Hypothalamic-Pituitary Relationships Flashcards
What connects the hypothalamus and the pituitary gland?
hypophysial stalk
What happens with cancers of the pituitary?
expand up hypophyseal stalk into brain and against optic nerves
Where are the cell bodies of the post pit neurons located?
supraoptic nucleus (SON) = ADH mostly
Paraventricular nucleus (PVN) = oxytocin mainly
How is the hypothalamus connected to the anterior pituitary?
both neural and hormonal
connected by hypothalamic-hypophysial portal vessels
What is distinct about the hormones released from the hypothalamus to the ant pit?
delivered directly and in high concentration via hypothalamic-hypophysial portal vessels
hormones do not appear in systemic circulation in high concentration
At what rate are hypothalamic hormones released?
in pulsatile manner and are entrained to circadian rhythms
What are the differences btw primary, secondary, and tertiary endocrine disorders?
primary = defect in peripheral endocrine gland
secondary = defect in pituitary gland
tertiary = defect in hypothalamus
What are the only 2 ant pit hormones secreted by the same cell type?
FSH and LH = secreted by gonadotrophs
What are the stimulating hypothalamic hormones?
TRH –> TSH
CRH –> ACTH
GnRH –> LH, FSH
GHRH –> GH
TRH –> prolactin
What are the inhibitory hapothalamic hormones?
Somatostatin –> inhibits GH secretion
PIF –> inhibits prolactin secretion
What is acromegaly?
prolonged, excessive secretion of GH in adult life
excessive growth of soft tissue, cartilage, and bone in face, hands, and feet
usually pituitary tumor
how does GH affect the liver?
stimulates IGF-1 transcription and secretion by the liver –> positive feedback back to the hypothalamus and negative feedback back to ant pit
How is GHRH regulated?
negative feedback
it inhibits its own secretion from the hypothalamus
What are the 3 causes of acromegaly?
primary GH excess = ant pit tumor
extrapituitary GH excess = tumor secreting GH outside of ant pit
GHRH excess = tumor secreting GHRH (outside hypothalamus?)
How do you diagnose acromegaly?
increased serum IGF-1 (measure first bc GH fluctuates thru day, IGF-1 remains constant)
failure to suppress GH after oral glucose tolerance test
pituitary mass seen on brain MRI
How is a pituitary tumor removed?
surgery via stranssphenoidal approach
if tumor > 1 cm –> radiation therapy considered
What are the medications that can treat acromegaly by lowering GH blood levels or blocking effects of GH?
octreotide or lanreotide = somatostatin analog
pegvisomant = GH receptor agonist
bromocriptine/cabergoline: dopamine receptor agaonist; may decrease GH secretion (<25% effective)
When is GH secreted?
in a pulsatile manner
highest at night
higher during pubertal growth than at any other age
What is GH deficiency due to?
decreased secretion of GHRH (hypothalamic dysfunction)
decreased GH secretion
failure to generate somatomedins
GH or somatomedin resistance
What is the most common cause of GH excess?
what occurs?
mostly due to GH-secreting pit adenoma
before puberty: gigantism
after puberty: acromegaly = increased periosteal bone and extremity growth, organ growth, insulin resistance and glucose intolerance
What is the diabetogenic effect of GH?
increase in blood glucose –> insulin resistance –> decreased glucose uptake and utilization
increased lipolysis in adipose tissue
results in increased blood insulin levels
How does GH affect protein synthesis?
increases protein syn and organ growth
incr uptake of AAs stim synthesis of DNA, RNA, and protein
mediated by somatomedins (IGF-1)
What GH effects are mediated by somatomedins?
protein synthesis and organ groth
linear growth due to increased metabolism and proliferation in chondrocytes
How does fasting affect GH levels?
fasting –> increased GH, decr somatostatin, decr insulin –> decreased protein synthesis and growth –> increased caloric mobilization
How does high prolactin affect FSH and LH?
high prolactin –> inhibits GnRH from hypothalamus –> decreased FSH and LH
How does dopamine affect prolactin?
decreases prolactin
What is the most common type of functional pit adenoma?
FSH and LH secreting –> increased prolactin –> hypogonadism adn galactorrhea
what are the 6 types of pituitary adenoma?
ACTH-secreting –> cushings
TSH-secreting
GH secreting
prolactinoma
ADH-secreting = diabetes insipidus
non-functioning adenoma
What is Sheehan syndrome?
postpartum hypopituitarism due to necrosis of pituitary gland
pit gland becomes enlarged during pregnancy –> postpartum hemorrhage causes BP drop –> pit necrosis
pts commonly present w/ agalactorrhea/difficulties in lactation
other hormone abnormalities can happen too
How is oxytocin made and regulated?
prepro-oxyphysin -(cleavage and packaging into vesicles)-> pro-oxyphysin –> goes down hypothalamic-hypophyseal tract –> oxytocin in post pit –> goes to breast and uterus
How is ADH synthesized and secreted?
prepropressophysin –> propressophysin –> goes down tract to post pit –> ADH in NPII –> released –> goes to kidney and arterioles
What are the triggers of ADH secretion?
decreased BP –> cardiac and aortic baroreceptors –> sensory neuron to hypothalamus
decreased arterial stretch –> atrial stretch receptors –> sensory neuron to hypothalamus
increased osmolarity –> hypothalamic osmoreceptors –> interneuron to hypothalamus
What is the strongest stimuli to ADH?
most sensitive to plasma osmolarity changes
How does ADH work in the renal collecting duct?
binds V2 receptor = Gs –> Adenylyl cyclase, cAMP –> PkA –> aquaporins added into apical membrane
What is diabetes insipidus?
lack of ADH or lack of ADH effect on renal collecting duct
lose water = frequent dilute urination
What can cause nephrogenic DI?
lithium
chronic disorders
*desmopressin tx doesn’t work
How is the water deprivation test for DI performed?
allow fluids overnight before test and give breakfast w/ no fluids
weigh pt
no fluid for 8 hrs; every 1-2 hr, weigh pt, empties bladder and test urine and plasma osmolarity
if plasma osm > 300 mOsM, STOP
