Defense & Barriers 2: (2) Endocrine Diseases of Adrenal Gland

Question 1

what 2 things are MOST important for Cushing’s diagnosis?
when should we NOT perform adrenal axis testing?
why? (2)

Answer 1

what 2 things?
–> HISTORY AND CLINICAL SIGNS ARE MOST IMPORTANT!!

when should we perform adrenal axis testing?
***DO NOT PERFORM ACTH TESTS ON DOGS WITH INCONSISTENT HISTORIES & CLINICAL SIGNS BECAUSE THESE TESTS ARE IMPERFECT; ONLY PERFORM TESTS IF ABSOLUTELY CONVINCED OF CUSHING’S!

why?
1. because if we see evidence of OVERPRODUCTION OF ACTH/CORTISOL, WE MUST TREAT! (legally)
2. If the dog doesn’t actually have Cushing’s, it can be DANGEROUS to put it on medications that REMOVE GCCs

Question 2

what 4 things MUST be consistent with Cushing’s in order to perform adrenal axis testing?

Answer 2

1. CBC/chem screen
2. history
3. clinical signs
4. PE

Question 3

what 4 things are often done for INITIAL diagnostics for Cushing’s?

Answer 3

1. CBC/chem
2. Urinalysis
3. Urine culture
4. Abdominal US

Question 4

what 3 things can be INCREASED on Cushing’s CBC/chem? give ONE reason for each

what 3 things can be PRESENT on Cushing’s CBC/chem? give ONE reason for each

Answer 4

INCREASED…
1. ALKALINE PHOSPHATASE (ALKP)
–> USUALLY increased because one of the ALKP isoenzymes is STEROID-INDUCED, so more GCCs = more ALP
2. ALANINE AMINOTRANSFERASE (ALT)
–> MAY be increased from hepatocytes leaking out due to hepatomegaly
3. ASPARTATE AMINOTRANSFERASE (AST)
–> MAY be increased from hepatocytes leaking out due to hepatomegaly

PRESENT…
1. LIPEMIA
–> GCCs cause lipolysis
2. HYPERCHOLESTEROLEMIA
3. HYPERGLYCEMIA
–> GCCs cause glycogenolysis

Question 5

relationship between cats & alkaline phosphatase levels? why?

Answer 5

cats DO NOT have ELEVATED ALKP like in DOGS WITH CUSHING’S

because ONE OF THE ALKP ISOENZYMES IS STEROID-INDUCED, but CATS LACK THIS ISOENZYME

Question 6

4 possible abdominal ultrasound findings/what they mean?

Answer 6

1. BILATERALLY PLUMP adrenals = PDH
2. Adrenal mass on one side and adrenal atrophy on the other = ADRENAL TUMOR
3. Diffusely enlarged, hyperechoic liver = Cushing’s
4. Metastasis
   –> Ex = into CAUDAL VENA CAVA (adenocarcinoma on adrenal gland)

Question 7

abdominal/thoracic rad findings in CUSHING’S? (5)
**specificity of the findings/contributing to diagnosis of cushing’s?

Answer 7

1. HEPATOMEGALY
2. GOOD ABDOMINAL DETAIL (from fat distributed there)
3. CALCINOSIS CUTIS
4. ECTOPIC calcification = often BRONCHIAL
5. Adrenal mass

** Radiographic findings are nonspecific and do not usually aid in the diagnosis of this disease, just can support it

Question 8

3 types of Cushing’s SCREENING tests?
what does screening mean in this context? (definition & whether it can differentiate between types of disease)

Answer 8

1. ACTH stimulation test
2. Low Dose Dexamethasone Suppression test
3. Urine cortisol:creatinine ratio

SCREENING = does animal have cushing’s or not? DOES NOT TELL YOU WHETHER DISEASE IS PDH OR AT

Question 9

ACTH stim test results in…
what type of test is this?
NORMAL dog? (PRE-ACTH and POST-ACTH)
CUSHING’S dog? (PRE-ACTH and POST-ACTH)?
what if BETWEEN parameters?

Answer 9

what type of test is this? = SCREENING FOR CUSHING’S

NORMAL dog…
PRE-ACTH serum cortisol concentration = 0.5-6 ug/dL
POST-ACTH serum cortisol concentration = <17 ug/dL

CUSHING’S dog…
PRE-ACTH serum cortisol concentration = 0.5-6 ug/dL
POST-ACTH serum cortisol concentration = >22 ug/dL

MANY DOGS CAN BE BETWEEN 17-22 ug/dL, and so WE NEED CLINICAL SIGNS, OTHER DIAGNOSTIC RESULTS, HISTORY TO HELP CONFIRM!

Question 10

low dose dexamethasone suppression test…
what type of test is this?
= what is this test looking to do?
procedure?
NORMAL vs. CUSHENOID dog?

Answer 10

what type of test is this? = SCREENING FOR CUSHING’S

this tests whether the body can SUPPRESS production of cortisol by the adrenal cortex when exposed to A LONG-ACTING CORTICOSTEROID like DEXAMETHASONE

procedure? = ADMINISTER DEX, measure SERUM CORTISOL and then wait 4-8 hours later to MEASURE AGAIN

NORMAL DOG = serum cortisol <1.0 ug/dL
CUSHENOID DOG = serum cortisol >1.4 ug/dL

Question 11

urine cortisol:creatinine ratio…
what type of test is this?
why is it helpful to measure THIS instead of SERUM CORTISOL?
NORMAL vs. CUSHENOID dog ratio high or low? (include if cortisol or creatinine is higher)

Answer 11

what type of test is this? = SCREENING FOR CUSHING’S

helpful?
SERUM CORTISOL can FLUCTUATE more, while urine cortisol:creatinine ratio measures CORTISOL FROM PAST 6-8 HOURS

NORMAL = LOW to NORMAL urine cortisol:creatinine ratio; CREATININE > CORTISOL
CUSHENOID = HIGH urine cortisol:creatinine ratio; CREATININE < CORTISOL

Question 12

for SCREENING tests for Cushing’s, which one is…
specific?
sensitive?
sensitive + EXTREMELY non-specific?
+ explain why!

Answer 12

ACTH stim = specific, used for dogs that we THINK have cushing’s
–> if NEGATIVE, then PET DOES NOT HAVE DISEASE
–> if POSITIVE, could be many things…
–> There can be other reasons for secretion of GCCs that are not considered in this test, including stress or diabetes mellitus

LDDS test = sensitive, good to help differentiate between Cushing’s & diabetes!
–> if POSITIVE, then PET HAS DISEASE!
–> Example = in a dog with PU/PD, if ALSO HIGH ALKP, then REASONABLE TO PURSUE ADRENAL AXIS TESTING

Urine cortisol:creatinine ratio = sensitive, EXTREMELY NON-SPECIFIC
–> if POSITIVE, then PET HAS DISEASE
–> if NEGATIVE, then PET COULD STILL HAVE DISEASE OR NOT
–> Cortisol in urine can rise due to stress/other reasons; if the PATIENT HAS THE DISEASE IT’LL BE POSITIVE, but IF IT’S NEGATIVE DOES NOT RULE OUT DISEASE

Question 13

define SPECIFICITY of a test

Answer 13

= the likelihood that a patient WITHOUT the disease will TEST NEGATIVE

Question 14

define SENSITIVITY of a test

Answer 14

= likelihood that a patient WITH disease will TEST POSITIVE

Question 15

2 types of DIFFERENTIATING tests for Cushing’s?

Answer 15

1. LDDS test
2. Endogenous ACTH concentration

Question 16

how can LDDS test act as a DIFFERENTIATING TEST between PDH and AT?
when can it NOT act as a differentiating test?

Answer 16

in THEORY, administering dex can cause…

PDH = ACTH is being CONSTANTLY SECRETED from PITUITARY, so adding DEX MIGHT just increase steroids enough to TRANSIENTLY SUPPRESS PITUITARY ACTION
–> causes <50% of BASELINE to be present after 4 HOURS

AT = CORTISOL is being CONSTANTLY SECRETED from ADRENALS, so ADDING DEX WILL NOT DO ANYTHING!! CORTISOL JUST SAYS HIGH

if there is NO SUPPRESSION (meaning that cortisol remains high) it COULD BE EITHER PDH OR AT
–> PDH doesn’t ALWAYS have ACTH suppression in response to dex

Question 17

endogenous ACTH concentration…
in a DOG WITH PDH?
in a DOG WITH AT?
when can this test NOT be differentiating? (range)

Answer 17

In a dog with PDH = ACTH can be NORMAL or HIGH
–> >45 pg/mL

In a dog with AT = ACTH will be LOW because EXCESS GCCs ARE SUPPRESSING IT!
–> <10 pg/mL

when is endogenous ACTH unable to differentiate between AT and PDH?
–> WHEN ENDOGENOUS ACTH IS BETWEEN 10-45 pg/mL

Question 18

what 3 diagnostics CANNOT be used as differentiating tests in CUSHING’S?

Answer 18

3 tests?
1. Abdominal US
2. CT
3. MRI

THESE SHOW STRUCTURES, so even if MASS on pituitary/adrenal gland, CANNOT TELL WHAT IT’S PRODUCING

Question 19

true/false
1. The ACTH stimulation test cannot distinguish between an adrenal tumor and pituitary dependent hyperadrenocorticism

2. The ACTH stimulation test is a specific adrenal axis test recommended when a patient might have other diseases (in addition to hyperadrenocorticism) causing stress and glucocorticoid secretion
3. The urine cortisol to creatinine test is a good screening test for diagnosis of Cushing’s disease
4. The low dose dexamethasone suppression test is a screening test that can also serve as a differentiating test, in some cases of pituitary dependent hyperadrenocorticism

Answer 19

1. The ACTH stimulation test cannot distinguish between an adrenal tumor and pituitary dependent hyperadrenocorticism = TRUE
2. The ACTH stimulation test is a specific adrenal axis test recommended when a patient might have other diseases (in addition to hyperadrenocorticism) causing stress and glucocorticoid secretion = TRUE
3. The urine cortisol to creatinine test is a good screening test for diagnosis of Cushing’s disease = FALSE
4. The low dose dexamethasone suppression test is a screening test that can also serve as a differentiating test, in some cases of pituitary dependent hyperadrenocorticism = TRUE

Question 20

diagnosis of IATROGENIC hyperadrenocorticism…
DOES NOT REQUIRE WHAT?
what should we base off of for DIAGNOSIS? (2, give explanation for second)

Answer 20

DOESN’T require DIFFERENTIATING TEST!

for diagnosis?
1. History and clinical signs
2. Serum cortisol should remain LOW after ACTH administration!
–> Once cortisol is LOW from exogenous cortisol administration, atrophy of adrenal glands = ACTH WON’T DO ANYTHING!

Question 21

5 options for cushing’s treatment? which is the most common?

Answer 21

1. TRILOSTANE** MOST IMPORTANT FORM OF TREATMENT!
2. LYSODREN
3. DEPRENYL
4. SURGERY
5. STEREOTACTIC RADIATION THERAPY

Question 22

TRILOSTANE…
= what is it?
what side effect of this medication should be considered BENIGN?
what is a potentially DANGEROUS side effect?
what ELSE can it be used to treat? risks?
what SIZE should we expect adrenals to be and why?

Answer 22

= a SYNTHETIC STEROID ANALOGUE that INHIBITS PRODUCTION OF STEROIDS by binding up SAME ENZYMES AS CORTISOL called 3-BETA-HYDROXYSTEROID DEHYDROGENASE to PREVENT PRODUCTION OF PREGNENOLONE –> CONVERSION TO CORTISOL

benign side effect?
–> HYPERKALEMIA is normal and NOT ASSOCIATED WITH OVERDOSE

dangerous side effect?
–> ADRENAL NECROSIS, but not super common! could be due to ACTH increase

what ELSE can it be used to treat?
–> ALOPECIA X, NO RISK OF ADDISON’S!

SIZE of adrenals?
–> usually LARGE because DECREASING CORTISOL –> MORE ACTH –> ADRENALS GROW