Hypercortisolism Flashcards
What does Cushing’s syndrome describe?
Chronic exposure to excess glucocorticoids (cortisol)
What is the glucocorticoid released by the adrenal cortices?
Cortisol
What is cortisol release controlled by?
ACTH release from the pituitary gland
What is ACTH release determined by?
CRH from the hypothalamus
What form of spontaneous HC is most common?
Pituitary dependent hypercortisolism (PDH)
What type of dogs is PDH more commonly seen in?
Small dogs
(mini poodle, dachshund, beagle, boston)
Where is the tumor in PDH?
Anterior pituitary
What does chronic stimulation by ACTH in PDH cause?
Bilateral adrenal enlargement
What breed of dogs are predisposed to AT?
German Shepherds
What would the expected endogenous ACTH release be in AT?
Very low due to negative feedback
What happens to the contra-lateral adrenal gland in AT?
Becomes atrophied
Cushing’s is:
An exam room diagnosis
Must see signs and have appropriate history
What are the signs of HC?
Polyuria
Polydipsia
Polyphagia
Difficulty jumping
Pot-bellied appearance
Stretching of carpal and tarsal ligaments
Bad hair coat
Where would you expect the lowest point of the abdomen to be in a HC patient?
The liver
Cranial abdominal organomegaly
Very consistent finding in HC dogs
What skin condition would be pathognomonic for HC?
Calcinosis cutis
What are potential consequences of HC?
Chronic infections
Poor healing post injury or surgery
Hypertension
Proteinuria
Pulmonary thromboembolism
Decrepitude
Poor quality of life
Only pursue a work-up for HC if one of the following applies:
Owner has a complaint
Clinical impression
Medical issue suggests HC
What findings on a CBC would be supportive of HC in a clinical patient?
Stress leukogram (neutrophilia, lymphopenia, monocytosis, eosinopenia)
Hematocrit is often increased
Platelets are often increased
What findings on a chemistry would be supportive of HC in a clinical patient?
Elevated ALP is the most consistent finding in dogs (usually 10-20x baseline)
Cholesterol is elevated (~350-380)
(Less consistently: mild elevation in glucose, BUN may be low, elevation in phosphorus)
What findings on urine analysis would be supportive of HC in a clinical patient?
Urine is usually dilute
UTI is common
Significant proteinuria is common
How long should you discontinue use of oral and topical steroids before adrenal testing?
> 72 hours
How long should you discontinue use of depo shots before adrenal testing?
> 4 weeks
When is the ACTH stim test routinely used for?
Monitoring of patients on treatment for HC
What will show an exaggerated response to the ACTH stim test?
Dogs with HC, chronic non-adrenal illness, dogs with AT (sometimes - can also be normal or flat line)
Why can the ACTH stim test be negative in dogs with AT?
The tumor may not have receptors for ACTH
Is the ACTH stim test good for cats?
No, very inaccurate
What is the protocol for the ACTH stim test?
Obtain a baseline blood sample, inject 5 micrograms/kg IM of cosyntropin, collect second serum sample after 60 mins
How do you interpret an ACTH stim test?
Normal dogs are usually between 7-17 micrograms/dl
Post-ACTH stim cortisol >22 micrograms/dl indicates HC in a dog
A flat line response (pre and post are <5 micrograms/dl) in a dog with signs of HC indicates iatrogenic disease or may be seen in AT
What does the LDDST investigate?
The feed-back loop between the adrenals and pituitary/hypothalamus
If the HPA axis is working appropriately, what should dexamethasone do?
Suppress CRF from the hypothalamus thereby stopping ACTH release by the pituitary gland
How long should cortisol release by the adrenals be stopped after administering dexamethasone?
At least 12 hours
With PDH, what should be expected after administration of dexamethasone?
Pituitary tumor is transiently inhibited or not affected at all by the dex
Cortisol production is evident at 8 hours post dose
With an AT, what should be expected after administration of dexamethasone?
No inhibition of cortisol production
Cortisol production continues unchanged over the 8 hours
What is the protocol for a LDDST?
Obtain a baseline blood sample, inject dexamethasone IV (0.01 mg/kg in dogs; 0.1 mg/kg in cats), collect second blood sample 4 hours later, collect third blood sample 8 hours later
What does a baseline cortisol tell you?
Nothing
How do you interpret a LDDST?
Look at the 8 hour value first
<1.4 mcg/dl indicates suppression of the HPA axis
>1.4 mcg/dl indicates HPA axis dysfunction
If the 8 hour value was >1.4 mcg/dl, look at the 4 hour value
<1.4 mcg/dl or <50% of baseline at 4 hours indicates PDH
Can you assume a dog has an AT if there is no suppression?
No
What test is generally regarded as superior to the ACTH stim test in dogs?
LDDST
What is the test of choice for cats with HC?
LDDST
What can you determine by a urine cortisol : creatinine ratio?
A normal result essentially rules out HC
What would you expect to see on ultrasonography of PDH?
Bilateral adrenal gland enlargement
Generally, fairly symmetrical
Some nodular changes are common
What would you expect to see on ultrasonography of a AT?
One large gland
Check for mets and invasion of surrounding structures
May note atrophied gland on the other side
What might radiography reveal?
AT, 50% are calcified and are visible on a lateral view
Does calcification of an AT indicate malignant potential?
No
What would you expect the endogenous ACTH level to be in PDH?
Elevated or normal
What would you expect the endogenous ACTH level to be in an AT?
Very low or undetectable
What is the current standard approach in dogs for PDH?
Medical therapy
What is the MOA for Trilostane?
Reversible enzyme inhibitor
Inhibits 3bHSD
What is 3bHSB essential for?
Synthesis of cortisol from cholesterol
How long does Trilostane last?
About 18 hours in most dogs
Administered with food in the morning
What is the recommended dosing?
Once daily for most dogs
BID in diabetics
BID if the effect wears off too soon (escape at night)
What is the recommended daily dose to start with?
2-3 mg/kg total daily dose
Round down to nearest capsule size
What is the recommended recheck schedule?
2 weeks after starting, 2-4 weeks later, 3 months later, and then every 4-6 months long term
What should you always do if the dog is unwell on recheck?
ACTH stim test
What might you see on a chem during a recheck and what does it indicate?
Increased potassium, indicates suppression of aldosterone, must decrease trilostane dose
If you get a result <0.7 mcg/dl in a post-acth stim cortisol what would you do?
Stop trilostane and do not restart until patient shows signs of HC
If you get a result 0.7-2.0 mcg/dl in a post-acth stim cortisol what would you do?
Stop trilostane for 48 hours, restart at 50% of previous dose
If you get a result 2.0-7.0 mcg/dl in a post-acth stim cortisol what would you do?
Continue at present dose
If you get a result >7 mcg/dl in a post-acth stim cortisol what would you do?
Consider a 25-50% increase if patient shows signs of HC
If the patient is clinically doing well, what tests might you run to ensure dosing is correct?
4 hr post dose cortisol or pre-trilostane cortisol
If you get a result >5.5 mcg/dl on a 4 hr post dose cortisol, what would you do?
Increase the dose by 25-50%
If you get a result >5 mcg/dl on a pre-trilostane cortisol, what would you do?
Increase dose by 25-50%
If you get a result >3 mcg/dl on a pre-trilostane cortisol with clinical signs, what would you do?
Increase dose by 25%
What is the most important factor when deciding about dose adjustments?
Clinical status
What are you going to do if a dog becomes ill on trilostane?
Stop trilostane, check electrolytes to rule out adrenal necrosis, do an ACTH stim test to assess adrenal function
What are the options for treatment of an AT?
Surgery
Medical therapy (Trilostane)
What is feline hyperadrenocorticism associated with?
Diabetes mellitus
What are the clinical signs of HC in a cat?
Unlikely to be pu/pd unless diabetic
Eat well but not ravenous
Skin issues are common - FRAGILE
Ventral alopecia
Plantigrade stance
Pot-belly appearance
Folded ear tips (pathognomonic, uncommon)
What laboratory changes are common in cats with HC?
Variable hyperglycemia
Hypercholesterolemia
NO increase in ALP
