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Endocrine (updated 2016) > 14 15 Adrenal Cortex - Cushing Addison > Flashcards

14 15 Adrenal Cortex - Cushing Addison Flashcards

1
Q

How is cortisol regulated? Describe the feedback loop

A

1) Higher brain centers stimulate the hypothalamus to produce CRH
2) CRH > portal system to stimulate production of ACTH by the Anterior Pituitary
3) ACTH > blood stream and stimulates the inner zone of adrenal cortex to release cortisol
4) cortisol > blood stream to affect target cells/tissues and INHIBITS secretion of CRH and ACTH

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2
Q

ACTH

A

39 aa polypeptide (protein hormone)
postions 1-24 common to ACTH in ALL species
high species conservation

Stimulates growth and steroid production of zona fasiculata and reticualris of adrenal cortex

acts via cAMP (2nd messenger)

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3
Q

Can ACTH be used cross species

A

Yes

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4
Q

What species only use cortisol

A

Cats, primates, horses, domestic livestock species, other mammals

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5
Q

What species uses cortisol and corticosterone

A

Dogs

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6
Q

What species use corticosterone

A

birds, rats, mice (rodents)

NO cortisol

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7
Q

What are some tissues that glucocorticoids affect

A

Metabolic, immune, blood, skeletal

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8
Q

What are the metabolic effects of glucocorticoids

A 
Promotes gluconeogenisis
Stimulates lipolysis
promotes protein degradation
stimulates glycogen formation
inhibit glucose uptake by many tissues
highly catabolic for most tissues
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9
Q

What is the only substrate that the CNS can use for energy

A

glucose

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10
Q

What are the main functions of adrenocortical steroids

A

maintain blood glucose - hyperglycemic

promotion glycogen storage

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11
Q

what are the potencies of the corticoid hormones

A

cortisol 3x > corticosterone = aldosterone

cortisol is the most potent

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12
Q

What are some immune functions of glucocorticoids

A

Potent anti-inflammatory role (used clinically)
Immunosuppression (at higher doses)
Potential for infections

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13
Q

How do glucocorticoids influence blood

A

increase neutrophils

decrease lymphocytes

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14
Q

How do glucocorticoids affect skeletal system

A

promote bone breakdown

Inhibits vit D

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15
Q

What does cortisol do at high level to T-lymphocytes

A

inhibit T-lymphocytes

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16
Q

What is the function of DHEA

A

primary androgen

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17
Q

What are the actions of DHEA and aldosterone?

A
  • may play a role in development of secondary sexual characteristics at puberty
  • Substrates for estrogens
  • may play a role in the preventing degenerative changes in aging
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18
Q

What are the effects of mineralocorticoids / aldosterone

A

Promote Na retention and K elimination
Water retention
H ion elimination

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19
Q

What is an example of a mineralcorticoid

A

aldosterone (major one, lower species use others)

NOT regulated by the pituitary

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20
Q

What is another name for Hyperandrenocorticim

A

cushing syndrome

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21
Q

What is the most common cause of spontaneous Cushing

A

excessive ACTH production

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22
Q

where is Cushing syndrome most common

A

Older dogs

rare in cats

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23
Q

What is suppressed in animals with primary adenocortical tumors

A

ACTH and CRH

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24
Q

What is iatrogenic Cushings

A

Cushing disease induced by clinician as a secondary effect of another treatment

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25
Q

What is the cause of iatrogenic Cushing

A

Exogenous glucocorticoids causing clinical signs of cortisol excess.
Stop giving glucocorticoids
Atrophy of zona fasiculata
Adrenal suppression despite signs of cortisol excess

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26
Q

What are some clinical symptoms of Cushing

A 
Polydipsia and polyuria
 - ~80% of dogs, most common symptom
Hyperphagia
Abdominal enlargement / pendulous abdomen
alopecia
muscle weakness / lethargy
*symptoms not identical in all animals
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27
Q

How quick does Cushing progress

A

disease is slowly progressive

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28
Q

What are the catabolic effects of Cushing

A 
Increase blood glucose
Muscle wasting 
Thin skin
truncal alopecia
Decreased bone density
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29
Q

How do you diagnose Cushing

A 
clinical symptoms
Elevated cortisol
 - serum/plasma
 - urinary
ACTH challenge
 - patients have increased capacity to make cortisol
low dose Dexamethasome test (DEX)
30
Q

What are two types of Cushing

A

1) Pituitary-dependent hyperandrenocorticism (PDH)
- more common in smaller dogs
2) Primary hyperandenocorticism / adrenocortical tumors
- equally common in both large and small breeds

31
Q

What is Pituitary-dependent hyperandrenocorticism (PDH)

A

secondary Cushing
increased ACTH production
most common (80%)

32
Q

Primary hyperadrenocorticism is caused by

A

adrenal tumors

33
Q

What is a low dose dexamethasone (DEX) test

A

can be used to diagnose If animal has Cushing
Normal animal : low dose DEX suppresses ACTH and secondary cortisol

Abnormal animal: low dose DEX does NOT suppress cortisol in animal with 1’ or 2’ Cushing

*does NOT distinguish 1’ vs 2’ Cushing

34
Q

What doesn’t low dose DEX determine

A

difference between tumor (1’) and PHD (2’) Cushing

35
Q

What does High-dose DEX test do

A

Suppress cortisol levels in PDH patients

cortisol levels NOT suppressed in patients with adrenal tumors

36
Q

What will ACTH levels be in dogs with PDH

A

ACTH is elevated in PDH

37
Q

What will ACTH levels be in dogs with adrenal tumors

A

ACTH is surpressed in adrenal tumors

38
Q

What is the most common treatment of PDH (2’ Cushing)

A

Lysodren

39
Q

What does Lysodern do to treat PDH

A
  • concentrated in adrenal cortex; mechanism of action unknown
  • Selective necrosis of zona fasiculata and reticularis
  • overdose can cause hypoadrenocorticism and/or destroy zona glomerulosa
40
Q

What would happen if you gave too much Lysodren to a dog

A

cause hypoadrenocorticism

41
Q

What is Addison disease

A

Hypoadrenocorticism: adrenal cortical insufficiency
uncommon in dogs, rare in cats
symptoms: weight loss, lethargy, dehydration
can be 1’ or 2’

42
Q

What is difference between primary and secondary diseases treatments in Addison and Cushing disease

A

Cushing- treated the same

Addison- different treatments

43
Q

What do you use to diagnose secondary Addison

A

ACTH

44
Q

What is the most common cause of primary adrenocortical failure

A

Autoimmune

45
Q

What is an important cause of secondary Addison

A

Iatrogenic (caused by clinician)

46
Q

How long does it take for ACTH to recover

A

months

47
Q

What is the treatment of primary Addison

A

Saline to combat dehydration followed by glucocoriticoids and mineral corticoids

48
Q

What is the treatment for secondary Addison

A

Glucocorticoid treatment (no need for mineralcoritoids) and identification of the underlying lesion

49
Q

What does the zona glomerulosa produce

A

Aldosterone

50
Q

What are the layers of the adrenal gland from the outside in?

A 
Capsule
Cortex
 - glomerulosa
 - fasiculata
 - reticularis
Medulla
51
Q

What hormone is produced in the adrenal cortex zona glomerulosa?

A

aldosterone

52
Q

What hormones are produced in the adrenal cortex fasciculata / reticularis?

A

cortisol
corticosterone
DHEA
Androstenedione

53
Q

What is the major glucocorticoid in most animals?

A

cortisol

54
Q

How is ACTH produced?

A

protein hormone produced by the anterior pituitary from a pro-opiomelanocortin molecule via proteolytic processing:

signal sequence + pre-pro-oprionmelanocortin
pro-opiomelanocortin (gets cleaved)
ACTH + (β-lipotropin)
ACTH + (𝛾-lipotropin + β-endorphin)

55
Q

What external factors can influence corticoids

A

diurnal variation

stress

56
Q

What are the general physiologic functions of glucocorticoids

A

metabolic
response to stress
immune
blood skeletal

57
Q

What are some hormones that are hyperglycemic?

A

glucocorticoids
growth hormone
epinephrine

58
Q

What is the functional value of glucocorticoids

A

rise in glucocorticoids during periods of reduced food availability will help to maintain serum glucose concentrations for CNS function at the expense of fat and protein

59
Q

What is the effect of glucocorticoids on the immune system?

A 
inhibit the immune system
 - inhibit inflammation (phospholipase)
 - inhibit T-lymphocytes (cell-mediated immunity)
 - dose-dependent 
     replacement physiological dose
     antiinflammatory dose
     immunosuppressive dose
60
Q

How does stress affect glucocorticoids?

A

long term stress response

  • proteins and fats converted to glucose or broken down for energy
  • increased blood sugar
  • suppression of immune system
61
Q

What sex steroids are produced by the zona fasciulata / reticularis?

A

DHEA

Androsteinedione a precursor molecule to testosterone which in turn a is precursor to the estrogens

62
Q

What is Spontaneous Cushing?

A

most commonly (80%) due to excessive ACTH production (2’) pituitary-dependent hyperadrenocorticism

can also arise from primary (1’) adrenocortical tumors

  • can be adenomas or carcinomas
  • both ACTH and CRH suppressed in animals w/ 1’ tumors
63
Q

What is Primary hyperandenocorticism

A

primary Cushing
caused by adrenal tumors
can be carcinomas or adenomas

64
Q

Differentiating Primary and Secondary Cushing

A

abdominal ultrasound
normal adrenals: PDH secondary Cushing
adrenal tumor: primary Cushing

65
Q

How do you treat Primary Cushing / Adrenal Tumors

A

adrenalectomy is treatment of choice
~50 of tumors malignane
Ketoconazole or Triostane to suppress cortisol is a non-surgical alternative
Lysodren can be used to chemoblate the tumor

66
Q

What is primary Addison (hypoadrenocorticism) disease? How is it diagnosed?

A 
decreased glucocorticoids cause lethargy and weakness
critical symptoms (dehydration) due to lack of mineral corticoids

diagnosis: hypoatremia, hyperkalemia

67
Q

What is secondary Addison (hypoadrenocorticism) disease? How is it diagnosed?

A

naturally occurring disease (rare)
- reduced secretion of ACTH by pituitary or CRH secreted by hypothalamus
iatrogenic

diagnosis: measure ACTH, cortisol measurement ACTH, cortisol after ACTH administration

68
Q

etiology of hypoadrenocorticism

A

loss of 85-90% of adrenocortical cells required before clinical symptoms appear
1’ adrenocortical failure-most common
- frequently autoimmune
2’ adrenocortical failure

69
Q

iatrogenic hypoadrenocorticism

A

lack of stimulation to the adrenals cause long term atrophy
- long-term exogenous glucocorticoid administration
abrupt cessation of glucocorticoid admin → inability of adrenals to supply body’s needs → signs of deficiency

recovery is slow (months)

70
Q

What is Equine Cushing or pituitary pars intermedia dysfunction (PPID)

A

results from tumor producing excessive amounts of ACTH in the pars intermedia (middle region of pituitary)

symptoms: same as in canine Cushing plus long wavy hair that doesn’t shed and laminitis

71
Q

How to you diagnose Equine Cushing

A

low dose dexamethasone test

elevated ACTH

72
Q

How do you treat Equine Cushing

A

pergolide (Prasend) - dopamine agonsit also used to treat Parkinson’s disease in humans

not curative

Endocrine (updated 2016) (19 decks)

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