14 15 Adrenal Cortex - Cushing Addison Flashcards
How is cortisol regulated? Describe the feedback loop
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
ACTH
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)
Can ACTH be used cross species
Yes
What species only use cortisol
Cats, primates, horses, domestic livestock species, other mammals
What species uses cortisol and corticosterone
Dogs
What species use corticosterone
birds, rats, mice (rodents)
NO cortisol
What are some tissues that glucocorticoids affect
Metabolic, immune, blood, skeletal
What are the metabolic effects of glucocorticoids
Promotes gluconeogenisis Stimulates lipolysis promotes protein degradation stimulates glycogen formation inhibit glucose uptake by many tissues highly catabolic for most tissues
What is the only substrate that the CNS can use for energy
glucose
What are the main functions of adrenocortical steroids
maintain blood glucose - hyperglycemic
promotion glycogen storage
what are the potencies of the corticoid hormones
cortisol 3x > corticosterone = aldosterone
cortisol is the most potent
What are some immune functions of glucocorticoids
Potent anti-inflammatory role (used clinically)
Immunosuppression (at higher doses)
Potential for infections
How do glucocorticoids influence blood
increase neutrophils
decrease lymphocytes
How do glucocorticoids affect skeletal system
promote bone breakdown
Inhibits vit D
What does cortisol do at high level to T-lymphocytes
inhibit T-lymphocytes
What is the function of DHEA
primary androgen
What are the actions of DHEA and aldosterone?
- 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
What are the effects of mineralocorticoids / aldosterone
Promote Na retention and K elimination
Water retention
H ion elimination
What is an example of a mineralcorticoid
aldosterone (major one, lower species use others)
NOT regulated by the pituitary
What is another name for Hyperandrenocorticim
cushing syndrome
What is the most common cause of spontaneous Cushing
excessive ACTH production
where is Cushing syndrome most common
Older dogs
rare in cats
What is suppressed in animals with primary adenocortical tumors
ACTH and CRH
What is iatrogenic Cushings
Cushing disease induced by clinician as a secondary effect of another treatment
What is the cause of iatrogenic Cushing
Exogenous glucocorticoids causing clinical signs of cortisol excess.
Stop giving glucocorticoids
Atrophy of zona fasiculata
Adrenal suppression despite signs of cortisol excess
What are some clinical symptoms of Cushing
Polydipsia and polyuria - ~80% of dogs, most common symptom Hyperphagia Abdominal enlargement / pendulous abdomen alopecia muscle weakness / lethargy *symptoms not identical in all animals
How quick does Cushing progress
disease is slowly progressive
What are the catabolic effects of Cushing
Increase blood glucose Muscle wasting Thin skin truncal alopecia Decreased bone density
How do you diagnose Cushing
clinical symptoms Elevated cortisol - serum/plasma - urinary ACTH challenge - patients have increased capacity to make cortisol low dose Dexamethasome test (DEX)
What are two types of Cushing
1) Pituitary-dependent hyperandrenocorticism (PDH)
- more common in smaller dogs
2) Primary hyperandenocorticism / adrenocortical tumors
- equally common in both large and small breeds
What is Pituitary-dependent hyperandrenocorticism (PDH)
secondary Cushing
increased ACTH production
most common (80%)
Primary hyperadrenocorticism is caused by
adrenal tumors
What is a low dose dexamethasone (DEX) test
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
What doesn’t low dose DEX determine
difference between tumor (1’) and PHD (2’) Cushing
What does High-dose DEX test do
Suppress cortisol levels in PDH patients
cortisol levels NOT suppressed in patients with adrenal tumors
What will ACTH levels be in dogs with PDH
ACTH is elevated in PDH
What will ACTH levels be in dogs with adrenal tumors
ACTH is surpressed in adrenal tumors
What is the most common treatment of PDH (2’ Cushing)
Lysodren
What does Lysodern do to treat PDH
- concentrated in adrenal cortex; mechanism of action unknown
- Selective necrosis of zona fasiculata and reticularis
- overdose can cause hypoadrenocorticism and/or destroy zona glomerulosa
What would happen if you gave too much Lysodren to a dog
cause hypoadrenocorticism
What is Addison disease
Hypoadrenocorticism: adrenal cortical insufficiency
uncommon in dogs, rare in cats
symptoms: weight loss, lethargy, dehydration
can be 1’ or 2’
What is difference between primary and secondary diseases treatments in Addison and Cushing disease
Cushing- treated the same
Addison- different treatments
What do you use to diagnose secondary Addison
ACTH
What is the most common cause of primary adrenocortical failure
Autoimmune
What is an important cause of secondary Addison
Iatrogenic (caused by clinician)
How long does it take for ACTH to recover
months
What is the treatment of primary Addison
Saline to combat dehydration followed by glucocoriticoids and mineral corticoids
What is the treatment for secondary Addison
Glucocorticoid treatment (no need for mineralcoritoids) and identification of the underlying lesion
What does the zona glomerulosa produce
Aldosterone
What are the layers of the adrenal gland from the outside in?
Capsule Cortex - glomerulosa - fasiculata - reticularis Medulla
What hormone is produced in the adrenal cortex zona glomerulosa?
aldosterone
What hormones are produced in the adrenal cortex fasciculata / reticularis?
cortisol
corticosterone
DHEA
Androstenedione
What is the major glucocorticoid in most animals?
cortisol
How is ACTH produced?
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)
What external factors can influence corticoids
diurnal variation
stress
What are the general physiologic functions of glucocorticoids
metabolic
response to stress
immune
blood skeletal
What are some hormones that are hyperglycemic?
glucocorticoids
growth hormone
epinephrine
What is the functional value of glucocorticoids
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
What is the effect of glucocorticoids on the immune system?
inhibit the immune system
- inhibit inflammation (phospholipase)
- inhibit T-lymphocytes (cell-mediated immunity)
- dose-dependent
replacement physiological dose
antiinflammatory dose
immunosuppressive doseHow does stress affect glucocorticoids?
long term stress response
- proteins and fats converted to glucose or broken down for energy
- increased blood sugar
- suppression of immune system
What sex steroids are produced by the zona fasciulata / reticularis?
DHEA
Androsteinedione a precursor molecule to testosterone which in turn a is precursor to the estrogens
What is Spontaneous Cushing?
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
What is Primary hyperandenocorticism
primary Cushing
caused by adrenal tumors
can be carcinomas or adenomas
Differentiating Primary and Secondary Cushing
abdominal ultrasound
normal adrenals: PDH secondary Cushing
adrenal tumor: primary Cushing
How do you treat Primary Cushing / Adrenal Tumors
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
What is primary Addison (hypoadrenocorticism) disease? How is it diagnosed?
decreased glucocorticoids cause lethargy and weakness critical symptoms (dehydration) due to lack of mineral corticoids
diagnosis: hypoatremia, hyperkalemia
What is secondary Addison (hypoadrenocorticism) disease? How is it diagnosed?
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
etiology of hypoadrenocorticism
loss of 85-90% of adrenocortical cells required before clinical symptoms appear
1’ adrenocortical failure-most common
- frequently autoimmune
2’ adrenocortical failure
iatrogenic hypoadrenocorticism
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)
What is Equine Cushing or pituitary pars intermedia dysfunction (PPID)
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
How to you diagnose Equine Cushing
low dose dexamethasone test
elevated ACTH
How do you treat Equine Cushing
pergolide (Prasend) - dopamine agonsit also used to treat Parkinson’s disease in humans
not curative
