Endo Exam 2

Cushings

Hyperadrenocorticism aka...

Aldosterone

The glomerulosa of the adrenal cortex produces _________.

Cortisol

The fasciculata of the adrenal cortex produces ________

Sex hormones

The reticularis of the adrenal cortex produces ________

Adrenal glands

HPA axis:

Hypothalamus > pituitary > _____________

Pituitary, adrenal

Cushing's can be either ________ or ________ dependent

Pituitary

Cushing's is usually ________ (pituitary/adrenal) dependent in dogs (85%)

ACTH

PDH Cushing's happens because there is a functional tumor in the pituitary that produces _________

Iatrogenic (exogenous glucocorticoids), food-dependent hypercortisolemia, ectopic tumor

What are the other rare forms of false cushings? (not adrenal/pituitary tumors)

3

A microadenoma is less than ___mm in diameter

3-10

Adenomas are ____mm

10

Macroadenomas are greater than ___mm in diameter

Macroadenoma

If a dog has cushing's and develops neuro signs, it's definitely a ____________.

Microadenomas

Most pituitary tumors are _________.

Pars distalis

Most pituitary tumors are found on the __________ (

Mass on pituitary causes increased ACTH production, which stimulates the adrenal glands to hypertrophy and increase cortisol production

Describe how pituitary-dependent cushing's works

Mass on adrenal gland causes increased cortisol production, which downregulates ACTH production from PG leading to atrophy of contralateral adrenal gland

Describe how adrenal-dependent cushing's works

50

____ of adrenal tumors are malignant

50

___ of adrenal tumors become mineralized

Adrenal

Pituitary or adrenal dependent Cushing's:

Contralateral adrenal atrophy

Iatrogenic HAC

What's it called when I give a dog prednisone and he develops cushing's signs?

0.5

Iatrogenic cushings is relatively common and dose as small as ___mg/kg/day can cause it.

Certain dogs are more sensitive to GCs than others

What is the typical signalment for pituitary dependent hyperadrenocorticism?

>20kg, older female dogs

What is the typical signalment for adrenal dependent hyperadrenocorticism?

Pituitary

Pituitary or adrenal dependent Cushing's:

Dachshunds, poodles, boxers, and terriers are most commonly affected

Adrenal

Pituitary or adrenal dependent Cushing's:

Seen more in females

Pituitary

Pituitary or adrenal dependent Cushing's:

Seen more in dogs less than 20kg

Polyphagia, PU/PD, pot belly, symmetrical alopecia, panting, MSK weakness

What are common cushing's clinical signs?

Elevated cortisol interferes with ADH

Why does cushing's cause PU/PD?

Hepatomegaly, full bladder, abdominal muscle weakness, fat redistribution

Why do cushing's dogs have pot bellies?

Very thick skin

Which of these is not a Cushing's-associated dermatologic problem?

•Alopecia

•Slow hair growth

•Hyperpigmentation

•Very thick skin

•Non-healing wounds

Calcinosis cutis

What is this cushing's-associated lesion (that is often seen peri-vulvar, on trunk, or on abdomen)

False

True/False: Cushing's is usually a grave prognosis

Thromboembolism, renal disease, diabetes mellitus, dystrophic calcification

What are some (uncommon) sequelae associated with Cushing's?

Stress leukogram, mild polycythemia, thrombocytosis

What can you see on the CBC for a cushing's pt?

Mature neutrophilia and lymphopenia

What's a stress leukogram? ;)

Elevated ALP and cholesterol, mild elevated glucose and ALT

What can you see on biochem panel for a cushing's pt?

Low USG, proteinuria, UTI

What can you see on a urinalysis of a cushing's pt?

False

True/False: This radiograph is diagnostic for cushing's

Hepatomegaly

What do you see on this radiograph associated with cushing's?

Localizing to pituitary or adrenal

Why do we care to ultrasound our cushing's pts?

Well

Dogs with HAC (cushing's) usually feel _____.

Stress stimulates the adrenal glands to produce cortisol

Why is it hard to diagnose cushing's in a sick dog?

Urine cortisol:creatinine

What lab test can be used as a rule-out tool for Cushing's?

To account for different USGs (creatinine goes up and down w USG)

Why do we compare cortisol to creatinine in urine?

$$$

Why not do a urine cortisol:creatinine as a regular screening tool for cushing's?

Low

All HAC tests have ____ specificity

ACTH Stim

What is the only test to diagnose iatrogenic HAC?

Cortisol

An ACTH stimulation test looks for an exaggerated response to synthetic ACTH.

We measure this response by measuring ______.

In 15-40% of dogs with Cushing's will have a normal result

ACTH stim test sensitivity is 60-85%

What does this even mean again?

50-60

The ACTH stim test sensitivity is lower for HAC! It's _____%

(HAC is harder to get a positive result)

10% of abnormal ACTH stim tests are false positives

ACTH stim test specificity is 90%

What does this mean?

Baseline cortisol, give ACTH (cortrosyn IV), test cortisol 1h later

List the steps for an ACTH stim test

Normal

The yellow line is a ______ ACTH stim test pattern

Cushings (but remember 10% of positives are false)

The red line is an _______ ACTH stim test pattern

Addisons (or exogenous steroid withdrawal)

The blue line is an ______ ACTH stim test pattern

90-95

The LDDST (low dose dex supression test) has a ______% sensitivity

(percent of dogs that have the disease and have an abnormal test result)

44-50

The LDDST (low dose dex supression test) has a ______% specificity

(percent of positive tests that are true positives)

Baseline cortisol, dexamethasone 0.01mg/kg IV, 4h and 8h post cortisol

How do you perform an LDDST?

Administering a steroid (dex) should suppress cortisol production in a normal animal (because the hypothalamus sees the steroid as cortisol and starts negative feedback)

What's the idea behind the LDDST?

Look at 8h cortisol. If cortisol is elevated it suggests HAC

What's the first step of LDDST interpretation?

Light blue

Which line is expected from a normal dog? (red, blue, or light blue)

Suppress & Escape- it started to suppress cortisol production but couldn't for the expected 8 hrs

What does the darker blue line show?

Pituitary

If you see a suppress + escape on your LDDST that means the dog has _______-dependent HAC

Red line

What line is expected for HAC?

True

True/False: Diagnosis of HAC should never be based on results of an LDDST alone

ACTH Stim

ACTH Stim vs. LDDST

1 hour test time

LDDST

ACTH Stim vs. LDDST

Extra blood draw

ACTH Stim

ACTH Stim vs. LDDST

Less sensitive

ACTH Stim

ACTH Stim vs. LDDST

More specific

LDDST

ACTH Stim vs. LDDST

Better for FAT HAC

ACTH Stim

ACTH Stim vs. LDDST

Can diagnose iatrogenic HAC

LDDST

ACTH Stim vs. LDDST

Can help localize the lesion to pituitary/adrenal

HDDST, endogenous plasma ACTH, abdominal imaging

The LDDST only helps you localize the lesion about 50% of the time (when you get the suppress+escape blue line).

What can you do with the red line result to help localize it better?

To see if we can get more suppress + escapes with a higher dex dose (more pituitary dependent)

Why do we run an HDDST?

Normal or high

With PDH (pituitary dependent HAC), we expect endogenous ACTH levels to be...

Low

With FAT, we expect endogenous ACTH levels to be...

Use another test, repeat

What if your endogenous ACTH test is ambiguous in helping you localize your lesion?

One large irregular gland, contralateral gland atrophied

What will the adrenal glands look like (u/s) in an animal with FAT?

Kinda normal maybe a little asymmetric or large

What will the adrenal glands look like (u/s) in an animal with PDH?

Bilateral small adrenal glands

What will adrenal glands look like (u/s) in an animal with IH (iatrogenic HAC)?

False

True/False: PDH and FAT HAC are treated the exact same way

Inhibit synthesis of cortisol, necrosis of adrenal cortex, surgically remove pituitary mass

What are the 3 treatments for PDH

Trilostane, ketoconazole

How can you suppress synthesis of cortisol in PDH patients?

3-B-hydroxteroid dehydrogenase

Trilostane is a competitive inhibitor of _____________ (which help makes cholesterol into cortisol) and is usually the first line approach

True

True/False: Trilostane is FDA approved for both HAC and FAT

CBC/chem with lytes at 2 and 4w, ACTH stim test or baseline cortisol at 4w

How do we monitor Trilostane after prescribing it?

Just measure cortisol level 1-2 hrs before next Trilostane is due

At 4w of Trilostane therapy, we do either an ACTH stim or baseline cortisol.

Baseline cortisol is ez how do we do it?

Lower your dose, check renal values + lytes, assess clinical signs, consider ACTH stim

You prescribed Trilostane to your first ever Cushing's pt 4 weeks ago and they are back for their baseline cortisol test! You followed the recommended dose per manufacturer.

The result is a cortisol of

Keep the dose

You prescribed Trilostane to your first ever Cushing's pt 4 weeks ago and they are back for their baseline cortisol test!

Your cortisol levels are >1.5 and all symptoms are controlled. What's your next move?

Increase dose or dosing frequency

You prescribed Trilostane to your first ever Cushing's pt 4 weeks ago and they are back for their baseline cortisol test!

Your cortisol levels are >1.5 and but the dog is still panting, PU/PD, and eating a lot. Next move?

2-4h after trilostane

When should the ACTH stim test be performed for Trilostane monitoring in regards to trilostane dose?

Stop trilostane. Evaluate renal values and lytes. Restart trilostane at 1/2 dose only if signs come back

You prescribed Trilostane to your first ever Cushing's pt 4 weeks ago and they are back for their ACTH stim test!

Cortisol is

Keep dose

You prescribed Trilostane to your first ever Cushing's pt 4 weeks ago and they are back for their ACTH stim test!

Cortisol is between 1.5-9 with controlled symptoms. Next move?

Increase dose by 25% and recheck ACTH stim in 4w

You prescribed Trilostane to your first ever Cushing's pt 4 weeks ago and they are back for their ACTH stim test!

Cortisol is >9. Next move?

HyperK, steroid withdrawal, hypoA, acute death

What are some side effects of trilostane?

Mitotane

Adrenocorticolytic w/ direct cytotoxic effect that is used off-label in animals as a longer term PDH tx

This one kinda sucks we don't really use it anymore we have better drugs now

Give a relatively high dose of Mitotane for ~7-10d, discontinue and ACTH stim test when dog shows clinical signs (or at 10d)

How does Mitotane induction work?

GI upset, lethargy, weakness, anorexia

What are common Mitotane side effects?

Send owners pred to give if they see symptoms

What can you do as a safety feature (to prevent Addisonian crisis) during Mitotane treatment?