Exam 8: L.3: Adrenal/Cushings Flashcards

1
Q

Adrenal gland

A

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

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

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2
Q

Hyperadrenocortiscism: etiologies

A

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

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3
Q

Hyperadrenocortiscism: typical signalment

A

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

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4
Q

Hyperadrenocortiscism: common presenting complaints (slow onset)

A

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

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5
Q

Hyperadrenocortiscism: physical exam

A

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

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6
Q

Hyperadrenocortiscism: associated conditions

A

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

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7
Q

Cushing’s: clinical pathologic funding

A

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

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8
Q

Cushing’s: lab data

A

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)

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9
Q

HAC: screening hormone assays/tests

A

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

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10
Q

ACTH stim test

A

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

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11
Q

ACTH stim

A

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

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12
Q

Low-dose dexamethasone suppression test

A

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

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13
Q

LDDST

A

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

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14
Q

Localizing/differentiating tests

A

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

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15
Q

HDDST

A

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)

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16
Q

Endogenous ACTH concentrations

A

1) dogs with PDH should have elevated ACTH levels

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

17
Q

Common pitfalls to avoid in diagnosis of HAC

A

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

18
Q

Remember

A

Most cases of hyperadrenocortiscism are due to PDH!

19
Q

HAC: medical treatment

A

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

20
Q

Trilostane (Vetoryl)

A

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

21
Q

Mitotane

A

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

22
Q

Mitotane vs. Trilostane

A

Mitotane: cytotoxic to adrenal; fewer administrations needed;

Trilostane: not directly cytotoxic but can cause adrenocortical necrosis

23
Q

Secondary adrenocortical insufficiency

A

Iatrogenic Cushing’s

24
Q

Iatrogenic Cushing’s: Pathophysiology

A

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

25
Q

Iatrogenic HAC: diagnosis

A

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

26
Q

Adrenal tumors

A

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