Pituitary Gland Path Flashcards
What inhibits ADH release
states of hypervolemia and increased atrial distention
describe the histological array of cells in the anterior pituitary
- eosinophilic cytoplasm (acidophil)
- basophilic cytoplasm (basophil)
- poorly staining cytoplasm (chromophobe)
Most common cause of hyperpituitarism
adenoma of anterior pituitary
4 causative genes that have been identified in adenomas
- MEN1
- CDKN1B
- PRKAR1A
- AIP
what is the most common form of clinically significant ischemic necrosis of the anterior pituitary
-Sheehan syndrome, also known as postpartum necrosis
What are the clinical symptoms of Nelson syndrome
- 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
are most pituitary carcinomas functional or not?
functional
What is one of the most common alterations in pituitary adenomas
G protein
Acidophil lactotroph adenomas are rare. these are called what? and characterized by what?
- densely granulated lactotroph adenoma
- diffuse cytoplasmic PIT-1 expression localization
What do patients with craniopharyngioma generally come to attention with
- headaches and visual disturbances
- children sometimes growth retardation
difference in the 2 types of craniopharyngiomas radiographically
- Adamantinomatous: frequently contains calcifications
- papillary: rarely calcifies
histology of papillary craniopharyngiomas
- 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
size of corticotroph adenomas
usually microadenomas
Somatotroph adenoma causes what in children?
adults?
- gigantism
- acromegaly
Average size of craniopharyngioma
3-4 cm
What is the most common hormone deficiency found in gonadotroph adenomas?
what does this deficiency cause?
- LH
- decreased energy and libido in men
- amenorrhea in PREmenopausal women
What factors are required for gonadotroph differentiation?
SF-1 and GATA-2
What are the 2 distinct histological variants of craniopharyngioma
- Adamantinomatous (children)
- Papillary (adults)
approximately 40% of somatotroph cell adenoma bear what mutations
GNAS that abrogate the GTPase activity of Gsa, leading to constitutive activation of Gsa, persistent generation of cAMP, and unchecked cellular proliferation
How do larger craniopharyngiomas impact prognosis
-they are more invasive but this does NOT impact prognosis
Excess production of ACTH by functioning corticotroph adenomas leads to what?
adrenal hypersecretion of cortisol and the development of hypercortisolism . . . Cushing SYNDROME
age distribution of craniopharyngioma
- bimodal
- childhood (5-15)
- adults 65 or older
General causes of hypopituitarism
- destructive processes like:
- ischemia
- surgery
- radiation
- inflammation
- non-functional pituitary adenoma
Some pituitary adenoma can secrete 2 hormones, what the most common combo?
GH and prolactin
second most common type of functioning pituitary adenoma?
Growth hormone secreting somatotroph adenoma
What is the posterior pituitary less susceptible to ischemic injury than anterior
receives its blood directly from arterial branches
Treatment of somatotroph adenoma
- surgically removed
- somatostatin analogs (inhibits pituitary GH secretion)
- GH receptor antagonists, prevents homone binding to target organs (Liver)
Describe the malignant tranformation of a craniopharyngioma into squamous carcinoma
- Very rare
- usually occurs after irradiation
Clinical manifestations of SIADH
- hyponatremia
- cerebral edema
- neurologic dysfunction
- although total body water is increased, blood volume remains normal, and peripheral edema does not develop
When can pathologic hyperprolactinemia occur
-lactotroph hyperplasia: losss of dopamine mediated inhibition of prolactin secretion
What are the inflammatory or infectious etiologies mentioned that can involve the hypothalamus and cause deficiencies of anterior pituitary and diabetes insipidus
sarcoidosis or tuberculous meningitis
epidemiolgy of gonadotroph adenoma
-most frequently found in middle-ages men and women when they become large enough to cause neurologic symptoms
Describe a Rathke cleft cyst (a cause of hypopituitarism)
- lined by ciliated cuboidal epithelium with occasional goblet cells and anterior pituitary cells
- can accumulate proteinaceous fluid and expand compromising the normal gland
What are the 6 terminally differentiated cell types in the anterior pituitary and what do they produce?
- Somatotrophs (growth hormone)
- Mammosomatotrophs (GH and prolactin)
- Lactotrophs (prolactin)
- corticotrophs (ACTH, POMC, MSH)
- Thyrotrophs (TSH)
- Gonadotrophs (FSH and LH)
describe why men and older women tend to have macroadenoma (lactotroph ones)
hormonal manifestation may be more subtle so it isn’t detected as early
Typical pituitary adenomas are grossly what
soft and well-circumscribed
Describe the Atypical adenoma
- elevated mitotic activity and nuclear p53 expression (TP53 mutation)
- aggressive
- invasion and recurrence
What signal oxytocin to be released?
dilation of the cervix and nipple stimulation in postnatal period
What % of the pituitary is the anterior
80%
in the most dramatic presentation of pituitary apoplexy it causes what?
- sudden onset of excruciating headache
- diplopia due to pressure on oculomotor nerves
- hypopituitarism
- cardiovascular collapse
- loss of consciousness
- sudden death
what size lactotroph adenoma does it take to cause hyperprolactinemia
- even small functional tumors secrete enough to cause hyperprolactinemia
- amount secreted proportional to tumor size
what are the less common causes of hyperpituitarism
- pituitary carcinomas
- hypothalamic disorders
Lactotroph adenomas have a propensity to undergo what?
-dystrophic calcification, rangin from isolated psammoma bodes to extensive calcification of virtually the entire tumor mass (“pituitary stone”)
Primary empty sella syndrome classically occurs in who?
-what do they present with?
- 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
What from the hypothalamus inhibits GH release
GIH (somatostatin)
Describe what happens in acromegaly
- 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
What signals ADH release?
- Decreased blood pressure, sensed by BAROreceptors in cardiac antra and carotids
- increased plasma osmotic pressure detected by OSMOreceptors
Histology of adamantinomatous craniopharyngioma
- 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
When hypercortisolism is due to excessive production of ACTH by the pituitary, it is called what
Cushing DISEASE
what 2 hormones are released from the posterior pituitary
- oxytocin
- ADH (vasopressin)
immunoreactivity in corticotroph adenomas
- POMC - ACTH precursor
- ACTH
- B-endorphin
What do children develop due to deficiency of GH
pituitary dwarfism
What is the most commonly implicated suprasellar tumor
gliomas and craniopharyngiomas
mutation of PIT-1 results in combined pituitary hormone deficiency, characterized by deficiencies of what hormones?
- GH
- prolactin
- TSH
explain nephrogenic diabetes insipidus
-renal tubular unresponsiveness to circulating ADH
What are physiologic causes of hyperprolactinemia
- pregnancy
- nipple stimulation during suckling in lactating women
- response to many types of stress
histology of somatotroph adenoma
- 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
SIADH causes what?
- excessive ADH
- resorption of excessive amounts of free water, resulting in hyponatremia
What is a clinically silent microadenoma called
pituitary incidentaloma
Cytoplasmic staining of corticotroph adenomas
- most often basophilic (densely granulated)
- occasionally chromophobic (sparsely granulated)
- both PAS+
Explain the symptom of pallor with hypopituitarism
-loss of stimulation of MSH (synthesized from same precursor molecule as ACTH) on melanocytes
describe the confinement and invasion of pituitary adenomas based on size
- 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)
What may a craniopharyngioma encroach on
- optic chiasm or cranial nerves
- may bulge into floor of third ventricle and base of brain
Explain what Sheehan syndrome is
- 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
Most cases of hypopituitarism arise from destructive processes directly involving what?
anterior pituitary
What are the most commonly secreted products of pituitary carcinomas
-prolactin and ACTH
GH stimulates hepatic secretion of what?
IGF-1
What do cysts of adamantinomatous craniopharyngiomas often contain?
- cholesterol rick, thick brown ish yellow fluid
- compared to “machine oil”
Diabetes insipidus can occur in a variety of conditions, including what?
- head trauma
- tumors
- inflammatory disorders of hypothalamus and pituitary
- surgical complications
What is the most frequent type of hyperfunctioning pituitary adenoma
lactotroph adenoma (30%)
activation mutations of what oncogene are observed in pituitary carcinomas
-HRAS
Other non skeletal and non appearance disturbances that can also be associated with excess GH
- gonadal dysfunction
- diabetes mellitus
- generalized muscle weakness
- HTN
- arthtitis
- congestive heart failure
- increased risk of GI cancers
What genetic abnormalities have been implicated in craniopharyngiomas?
- WNT signaling pathways
- including activating mutations of gene encoding B-catenin
2 distinct compenents of the pituitary gland
- Anterior (Adenohypophysis)
- Posterior (Neurohypophysis)
Clinically relevant posterior pituitary syndromes
- diabetes insipidus
- SIADH
What does oxytocin do
- stimulates uterine contractions
- stimulates smooth muscle around lactiferous ducts
the a-subunit of Gs is encoded by what gene on what chromosome
- GNAS
- 20q13
What is a benign tumor that causes a hypothalamic lesion . .leading to hypopituitarism
craniopharyngioma
Why can gonadotroph adenomas be difficult to recognize
They secrete hormones inefficiently and variably, and the secretory products usually do not cause a recognizable clinical syndrome
The overwhelming majority of lactotroph adenomas are comprised of what?
- chromophobic cells with juxtanuclear localization of the transcription factor PIT-1
- known as sparsely granulated lactotroph adenoma
what does LH induce?
ovulation and formation of corpora lutea in ovary
Describe the gross features of craniopharyngioma
- may be encapsulated and solid
- more commonly cystic and sometimes multiloculated
Prognosis of craniopharyngioma
- excellent recurrence free and overall survival
- especially those less than 5 cm
What does FSH stimlulate?
formation of graafian follicles in the ovary
Gonadotropin deficiency leads to what?
- amenorrhea and infertility in women
- decreased libido, impotence, and loss of pubic and axillary hair in men
What % of the anterior pituitary parenchyma needs to be lost or absent in order to get hypofunction
75%
What is essential in a pituitary carcinoma
presence of craniospinal or systemic metastases
Nonfunctional adenomas are more likely to be what size designation
macroadenoma because they are likely to come to clinical attention at a later stage
what causes diabetes insipidus?
characterized by what?
ADH deficiency
- excessive urination (polyuria)
- due to inability of the kidney to resorb water properly from urine
what can be given to pregnant women to induce labor?
synthetic oxytocin
what can cause loss of dopamine mediated inhibition of prolactin secretion
- 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
causes of hypopituitarism
- 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
What adenomas do NOT have GNAS mutations
- thyrotroph
- lactotroph
- gonadotroph
their hypothalamic release hormones do not act via cAMP-dependent pathways
Pituitary necrosis may also be encountered in other conditions such as?
- DIC
- sickle cell anemia
- elevated intracranial pressure
- traumatic injury
- shock of any origin
what is a craniopharyngioma thought to arise from?
vestigial remnants of Rathke pouch
General causes of hyperpituitarism
- pituitary adenoma
- hyperplasia
- carcinoma
- secretion of hormones by nonpituitary tumors
- hypothalamic disorders
Hypothalamic suprasellar tumors may induce what?
hypofunction or hyperfunction of the anterior pituitary, diabetes insipidus, or combos of these
production of most pituitary hormones is controlled In large part by positively and negatively acting factors from what?
hypothalamus–>portal vascular system–>anterior Pit.
What happens when effective control of GH levels is achieved
-the characteristic tissue over growth and related symptoms gradually recede and metabolic abnormalities improve
The diagnosis of pituitary GH excess relies on what?
- 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
How are lactotroph adenomas treated?
- surgery
- more commonly, Bromocriptine, a dopamine receptor agonist that causes the lesions to diminish in size
Size of somatotroph adenoma when it comes to attention
usually big because the manifestation of excessive GH may be subtle
What kind of cells are in the posterior pituitary?
modified glial cells termed pituicytes and axonal processes extending from the hypothalamus through the pituitary stalk to the posterior lobe (axon terminals)
What are frequent causes of SIADH
- Secretion of ectopic ADH by malignant neoplasms
- Drugs
- CNS disorders
- infections
- trauma
What molecular abnormalities are associated with aggressive adenomas
- overexpression of cyclin D1
- mutations of TP53
- epigenetic silencing of retinoblastoma gene (RB)
If he increased levels of GH are present after closure of the epiphyses, what develops?
Acromegaly
Age for pituitary adenomas
- usually adults
- peak: 35-60
Histology of typical pituitary adenoma
- 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
Somatotrophs, mammasomatotrophs, and lactotrophs are derived from stem cells that express what?
PIT-1
What kind of patients can develop life threatening dehydration due to diabetes insipidus?
patients who are obtunded, bedridden, or otherwise limited in their ability to obtain water
results from mass effects
- bitemporal hemianopsia
- elevated intracranial pressure (headache, nausea, vomiting)
- pituitary apoplexy
neurologic symptoms found in gonadotroph adenoma
- impaired vision
- headaches
- diplopia
- pituitary apoplexy
among the earliest changes referable to mass effect are radiographic abnormalities of the sells turcica, including what?
- sellar expansion
- bony erosion
- disruption of the diaphragma sella
When large destructive pituitary adenomas develop in patients after surgical removal of the adrenal glands for treatment of Cushing syndrome
Nelson syndrome . . loss of inhibitory effect of adrenal corticosteroids on a preexisting corticotroph microadenoma
epidemiology of lactotroph adenoma
- more women than men
- between ages 20 and 40 due to sensitivity of menses to disruption by hyperprolactinemia
the increased serum levels of prolactin from a lactotroph adenoma cause what symptoms
- Amenorrhea
- galactorrhea
- loss of libido
- infertility
What are the 2 type of empty sella syndrome?
- 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
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 generalized increase in body size with disproportionately long arms and legs
What hormone is usually the predominant secreted hormone in gonadotroph adenomas
FSH
clincal manifestations of diabetes insipidus
- excretion of large volumes of dilute urin with a lower than normal specific gravity
- serum sodium and osmolality are increased
- thirst and polydipsia
What from hypothalamus inhibits prolactin release
PIF (dopamine)
where are oxytocin and ADH made?
Stored?
- hypothalamus
- Axon terminals
Size designation for pituitary adenomas
- < 1cm: microadenoma
- > 1 cm: macroadenoma
lactotroph adenoma underlies almost a quarter of cases of what?
amenorrhea
What malignant neoplasm often causes ectopic secrtion of ADH and causes SIADH
small cell carcinoma of the lung
Large pituitary adenomas, particularly nonfunctioning ones may cause what?
Hypopituitarism by encroaching on and destroying the adjacent anterior pituitary parenchyma
Any condition or treatment that destroys part or all of the pituitary gland, such as ablation of the pituitary by surgery or radiation
empty sella syndrome
Hypopituitarism accompanied by evidence of posterior pituitary dysfunction in the form of diabetes insipidus is almost always of what origin?
hypothalamic
