the AP

A

inhibits GH release from the AP

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40
Q

GnRH (gonadotropin releasing hormone) does what on the AP

A

it stimulates the release of FSH and LH

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41
Q

what hormones are released from the posterior pituitary what are their actions

A

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

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42
Q

what are the 3 clinical manifestatins of pituitary disease

A

hyperpituitarism, hypopituitarism, mass effect

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43
Q

what is hyperpituitarism?

A

excess secretion of trophic hormones

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44
Q

what is hyperpituitarism usually causes by?

A

hyperplasia, adenoma, carcinomas of the anterior pituitary

secretion of hormones by non-pituitary tumors, or hypothalamic disorders

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45
Q

what is hypopituitarism

A

def. of trophic hormones

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46
Q

what causes hypopituitarism

A

ischemic injury, surgery/radiation, inflammatory disorders, mass effects (nonfunctinal pituitary adenomas)

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47
Q

what is mass effect of the pituitary

A

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)

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48
Q

what is a cause of mass effect in the pituitary

A

pituitary apoplexy which is rapid enlargement of the pituitary following acute hemorrhage into an adenoma (emergency!!)

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49
Q

clinical manifestations of posterior pituitary disease usually come to clinical attention due to?

A

differences in ADH secretion that alteral fluid and electrolyte balance

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50
Q

symptoms of increased intracranial pressure

A

headaches, N/V, hypertension, bradycardia, shallow breathing, papilledema

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51
Q

bilateral temporal hemianopsia is caused by?

A

compression of the optic chiasm

52
Q

the optic chiasm lies above the _

A

diaphragma sellae

53
Q

the most common sign that a pituitary tumor has extended beyond the confines of the sella turcica is a ?

A

visual defect caused by the gorwth pressing on the optic chiasm

54
Q

what is bitemporal hemianopsia

A

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

55
Q

what is the most common cause of hyperpituitarusm?

A

adenoma (benign tumor) in the anterior lobe

they are classified on the basis of the hormoes and cell types they express

56
Q

less common causes of hyperituitarism include pituitary _ or some _ disorders

A

carcinomas

hypothalamic disorders

57
Q

large pituitary adenomas particularly nonfunctioning ones may cause hypopitutarism by ?

A

destroying adjacent normal tissue in the anterior pituitary by mass effect

common in gonadotrophs (typical for them to have mass effect)

58
Q

what are null cell adenomas

A

a tumor that only presents as a mass effect

59
Q

what are the associated syndromes of a somatotroph adenoma

A

gigantism and acromegaly

60
Q

what are the associated syndromes with lactotroph adenomas?

A

galactorrhea, amenorrhea, sexual dysfunction and infertility

61
Q

what is the associated syndrome with a thyrotroph adenoma

A

hyperthyroidism

62
Q

what is the associated syndrome with a corticotroph adenoma

A

cushing syndrome, nelson syndrome, mass effect

63
Q

what is the associated syndrome of a gonadotroph adenoma

A

mass effect, hypopituitarism

64
Q

a microadenoma is how big?

how big is a macroadenoma?

Giant adenoma?

A

less than 1cm- micro
1-4cm- macro
>4- giant

65
Q

lactoptrophs secrete?

somatotrophs secrete?

A

prolactin

growth hormone

66
Q

peak age of a pituitary adenoma?

the majority of pituitary adenomas are?

A

35-60

majority are silent (incidentalomas)

size matters!!!

67
Q

nonfunctional adenomas tend to be _ (smaller/larger) and come to attention due to _ _ not excess hromone production

A

larger

mass effect

68
Q

what are the factors that aid in the pathogenesis of a pituitary adenoma

A

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.

69
Q

GNAS activating mutation leads to _ adenoma

A

somatotroph

70
Q

USP8 activating mutation leads to _ adenoma

A

corticotroph adenoma

71
Q

PRKAR1A germline inactivating mutations results in a _ comples and what type of adenomas

A

carney complex

somatotroph or lactotroph adenoma

72
Q

MEN1 germinle inactivating mutations are associated with what pituitary adenomas

A

somattrophs, lactotroph, and corticotroph

73
Q

CDKN1B a germline inactivating mutation leads to what adenoma

A

corticotroph

(men-1-like)

74
Q

AIP germline inactivating muation also known as _ _ _ _ syndrome causes what kind of adenomas

A

familial isolated pituitary adenoma syndrome
somatotroph and lactotrophs

usually younger than 35 y/o

75
Q

HRAS is a somatic activating mutation causes what pituitary tumor?

A

pituitary carcinoma

76
Q

germline inactivating mutation in DICER1 leads to what pituitary tumor

A

pituitary blastoma

77
Q

what is a carney complex

A

a hereditary condition that caues spotty skin pigmentation- eyes, conjunctiva, genital area, myxomas (connective tissue tumors) - in the heart and other endocrine gland tumors

78
Q

typical pituitary adeomas are soft well circumscribed and may or may not be confined to the _

A

sella (they can erode through or extend up through the diaphragma sella into the supresellar region and compress the optic chiasm and cranial nerves

79
Q

if a pituitary adenoma is not _ it can infiltrate adjacent tissue and are termed aggressive

A

encapsulated

80
Q

macroadenomas are more likely invasive with foci of?

A

hemorrhage and necrosis

81
Q

what is the histology of a pituitary adenoma?

A

uniform monomorphic polygonal cells in sheets or cords with ABSENT supporting reticulin

soft gelatinous mass

82
Q

IHC is used to idnetify subtypes of pituitary adenomas _ is low in normal pituitary adenomas and high in aggressive ones

A

Ki67

83
Q

What is the most common secretory adenoma?

A

prolactinoma (lactotroph adenoma)

84
Q

what are the presentations of a lactotroph adenoma/prolactinoma

A

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

85
Q

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

A

chromophobe cells
juxtanuclear
PIT-1

eosinophilic
cytoplasmic
PIT01

86
Q

prolactin can be demonstrated within cytoplasmic secretory granules with _ stains and _

A

immunohistochemical stains and estrogen receptor alpha/PIT-1

87
Q

lactotroph adenomas undergo _ _ ranging from isolated _ bodies to extensive _

A

dystrophic calcification

isolated psamomma bodies

extensive calcifications (pituitary stone)

serum prolactin levels correlate with the size of the prolactinoma

88
Q

what can cause hyperprolactenemia without an adenoma

A

pregnancy, lactation/nipple stimulation, loss of dopamine, renal failure, hypothyroidism

89
Q

loss of dopmaine leads to lactotroph _

A

hyperplasia

90
Q

what causes a loss of dopamine

A

damage to the dopaminergic neurone, drugs , mass etc.

91
Q

how does renal failre increase prolactin

A

it increases the production of prolactin and decreases the clearance of it

92
Q

how does hypothyroidism cause hyperprolactinemia

A

high TRH can stumulate prolactin production

93
Q

how can you treat a prolactinoma

A

with surgery: transphenoidal , craniotomy, radiation

or dopamine agonsitsL bromocriptine and cabergoline

94
Q

a somatotroph adenoma causes?

A

gigantism in kids and acromegaly in adults

95
Q

in a somatotroph adenoma there are persistantly elevated levels of _ which stimulate hepatic secretion of _

A

GH

insuling like growth factor (IGF-1)

96
Q

what is the histology of somatotroph adenomas?

A

densely granulated somatotroph adeomas with esoinophilic cells with granular cytoplasm and large central nucleus

can have a sparsely granulate variant with chromophobe as well

97
Q

bihormonal _ adenomas sythesize both GH and prolactin in the same cell

A

mammosomatotrophs

98
Q

sparsely granulated somatotroph adenomas tend to be more _ than densely granulated adenomes and may be less responsive to _

A

aggressive

somatostain analogeus (growth hormone inhibitor)

99
Q

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

A

gigantism

100
Q

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

A

acromegaly

101
Q

features of acromegaly

A

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

102
Q

GH excess can cause

A

gondal dysfunction, diabetes, generalized muscle weakness, HTN, arthritis, CHF and increased risk of GI cancer

103
Q

how do you diagnose acromegaly/somatotroph adenoma

A

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)

104
Q

how do you treat acromegaly/somatotroph adenoma

A

surgical removal

somatostatin analaouge

GH receptor antagonsits

105
Q

corticotroph adenomas are usually _ (microadenoma/macradenomas) and secrete _ which leads to?

A

microadenomas

ACTH

cushing syndrome

106
Q

what is the histology of a corticotroph adenoma

A

basophilic meaning densely granulated or chromophobic meaning sparesely granulateld

107
Q

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!

A

PAS

TPIT

crooke cell adenoma

108
Q

how do you treat cortioctroph adenomas

A

somatostatin analogs or brombocriptine or surgery

109
Q

how do you treat cushing syndrome

A

bromocriptine

110
Q

what is cushing syndrome

A

hypercortisolism

it presents with central obesity, diabetes, hirsutism, adernal hyperplasia

111
Q

what is the most common cause of cushing syndrome

A

iatrogenic, administration of glucocorticoids

112
Q

what is cushing DISEASE

A

hypercortiloism from a pituitary ACTH adenoma (corticotroph adenoma)

113
Q

signs of hypercortisolism

A

thin skin, stria, centripetal obesity, moon facies, hirutism

114
Q

if it is conformed that a patient is making too much cortisol then a _ _ _ _ test is preformed.

A

low dose dexamethasone suppression test

given a 1mg dexamethasone steroid pill at 11pm

if levels of cortisol do not suppress cushing syndrome is confirmed

115
Q

how can you check cortisol levels

A

24 hr urine cortisol level

salivary cortisol

116
Q

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:

A

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

117
Q

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:

A

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

118
Q

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:

A

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

119
Q

how can an ectopic ACTH cause cushing syndrome

A

ectopic ACTH could be coming from a paraneoplastic syndrome: small cell carcinoma of the lung, pancres, or brain tumors

120
Q

what is nelson syndrome

A

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

121
Q

why does hyperpigmentation increase in nelson syndrome

A

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

122
Q

gonadotroph adenomas produce _ and cause what?

A

LH and FSH

**need a larger amount to cause symptoms: low energy, decreased libido, amenorrhea

impaired vision, headache, diplopia on middle aged women

123
Q

thyrotrope adenomas secrete and cause

A

TSH and they can cause hyperthyroidism

124
Q

plurihormonal adenomas express _ and are aggressive

A

PIT-1

125
Q

do null cell adenomas have hormonal markers?

they present with?

they can grow slowly or rapidly and cause _

A

no

mass effects (hypopituitarism)

rapid= pituitary apoplexy

126
Q

pituitary carcinomas are usually functional and secrete _ and _, they have craniospinal or _ metz

A

prolactin and ACTH

systemic

127
Q

pituitary blastomas occur in _ year olds and has a _ mutation, They have symptoms of _ disease and look like what on histology

A

2 y/o

DICER1

cushings disease

small round blue cells on histology

ENRP Exam 2 (13 decks)

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