Pituitary Gland B&B Flashcards
where is the pituitary gland found within the brain?
sits in a small cavity of the sphenoid bone called the sella turcica
what does it mean that the pituitary gland is a circumventricular organ (CVO)?
does not contain blood brain barrier – connects to the medium eminence of the hypothalamus via the pituitary stalk
from what embryonic tissue is the posterior pituitary gland derived?
A.k.a. neurohypophysis – derived from neural ectoderm in the floor of the forebrain
from what is the anterior pituitary gland derived?
aka adenohypophysis - derived from Rathke’s pouch, outgrowth of oral cavity
What are the five cell types of the anterior pituitary gland?
- corticotrophs —> ACTH
- thyrotrophs —> TSH
- gonadotrophs —> LH, FSH
- somatotrophs —> GH (aka somatotrophin)
- lactotrophs —> prolactin
Which two inhibitory hormones are secreted from the hypothalamus and act on the anterior pituitary via the hypothalamic portal system?
- dopamine - inhibits prolactin
- somatostatin - inhibits GH (aka somatotropin) and TSH
all others are stimulatory (CRH, TRH, GnRH, GHRH)
describe the mechanism by which dopamine inhibits prolactin release from the anterior pituitary
hypothalamus releases dopamine, which binds inhibitory D2 receptors on lactotrophs —> decreased prolactin secretion
Levels of which hormone from the anterior pituitary will increase following destruction of the hypothalamus?
prolactin – under inhibitory control from the hypothalamus via dopamine (binds inhibitory D2 receptors on lactotrophs)
Explain why hypothyroidism is in the differential for pituitary enlargement in hyperprolactinemia
TRH (thyrotropin-releasing hormone) induces prolactin release
in hypothyroidism, the body responds by increasing TRH —> predisposes to hyperprolactinemia
Which hormone is responsible for the growth in pituitary size seen during pregnancy?
estrogen stimulates gene transcription and prolactin release within lactotrophs during pregnancy —> pituitary can grow in size
what is the effect of prolactin on gonadotropin releasing hormone (GnRH)?
GnRH (hypothalamus) stimulates FSH and LH secretion from anterior pituitary
prolactin (which rises during pregnancy) inhibits GnRH —> lack of FSH and LH signaling results in cessation of ovulation and menstruation
given that prolactin rises in pregnancy, why does milk production not occur in pregnancy?
Estradiol and progesterone block prolactin’s effect on milk – after childbirth, these hormones fall and milk production occurs
what kind of drugs are cabergoline and bromocriptine?
dopamine agonists - can treat Parkinson’s and prolactinomas (inhibit release via D2 receptors)
what diseases result from pituitary adenomas originating in the following cell types, and which is most common?
a. lactotrophs
b. thyrotrophs
c. corticotrophs
d. somatotrophs
a. lactotrophs —> prolactinoma/ hyperprolactinemia (most common)
b. thyrotrophs —> central hyperthyroidism
c. corticotrophs —> Cushing’s disease (excess cortisol)
d. somatotrophs —> acromegaly / gigantism
what is the classic cause of bitemporal hemianopsia?
pituitary adenomas - cause compression of the superior optic chiasm
loss of temporal (outside) vision on both sides - recall the nerves of the optic chiasm cross over
how would a prolactinoma (hyperprolactinemia) present in females vs males?
females - amenorrhea (inhibited GnRH —> lack of FSH, LH), galactorrhea, fractures (low estrogen —> low bone density)
males - “hypogonadotropic hypogonadism” —> decreased libido, infertility, gynecomastia
which pituitary adenoma can be treated with cabergoline and bromocriptine?
these are dopamine agonists, which can treat prolactinoma
inhibit prolactin release via D2 receptor binding
what would you predict the side effects are of the following drugs: haloperidol, risperidone, metoclopramide
haloperidol and risperidone are antipsychotics, metoclopramide is an antiemetic - all are dopamine antagonists; block D2 (dopamine2) receptors
this causes an increase in prolactin —> amenorrhea, breast engorgement, galactorrhea, sexual dysfunction
also cause Parkinsonian symptoms
what kind of drugs are haloperidol, risperidone, and metoclopramide
haloperidol and risperidone: antipsychotics
metoclopramide: antiemetic
all are dopamine antagonists; block D2 (dopamine2) receptors
what would be the effects of hemorrhage, ischemia, or a compressing mass to the anterior pituitary?
ACTH deficiency —> shock/hypotension (low cortisol)
TSH deficiency —> hypothyroidism
LH/FSH deficiency —> hypogonadism
why wouldn’t hemorrhage of the anterior pituitary present with salt wasting?
aldosterone is controlled by the RAAS system, therefore, its function is not lost
from what is a craniopharyngioma derived?
benign tumor in children 10-14yo, derived from remnants of Rathke’s pouch (embryonic source of pituitary gland)
presents with symptoms of compression of pituitary gland: hypopituitarism, headache, visual field defects, also behavioral change via frontal lobe dysfunction
benign tumor in children 10-14yo, derived from remnants of Rathke’s pouch
craniopharyngioma
presents with symptoms of compression of pituitary gland: hypopituitarism, headache, visual field defects, also behavioral change via frontal lobe dysfunction
Pt is an 11yo F presenting with hypopituitarism, headache, bilateral temporal vision loss, and behavioral changes as noted by her parents. What is most likely going on?
craniopharyngioma: benign tumor in children 10-14yo, derived from remnants of Rathke’s pouch (embryonic source of pituitary gland)
what is empty sella syndrome and who will it most likely present in?
enlarged sella turcica (where pituitary gland sits) partially filled with CSF —> compresses pituitary gland, causing hypopituitarism
more common in women with obesity/ HTN
what occurs in pituitary apoplexy?
sudden hemorrhage into the pituitary gland, usually from pre-existing adenoma
presents with shock/ severe hypotension (loss of cortisol), diplopia (pressure on oculomotor nerves), and sudden onset of severe headache
on rounds, a patient receiving treatment for a pituitary adenoma complains of a sudden, severe headache and loss of vision, and is showing signs of shock - what are you concerned about?
pituitary apoplexy: sudden hemorrhage into the pituitary gland, usually from pre-existing adenoma
presents with shock (loss of cortisol), diplopia (pressure on oculomotor nerves), and sudden onset of severe headache
sheehan syndrome
postpartum hemorrhage (ischemic necrosis) of pituitary gland - recall pituitary enlarges in pregnancy, making it vulnerable to infarction from hypovolemic shock
presents as shock (hypotension) after delivery or failure to lactate (due to hypopituitarism)
Shortly after giving birth, a women goes into shock. She also had been failing to lactate. What are you worried about?
Sheehan syndrome: postpartum hemorrhage of pituitary gland - recall pituitary enlarges in pregnancy, making it vulnerable to infarction from hypovolemic shock
presents as shock (hypotension) after delivery or failure to lactate (due to hypopituitarism)
somatotrophin, aka _____, is important for…
somatotrophin = growth hormone
protein hormone, important for linear (height) growth in childhood
released in pulsatile manner (undetectable levels in between)
name 3 things that stimulate and inhibit release of growth hormone (somatotrophin) from the anterior pituitary
stimulate:
1. GHRH (hypothalamus)
2. sleep
3. exercise
inhibit:
1. glucose
2. somatostatin (hypothalamus)
3. IGF-1 (insulin like growth factor 1)
what occurs immediately after growth hormone binds its receptor?
protein hormone, binds membrane receptor —> activates JAK2 (cytoplasmic tyrosine kinase)
this causes phosphorylation of tyrosine residues within JAK2 itself and GH receptor - forms binding sites for signaling molecules —> altered gene expression
what happens when growth hormone binds receptors in the liver?
causes secretion of IGF-1 (insulin like growth factor 1, aka somatomedin) - mediates effects of growth hormone
levels of IGF-1 can be measured in serum as indicator of GH function
what is the effect of growth hormone on glucose metabolism?
decreases glucose uptake (anti-insulin) / raises blood sugar (“diabetogenic”)
peripheral tissues exposed to GH become insulin resistant, inducing hyperinsulinemia
what is the effect of growth hormone on fatty acid metabolism?
promotes lipolysis via activation of hormone sensitive lipase
indirect effects of growth hormone are mediated by IGF-1 and include… (3)
IGF-1 = insulin like growth factor
- activation of chondrocytes —> increased linear growth
- increase lean muscle mass
- increase organ size
what is the consequence of growth hormone excess in children vs adults?
children —> gigantism (linear growth, very tall child)
adults —> acromegaly (large jaw, coarse facial features, large hands/feet)
how does acromegaly present in adults?
result of excessive growth hormone, insidious onset (~12 years)
—> enlarged jaw, coarse facial features, large hands/feet, organ enlargement, joint pain (cartilage enlargement), CV disease
also presents with insulin resistance/ diabetes (GH is anti-insulin)
Pt is a 36yo M presenting to his GP with joint pain. He notes he recently stopped fitting in his shoes and had to buy a size larger. He is well appearing but you note he has a very prominent jaw. Labs are indicative of diabetes. What is likely going on?
acromegaly: result of excessive growth hormone, insidious onset (~12 years)
—> enlarged jaw, coarse facial features, large hands/feet, organ enlargement, joint pain (cartilage enlargement), CV disease
also presents with insulin resistance/ diabetes (GH is anti-insulin)
what kind of drug is octreotide, and what can it be used to treat (4)?
analog of somatostatin - suppresses release of growth hormone (somatotropin), can be used to treat acromegaly (note bony abnormalities/ joint symptoms do not regress)
can also be used to treat carcinoid syndrome, glucagonoma/insulinoma, and upper GI bleeding (decreases splanchnic blood flow)
Cushing’s syndrome vs Cushing’s disease - which presents with hyperpigmentation?
Cushing’s syndrome: high levels of cortisol coming from adrenal gland, NOT driven by ACTH
Cushing’s disease: high levels of cortisol secretion induced by high levels of ACTH from pituitary gland - also presents with hyperpigmentation (recall POMC is precursor of both ACTH and MSH)
what is proopiomelanocortin a precursor of?
aka POMC: produced by pituitary gland, precursor of both ACTH and alpha/beta/gamma MSH (melanocyte stimulating hormone)
(POMC gets split into multiple products)
this hormone, produced by the paraventricular nuclei of the hypothalamus, causes milk release in response to suckling. what is?
oxytocin - released from posterior pituitary in response to afferent fibers in the nipple, triggers contraction of myoepithelial cells in the breast
what are the therapeutic uses of pitocin during labor?
pitocin = synthetic oxytocin, which causes uterine contractions
can be used to 1. induce labor and 2. stop heavy postpartum uterine bleeding (via contraction of uterus)
what are the most common genetic alterations found in non-spontaneous pituitary adenomas?
G-protein mutations, such as in GNAS gene which encodes Gs-alpha
GNAS mutation leads to constitutive activation of Gs-alpha —> persistent cAMP generation, unchecked cellular proliferation (~40% of somatotroph cell adenomas)
How do pituitary adenomas appear histologically?
Cellular monomorphism - relatively uniform, polygon cells in sheets, cords, or papillae
Connective tissue is sparse
hypopituitarism accompanied by evidence of posterior pituitary dysfunction in the form of diabetes insipidus is almost always of _____ origin
hypothalamic
which type of lung cancer is known to cause ectopic secretion of ADH?
small-cell carcinoma - can induce SIADH (syndrome of inappropriate ADH secretion)
