Exam 8: L.3: Adrenal/Cushings

Question 1

Adrenal gland

Answer 1

G: Salt (aldosterone)
F: sugar (cortisol)
R: sex (androgens)

Functional adrenal tumor: produces a lot of cortisol despite pituitary decreasing production of ACTH

Question 2

Hyperadrenocortiscism: etiologies

Answer 2

1) spontaneous
- pituitary -dependent hyperadrenocortiscism (pituitary tumor-most from pars this distalis)
- functional adrenal tumors (FAT)
2) iatrogenic disease (exogenous glucocorticoid administration)

Question 3

Hyperadrenocortiscism: typical signalment

Answer 3

1) 7-9 years of age
2) PDH: there are high risk breeds
- dogs <20 kg: 85% of HAC is due to PDH
3) FAT: higher risk breeds = GSD, Dachsund, Labrador
- dogs >20 kg: 50% PDH, 50% FAT

Systemic impact of excess glucocorticoids: skin, liver, muscle, CNS

Question 4

Hyperadrenocortiscism: common presenting complaints (slow onset)

Answer 4

1) PU/PD
2) polyphagia
3) abdominal enlargement-obesity
4) hair loss, skin infection
5) panting*= = >this may be the 1st thing owner’s notice!
6) muscle weakness/lethargy

NOTE: important to note that these dogs are not generally sick

Question 5

Hyperadrenocortiscism: physical exam

Answer 5

1) conformational changes: hepatomegaly, abdominal muscle weakness, increased intra-abdominal fat, muscle atrophy
= pendulous abdomen*
2) cutaneous changes: symmetrical alopecia, comedones, coat color changes, hyperpigmentation, scale

Question 6

Hyperadrenocortiscism: associated conditions

Answer 6

1) hypercoagulability: thromboembolism
- thrombocytosis, loss of anti-thrombin in the urine
2) hypertension (>50% of dogs)
- due to excessive secretion of renin
3) hypercalcemia and urinary calculi
4) proteinuria
5) myopathy
6) DM
7) infections

Question 7

Cushing’s: clinical pathologic funding

Answer 7

1) CBC
- stress leukogram (lymphopenia, neutrophilia, monocytosis)
- hemoconcentration
2) biochem
- elevated ALP (most common abnormality) seen in 85-95% of cases: ALP isomers from bone, liver, glucocorticoids (cortisol)
- increase in plasma glucose
- hypercholesterolemia
- lipemia

Question 8

Cushing’s: lab data

Answer 8

1) electrolytes
- occasionally increased sodium and decreased potassium
2) urinalysis
- dilute urine (often <1.015) in 85% of cases
- proteinuria in about 50% of dogs (hypertension)
- glucosuria
- evaluate for UTI (50% of cases)

Question 9

HAC: screening hormone assays/tests

Answer 9

1) ACTH stimulation test
2) low-dose dexamethasone suppression test
3) urine cortisol-creatinine ratio

Question 10

ACTH stim test

Answer 10

1) administration of a supra-physiologic dose of ACTH causes the adrenals to maximally secrete cortisol
2) dogs with HAC have larger, more active adrenals and will produce more cortisol than unaffected animals**
3) majority of dogs with PDH will show inexcessiveresponse
- dogs with FAT show variable response

Advantage: safe, simple, quick
disadvantage: lower sensitivity them LDDST, cannot differentiate PDH from FAT

Question 11

ACTH stim

Answer 11

1) ACTH response can be normal in 15-30% of dogs with PDH!
- If you are suspicious of PDH and get a normal ACTH response, do NOT rule out PDH = => do LDDST
2) preferred test for diagnosis of iatrogenic HAC
3) only test recommended for monitoring response to therapy for HAC

Question 12

Low-dose dexamethasone suppression test

Answer 12

1) measure baseline cortisol
2) give dexamethasone IV
3) measure cortisol at 4 and 8 hours post (normally cortisol should decrease)

4) dogs with PDH show relative resistance to the suppressive effects of dexamethasone on ACTH secretion
5) dogs with FAT: have very low circulating ACTH concentration, dexamethasone has little to no effect on cortisol secretion
6) **may be the single best test to screen for HAC

Question 13

LDDST

Answer 13

1) **a result of >1.4 ug/dL at the 8 HOUR measurement of cortisol is consistent HAC
2) decrease at the 4 hour measurement
- <1.4 ug/dL OR
- <50% of basal cortisol
- consistent with PDH!
3) no decrease at the 4 hour measurement by above criteria
- cannot differentiate PDH from FAT
- 35% OF DOGS WITH PDH do NOT have a decrease at 4 hour cortisol

Advantages: high sensitivity, differentiates PDH from FAT in 40% of dogs with HAC
disadvantages: lower specificity than ACTH stim; requires 8 hours to complete

Question 14

Localizing/differentiating tests

Answer 14

1) LDDST (differentiates 40% of canine with PDH)
2) HDDST
3) endogenous ACTH concentrations
4) diagnostic imaging
- if PDH = = > high ACTH levels cause bilateral adrenomegaly
- if FAT will sign = >large functional adrenal tumor with a small contralateral adrenal gland

Question 15

HDDST

Answer 15

1) protocol is similar to LDDST, but dose of dexamethasone is increased
2) administration of a high dose of dexamethasone does NOT cause cortisol suppression in dogs with FAT
3) 75% of dogs with PDH will suppress at the 4 and/or 8 hour measurement
4) disadvantage of HDDST: it can NEVER confirm the presence of FAT (it will not suppress)

Question 16

Endogenous ACTH concentrations

Answer 16

1) dogs with PDH should have elevated ACTH levels

2) dogs with FAT should have decreased levels due to negative feedback

Question 17

Common pitfalls to avoid in diagnosis of HAC

Answer 17

1) in dogs with no clinical signs, pursuing:
- endocrine testing based on abnormal lab values
- testing for “occult HAC”
2) ruling out disease because:
- blood analysis normal
- adrenal glands are normal in size
3) without considering clinical presentation, diagnosis based on:
- ACTH stimulation test results
- LDDST test results
4) reliance on ACTH stim test
5) failure to recognize that false positive and false negative results occur with tests of the pituitary-adrenocortical axis

Question 18

Remember

Answer 18

Most cases of hyperadrenocortiscism are due to PDH!

Question 19

HAC: medical treatment

Answer 19

1) Trilostane
- FDA approved in dogs
2) Mitotane
3) ketoconazole
- affects steroid synthesis
4) L-deprenyl (Anipryl)
- FDA approved in dogs (controversial drug-no change in basal and post-ACTH cortisol levels)
- dopamine secretion from hypothalamus inhibits ACTH secretion from pituitary
- L-deprenyl inhibits dopamine degradation
- increasing dopamine activity may inhibit ACTH over secretion

Question 20

Trilostane (Vetoryl)

Answer 20

1) block steroidogenesis pathway
- lowering cortisol and aldosterone
2) 70% improve PD/PU/PP within 4 weeks; skin improvement within 3 months

Question 21

Mitotane

Answer 21

1) adrenolytic
- zona fasciculata and reticularis
2) stop medication if dog vomits, has diarrhea, becomes inappetent or depressed
3) owners have prednisone for emergency use
4) perform ACTH stim test every 7-10 days until adequate suppression

Question 22

Mitotane vs. Trilostane

Answer 22

Mitotane: cytotoxic to adrenal; fewer administrations needed;

Trilostane: not directly cytotoxic but can cause adrenocortical necrosis

Question 23

Secondary adrenocortical insufficiency

Answer 23

Iatrogenic Cushing’s

Question 24

Iatrogenic Cushing’s: Pathophysiology

Answer 24

1) glucocorticoid therapy resulting in clinical HAC
- PD, PU, PP
- hematology consistent with HAC
- cutaneous changes: alopecia, comedones, calcinosis cutis, etc
- may be caused by systemic or topical administration
2) supraphysiologic glucocorticoid therapy leading to suppression of HPA axis
- decreased CRF release from hypothalamus
- decreased ACTH release from pituitary
- selected atrophy of zona fasciculata
- selected atrophy of zona fasciculata

Question 25

Iatrogenic HAC: diagnosis

Answer 25

1) history of glucocorticoid administration
2) physical findings
3) ACTH stimulation test
- it shows a suppressed adrenal response (due to atrophy of adrenal fasciculata; no significant change in cortisol level post-stimulation)
- similar to primary hypoadrenocortiscism

Question 26

Adrenal tumors

Answer 26

1) 41% adrenocortical (most are functional)
2) 32% pheochromocytoma (medulla-secrete predominantly norepinephrine)
- surgery is only effective treatment
3) most adrenocortical tumors are functional
- glucocorticoid producing tumors are most common (HAC)
- aldosterone secreting tumors are very rare in dogs, more common in cats
- adrenalectomy is treatment of choice