Flashcards in Pituitary physiology II Deck (23):
What should I know about the kinetics of CRH and ACTH? Where is CRH made
CRH is released in a biphasic pattern and is made by the paraventricular nuclei of the hypothalamus
ACTH has a very short plasma half life and can cause wide and rapid fluction of cortisol
Describe feedback in the adrenal axis. What factors promote CRH release?
CRH is released. Vasopressin/ADH, fever, stress, hypoglycemia, and surgery promote this. Pit releases ACTH. Adrenals release cortisol
coristol inhbits synthesis and release of CRH and also the actions of CRH, ACTH, and antidiuretic hormone/vasopressin (from the posterior pituitary).
Pts who are cortisol deficient have too much ADH and become hyponatremic
release of ACTH in response to surgery and stress is mediated by afferent nerve impulses- can be suppressed by epidurals
note that hypoglycemia promotes CRH release but has no direct effect on ACTH release
What is the role of CRH in pregnancy?
secreted by the placenta. levels incr. during late pregnancy and delivery
What are some non-CRH ACTH secretagogues? What inhibits CRH-mediated ACTH secretion
ADH,angiotensin II, opioids, CCK
oxytocin inhibits CRH mediated ACTH secretion
What should I know about synthesis of ACTH within the corticotroph?
made from a big POMC molecule.
POMC synthesis is stimulated by CRH
CRH binds the the CRH 1 receptor, activates adenylyl cyclase, and stimulates cAMP
ADH/vasopressin doesn't promote POMC production
Why do people with addison's disease become hyperpigmented?
excess ACTH binds to melanocyte stimulating hormone receptors.
What is the role of time of day on ACTH and cortisol levels?
Amplitude of aCTH release is highest in the last hour of sleep. plasma ACTH and serum cortisol are thus highest at the time you wake up and are low in the afternoon and evening.
episodic release of ACTH is independent of plasma cortisol levels
plasma ACTH levels fall more quickly than serum cortisol levels d/t cortisol's slower clearance from plasma
categorization of adrenalcortical deficiency
primary: destruction or dysfunction of adrenal cortex (autoimmune, mets, hemorrhage, infection, congenital adrenal hyperplasia)
secondary: deficient pituitary ACTH secretion: mets, adenomas, infiltrative disease
What is cushing syndrome?
too much cortisol! 65% of cases are pituitary dependent- cortisol doesn't inhibit ACTH production? Often due to pituitary tumor)
What should I know about evaluation of the HPA axis?
random measurements of serum cortisol are usually not helpful in the diagnosis of HPA axis. Nonetheless- cortisol >15 makes adrenal insufficency unlikely; cortisol <5 ug/dL makes you suspicious
Describe the growth hormone axis (sorry)
GHRH stimulates GH secretion
It also stimulates somatotroph proliferation.
GH stimualtes the production of IGF-1, which has a negative effect on pituitary and on the hypothalamus
somatostatin inhibits the secretion of GH and TSH
Where are the GHRH-secreting neurons located?
Where are the somatostatin-secreting neurons located?
periventricular region above the optic chiasm, and in D cells of pancreatic islets, the gastrointestinal mucosa, and the C cells/parafollicular cells of the thyroid
What are other GH secretagogues/conditions that promote GH release?
ghrelin. ghrelin derives from the stomach- it both increases GHRH and decreases somatosatin
emothional, physical, and chemical stresses promote GH, including surgery, trauma, and exercise
hypoglycemia, protein meals, and IV infusion of amino acids cause GH release
What inhibits GH release?
glucose administration, somatostatin
What does GH do?
bind to receptors (homodimers), located mostly in the liver. induces a JAK/STAT transcription activation pathway. Causes lipolysis, incr. amino acid uptake, and increased insulin resistance
GH pulsatility in adults
circadian rhythm- max release in the second half of the night. about 10 releases per day.
extra GH release in puberty
in kids and YAs, most GH release in early night
begins in fetal life
GH lower in older people and in obese people
What are the usual causes of GH deficiency and how to you make the diagnosis?
usually caused by a hypothalamic prob
you diagnose with IGF-1 levels- GH samples aren't useful because of pulsatile nature
then, see if IGF-1 rises appropriately to a physiologcial stimulus like hypoglycemia, exercise, clonidine (alpha-agonist), GHRH stimuation.
in kids you will see short stature
it is very hard to test GH levels
clinical manifestation of GH deficiency
depends on age
adults: decr. physical performance and impaired psychological well-being. can cause reduced bone density/osteoporosis, reduced cardiac function, central obesity, incr. insulin sensitivity, and emotional problems
therefore, goals of treatment are different.
What are the causes of growth hormone excess
hypothatlamic or pituitary GH excess most common
ectopic GH excess possible
What happens if you get excess GH in early life?
symmetrical enlargement of body resulting in true giant with overgrowth of long bones, CT, and visceral organs
What happens if you get excess GH after body growth has stopped?
elongation of long bones not possible- growth plates have closed- growth of cancellous bones instead
protruding jaw, thickening of phalanges,a nd overgrowth of visceral organs