Corticosteroids

Question 1

What is the general mechanism of glucocorticoids?

Answer 1

Binds to receptor, translocates as complex into nucleus to regulate transcription

Reason for delayed response

Question 2

What is pseudo Cushing’s?

Answer 2

A physiological hypercortisolism associated with disorders other than Cushing’s syndrome

Inflammatory stress, severe obesity, malnutrition, psychological stress, chronic alcoholism

Question 3

What are the symptoms of Cushing’s Syndrome?

Answer 3

Central obesity, moon face

Growth of neck fat pads

Excessive sweating

Muscle wastage

Skin striae

Question 4

How is cushing’s often first diagnosed?

Answer 4

Psychiatric issues leading to neurological stress

Question 5

What are the tests for Cushing’s?

Answer 5

Rule out exogenous glucocorticoids

24 hour urine coritsol

Late night salivary cortisol - is it higher than it should be?Pay attention to patient’s routine

Question 6

What is the Dexamethasone test?

Answer 6

Suppression test used to assess the status of the HPA axis

Should reduce cortisol levels by suppressing CRH and ACTH

Question 7

What are the pharmacological options for cushing’s?

Answer 7

Total ablation of cortisol, followed by GC replacement

Normalization

Question 8

What three drugs inhibit cortisol production?

Answer 8

Ketoconazole (NIZORAL) - inhibits production

Metyrapone - inhibits production

Etomidate - inhibits production

Mitotane - adrenolytic

Mifepristone - inhibits action

Question 9

What is the mechanism and side effects for Ketocanozole?

Answer 9

Inhibits CYP17, inhibiting GC and androgen synthesis

Adrenal insufficiency

Question 10

What is the mechanism and side effects for metyrapone?

Answer 10

Inhibits CYP11b1, reducing cortisol synthesis

Hirsuitism

Nausea, headace, sedation and rash

Question 11

What is the mechanism for etomidate?

Answer 11

Anesthetic drug that blocks CYP11B1

Question 12

What is the mechanism and side effects for mitotane?

Answer 12

Acts on adrenocortical cell mitochondria to inhibit CYP11B1

Metabolized to acyl chloride that causes mitochondrial destruction and necrosis

Not used during pregnancy

Question 13

What is the mechanisms and side effects for mifepristone?

Answer 13

Blocks release of GC receptors from chaperone proteins

Also used for abortion

Vaginal bleeding, abdominal pain, GI upset, diarrhea, headache

Question 14

What is Cosyntropin?

Answer 14

Synthetic ACTH

Used for primary adrenal insufficiency (Addison’s disease)

Question 15

What do you use to treat Primary insufficiency?

Answer 15

Glucocorticoids and mineralcorticoids

Possible isotonic saline

Question 16

What do you use to treat secondary insufficiency?

Answer 16

Hydrocortisone or prednisone

MCs may not be needed

Question 17

Whats the most common cause of CAH?

Answer 17

Deficiency in CYP21

Leads to increased DHEA and androgens

Females - pseudohermaphroditism

Males - percocious puberty

Question 18

What is the goal of replaccement therapy?

Answer 18

Provide sufficient hormone to maintain normal function

Simulate normal circadian rhythm

Question 19

What are the withdrawal effects of glucocorticoids?

Answer 19

HPA suppression - leads to secondary adrenocortical insufficiency

Can last up to 12 months