83. & 84. Adrenal Cortex

Front 1

3 Functional zones of the Adrenal Cortex:

Back 1

-Zona glomerulosa - outermost
-Zona fasciculata
-Zona reticularis - innermost

Front 2

What does the zona glomerulosa secrete?

Back 2

Aldosterone

Front 3

What do the Zona fasciculata and reticularis secrete?

Back 3

Cortisol and androgens

Front 4

What does the adrenal medulla secrete?

Back 4

Catecholamines

Front 5

What is the first molecule that is needed for making steroid hormones in the adrenal cortex?

Back 5

CHOLESTEROL!

Front 6

How many carbons are in cholesterol?

Back 6

27

Front 7

What is needed for cholesterol to be taken up by the adrenal cortex cells into their inner mitochondrial membrane?

Back 7

ACTH must bind its receptor and activate adenylate cyclase for cAMP increase.

Front 8

So what is the step that needs cAMP increased so cholesterol is taken up into the inner mitochondrial membrane?

Back 8

The rate limiting step

Front 9

Why does cholesterol have to get into the inner mitochondrial membrane anyway?

Back 9

Because that's where Desmolase is, which converts Cholesterol to Pregnenalone

Front 10

What happens to pregnenolone?

Back 10

It goes back into the cytosol and gets converted to either Progesterone, or 17-hydroxypregnenalone.

Front 11

What enzyme acts on either pregnenolone or progesterone?

Back 11

17-alpha hydroxylase

Front 12

What are the products of 17-alpha hydroxylase?

Back 12

Either 17-hydroxyprogesterone or 17-hydroxypregnenalone.

Front 13

What is the product if 17-20 lyase acts on 17-hydroxypregnenalone?

Back 13

DHEA - dehydroepiandrosterone

Front 14

What is the product if 17 20 lyase acts on 17-hydroxyprogesterone?

Back 14

Androstenedione

Front 15

What does 17-hydroxyprogesterone become if it doesn't get turned into an androgen?

Back 15

11-deoxycortisol, then Cortisol.

Front 16

What happens to progesterone if it doesn't get acted on by 17-hydroxylase?

Back 16

It gets converted to corticosterone and ultimately aldosterone.

Front 17

What is deficiency of 21-hydroxylase called?

Back 17

Congenital adrenal hyperplasia

Front 18

Why do we care about CAH?

Back 18

Because it's the most common genetic defect in kids.

Front 19

What are the effects of 21-hydroxylase deficiency?

Back 19

-Inability to make cortisol
-Overabundance of ACTH
-Hyperplasia of the adrenals

Front 20

As the adrenals ramp up their conversion of cholesterol to pregnenolone via the stimulation of all that ACTH, what happens?

Back 20

They can't make cortisol obviously, so it gets shunted into the androgen pathway

Front 21

What happens to females with CAH?

Back 21

Virilization

Front 22

How do Cortisol and Corticosterone compare in terms of potency of strength?

Back 22

Cortisol is about 2x more potent

Front 23

What corticosteroid is used for inflammation and asthma?

Back 23

Prednisone - 4X more potent than cortisol.

Front 24

What is the most potent synthetic corticosteroid?

Back 24

Dexamethasone

Front 25

What is dexamethasone used for?

Back 25

Treating CAH

Front 26

What steroid hormone has the highest concentration in the plasma? What is 2nd highest?

Back 26

DHEA - highest
Cortisol - second

Front 27

What are 3 forms of cortisol in the blood?

Back 27

-CBG bound
-free
-albumin bound

Front 28

What protein has the highest affinity for cortisol? Where is it made?

Back 28

CBG - in the liver

Front 29

What form of cortisol is biologically active?

Back 29

Only free and unbound

Front 30

What type of cortisol do we measure? Why?

Back 30

Bound - because normally 95% of cortisol is circulating bound to CBG, it's a fairly good estimate of total levels.

Front 31

What are cortisol's 2 effects on the CNS? (hypothalamus)

Back 31

-Decreases CRH
-Increases appetite

Front 32

How does Cortisol affect the cardiovascular system?

Back 32

It maintains sensitivity to vasoconstrictors by allowing epinephrine to exert its effect.

Front 33

What do we call the effect Cortisol has on the CV system's sensitivity to epinephrine?

Back 33

Permissive

Front 34

How does cortisol affect the liver?

Back 34

Increases gluconeogenesis

Front 35

How does cortisol affect the lungs?

Back 35

Causes fetal lung development

Front 36

How does cortisol affect the pituitary? Kidney?

Back 36

Pituitary - decreases ACTH
Kidney - increases the GFR

Front 37

How does cortisol affect bone?

Back 37

-Increases bone resorption
-Decreases bone formation

Front 38

How does cortisol affect muscle?

Back 38

-Catabolizes it
-Decreases its insulin sensitivity

Front 39

How does cortisol affect the immune system?

Back 39

Suppresses it

Front 40

How does cortisol affect connective tissue?

Back 40

Decreases collagen synthesis.

Front 41

What 4 effects does CORTISOL have on MUSCLE's intermediate metabolism?

Back 41

1. Increases protein breakdown
2. Decreases protein synthesis
3. Decreases glucose utilization
4. Decreases insulin sensitivity

Front 42

What 3 effects does CORTISOL have on ADIPOCYTE intermediate metabolism?

Back 42

1. Decreases glucose utilization
2. Decreases insulin sensitivity
3. Increases lipolysis

Front 43

What are the 2 general effects of Cortisol on intermediate metabolism?

Back 43

1. Increased gluconeogenesis
2. Decreased glucose uptake

Front 44

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?

Back 44

Give a shot of hydrocortisone because the patient probably has adrenal insufficiency.

Front 45

How long would it take to see the hydrocortisone shot take effect?

Back 45

4-6 hours

Front 46

Why do patients with adrenal insufficiency not respond to the normal vasoconstrictors?

Back 46

Because they lack Cortisol's permissive effect of maintaining sensitivity to epinephrine.

Front 47

How would you confirm adrenal insufficiency in this patient?

Back 47

By checking their ACTH levels which would be high.

Front 48

What is the gene from which Cortisol is transcribed?

Back 48

The POMC gene

Front 49

What does POMC stand for?

Back 49

Pro-opio-melano-cortin

Front 50

What allows corticotrophs to make ACTH even though the POMC gene has the capability of making Melanocyte stim hormone, y-lipotropin, b-endorphin, etc?

Back 50

The protein product of post translational processing is determined by the enzymes in that cell; corticotrophs have the enzyme that makes ACTH.

Front 51

What are the 2 enzymes that cleave the POMC gene?

Back 51

PC1 (prohormone convertase 1)
PC2 (same but 2)

Front 52

What enzyme does the anterior pituitary have? Why?

Back 52

PC1 - because this is what cleaves the ACTH product

Front 53

Where is PC2 found? Why?

Back 53

In the hypothalamus - because this is what results in MSH

Front 54

What stimulates the release of ACTH from the anterior pituitary?

Back 54

CRH from the hypothalamus.

Front 55

What stimulates the hypothalamus to make CRH?

Back 55

Stress like decreased blood sugar or hypotension.

Front 56

What happens when Stress/CRH stimulate ACTH release?

Back 56

It stimulates Cortisol secretion by the adrenal cortex.

Front 57

What happens when Cortisol is released?

Back 57

It inhibits more release of ACTH and CRH, and relieves the stress.

Front 58

How fast does cortisol synthesis and secretion go up in response to stress?

Back 58

Very fast - within minutes.

Front 59

How fast do the effects of cortisol appear?

Back 59

Not very fast - blood pressure doesn't increase for about 4-6 hours.

Front 60

What type of pattern is the normal daily cortisol release?

Back 60

Circadian

Front 61

When do cortisol levels rise and peak?

Back 61

Rise at 4am
Peak at 8am

Front 62

When do cortisol levels reach their low during the day?

Back 62

At midnight

Front 63

What happens to normal people when you inject them with insulin?

Back 63

They become hypoglycemic.

Front 64

What is hypoglycemia?

Back 64

Stress

Front 65

What are the 3 responses to an insulin injection in a FASTED individual in the initial 30 min?

Back 65

1. Blood glucose drops immediately
2. ACTH goes up starting at 30 min
3. Cortisol goes up then too

Front 66

What happens in fasted patients with hypopituitarism when you inject insulin?

Back 66

1. Glucose drops
2. ACTH fails to go up
3. Cortisol fails to go up

Front 67

How would you test to see if that patient had primary adrenal insufficiency?

Back 67

By giving CRH - if ACTH did go up, then that wouldn't be hypopituitarism, but adrenal insufficiency.
-Kill 2 birds w/ 1 stone

Front 68

What is the most common form of primary adrenal insufficiency?

Back 68

Congenital Adrenal Hyperplasia

Front 69

And why do we care about CAH?

Back 69

Because it's the most common Congenital defect by far

Front 70

How do you treat CAH?

Back 70

With Dexamethasone

Front 71

What is the primary cause of adverse symptoms in CAH?

Back 71

-Loss of neg feedback
-Increased CRH/ACTH
-Increased pregnenalone pumps into making androgens - virilism

Front 72

What do we call underproduction of cortisol? Overproduction?

Back 72

Under: adrenal insufficiency
Over: Cushing's

Front 73

What is another name for primary adrenal insufficiency?

Back 73

Addison's

Front 74

What is 2ndary adrenal insufficiency?

Back 74

When hypopituitarism causes atrophy, adrenal production of cortisol is then insufficient.

Front 75

What is the cause of Cushing's?

Back 75

A pituitary tumor that oversecretes ACTH

Front 76

If there's overproduction of Cortisol in Cushing's, why doesn't it inhibit more ACTH output?

Back 76

Because it's a tumor and refuses to be bossed around.

Front 77

What is ACTH independent cushing's?

Back 77

Overproduction of cortisol caused by an adrenal gland tumor.

Front 78

What are ACTH levels in ACTH-independent cushing's?

Back 78

Low

Front 79

What is the cause of ACTH-dependent cushing's that is unrelated to the pituitary?

Back 79

An ectopic ACTH-secreting tumor

Front 80

How do you diagnose whether the tumor is pituitary or ectopic in ACTH-dependent cushing's?

Back 80

By doing inferior petrosal sinus sampling to see if there is more ACTH in the pituitary than in the peripheral blood.

Front 81

If there is an ACTH gradient, what does it tell you?

Back 81

That the tumor is in the pituitary.

Front 82

If there isn't a gradient what does that tell you?

Back 82

The ACTH-secreting tumor is ectopic.

Front 83

What are the 2 most common causes of Primary Adrenal Insufficiency?

Back 83

80% Autoimmune
20% Tuberculosis

Front 84

And what do we call primary adrenal insufficiency?

Back 84

Addison's

Front 85

What causes 2ndary adrenal insufficiency?

Back 85

Hypopituitarism which means there is no trophic stimulation of the adrenals so they shrink.

Front 86

What is Congenital Adrenal Hyperplasia?

Back 86

Primary adrenal insufficiency

Front 87

What are the 4 MAJOR FEATURES in patients who present with primary adrenal insufficiency?

Back 87

1. Weakness
2. Fatigue
3. Anorexia
4. Weight loss

Front 88

Why is it VERY important to treat these patients IMMEDIATELY?

Back 88

Because it's fatal and soooo treatable and I don't want to be sued for malpractice.

Front 89

Why do patients with primary adrenal insufficiency become darker?

Back 89

Because the gene sequence for ACTH also includes MSH - when it's ramped up trying to get the adrenals to work, MSH increases.

Front 90

What is Cosyntropin?

Back 90

The ACTH type that is given to stimulate the adrenals and test for insufficiency.

Front 91

When Adrenal Insufficiency is suspected, what should you do?

Back 91

1. Test a basal plasma sample for ACTH and Cortisol levels
2. Give Cosyntropin
3. Measure cortisol at 30 min

Front 92

If cortisol levels are below normal after giving Cosyntropin, what does it mean?

Back 92

The patient isn't responding to ACTH; adrenal insufficiency

Front 93

How do you deterine if the adrenal insufficiency is primary or secondary?

Back 93

Primary: ACTH will be high

Secondary: ACTH will be low

Front 94

What are the main symptoms of Cushing's?

Back 94

-Moon face
-Fat pads
-Red cheeks
-Pendulous abdomen
-Bruising
-Thin skin / striae

Front 95

What are common side effects of Cushing's in women?

Back 95

-Hirsutism
-Menstrual disorders

Front 96

What does Cushing's do to BP?

Back 96

Hypertension - due to too much aldosterone

Front 97

What are the 2 forms of ACTH-dependent Cushing's Syndrome?

Back 97

-Cushing's disease (pituitary tumor)
-ectopic tumor

Front 98

What is the cause of ACTH-independent Cushing's syndrome?

Back 98

An adrenal tumor

Front 99

What do the vast majority of patients with ACTH dependent cushing's have?

Back 99

A pituitary tumor

Front 100

How do you determine if Cushing's is ACTH dependent or independent?

Back 100

MEASURE ACTH!

Front 101

If ACTH is high, how do you determine if it's a pituitary tumor or ectopic?

Back 101

Inferior petrosal sinus sampling.