Exam 8: L.3: Adrenal/Cushings Flashcards
Adrenal gland
G: Salt (aldosterone)
F: sugar (cortisol)
R: sex (androgens)
Functional adrenal tumor: produces a lot of cortisol despite pituitary decreasing production of ACTH
Hyperadrenocortiscism: etiologies
1) spontaneous
- pituitary -dependent hyperadrenocortiscism (pituitary tumor-most from pars this distalis)
- functional adrenal tumors (FAT)
2) iatrogenic disease (exogenous glucocorticoid administration)
Hyperadrenocortiscism: typical signalment
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
Hyperadrenocortiscism: common presenting complaints (slow onset)
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
Hyperadrenocortiscism: physical exam
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
Hyperadrenocortiscism: associated conditions
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
Cushing’s: clinical pathologic funding
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
Cushing’s: lab data
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)
HAC: screening hormone assays/tests
1) ACTH stimulation test
2) low-dose dexamethasone suppression test
3) urine cortisol-creatinine ratio
ACTH stim test
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
ACTH stim
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
Low-dose dexamethasone suppression test
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
LDDST
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
Localizing/differentiating tests
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
HDDST
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)
Endogenous ACTH concentrations
1) dogs with PDH should have elevated ACTH levels
2) dogs with FAT should have decreased levels due to negative feedback
Common pitfalls to avoid in diagnosis of HAC
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
Remember
Most cases of hyperadrenocortiscism are due to PDH!
HAC: medical treatment
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
Trilostane (Vetoryl)
1) block steroidogenesis pathway
- lowering cortisol and aldosterone
2) 70% improve PD/PU/PP within 4 weeks; skin improvement within 3 months
Mitotane
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
Mitotane vs. Trilostane
Mitotane: cytotoxic to adrenal; fewer administrations needed;
Trilostane: not directly cytotoxic but can cause adrenocortical necrosis
Secondary adrenocortical insufficiency
Iatrogenic Cushing’s
Iatrogenic Cushing’s: Pathophysiology
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
Iatrogenic HAC: diagnosis
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
Adrenal tumors
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
