Pharm adrenal steroids

Question 1

what are the layers of the adrenal gland

Answer 1

zona glomerulosa, zona fasciculata, zona reticularis

Question 2

what does zona glomerulosa make

Answer 2

aldosterone

Question 3

what does zona fasciculata make

Answer 3

glucocorticoids (cortisol)

Question 4

what does zona reticularis make

Answer 4

cortisol and androgens

Question 5

Common enzyme for androgens and cortisol

Answer 5

17-alpha hydroxylase

Question 6

common enzyme for aldosterone and cortisol

Answer 6

21-beta hydroxylase

Question 7

mineralcorticoids

Answer 7

aldosterone and deoxycorticosterone (DOC)

cortisol has weak mineralcorticoid activity

Question 8

glucocorticoids

Answer 8

cortisol

Question 9

cortisol mechanism of action

Answer 9

works within nucleus (diffuses through membrane)

Question 10

what controls the release of cortisol from the adrenal gland?

Answer 10

ACTH from anterior pituitary

Question 11

what controls the release of ACTH from the anterior pituitary?

Answer 11

CRH from hypothalamus

Question 12

glucocorticoid effects

Answer 12

stress hormone
carbohydrate metabolism
immune function

Question 13

glucocorticoid metabolic effects

Answer 13

• increase gluconeogenesis,
• release amino acids through muscle catabolism,
• inhibit peripheral glucose uptake,
• simulate lipolysis,
• maintain adequate glucose for brain!
• increase blood pressure
• decrease bone formation

Question 14

how does glucocorticoid increase blood pressure?

Answer 14

upregulates alpha 1 receptors on arterioles and leads to increased sensitivity to norepi and epi

Question 15

glucocorticoid anti-inflammatory effects

Answer 15

upregulation of anti-inflammatory proteins, down regulation or pro-inflammatory, decreased leukocyte presence and function at site of inflammation

Question 16

mineralcorticoid effects

Answer 16

-active in distal convoluted and collecting tubules maintaining electrolyte balance and intravascular volume

Question 17

what are the most significant regulators of aldosterone secretion?

Answer 17

increased potassium, angiotensin II

ACTH, sodium deficiency

Question 18

mineralcorticoid specificity with aldosterone receptors

Answer 18

cortisol binding AR is prevented by 11 beta-hydroxysteroid dehydrogenase type 2
(cortisol –> cortisone)

Question 19

pharmacologic uses of corticosteroids

Answer 19

• adrenal insufficiency
• establish diagnosis and cause of cushing’s syndrom
• treat inflammatory, allergic, immunological disorders

Question 20

what is the synthetic mineralcorticoid? difference from cortisol?

Answer 20

fludrocortisone

-very high mineralcorticoid effect with a longer duration of action

Question 21

what are the disorders of adrenal function?

Answer 21

adrenocortical insufficiency
congenital adrenal hyperplasia
cushing’s syndrome
aldosteronism

Question 22

primary vs secondary adrenocortical insufficiency

Answer 22

primary: anatomic destruction of adrenal gland (autoimmune)
secondary: decreased pituitary production of ACTH

Question 23

causes for secondary adrenal insufficiency

Answer 23

ACTH deficiency due to iatrogenic and hypopituitarism

Question 24

primary adrenal insufficiency symptoms/signs

Answer 24

weakness, fatigue, nausea, vomiting, diarrhea, salt craving, postural dizziness, anorexia, weight loss, skin pigmentation

Question 25

primary adrenal insufficiency labs

Answer 25

hyponatremia, hyperkalemia, anemia, eosinophilia, azotemia

Question 26

secondary adrenal insufficiency symptoms/signs

Answer 26

same as primary except NO hyperpigmentation (ACTH is low not elevated) and near-normal aldosterone levels

Question 27

how to diagnose adrenal insufficiency

Answer 27

measure plasma cortisol level at baseline and 30-60 min after cosyntropin (synthetic ACTH) if cortisol is greater than 18 = normal if cortisol is less than 18 = abnormal

Question 28

diagnosis adrenal insufficiency: primary vs secondary

Answer 28

``` primary = low cortisol and high ACTH secondary = low cortisol and low ACTH ```

Question 29

causes for acute adrenal insufficiency "adrenal crisis"

Answer 29

rapid withdrawal of steroids from someone how has been on them for a long time

Question 30

signs/symptoms of adrenal crisis

Answer 30

volume depletion and hypotension, lassitude, nausea, vomiting, hyperkalemia, hyponatremia (mineralcorticoid deficiency, increased ADH)

Question 31

treatment of adrenal crisis

Answer 31

- support with large amounts of IV fluids | - high-dose IV glucocorticoid (dexamethasone if no previous dx of adrenal insufficiency, or hydrocortisone)

Question 32

treatment of chronic adrenal insufficiency

Answer 32

- maintenance therapy: glucocorticoid replacement (hydrocortisone 2x per day) and mineralocorticoid replacement (fludrocortison, liberal salt intake) - stress dosing

Question 33

congenital adrenal hyperplasia

Answer 33

inherited AR disorders caused by deficient adrenal corticosteroid synthesis d/t mutations of genes involved with adrenal steroidogenesis -enzyme deficiency

Question 34

what is the MCC of congenital adrenal hyperplasia? what does it cause?

Answer 34

21-hydroxylase deficiency | cuases inability to make aldosterone and cortisol which causes increased androgens

Question 35

what is measured for diagnosis of 21-hydroxylase deficiency?

Answer 35

17-OH-progesterone (if it is raised means there is 21-hydroxylase deficiency)

Question 36

21-hydroxylase deficiency treatment

Answer 36

steroids (dexmethasone, prednisone, hydrocortisone) | if salt-wasting, also add fludrocortisone

Question 37

glucocorticoid excess

Answer 37

Cushing's syndrome caused by 1. ACTH dependent (pituitary adenoma or ectopic ACTH production) 2. ACTH independent (adrenal adenoma and adrenal carcinoma) 3. iatrogenic

Question 38

signs and symptoms of Cushing's syndrome

Answer 38

weight gain (truncal), moon face, HTN, bruising, thin skin, striae, ankle edema, proximal myopathy, hirsutism, psychiatric dysfxn, backache, muscle weakness, loss of scalp hair, fractures

Question 39

cushing disease

Answer 39

pituitary ademona causing the glucocorticoid excess

Question 40

diagnosis of cushing's syndrome

Answer 40

-ACTH (high = dependent, low = independent) -24-hr urine free cortisol excretion -low-dose overnight dexamethasone suppression test (less than 1.8 is normal) -midnight salivary cortisol level need at least TWO of these tests positive

Question 41

medical treatment of cushing's syndrome

Answer 41

``` aminoglutethimide ketoconazole mitotane metyrapone mifepristone ```

Question 42

aminoglutethimide mechanism and use

Answer 42

blocks conversion of cholesterol to pregnenolone (treats cushing's)

Question 43

ketoconazole mechanism and use

Answer 43

antifungal imidazole derivative. potent, nonselective inhibitor of adrenal and gonadal steroid synthesis (treats cushing's)

Question 44

mitotane mechanism and use

Answer 44

related to DDT insecticides. nonselective cytotoxic action on adrenal cortex - bad SE (treats cushing's)

Question 45

metyrapone mechanism and use

Answer 45

relatively selective inhibitor of 11-hydroxylation. interferes with cortisol and corticosterone synthesis -can be used diagnostically to test anterior pituitary (ACTH levels should rise in compensatory response to decreased cortisol and corticosterone as should precursor 11-deoxycortisol) (treats cushing's)

Question 46

mifepristone mechanism

Answer 46

initally developed as progesterone receptor antagnoist | -has glucocorticoid receptor antagonist activity at higher concentrations (only binds glucocorticoid receptor)

Question 47

mifepristone use

Answer 47

cushing's syndrome - controls hyperglycemia secondary to hypercortisolism in adults with endogenous cushing's syndrome who have failed or are not candidates for surgery -also used for rapid treatment of cortisol-induced psychosis

Question 48

mifepristone side effects

Answer 48

fatigue, nausea, headache, hypokalemia, arthralgias, edema and endometrial thickening also: adrenal insufficiency

Question 49

pasireotide mechanism and uses

Answer 49

somatostatin analog binds to somatostatin receptors and blocks release of ACTH from the corticotropes via high affinity for somatostatin receptor subtype 5 use: cushing's disease pituitary

Question 50

pasireotide side effects

Answer 50

hyperglycemia and gastrointestinal symptoms

Question 51

aldosteronism

Answer 51

increased aldosterone, decreased renin d/t HTN and hypokalemia

Question 52

when to screen for primary aldosteronism

Answer 52

- HTN with hypokalemia - resistant HTN - adrenal incidentaloma - HTN early onselt - severe HTN

Question 53

treatment for priamry aldosteronism

Answer 53

surgery for unilateral adenoma and medical for bilateral adrenal hyperplasia (spironolactone and eplerenone - aldosterone receptor blocking agents)

Question 54

difference between spironolactone and eplerenone

Answer 54

eplerenone is newer with less antiandrogen effects

Question 55

nonendocrinologic use of corticosteroids

Answer 55

for suppressing inflammatory and immune response

Question 56

acute side effects of corticosteroids

Answer 56

insomnia, behaviour changes (hypomania, acute psychosis), acute peptic ulcers, acute pancreatitis (rare)

Question 57

withdrawal from steroid therapy

Answer 57

- adrenal suppression can occur after 2 weeks - withdrawal syndrome of anorexia, nausea, vomiting, weight loss, lethargy, headache, fever, joint or muscle pain, postural hypotension d/t dependence - need to taper off steroid therapy (2-12 months)