Adrenocorticosteroids

Question 1

MOA of somatropin/somatrem

Answer 1

agonists of growth hormone receptor (won’t be effective if the receptor is defective)

Question 2

MOA of mecasermin

Answer 2

analog of insulin like growth factor 1 (IGF-1)

Question 3

glucocorticoids are steroid hormones that bind to the receptor in ______ (part of cell) and then causes ______

Answer 3

cytoplasm and then this complex binds to the promoter region in the DNA (Glucocorticoid response element) which then ↑ transcription of proteins

Question 4

cortisol causes glycogen synthesis/degradation

Answer 4

glycogen synthesis (quick available energy for fight/flight)

also ↑ gluconeogenesis

Question 5

what bone pathology is related to cortisol release

Answer 5

osteoporosis because it has catabolic effects on bone

Question 6

where can we see catabolic effects of cortisol?

Answer 6

• bone
• protein
• peripheral fat and skin (↑ lipolysis)
• lymphoid and connective tissue
• muscle

Question 7

what is a side effect of glucocorticoids in children?

Answer 7

• growth retardation

Question 8

cortisol causes ↓ T and B cells, monocytes, eosinophils and basophils but ↑ _______ (overall IMMUNOSUPPRESSIVE)

Answer 8

neutrophils

Question 9

why is cortisol immunosuppressive even thought you see neutrophilia

Answer 9

• cortisol ↓’s the expression of selectin so then immune cells cannot migrate to sites of infection

Question 10

glucocorticoids (cortisol) causes vaso_______

Answer 10

vasoconstriction due to the suppression of mast cell degranulation because there is ↓ histamine release and capillary permeability

Question 11

what are the major anti inflammatory effects of cortisol in the production of lipoxygenases and cyclooxygenases

Answer 11

• ↑ annexin I (inhibits PLA2)
• ↑ IkB (↓ NF-KB → ↓ expression of Cycloxygenase 2)
• ↑ MAPK phosphatase I (inactivates PLA2 and other MAPK activated pro inflammatory pathways )

Question 12

mineralocorticoids have a similar MOA to that of glucocorticoids.
mineralocorticoids cause ↑ expression of _____ and _____

Answer 12

Na/K ATPase and ENaC

Question 13

Fludracortisone is a _______

Answer 13

synthetic mineralocorticoid (aldosterone)

Question 14

metabolic acidosis/alkalosis is an AE of mineralocorticoids

Answer 14

metabolic alkalosis (↑ excretion of K and H)

Question 15

glucocorticoids given for long term have low/high salt retaining properties

Answer 15

LOW;

ex. triamcinolone and dexamethasone

Question 16

discuss the anti-inflammatory and salt retaining activity of mineralocorticoids

Answer 16

high salt retaining activity

lower anti inflammatory activity

Question 17

what is Addison’s disease

Answer 17

adrenocortical insufficiency;
weakness, fatigue, weight loss, hypotension, hyperpigmentation (↑ ACTH), cannot maintain blood glucose levels during fasting

Question 18

what is the treatment for Addison’s disease

Answer 18

• daily oral hydrocortisone + mineralocorticoid (fludrocortisone)

CHRONIC SETTING

DO NOT give glucocorticoids that don’t have salt retaining effects because these patients don’t have mineralocorticoids or glucocorticoids

Question 19

what is the treatment plan of acute adrenocortical insufficiency

Answer 19

large amounts of corticosteroids + fluids/electrolytes

give salt retaining hormone one hydrocortisone levels are reduced

Question 20

what is the difference between Cushing’s Disease and Cushing’s syndrome

Answer 20

Cushing’s Disease: due to ACTH production from the pituitary

Cushing’s syndrome: excess corticosteroids due to other reasons

Question 21

in addition to buffalo hump, moof facies, truncal obesity, emotional disturbances and peripheral muscle wasting, what are tother clinical features of Cushing’s Disease

Answer 21

skin ulcers (due to poor wound healing as a result of ↑ cortisol) and purpura

Question 22

_________ (drug) is given to treat hyperaldosteronism

Answer 22

spironolactone

Question 23

________ suppression test is used to diagnose Cushing’s syndrome

Answer 23

dexamethasone; will see suppression of cortisol in individuals with pituitary dependent Cushing’s syndrome (NOT from adrenal tumor)

Question 24

what type of drug is mifepristone?

Answer 24

glucocorticoid antagonist (and a antagonist at progesterone receptor)

Question 25

what type of drug is spironolactone

Answer 25

mineralocorticoid antagonist by being a competitive inhibitor at the aldosterone receptor and also a androgen antagonist

Question 26

what are 3 clinal applications of spironolactone

Answer 26

- aldosteronism - hirsutism in women (acts as an androgen antagonist) - diuretic

Question 27

what drug would you use in someone with an inoperable ectopic ACTH syndrome/adrenal carcinoma

Answer 27

mifepristone

Question 28

what type of mineralocorticoids should be given to patients with Addison's?

Answer 28

those with salt retaining ability such as fludrocortisone

Question 29

what is the result of administering aminogluthemide? How?

Answer 29

causes the reduction in synthesis of ALL hormonally active steroids because it inhibits the conversation of cholesterol to pregnenolone

Question 30

_________ inhibits the conversation of cholesterol to pregnenolone

Answer 30

aminogluthemide

Question 31

________ is a drug that can be used to inhibit both adrenal and gonadal steroid synthesis

Answer 31

ketoconazole

Question 32

_________ is the only steroid inhibiting drug that can be given to pregnant patients with Cushing's

Answer 32

Metyrapone

Question 33

what is the MOA of metyrapone?

Answer 33

inhibits 11 β hydroxylase which converts 11 deoxycortisol to cortisol

Question 34

what are AE of metyrapone

Answer 34

- salt and water retention - hirsutism (↑ androgen synthesis due to shunting form inhibiting 11 β hydroxyls) - dizziness - GI disturbances

Question 35

in addition to clinical features, diagnosis ________ deficiency can be confirmed by a high level of 17 α hydroxyprogesterone in the blood in a morning sample

Answer 35

21 hydroxylase deficiency

Question 36

with CAH deficiency can present as MALE ambiguous genitalia?

Answer 36

17 α hydroxylase deficiency because there is dec production fo sex steroids (and ↓ production of glucocorticoids) resulting I reduced levels of both gonadal and adrenal sex hormones females will have delayed puberty and absent secondary sexual characteristics or primary amenhorrhea

Question 37

do you see HTN with 17 α hydroxylase deficiency

Answer 37

NO because aldosterone is under the control of the RAAS\

Question 38

plasma metanephrine testing (more sensitive) or 24 hour urinary metanephrines (more specific) is used to screen for ________

Answer 38

pheochromocytoma

Question 39

the most common product that is secreted in neuroblastoma is ______ but catecholamines are also secreted

Answer 39

dopamine; (metabolites: HVA and VMA)