Pituitary physiology II

Question 1

What should I know about the kinetics of CRH and ACTH? Where is CRH made

Answer 1

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

Question 2

Describe feedback in the adrenal axis. What factors promote CRH release?

Answer 2

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

Question 3

What is the role of CRH in pregnancy?

Answer 3

secreted by the placenta. levels incr. during late pregnancy and delivery

Question 4

What are some non-CRH ACTH secretagogues? What inhibits CRH-mediated ACTH secretion

Answer 4

ADH,angiotensin II, opioids, CCK

oxytocin inhibits CRH mediated ACTH secretion

Question 5

What should I know about synthesis of ACTH within the corticotroph?

Answer 5

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

Question 6

Why do people with addison’s disease become hyperpigmented?

Answer 6

excess ACTH binds to melanocyte stimulating hormone receptors.

Question 7

What is the role of time of day on ACTH and cortisol levels?

Answer 7

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

Question 8

categorization of adrenalcortical deficiency

Answer 8

primary: destruction or dysfunction of adrenal cortex (autoimmune, mets, hemorrhage, infection, congenital adrenal hyperplasia)
secondary: deficient pituitary ACTH secretion: mets, adenomas, infiltrative disease

Question 9

What is cushing syndrome?

Answer 9

too much cortisol! 65% of cases are pituitary dependent- cortisol doesn’t inhibit ACTH production? Often due to pituitary tumor)

Question 10

What should I know about evaluation of the HPA axis?

Answer 10

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

Question 11

Describe the growth hormone axis (sorry)

Answer 11

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

Question 12

Where are the GHRH-secreting neurons located?

Answer 12

arcuate nuclei

Question 13

Where are the somatostatin-secreting neurons located?

Answer 13

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

Question 14

What are other GH secretagogues/conditions that promote GH release?

Answer 14

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

Question 15

What inhibits GH release?

Answer 15

glucose administration, somatostatin

Question 16

What does GH do?

Answer 16

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

Question 17

GH pulsatility in adults

Answer 17

pulsatile release
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

Question 18

What are the usual causes of GH deficiency and how to you make the diagnosis?

Answer 18

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

Question 19

clinical manifestation of GH deficiency

Answer 19

depends on age
kids: short
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.

Question 20

What are the causes of growth hormone excess

Answer 20

hypothatlamic or pituitary GH excess most common

ectopic GH excess possible

Question 21

What happens if you get excess GH in early life?

Answer 21

gigantism.
rare
symmetrical enlargement of body resulting in true giant with overgrowth of long bones, CT, and visceral organs

Question 22

What happens if you get excess GH after body growth has stopped?

Answer 22

acromegaly
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

Question 23

Dx of excess GH

Answer 23

can’t use random serum GH
measure IGF-1 serially
pts with GH excess don’t suppress GH after glucocse administration