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101 Cards in this Set

  • Front
  • Back
3 Functional zones of the Adrenal Cortex:
-Zona glomerulosa - outermost
-Zona fasciculata
-Zona reticularis - innermost
What does the zona glomerulosa secrete?
What do the Zona fasciculata and reticularis secrete?
Cortisol and androgens
What does the adrenal medulla secrete?
What is the first molecule that is needed for making steroid hormones in the adrenal cortex?
How many carbons are in cholesterol?
What is needed for cholesterol to be taken up by the adrenal cortex cells into their inner mitochondrial membrane?
ACTH must bind its receptor and activate adenylate cyclase for cAMP increase.
So what is the step that needs cAMP increased so cholesterol is taken up into the inner mitochondrial membrane?
The rate limiting step
Why does cholesterol have to get into the inner mitochondrial membrane anyway?
Because that's where Desmolase is, which converts Cholesterol to Pregnenalone
What happens to pregnenolone?
It goes back into the cytosol and gets converted to either Progesterone, or 17-hydroxypregnenalone.
What enzyme acts on either pregnenolone or progesterone?
17-alpha hydroxylase
What are the products of 17-alpha hydroxylase?
Either 17-hydroxyprogesterone or 17-hydroxypregnenalone.
What is the product if 17-20 lyase acts on 17-hydroxypregnenalone?
DHEA - dehydroepiandrosterone
What is the product if 17 20 lyase acts on 17-hydroxyprogesterone?
What does 17-hydroxyprogesterone become if it doesn't get turned into an androgen?
11-deoxycortisol, then Cortisol.
What happens to progesterone if it doesn't get acted on by 17-hydroxylase?
It gets converted to corticosterone and ultimately aldosterone.
What is deficiency of 21-hydroxylase called?
Congenital adrenal hyperplasia
Why do we care about CAH?
Because it's the most common genetic defect in kids.
What are the effects of 21-hydroxylase deficiency?
-Inability to make cortisol
-Overabundance of ACTH
-Hyperplasia of the adrenals
As the adrenals ramp up their conversion of cholesterol to pregnenolone via the stimulation of all that ACTH, what happens?
They can't make cortisol obviously, so it gets shunted into the androgen pathway
What happens to females with CAH?
How do Cortisol and Corticosterone compare in terms of potency of strength?
Cortisol is about 2x more potent
What corticosteroid is used for inflammation and asthma?
Prednisone - 4X more potent than cortisol.
What is the most potent synthetic corticosteroid?
What is dexamethasone used for?
Treating CAH
What steroid hormone has the highest concentration in the plasma? What is 2nd highest?
DHEA - highest
Cortisol - second
What are 3 forms of cortisol in the blood?
-CBG bound
-albumin bound
What protein has the highest affinity for cortisol? Where is it made?
CBG - in the liver
What form of cortisol is biologically active?
Only free and unbound
What type of cortisol do we measure? Why?
Bound - because normally 95% of cortisol is circulating bound to CBG, it's a fairly good estimate of total levels.
What are cortisol's 2 effects on the CNS? (hypothalamus)
-Decreases CRH
-Increases appetite
How does Cortisol affect the cardiovascular system?
It maintains sensitivity to vasoconstrictors by allowing epinephrine to exert its effect.
What do we call the effect Cortisol has on the CV system's sensitivity to epinephrine?
How does cortisol affect the liver?
Increases gluconeogenesis
How does cortisol affect the lungs?
Causes fetal lung development
How does cortisol affect the pituitary? Kidney?
Pituitary - decreases ACTH
Kidney - increases the GFR
How does cortisol affect bone?
-Increases bone resorption
-Decreases bone formation
How does cortisol affect muscle?
-Catabolizes it
-Decreases its insulin sensitivity
How does cortisol affect the immune system?
Suppresses it
How does cortisol affect connective tissue?
Decreases collagen synthesis.
What 4 effects does CORTISOL have on MUSCLE's intermediate metabolism?
1. Increases protein breakdown
2. Decreases protein synthesis
3. Decreases glucose utilization
4. Decreases insulin sensitivity
What 3 effects does CORTISOL have on ADIPOCYTE intermediate metabolism?
1. Decreases glucose utilization
2. Decreases insulin sensitivity
3. Increases lipolysis
What are the 2 general effects of Cortisol on intermediate metabolism?
1. Increased gluconeogenesis
2. Decreased glucose uptake
If a patient comes into the ER and is very hypotensive and doesn't respond to an injection of the normal vasoconstrictors, what should you do?
Give a shot of hydrocortisone because the patient probably has adrenal insufficiency.
How long would it take to see the hydrocortisone shot take effect?
4-6 hours
Why do patients with adrenal insufficiency not respond to the normal vasoconstrictors?
Because they lack Cortisol's permissive effect of maintaining sensitivity to epinephrine.
How would you confirm adrenal insufficiency in this patient?
By checking their ACTH levels which would be high.
What is the gene from which Cortisol is transcribed?
The POMC gene
What does POMC stand for?
What allows corticotrophs to make ACTH even though the POMC gene has the capability of making Melanocyte stim hormone, y-lipotropin, b-endorphin, etc?
The protein product of post translational processing is determined by the enzymes in that cell; corticotrophs have the enzyme that makes ACTH.
What are the 2 enzymes that cleave the POMC gene?
PC1 (prohormone convertase 1)
PC2 (same but 2)
What enzyme does the anterior pituitary have? Why?
PC1 - because this is what cleaves the ACTH product
Where is PC2 found? Why?
In the hypothalamus - because this is what results in MSH
What stimulates the release of ACTH from the anterior pituitary?
CRH from the hypothalamus.
What stimulates the hypothalamus to make CRH?
Stress like decreased blood sugar or hypotension.
What happens when Stress/CRH stimulate ACTH release?
It stimulates Cortisol secretion by the adrenal cortex.
What happens when Cortisol is released?
It inhibits more release of ACTH and CRH, and relieves the stress.
How fast does cortisol synthesis and secretion go up in response to stress?
Very fast - within minutes.
How fast do the effects of cortisol appear?
Not very fast - blood pressure doesn't increase for about 4-6 hours.
What type of pattern is the normal daily cortisol release?
When do cortisol levels rise and peak?
Rise at 4am
Peak at 8am
When do cortisol levels reach their low during the day?
At midnight
What happens to normal people when you inject them with insulin?
They become hypoglycemic.
What is hypoglycemia?
What are the 3 responses to an insulin injection in a FASTED individual in the initial 30 min?
1. Blood glucose drops immediately
2. ACTH goes up starting at 30 min
3. Cortisol goes up then too
What happens in fasted patients with hypopituitarism when you inject insulin?
1. Glucose drops
2. ACTH fails to go up
3. Cortisol fails to go up
How would you test to see if that patient had primary adrenal insufficiency?
By giving CRH - if ACTH did go up, then that wouldn't be hypopituitarism, but adrenal insufficiency.
-Kill 2 birds w/ 1 stone
What is the most common form of primary adrenal insufficiency?
Congenital Adrenal Hyperplasia
And why do we care about CAH?
Because it's the most common Congenital defect by far
How do you treat CAH?
With Dexamethasone
What is the primary cause of adverse symptoms in CAH?
-Loss of neg feedback
-Increased CRH/ACTH
-Increased pregnenalone pumps into making androgens - virilism
What do we call underproduction of cortisol? Overproduction?
Under: adrenal insufficiency
Over: Cushing's
What is another name for primary adrenal insufficiency?
What is 2ndary adrenal insufficiency?
When hypopituitarism causes atrophy, adrenal production of cortisol is then insufficient.
What is the cause of Cushing's?
A pituitary tumor that oversecretes ACTH
If there's overproduction of Cortisol in Cushing's, why doesn't it inhibit more ACTH output?
Because it's a tumor and refuses to be bossed around.
What is ACTH independent cushing's?
Overproduction of cortisol caused by an adrenal gland tumor.
What are ACTH levels in ACTH-independent cushing's?
What is the cause of ACTH-dependent cushing's that is unrelated to the pituitary?
An ectopic ACTH-secreting tumor
How do you diagnose whether the tumor is pituitary or ectopic in ACTH-dependent cushing's?
By doing inferior petrosal sinus sampling to see if there is more ACTH in the pituitary than in the peripheral blood.
If there is an ACTH gradient, what does it tell you?
That the tumor is in the pituitary.
If there isn't a gradient what does that tell you?
The ACTH-secreting tumor is ectopic.
What are the 2 most common causes of Primary Adrenal Insufficiency?
80% Autoimmune
20% Tuberculosis
And what do we call primary adrenal insufficiency?
What causes 2ndary adrenal insufficiency?
Hypopituitarism which means there is no trophic stimulation of the adrenals so they shrink.
What is Congenital Adrenal Hyperplasia?
Primary adrenal insufficiency
What are the 4 MAJOR FEATURES in patients who present with primary adrenal insufficiency?
1. Weakness
2. Fatigue
3. Anorexia
4. Weight loss
Why is it VERY important to treat these patients IMMEDIATELY?
Because it's fatal and soooo treatable and I don't want to be sued for malpractice.
Why do patients with primary adrenal insufficiency become darker?
Because the gene sequence for ACTH also includes MSH - when it's ramped up trying to get the adrenals to work, MSH increases.
What is Cosyntropin?
The ACTH type that is given to stimulate the adrenals and test for insufficiency.
When Adrenal Insufficiency is suspected, what should you do?
1. Test a basal plasma sample for ACTH and Cortisol levels
2. Give Cosyntropin
3. Measure cortisol at 30 min
If cortisol levels are below normal after giving Cosyntropin, what does it mean?
The patient isn't responding to ACTH; adrenal insufficiency
How do you deterine if the adrenal insufficiency is primary or secondary?
Primary: ACTH will be high

Secondary: ACTH will be low
What are the main symptoms of Cushing's?
-Moon face
-Fat pads
-Red cheeks
-Pendulous abdomen
-Thin skin / striae
What are common side effects of Cushing's in women?
-Menstrual disorders
What does Cushing's do to BP?
Hypertension - due to too much aldosterone
What are the 2 forms of ACTH-dependent Cushing's Syndrome?
-Cushing's disease (pituitary tumor)
-ectopic tumor
What is the cause of ACTH-independent Cushing's syndrome?
An adrenal tumor
What do the vast majority of patients with ACTH dependent cushing's have?
A pituitary tumor
How do you determine if Cushing's is ACTH dependent or independent?
If ACTH is high, how do you determine if it's a pituitary tumor or ectopic?
Inferior petrosal sinus sampling.