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What is the most common pituitary adenoma?
Prolactinoma- ammenorrhea, galactorrhea, low libido, infertility due to it's inhibition of GnRH
Which drugs shrink prolactinomas?
Bromocriptine or cabergoline (dopamine agonists)
In what situations is GH stimulated?
sleep, stress, hypoglycemia, starvation, low protein levels
What are the 5 types of cells in the anterior pituitary?
Which cells of the a.pit are acidophilic, basophilic, chromophobic?
Acidophilic = Somatotrophs and Lactotrophs "ASL"
Basophilic: C, T, G
An increase in plasma osmotic pressure would have what effect on ADH?
Increase ADH secretion.
What is pituitary apoplexy?
acute hemmorhage into an adenoma causing rapid enlargement of the lesion
What would a pituitary infarction produce?
How would you characterize a prolactinoma and it's secretions?
Benign adenoma. Capable of secreting Prolactin and GH.
What is the threat that a large nonfunctioning pituitary adenoma poses on the pituitary gland?
may cause hypopituitarism as they encroach and destroy the adjacent tissue....basically they're useless and cause harm!
Which type of adenomas are likely to come attention to later?
Macroadenomas (> 1 cm)...because they are likely to be silent and hormone negative
When G proteins are inactive, what are they bound to?
Why is the activation of Gsalpha transient?
because the alpha subunit has inherent GTPase activity. remember, it needs to be bound to GTP to be active.
GDP = inactive
GTP = active
What is the greatest molecular abnormality leading to pituitary adenomas?
G-protein mutations due to errors in GNAS gene which codes the alpha subunit of G proteins.
Which hormones do NOT use cAMP as a secndary messenger and therefore are not effected by GNAS mutations?
3. Gonadotrophs -not corticotrophs and somatotrophs
What is the gene product of MEN-1?
Tumor supressor protein, " Menin". mutation in these leads to tumors in endocrine organs, including the pituitary.
What is Carney complex?
autosomal-dominant disorder characterized by pituitary and other endocrine disorders
What is responsible for causing the Carney complex?
mutation in the protein kinase A regulatory subunit 1a PPKAR1A
This is a pituitary adenoma predisposing gene, which causes pats to often present with acromegaly
What are the physical characteristics of a typical pituitary adenoma?
soft, well circumscribed.
-polygonal cells in sheets or cords.
-sparse reticulin (what makes it soft)
-sparse mitotic activity
-cellular monomorphism (it's either all acidophilic, basophillic or chromophobic NOT a mix b/w all of these which would be normal)
Cells that have p53 immunoreactivity have brisk mitotic activity, these are called ATYPICAL ADENOMAS because they are more aggresive
Prolactinomas have a propensity to undergo which process?
Which things could lead to prolactinomas other than a tumor type deal?
estrogen, hypothyroidism, renal failure
How does GH effect amino acids?
increases their uptake into muscles
How does GH effect the liver?
Increases IGF-1 (somatomedin) synthesis by the liver
What does IGF-1 stimulate?
bone, cartilage, soft tissue growth
Is there linear bone growth in an adult with increased GH?
no! only lateral, because epiphyseal plates have fused
What is the epiphyseal plate?
a hyaline cartilage plate at the metaphysis at each end of the long bone.
Hyaline cartilage matrix is mostly made up of type II collagen and Chondroitin sulfate
What is a common cause of death from acromegaly?
cardiomyopathy (heart muscle weakness)
but how if a.a are being taken up by muscles?!
Histologically, how do we type GH cell containing adenomas?
1.sparsely granualted v.s 2. densely granulated
Describe the densely granulated cells of a GH adenoma?
-cytokeratin staining in perinuclear distribution
Describe the sparsely granulated cells of a GH adenoma?
-cytological and nuclear pleopmorphism
-weak staining for GH
What are some other diseases associated with acromegaly?
-muscle weakness --> cardiomyopathy --> death
How can you treat acromegaly?
use somatostatin analong: ocreotide
GH receptor antagonist
What type of adenomas are corticotroph adenomas?
microadenomas, stain with PAS b/c of carbs,
What is a side effect of removing the adrenal glands of someone with cushing syndrome?
cushings syndrome: problem is in adrenal gland
cushings disease: pituitary tumor
Nelson Syndrome: large destructive adenomas.
hypercortisolism wont develop tho because there arent any adrenal glands. BUT you can have hyperpigmentation because of the stimulatory effect on other products of the ACTH precursor molecule on melanocytes.
Are plurihormal adenomas usually benign?
no! usually agressive
What efffect to gonadotroph adenomas have oh gonadal function?
paradoxical, cause decreased gonadal fxn.
In a gonadotroph adenoma, what is predominantly secreted?
What is a silent variant or a null cell adenoma?
non-functioning pituitary adenoma
Describe pituitary carcinomas?
rare and functional.
prolactin and ACTH being most common secreted products.
what is the most common cause of hypopituitarism in adutls?
Nonfunctioning (null) pituitary adenoma
What are the components of MEN1?
-pituitary adenoma (hypopit associated)
-pancreatic tumor (Zollinger Ellison syndrome, or insulinoma)
What is the most common cause of hypopituitarism in children?
What is a cranipharyngioma?
BENIGN tumor formed from remnants of Rathkes pouch.
-cystic, hemmorhagic, calcification
-commonly causes bitemporal hemianopia
-can cause diabetes insipidus
Rathkes pouch is ectoderm from the oral cavity that gives rise to the anterior pituitary.
It is located above the sella turcica and extends down into the sella turcica, destroying it's fxn.
What is Sheehans post partum necrosis?
hypovolemic shock after delivery (from loss of blood) causes infarction and sudden cessation of lactation due to loss of prolactin
In hypofunction of the pituitary, how much of the parenchymas must be lost?
Hypopituitarism accompanied by posterior pituitary function almost always originates where?
in the hypothalamus
what type of hemorrhage can cause hypopituitarism?
what are some of the immediate effects of pituitary apoplexy?
headache, diplopia (pressure on occulomotor nerves), hypopituitarism
Which pituitary gland is least susceptible to infarction?
what type of epithelium characterizes a Rathke cleft cyst?
ciliated cuboidal with goblet
What are the two types of "Empty sella turcica"?
1. Primary- there is a defect in the base of the sella turcica allowing arachnoid and CSF to herniate into it and displace the pituitary --> hypopituitarism
2. Secondary- there is an adenoma, and it is either ressected or undergoes spontaneous infarction and shrinks causing and enlarged literally empty sella turcica or one with a small pituitary --> hypopituitarism
Which type of pt.s are classicaly affected by empty sella turcia?
Obese women with multiple pregnancies. and HTN
What increases in secretion often from Empty sella turcica syndrome?
hyperprolactinemia (b/c of loss of inhibition from the hypothalamus)
Which inflammatory diseases can cause deficiences of anterior pituitary and diabetes insipidus?
sarcoidosis, tuberculos meningitis
What will a person often look like if they have hypopituitarism?
pale because of loss of stimulatory effects of MSH on melanocytes
What is SIADH?
Syndrome of innaprorpiate ADH secretion...too much ADH running around can cause hyponatremia
What is the most common cause of SIADH?
ectopic DH malignant neoplasms especially small cell carcinomas of the lung.
Posterior pituitary stores and releases what?
Stores ADH and releases oxytocin
What are the two types of craniopharyngiomas and which are common in what group?
1. adamantinomatous (kids)- calcification, nests/cords of stratified squamous epithelium embedded in reticulum. palisading in the periphery, wet keratin*. the cysts are brownish and full of chosterol which looks like "machine oil"
2. papillary (adults)
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