Adrenal Pharmacology

Question 1

Cortisol and Cortisone in CNS, muscle, liver, adipose

Answer 1

Cortisone –(11beta-hydroxylase 1)-> cortisol

Question 2

Cortisol and Cortisone in kidney and colon

Answer 2

Cortisol –(11beta-hydroxylase 2)-> cortisone

Question 3

Basal cortisol levels?

Answer 3

limited utility because of oscillating patterns and circadian rhythm pattern

Question 4

ACTH stimulation test for diagnosing hypocortisolism

Answer 4

Addison’s disease, iatrogenic withdrawal from glucocorticoids
Short Test - give small dose, check cortisol levels 1 hour later
Long Test - give large dose, check at intervals
- Addison’s disease (primary) -> cortisol reduced at all timepoints
- Secondary disease -> delayed response

Question 5

5 Tests to establish hypercortisolism

Answer 5

1. 24 hr urine cortisol (high cortisol confirms hypercortisolism)
2. Late night salivary (>2 tests –> loss of pattern indicative of Cushings)
3. Special populations (pregnancy, epilepsy)
4. Once its established –> baseline ACTH (low ACTH indicates independent disease, high ACTH indicates dependent disease)
5. Dex Test

Question 6

Dexamethasone Challenge Test

Answer 6

1. Low dose -> failure to suppress cortisol after dose of dexamethasone (loss of negative feedback) -> confirms
   - if cortisol is lower than normal, axis is working and Cushing is ruled out
2. High dose -> pituitary adenoma will show some reduction to high dex, ectopic tissue tumor will NOT

Question 7

Cushing syndrome caused by adrenal tumor

Answer 7

Low dose test –> no change
ACTH level –> low
High dose test –> not needed

Question 8

Cushing syndrome caused by ectopic ACTH tumor

Answer 8

Low dose test –> no change
ACTH level –> high
High dose test –> no change

Question 9

Cushing syndrome caused by pituitary tumor

Answer 9

Low dose test –> no changed

High dose test –> normal suppression

Question 10

Less Used diagnostic test

Answer 10

CRH/F stimulation test

• CRH stimulation used to distinguish Cushings from ectopic ACTH tumor
• Cushings will respond, ectopic tumors will not
• administer CRH –> ACTH/cortisol increase

Question 11

Glucocorticoid effects

Answer 11

CV -> positive iontropic, increase BP (Na/H2O retention -> some mineralocorticoid activity)
CNS -> lowers seizure threshold, behavioral
GI -> increase acid, suppress immune, decrease Ca absorption
Bone -> direct inhibition of osteoclasts, stim PTH
Muscle -> hypokalemia, muscle wasting
Heme -> inhibits extravasation, suppress lymphocytes

Question 12

Therapeutic Uses of Glucocorticoids

Answer 12

substitution and replacement of adrenal insufficiency……and many more!

• anti-inflammatory
• immunosuppressants
• anti-allergic

Question 13

Natural vs. Synthetic

Answer 13

Synthetic are higher potency, less protein bound, and longer half-life
Cortisol has equal gluco and mineral activity
Prednisone, methylprednisone, dexa have all gluc activity
Fludrocortisone has mineral activity
* Addition of side chains enhance the potency

Question 14

Active vs Inactive Cortisol

Answer 14

Cortisol (Prednisolone) is reduced and active
Cortisone (Prednisone) is oxidized and inactive
- prednisione gets activated in liver by 11beta-hydroxylase

Question 15

Substitution/Replacement of adrenal insufficiency

Answer 15

Acute Adrenal Insufficiency -> sudden stop in glucocorticoids meds (IV Cortisol)
Chronic Primary Adrenal Insufficiency -> addisons (cortisol/fludrocortisone if needed)
Secondary Adrenal Insufficiency -> give cortisol
Congenital Adrenal Hyperplasia -> due to 21-hydroxylase deficiency -> give cortisol and fludrocortisone

Question 16

Considerations when giving glucocorticoids

Answer 16

can produce toxicity
dose is determined by trial and error
high doses may be used in acute situations
gradual steroid withdrawal following chronic administration

Question 17

Side Effects from Glucocorticoids

Answer 17

Hyperglycemia --> may need insulin
Infection
Peptic ulcer
Myopathy
Osteoporosis
Mineralocorticoid effects
- licorice slows down conversion of cortisol to cortisone

Question 18

ACTH utility

Answer 18

it is a protein -> half-life of 10-15 minutes

- must be injected, mostly hydrolyzed by blood and tissue enzymes

Question 19

Treatment of Cushings

Answer 19

surgery and support with glucocorticoids until recovery of ACTH function

• radiation for poor surgery candidates
• medical treatment

Question 20

Medical Treatment of Cushings

Answer 20

Ketoconazole -> inhibits side-chain cleavage
- antifungal -> inhibit fungal cyto P450
- blocks glucocorticoid and androgen synthesis
Aminoglutethimide -> inhibits side-chain cleavage enzyme
Etomidate -> inhibits 11beta-hydroxylase
Metyrapone -> inhibits 11beta-hydroxylase in adrenal gland