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Endocrine 2 > Pituitary Gland Path > Flashcards

Pituitary Gland Path Flashcards

1
Q

What inhibits ADH release

A

states of hypervolemia and increased atrial distention

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2
Q

describe the histological array of cells in the anterior pituitary

A
  • eosinophilic cytoplasm (acidophil)
  • basophilic cytoplasm (basophil)
  • poorly staining cytoplasm (chromophobe)
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3
Q

Most common cause of hyperpituitarism

A

adenoma of anterior pituitary

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4
Q

4 causative genes that have been identified in adenomas

A
  • MEN1
  • CDKN1B
  • PRKAR1A
  • AIP
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5
Q

what is the most common form of clinically significant ischemic necrosis of the anterior pituitary

A

-Sheehan syndrome, also known as postpartum necrosis

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6
Q

What are the clinical symptoms of Nelson syndrome

A
  • Hypercortisolism does NOT develop
  • patients present with mass effects due to the pituitary tumors
  • can be hyperpigmentation because of the stimulatory effect of other products of the ACTH precursor molecule on melanocytes
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7
Q

are most pituitary carcinomas functional or not?

A

functional

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8
Q

What is one of the most common alterations in pituitary adenomas

A

G protein

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9
Q

Acidophil lactotroph adenomas are rare. these are called what? and characterized by what?

A
  • densely granulated lactotroph adenoma

- diffuse cytoplasmic PIT-1 expression localization

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10
Q

What do patients with craniopharyngioma generally come to attention with

A
  • headaches and visual disturbances

- children sometimes growth retardation

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11
Q

difference in the 2 types of craniopharyngiomas radiographically

A
  • Adamantinomatous: frequently contains calcifications

- papillary: rarely calcifies

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12
Q

histology of papillary craniopharyngiomas

A
  • both solid sheets and papillae lined by well-differentiated squamous epithelium
  • lack keratin, calcifications, and cysts
  • the squamous cells of the solid sections lack the peripheral palisading
  • do NOT typically generate a spongy reticulum in internal layers
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13
Q

size of corticotroph adenomas

A

usually microadenomas

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14
Q

Somatotroph adenoma causes what in children?

adults?

A
  • gigantism

- acromegaly

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15
Q

Average size of craniopharyngioma

A

3-4 cm

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16
Q

What is the most common hormone deficiency found in gonadotroph adenomas?
what does this deficiency cause?

A
  • LH
  • decreased energy and libido in men
  • amenorrhea in PREmenopausal women
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17
Q

What factors are required for gonadotroph differentiation?

A

SF-1 and GATA-2

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18
Q

What are the 2 distinct histological variants of craniopharyngioma

A
  • Adamantinomatous (children)

- Papillary (adults)

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19
Q

approximately 40% of somatotroph cell adenoma bear what mutations

A

GNAS that abrogate the GTPase activity of Gsa, leading to constitutive activation of Gsa, persistent generation of cAMP, and unchecked cellular proliferation

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20
Q

How do larger craniopharyngiomas impact prognosis

A

-they are more invasive but this does NOT impact prognosis

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21
Q

Excess production of ACTH by functioning corticotroph adenomas leads to what?

A

adrenal hypersecretion of cortisol and the development of hypercortisolism . . . Cushing SYNDROME

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22
Q

age distribution of craniopharyngioma

A
  • bimodal
  • childhood (5-15)
  • adults 65 or older
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23
Q

General causes of hypopituitarism

A
  • destructive processes like:
  • ischemia
  • surgery
  • radiation
  • inflammation
  • non-functional pituitary adenoma
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24
Q

Some pituitary adenoma can secrete 2 hormones, what the most common combo?

A

GH and prolactin

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25
Q

second most common type of functioning pituitary adenoma?

A

Growth hormone secreting somatotroph adenoma

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26
Q

What is the posterior pituitary less susceptible to ischemic injury than anterior

A

receives its blood directly from arterial branches

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27
Q

Treatment of somatotroph adenoma

A
  • surgically removed
  • somatostatin analogs (inhibits pituitary GH secretion)
  • GH receptor antagonists, prevents homone binding to target organs (Liver)
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28
Q

Describe the malignant tranformation of a craniopharyngioma into squamous carcinoma

A
  • Very rare

- usually occurs after irradiation

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29
Q

Clinical manifestations of SIADH

A
  • hyponatremia
  • cerebral edema
  • neurologic dysfunction
  • although total body water is increased, blood volume remains normal, and peripheral edema does not develop
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30
Q

When can pathologic hyperprolactinemia occur

A

-lactotroph hyperplasia: losss of dopamine mediated inhibition of prolactin secretion

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31
Q

What are the inflammatory or infectious etiologies mentioned that can involve the hypothalamus and cause deficiencies of anterior pituitary and diabetes insipidus

A

sarcoidosis or tuberculous meningitis

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32
Q

epidemiolgy of gonadotroph adenoma

A

-most frequently found in middle-ages men and women when they become large enough to cause neurologic symptoms

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33
Q

Describe a Rathke cleft cyst (a cause of hypopituitarism)

A
  • lined by ciliated cuboidal epithelium with occasional goblet cells and anterior pituitary cells
  • can accumulate proteinaceous fluid and expand compromising the normal gland
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34
Q

What are the 6 terminally differentiated cell types in the anterior pituitary and what do they produce?

A
  • Somatotrophs (growth hormone)
  • Mammosomatotrophs (GH and prolactin)
  • Lactotrophs (prolactin)
  • corticotrophs (ACTH, POMC, MSH)
  • Thyrotrophs (TSH)
  • Gonadotrophs (FSH and LH)
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35
Q

describe why men and older women tend to have macroadenoma (lactotroph ones)

A

hormonal manifestation may be more subtle so it isn’t detected as early

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36
Q

Typical pituitary adenomas are grossly what

A

soft and well-circumscribed

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37
Q

Describe the Atypical adenoma

A
  • elevated mitotic activity and nuclear p53 expression (TP53 mutation)
  • aggressive
  • invasion and recurrence
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38
Q

What signal oxytocin to be released?

A

dilation of the cervix and nipple stimulation in postnatal period

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39
Q

What % of the pituitary is the anterior

A

80%

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40
Q

in the most dramatic presentation of pituitary apoplexy it causes what?

A
  • sudden onset of excruciating headache
  • diplopia due to pressure on oculomotor nerves
  • hypopituitarism
  • cardiovascular collapse
  • loss of consciousness
  • sudden death
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41
Q

what size lactotroph adenoma does it take to cause hyperprolactinemia

A
  • even small functional tumors secrete enough to cause hyperprolactinemia
  • amount secreted proportional to tumor size
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42
Q

what are the less common causes of hyperpituitarism

A
  • pituitary carcinomas

- hypothalamic disorders

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43
Q

Lactotroph adenomas have a propensity to undergo what?

A

-dystrophic calcification, rangin from isolated psammoma bodes to extensive calcification of virtually the entire tumor mass (“pituitary stone”)

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44
Q

Primary empty sella syndrome classically occurs in who?

-what do they present with?

A
  • obese women with a history of multiple pregnancies
  • visual field defects and occasionally with endocrine anomalies such as hyperprolactinemia, due to interruption of inhibitory hypothalamic inputs
  • Sometimes the loss of functioning parenchyma is sufficient to produce hypopituitarism
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45
Q

What from the hypothalamus inhibits GH release

A

GIH (somatostatin)

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46
Q

Describe what happens in acromegaly

A
  • growth most conspicuous in skin and soft tissues, viscera (thyroid, heart, liver, and adrenals) and bones of face, hand and feet
  • bond density may increase (hyperostosis) in both spine and hips
  • enlargement of the jaw results in its protrusion (prognathism)
  • broadening of the lower face
  • the feet and hands are enlarged
  • fingers become thickened and sausage like
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47
Q

What signals ADH release?

A
  • Decreased blood pressure, sensed by BAROreceptors in cardiac antra and carotids
  • increased plasma osmotic pressure detected by OSMOreceptors
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48
Q

Histology of adamantinomatous craniopharyngioma

A
  • nests or cords of stratified squamous epithelium embedded in a spongy “reticulum” that becomes more prominent in internal layers
  • “palisading” of the squamous epithelium is frequently observed in periphery
  • compact, lamellar deratin formations (“wet keratin”) is a DIAGNOSTIC FEATURE
  • DYSTROPHIC calcification is frequent finding
  • extend fingerlets of epithelium into brians –> brisk glial reaction
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49
Q

When hypercortisolism is due to excessive production of ACTH by the pituitary, it is called what

A

Cushing DISEASE

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50
Q

what 2 hormones are released from the posterior pituitary

A
  • oxytocin

- ADH (vasopressin)

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51
Q

immunoreactivity in corticotroph adenomas

A
  • POMC - ACTH precursor
  • ACTH
  • B-endorphin
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52
Q

What do children develop due to deficiency of GH

A

pituitary dwarfism

53
Q

What is the most commonly implicated suprasellar tumor

A

gliomas and craniopharyngiomas

54
Q

mutation of PIT-1 results in combined pituitary hormone deficiency, characterized by deficiencies of what hormones?

A
  • GH
  • prolactin
  • TSH
55
Q

explain nephrogenic diabetes insipidus

A

-renal tubular unresponsiveness to circulating ADH

56
Q

What are physiologic causes of hyperprolactinemia

A
  • pregnancy
  • nipple stimulation during suckling in lactating women
  • response to many types of stress
57
Q

histology of somatotroph adenoma

A
  • Densely granulated (monomorphic acidophilic cells) or Sparsely granulated (chromophobe cells)
  • Densely: strong cytoplasmic GH
  • Sparsely: nuclear and cytologic pleomorphism and focal, weak staining for GH
58
Q

SIADH causes what?

A
  • excessive ADH

- resorption of excessive amounts of free water, resulting in hyponatremia

59
Q

What is a clinically silent microadenoma called

A

pituitary incidentaloma

60
Q

Cytoplasmic staining of corticotroph adenomas

A
  • most often basophilic (densely granulated)
  • occasionally chromophobic (sparsely granulated)
  • both PAS+
61
Q

Explain the symptom of pallor with hypopituitarism

A

-loss of stimulation of MSH (synthesized from same precursor molecule as ACTH) on melanocytes

62
Q

describe the confinement and invasion of pituitary adenomas based on size

A
  • Small: confined to sells turcica
  • with expansion: frequently erode the sella turcica and anterior clinoid processes
  • Larger ones extend superiorly through the diaphragm sella into the suprasellar region and often compress the optic chiasm and adjacent structures (like cranial nerves)
63
Q

What may a craniopharyngioma encroach on

A
  • optic chiasm or cranial nerves

- may bulge into floor of third ventricle and base of brain

64
Q

Explain what Sheehan syndrome is

A
  • during pregnancy the anterior pituitary enlarges to almost twice normal
  • the blood supply does not increase (low pressure venous system)–>relative hypoxia
  • any further reduction in blood supply caused by obstetric hemorrhage or shock may precipitate infarction of anterior lobe
65
Q

Most cases of hypopituitarism arise from destructive processes directly involving what?

A

anterior pituitary

66
Q

What are the most commonly secreted products of pituitary carcinomas

A

-prolactin and ACTH

67
Q

GH stimulates hepatic secretion of what?

A

IGF-1

68
Q

What do cysts of adamantinomatous craniopharyngiomas often contain?

A
  • cholesterol rick, thick brown ish yellow fluid

- compared to “machine oil”

69
Q

Diabetes insipidus can occur in a variety of conditions, including what?

A
  • head trauma
  • tumors
  • inflammatory disorders of hypothalamus and pituitary
  • surgical complications
70
Q

What is the most frequent type of hyperfunctioning pituitary adenoma

A

lactotroph adenoma (30%)

71
Q

activation mutations of what oncogene are observed in pituitary carcinomas

A

-HRAS

72
Q

Other non skeletal and non appearance disturbances that can also be associated with excess GH

A
  • gonadal dysfunction
  • diabetes mellitus
  • generalized muscle weakness
  • HTN
  • arthtitis
  • congestive heart failure
  • increased risk of GI cancers
73
Q

What genetic abnormalities have been implicated in craniopharyngiomas?

A
  • WNT signaling pathways

- including activating mutations of gene encoding B-catenin

74
Q

2 distinct compenents of the pituitary gland

A
  • Anterior (Adenohypophysis)

- Posterior (Neurohypophysis)

75
Q

Clinically relevant posterior pituitary syndromes

A
  • diabetes insipidus

- SIADH

76
Q

What does oxytocin do

A
  • stimulates uterine contractions

- stimulates smooth muscle around lactiferous ducts

77
Q

the a-subunit of Gs is encoded by what gene on what chromosome

A
  • GNAS

- 20q13

78
Q

What is a benign tumor that causes a hypothalamic lesion . .leading to hypopituitarism

A

craniopharyngioma

79
Q

Why can gonadotroph adenomas be difficult to recognize

A

They secrete hormones inefficiently and variably, and the secretory products usually do not cause a recognizable clinical syndrome

80
Q

The overwhelming majority of lactotroph adenomas are comprised of what?

A
  • chromophobic cells with juxtanuclear localization of the transcription factor PIT-1
  • known as sparsely granulated lactotroph adenoma
81
Q

what does LH induce?

A

ovulation and formation of corpora lutea in ovary

82
Q

Describe the gross features of craniopharyngioma

A
  • may be encapsulated and solid

- more commonly cystic and sometimes multiloculated

83
Q

Prognosis of craniopharyngioma

A
  • excellent recurrence free and overall survival

- especially those less than 5 cm

84
Q

What does FSH stimlulate?

A

formation of graafian follicles in the ovary

85
Q

Gonadotropin deficiency leads to what?

A
  • amenorrhea and infertility in women

- decreased libido, impotence, and loss of pubic and axillary hair in men

86
Q

What % of the anterior pituitary parenchyma needs to be lost or absent in order to get hypofunction

A

75%

87
Q

What is essential in a pituitary carcinoma

A

presence of craniospinal or systemic metastases

88
Q

Nonfunctional adenomas are more likely to be what size designation

A

macroadenoma because they are likely to come to clinical attention at a later stage

89
Q

what causes diabetes insipidus?

characterized by what?

A

ADH deficiency

  • excessive urination (polyuria)
  • due to inability of the kidney to resorb water properly from urine
90
Q

what can be given to pregnant women to induce labor?

A

synthetic oxytocin

91
Q

what can cause loss of dopamine mediated inhibition of prolactin secretion

A
  • damage of dopaminergic neurons of the hypothalamus
  • damage to the pituitary stalk (head trauma)
  • exposure to drugs that block dopamine receptors on lactotroph cells
  • any mass in suprasellar compartment (pituitary adenoma) may interfere with inhibitory effect of hypothalamus on prolactin secretion (mild elevation in serum prolactin in a person with a pituitary adenoma does not necessarily indicate a prolactin secreting tumor)
  • renal failure
  • hypothyroidism
92
Q

causes of hypopituitarism

A
  • Tumors and other mass lesions
  • Traumatic brain injury and subarachnoid hemorrhage
  • Pituitary surgery or radiation
  • pituitary apoplexy
  • ischemic necrosis
  • Rathke cleft cyst
  • empty sella syndrome
  • hypothalamic lesions
  • inflammatory disorders and infections
  • Genetic defects
93
Q

What adenomas do NOT have GNAS mutations

A
  • thyrotroph
  • lactotroph
  • gonadotroph

their hypothalamic release hormones do not act via cAMP-dependent pathways

94
Q

Pituitary necrosis may also be encountered in other conditions such as?

A
  • DIC
  • sickle cell anemia
  • elevated intracranial pressure
  • traumatic injury
  • shock of any origin
95
Q

what is a craniopharyngioma thought to arise from?

A

vestigial remnants of Rathke pouch

96
Q

General causes of hyperpituitarism

A
  • pituitary adenoma
  • hyperplasia
  • carcinoma
  • secretion of hormones by nonpituitary tumors
  • hypothalamic disorders
97
Q

Hypothalamic suprasellar tumors may induce what?

A

hypofunction or hyperfunction of the anterior pituitary, diabetes insipidus, or combos of these

98
Q

production of most pituitary hormones is controlled In large part by positively and negatively acting factors from what?

A

hypothalamus–>portal vascular system–>anterior Pit.

99
Q

What happens when effective control of GH levels is achieved

A

-the characteristic tissue over growth and related symptoms gradually recede and metabolic abnormalities improve

100
Q

The diagnosis of pituitary GH excess relies on what?

A
  • documentation of elevated serum GH and IGF-1 levels
  • failure to suppress GH production in response to an oral load of glucose is one of the most sensitive tests for acromegaly
101
Q

How are lactotroph adenomas treated?

A
  • surgery

- more commonly, Bromocriptine, a dopamine receptor agonist that causes the lesions to diminish in size

102
Q

Size of somatotroph adenoma when it comes to attention

A

usually big because the manifestation of excessive GH may be subtle

103
Q

What kind of cells are in the posterior pituitary?

A

modified glial cells termed pituicytes and axonal processes extending from the hypothalamus through the pituitary stalk to the posterior lobe (axon terminals)

104
Q

What are frequent causes of SIADH

A
  • Secretion of ectopic ADH by malignant neoplasms
  • Drugs
  • CNS disorders
  • infections
  • trauma
105
Q

What molecular abnormalities are associated with aggressive adenomas

A
  • overexpression of cyclin D1
  • mutations of TP53
  • epigenetic silencing of retinoblastoma gene (RB)
106
Q

If he increased levels of GH are present after closure of the epiphyses, what develops?

A

Acromegaly

107
Q

Age for pituitary adenomas

A
  • usually adults

- peak: 35-60

108
Q

Histology of typical pituitary adenoma

A
  • uniform, polygonal cells arrayed in sheets or cords
  • Supporting connective tissue (reticulin) is SPARSE–>soft gelatinous consistency
  • mitotic activity sparse
  • cytoplasm may be acidophilic, basophilic, or chromophobic . . but generally uniform
  • MONOMORPHISM AND ABSENCE OF RETICULIN NETWORK distinguishes it from normal
109
Q

Somatotrophs, mammasomatotrophs, and lactotrophs are derived from stem cells that express what?

A

PIT-1

110
Q

What kind of patients can develop life threatening dehydration due to diabetes insipidus?

A

patients who are obtunded, bedridden, or otherwise limited in their ability to obtain water

111
Q

results from mass effects

A
  • bitemporal hemianopsia
  • elevated intracranial pressure (headache, nausea, vomiting)
  • pituitary apoplexy
112
Q

neurologic symptoms found in gonadotroph adenoma

A
  • impaired vision
  • headaches
  • diplopia
  • pituitary apoplexy
113
Q

among the earliest changes referable to mass effect are radiographic abnormalities of the sells turcica, including what?

A
  • sellar expansion
  • bony erosion
  • disruption of the diaphragma sella
114
Q

When large destructive pituitary adenomas develop in patients after surgical removal of the adrenal glands for treatment of Cushing syndrome

A

Nelson syndrome . . loss of inhibitory effect of adrenal corticosteroids on a preexisting corticotroph microadenoma

115
Q

epidemiology of lactotroph adenoma

A
  • more women than men

- between ages 20 and 40 due to sensitivity of menses to disruption by hyperprolactinemia

116
Q

the increased serum levels of prolactin from a lactotroph adenoma cause what symptoms

A
  • Amenorrhea
  • galactorrhea
  • loss of libido
  • infertility
117
Q

What are the 2 type of empty sella syndrome?

A
  • Primary: a defect in the diaphragma sella allows the arachnoid mater and cerebrospinal fluid to herniate into the sella, expanding the sella and compressing the pituitary
  • Seconday: a mass, such as pituitary adenoma, enlarges the sella and is then either surgically removed or undergoes infarction, leading to loss of pituitary function
118
Q

If a somatotroph adenoma appears in children before the epiphyses have closed, the elevated levels of GH and IGF-1 result in gigantism. This is characterized by what?

A

a generalized increase in body size with disproportionately long arms and legs

119
Q

What hormone is usually the predominant secreted hormone in gonadotroph adenomas

A

FSH

120
Q

clincal manifestations of diabetes insipidus

A
  • excretion of large volumes of dilute urin with a lower than normal specific gravity
  • serum sodium and osmolality are increased
  • thirst and polydipsia
121
Q

What from hypothalamus inhibits prolactin release

A

PIF (dopamine)

122
Q

where are oxytocin and ADH made?

Stored?

A
  • hypothalamus

- Axon terminals

123
Q

Size designation for pituitary adenomas

A
  • < 1cm: microadenoma

- > 1 cm: macroadenoma

124
Q

lactotroph adenoma underlies almost a quarter of cases of what?

A

amenorrhea

125
Q

What malignant neoplasm often causes ectopic secrtion of ADH and causes SIADH

A

small cell carcinoma of the lung

126
Q

Large pituitary adenomas, particularly nonfunctioning ones may cause what?

A

Hypopituitarism by encroaching on and destroying the adjacent anterior pituitary parenchyma

127
Q

Any condition or treatment that destroys part or all of the pituitary gland, such as ablation of the pituitary by surgery or radiation

A

empty sella syndrome

128
Q

Hypopituitarism accompanied by evidence of posterior pituitary dysfunction in the form of diabetes insipidus is almost always of what origin?

A

hypothalamic

Endocrine 2 (10 decks)

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