Adrenal Cortex

Question 1

Describe the parent molecule that all adrenal steroids are derived.

Answer 1

Cholesterol; Is modified by enzymes to make other steroid hormones

Question 2

List the major actions of glucocorticoids

Answer 2

You don’t want lots of glucocorticoids floating around all of the time. Rise in glucocorticoids during periods of reduced food availability will help maintain serum glucose concentrations for CNS function at the expense of fat and protein; CNS only uses glucose Physiological function of glucocorticoids: Metabolic: Glucose “sparing – promotes gluconeogenesis, Stimulates lipolysis, Promotes protein degradation, Stimulates glycogen formation, Inhibits glucose uptake by many tissues, Catabolic for most tissues Response to stress Immune- Potent anti-inflammatory role (used clinically), Immunosuppression (at higher doses), Potential for infections Blood- Increases neutrophils, decrease lymphocytes Skeletal- Can promote bone breakdown, Inhibits vitamin D

Question 3

List stimuli that alter ACTH secretion

Answer 3

cortisol inhibits secretion of CRH and ACTH; CRH stimulates the production of ACTH

Question 4

Describe the actions of aldosterone on ion metabolism

Answer 4

not regulated by the pituitary; promotes Na retention and K elimination, involved in water retention and H ion elimination

Question 5

Describe with diagrams the regulatory system that controls the secretion rate of aldosterone

Answer 5

Question 6

Describe with diagrams the regulatory system that controls the secretion rate of cortisol

Answer 6

Question 7

List the major symptoms of Cushing’s disease in the dog

Answer 7

PU/PD, hyperphagia, abdominal enlargement (pendulous), alopecia, muscle weakness, lethargy

Question 8

Describe the effect of ACTH on the adrenal cortex

Answer 8

acts on the 2 inner zones, promotes the secretion of glucocorticoids (cortisol/corticosterone)

Question 9

Describe the mechanism of ACTH action

Answer 9

acts via cAMP, negative feedback system loop

Question 10

Describe the role glucorticoids play in regulating ACTH secretion

Answer 10

negative feedback loop, high levels of cortisol suppress CRH/ACTH production

Question 11

Name two species where cortisol is the most critical glucocorticoid

Answer 11

cats, horses

Question 12

Name two species where corticosterone is the most critical glucocorticoid

Answer 12

rats, mice

Question 13

Name a species where both cortisol and corticosterone are major glucocorticoids

Answer 13

dogs

Question 14

Describe why administration of synthetic glucocorticoid causes atrophy of the adrenal zones that normally make glucocorticoid

Answer 14

exogenous cortisol in system, decrease CRH/ACTH (feedback), decrease endogenous cortisol secretion, atrophy of cells

Question 15

Describe why a hypoglucocorticoid state frequently results following cessation of exogenous glucocorticoid treatment

Answer 15

atrophy of cells, ACTH stimulation of endogenous cortisol not as effective

Question 16

Define and describe iatrogenic Cushing’s.

Answer 16

Clinical caused by treatment of other disorders by high doses of cortisol; ex.- use of glucocorticoids in immune suppression can lead to a short term Cushnoid state

Question 17

Explain what sex steroids are produced by the adrenal cortex

Answer 17

Zona reticularis- DHEA: primary androgen; androstenedione

Question 18

Explain the actions of sex steroids produced by the adrenal cortex

Answer 18

DHEA/androstenedione- development of secondary sex characteristics at puberty; serve as substrates for production of estrogens; may play role in preventing degenerative changes in ageing

Question 19

Describe why production of high levels of adrenal steroids sometimes leads to estrogenic effect

Answer 19

Because they can serve as substrates for the production of estrogens

Question 20

Describe the effect of glucocorticoids on the immune system

Answer 20

high doses can cause immunosuppression

• inhibits inflammation/T-lymphocytes production

Question 21

Understand the mechanism of action and principle toxicities of the adrenolytic drug o,p’-DDD (mitotane) and appropriate approaches to its use for the treatment of hyperadrenocorticism

Answer 21

selective necrosis of inner zone cells (mechanism unknown); used in treatment of secondary or PDH (pituitary-dependent hyperadrenocorticism)

Question 22

DHEA

Answer 22

primary androgen, sex steroid produce by the adrenal gland (zona reticularis)

Question 23

androstenedione

Answer 23

sex steroid produced by the adrenal gland (zona reticularis)

Question 24

glucocorticoid

Answer 24

cortisol/corticosterone; produced by adrenal gland; diurnal variation, can be influenced by stress

Question 25

mineralocorticoid

Answer 25

produced by the adrenal gland in the zona glomerulosa/articuate; not regulated by the pituitary; promotes Na retention, K elimination, water retention, H ion elimination

Question 26

zona glomerulosa

Answer 26

produces mineralcorticoids, not regulated by the pituitary gland

(salt)

Question 27

zona fasiculata

Answer 27

produces glucocorticoids (cortisol/corticosterone); acted on by ACTH from pituitary

(sugar)

Question 28

zona reticularis

Answer 28

produces sex steroids (DHEA/androstenedione); acted on by ACTH from pituitary

(sex)

Question 29

corticosterone

Answer 29

only glucocorticoid in birds, rats, mice

dogs have both corticosterone and cortisol

Question 30

T cells

Answer 30

T cell production is inhibited by high doses of glucocorticoids if given at an immunosuppressive dose

Question 31

compare/contrast long and short term stress

Answer 31

long term stress: adrenal cortex; leads to retention of sodium and water by kidneys, increased blood volume and blood pressure, proteins and fats converted to glucose or broken down for energy, increased blood sugar, suppression of immune system

short term stress: adrenal medulla; release of catecholamines; increased HR, BP, liver converts glycogen to glucose and releases glucose to the blod, dilation of bronchioles, increased metabolic rate, changed blood flow

Question 32

Cushing’s syndrome

Answer 32

Hyperadrenocorticism

Diagnosis- ACTH challenge (suppressed in primary, elevated in secondary)

Primary- tumor; tumor removal

Secondary- PDH; treatment- mitotane, selective destruction of cells

symptoms- PU/PD, pendulous abdomen, hyperphagia, lethargy, muscle weakness

Question 33

Addison’s disease

Answer 33

Hypoadrenocorticism

Primary (most common)- includes changes in Na and K values as well; treat with glucocorticoids and mineralcorticoids

Secondary- can be natural or iatrogenic; diagnose with ACTH stim test; treat with glucocorticoids

Symptoms- weight loss, lethargy, hypovolemia

Question 34

ACTH challenge

Answer 34

159-161

Question 35

iatrogenic

Answer 35

clinically caused; ex.- Primary hypoadrenocorticism

Question 36

hydrocortisone

Answer 36

short-acting glucocorticoid, weak, common in OTC topicals

Question 37

prednisone/prednisolone

Answer 37

intermediate acting, 4x more potent that hydrocortisone; has glucocorticoid and mineralcorticoid affects

(oral)

Question 38

dexamethasone

Answer 38

long acting, only glucocorticoid effects; 25-30x more potent than hydrocortisone

(injection)

Question 39

adrenolytic

Answer 39

inhibiting the action of the adrenergic nerves, or the response to epinephrine

Question 40

Lysodren

Answer 40

used in chemotherapy of adrenal tumors in hyperadrenocorticism