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What are the 3 layers of the adrenal cortex?
zona glomerulosa
zona fasciculata
zona reticularis
what hormone stimulates the adrenal cortex?
ACTH
what hormones does the adrenal cortex secrete?
aldosterone
cortisol
DHEA
what is the most important glucocorticoid?
cortisol
what is the most important minerocorticoid?
aldosterone
what is the source of most hormones produced in the adrenal cortex?
cholesterol
what are mineralcorticoids used for?
sodium reabsorption
what is the function of gluococorticoids?
control glucose concentration during stress
keeps us from starvation
what hormone is release by stress?
CRH
explain the pathway for stress, hypothalamus, CRH, ACTH, cortisol, anterior pituitary, and adrenal cortex
Stress increases the activity of the hypothalamus, which increases its production of CRH.  The CRH acts on the anterior pituitary, which then produces more ACTH which acts on the adrenal cortex.  The adrenal cortex then produces cortisol that acts as inhibitor feedback on the anterior pituitary.  The cortisol also acts as inhibitor feedback on the hypothalamus, making the two organs stop producing ACTH and CRH, respectively.
what are the effects of glucocorticoids?
stimulate gluconeogenesis
increase hepatic glycogen
increase blood glucose
increase lipolysis
catabolic (negative N balance)
block inflammatory response
suppress immune system
stimulate gastric acid secretion
what are the effects of corticosteroids on carb and protein metabolism
corticosteroids protect dependent tissues (brain, heart) from starvation
stimulates the liver to form glucose
what is a problem with glucocorticoids in diabetic patients?
can worsen glycemic control
what is the effect of glucocorticoids on lipids?
redistributes body fat (cushings syndrme to start buffalo bump or moon facies
truncal adipocytes respond predominantly to insulin and clucorticoids induced hyperglycemia
CNS effects of glucocorticoids
mood elevation
euphoria
insomnia
increased motor activity
anxiousness
depression
psychosis
WHY?  neurosteroids regulate neural excitability
effect of mineralcorticoids on Na, K, H
increases Na reabsorption
increase K excretion
increases H excretion
describe primary adrenal insufficiency
decreased cortisol production by adrenal cortex.  the hypothalamus tries to compensate by producing extra ACTH but doesn't work. end with low levels of cortisol and high levels of ACTH
describe secondary renal insufficiency
no ACTH production induces low levels of cortisol
describe cushing's disease
type of hypercorticosolism where both ACTH and cortisol are overproduced
describe an adrenal tumor
increases the amount of cortisol secreted, and the hypothalamus tries to compensate by lowering ACTH produduced so the adrenal cortexc isn't as stimulated, but the tumor keeps cortisol production high.  so low ACTH and high cortisol
describe an ectopic tumor
tumor produces ACTH, which leads to increased cortisol.  the cortisol arrives at the hypothalamus and decreases ACTH production, but the ectopic tumor keeps producing cortisol.  so ACTH lower and cortisol high.
cushing's syndrome symptoms
obesity
HTN
hyperglycemia
amenorrhea or impotence
hirsutism
purple striae
moon facies
osteoporosis
personality change
treatment of cushing's disease
removal of pituitary tumor, pituitary irradiation, or use inhibitors of steroidogenesis
treatment of adrenal or ectopic tumor
surgical removal
what is the most potent corticosteroid?
dexamethasone
from least potent to most potent, list the steroids.
cortisol
prednisolone
6-methyprednisone
9-fluorocortisol
triamcinolone
betamethasone
dexamethasone
what is the corticosteroid with the highest sodium retaining potency?
flurocortisol
what is the MOA for corticosteroid's anti-inflammatory properties?
decrease capillary dilation = decreased cellular exudation = decreased fibrin deposition = inhibit prostaglandin synthesis = decrease release of biogenic amines = stabilization of lysosomal membranes = inhibition of white cell mobilization
what is the MOA for corticosteroid's immunosuppressive properties?
inhibit T lymphocyte proliferation, inhibit immunoglobulin synthesis, kill B lymphocytes
what is MOA for corticosteroids decreased Ab production?
inhibit complementary formation
skin ADR for steroids
thinning of skin
acne
hirsutism
GI steroid ADR
peptic ulceration
CNS steroid ADR
euphoria
depression
nervousness
psychosis
fluid and electrolyte steroid ADR
na retention
k loss
negative Ca balance
HTN
ways to avoid iatrogenic (doctor promoted) adrenal insufficiency
withdrawal from steroid therapy slowsly for treatment 2-4 weeks
alternate day steroid therapy to simulate normal diurnal rhythm
inhibitors of steroidogenesis
aminoglutethimide
what is function of aminoglutethimide?
cholesterol side chain cleavage inhibitor
inhibits CYP11A1
used in treatment of cushing's dyndrome, congenital adrenal hyperplasia, metastatic breast or prostatic cancer
what is MOA for aminoglutethimide?
catlayzes initial and rate limiting step
decreases hypersecretion of cortisol
which CYP's are inhibited by ketoconazole?
cyp 17 and cyp 11a1
what is the most effective inhibitor to treat cushing's disease
ketoconazole
what is the best time of day to give dexamethasone?
give in late evening = greater suppression of symptoms of cushings syndrome
what is ACTH used for?
differential diagnosis of primary vs secondary adrenal insufficiency
corticotropin injection
parenteral admin only.
ACTH zinc preparations prolong duration of action
cosyntropin injection
parenteral only
ACTH 1-24
what is better, corticoptroin injection or cosyntropin injection?
cosyntropin - fewer allergic rxns and longer duration of action
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