Adrenal Pathophys (Fisher)

Question 1

The major action of ACTH on the adrenal gland is:

Answer 1

stimulate conversion of cholesterol

to pregnenolone

Question 2

What are the major intermediates in the synthesis of cortisol?

Answer 2

cholesterol&raquo_space; pregnenolone&raquo_space; 17alpha-hydroxyprogesterone&raquo_space; 11-deoxycortisol&raquo_space; cortisol

Question 3

Where does P-450scc catalyze the rate-limiting step in cortisol synthesis?

Answer 3

mitochondria

Question 4

Defects in the enzymes along the cortisol synthesis pathway will result in:

Answer 4

shunting of substrates in the direction of androgen synthesis

Question 5

Cortisol acting at both ____ + _____ serves

as a negative feedback on the production of ACTH.

Answer 5

anterior pituitary and hypothalamic

Question 6

ATCH excess leads to:

Answer 6

hypertrophy and hyperplasia of adrenal cortex

Question 7

ATCH deficiency leads to:

Answer 7

decreased “steroidogenesis” and adrenal cortex atrophy

Question 8

3 mechanisms of neuroendocrine control of ATCH release

Answer 8

1) circadian/diurnal rhythm with episodic secretion
2) response to stress
3) feedback inhibition by cortisol; ** can override 1 and 2

Question 9

Metabolism of androgens is unique in that:

Answer 9

it may result in degradation, inactivation, or (in certain instances) enhancement of potency

Question 10

How does hypothyroidism affect cortisol?

Answer 10

↓metabolism and ↓excretion

Question 11

How does hyperthyroidism affect cortisol?

Answer 11

↑metabolism and ↑excretion

Question 12

How do starvation/anorexia affect cortisol?

Answer 12

↓clearance of cortisol

Question 13

How does pregnancy affect cortisol?

Answer 13

↓cortisol due to ↑CBG

Question 14

In the plasma, cortisol is bound mainly to:

Answer 14

corticosteroid-binding globulin

and albumin, to a lesser extent

Question 15

Androgens are primarily bound to:

Answer 15

albumin

Question 16

Measurement of a 24-hour urinary free cortisol is a useful indicator of:

Answer 16

total cortisol production by the adrenal (because only free cortisol is filtered by the kidney)

Question 17

Measuring acute adrenal response to synthetic ACTH is used to diagnose:

Answer 17

both primary and secondary adrenal insufficiency, although it will not distinguish one from the other

Question 18

The rapid ACTH stimulation test is a stimulus for:

Answer 18

aldosterone + cortisol

Question 19

What would be the result of a rapid ACTH stimulation test be if the patient had primary adrenal insufficiency due to destruction of the cortex?

Answer 19

neither aldosterone nor cortisol will be responsive to exogenous ACTH

Question 20

What would be the result of a rapid ACTH stimulation test be if the patient had secondary adrenal insufficiency? (Why?)

Answer 20

aldosterone, but not cortisol, will respond acutely to ACTH

zona glomerulosa is usually intact

Question 21

Infusion of saline + dexamethasone + cosyntropin is used to:

Answer 21

diagnose adrenal insufficiency, and distinguish between primary and secondary (after 2+ days)

nml = increase in cortisol
primary = no increase in cortisol
secondary = slight increase in cortisol, which increases with infusion

Question 22

How does metyrapone test pituitary-adrenal reserve?

Answer 22

1. Metyrapone blocks the synthesis of cortisol (inhibits 11ß-hydroxylase)
2. ACTH is stimulated when cortisol decreases
3. 11-deoxycortisol subsequently increases if hypothalamic-pituitary-adrenal axis is nml

Question 23

How does insulin-induced hypoglycemia test pituitary-adrenal reserve?

Answer 23

Hypoglycemia induces a CNS stress response, which causes release of ACTH from pituitary and a rise in cortisol in normal pt

Question 24

What does Corticotropin Releasing Hormone stimulate, and what does this diagnose or rule out?

Answer 24

• -pituitary failure = no response
• -primary adrenal failure = stimulates exaggerated increase in serum ACTH
• -hypothalamic disorder = delayed effect

Question 25

Primary Adrenocortical Insufficiency: | Etiologies?

Answer 25

``` o Most common: autoimmune adrenalitis o TB o Amyloidosis o Bilateral adrenalectomy o Adrenal vein thrombosis, adrenal artery embolus o Metastatic carcinoma ```

Question 26

Primary Adrenocortical Insufficiency: | Presentation?

Answer 26

``` o Female o Hyperpigmentation o Hypotension (**May lead to azotemia + mild acidosis) o Weak o Nausea, vomiting ```

Question 27

Primary Adrenocortical Insufficiency: | Labs?

Answer 27

o hyponatremia o hyperkalemia o elevated ACTH

Question 28

In Primary Adrenocortical Insufficiency, what may occur following exposure to stress?

Answer 28

“acute adrenal crisis” 1. hypovolemic shock (due to anorexia, NV, and volume depletion via increase Na in urine) 2. weakness 3. Hyponatremia and hyperkalemia 4. abdominal pain 5. fever (infection or hypoadrenalism)

Question 29

Bilateral Acute Adrenal hemorrhage: | Presentation?

Answer 29

1. pain in abdomen, flank, or back (+ tenderness) 2. hypotension → shock 3. azotemia 2o to volume depletion

Question 30

Bilateral Acute Adrenal hemorrhage causes primary adrenocortical insufficiency due to damage to:

Answer 30

both adrenal cortices

Question 31

Secondary Adrenocortical Insufficiency: | Most common cause?

Answer 31

exogenous glucocorticoid therapy

Question 32

Congenital Adrenal Hyperplasia leads to:

Answer 32

abnormalities of secondary sexual development and electrolyte imbalance

Question 33

Congenital Adrenal Hyperplasia is caused by:

Answer 33

Enzymatic defects in the pathway of cortisol synthesis, which shunts substrates into androgen synthesis

Question 34

What enzyme deficiency is responsible for ambiguous female genitalia?

Answer 34

21-hydrolase deficiency (can be in cortisol pathway or cortisol + aldoseterone pathway)

Question 35

ACTH dependent causes of Cushing's?

Answer 35

Ectopic ATCH syndrome (tumors) | Extoptic CRH syndrome

Question 36

ACTH independent causes of Cushing's?

Answer 36

* Adrenal adenoma * Adrenal carcinoma * Micronodular and macronodular hyperplasia

Question 37

Pseudo-cushing’s syndrome is related to what conditions?

Answer 37

major depressive disorder and alcoholism

Question 38

To diagnose Cushing’s dz, you need what 3 tests?

Answer 38

(1) 24 hr urine free cortisol: shows excess ATCH (2) measurement of plasma cortisol and ATCH (↑ATCH and cortisol): shows dependence of cortisol on secretion of ATCH (3) high-dose dex suppression test: show pituitary source of ATCH

Question 39

Loss of circadian rhythm of plasma cortisol is symptomatic of:

Answer 39

Cushing's

Question 40

Dexamethasone suppression test: Low dose will determine if the patient has... High dose will distinguish...

Answer 40

Cushing's (cortisol will increase, no resp to GC) Cushing's from ectopic ATCH syndrome