Term
| What stimulates secretion of aldosterone from the adrenal glands? |
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Definition
ACTH (pituitary)
increased Angiotensin II
hyperkalemia
hypernatremia |
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Term
| how does normal circadian rhythm of cortisol vary between common domestic species? |
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Definition
peak [cortisol] occurs in the morning in dogs and horses and at night in cats
** the overall degree of daily variation of cortisol is quite low, but should be taken into account when assessing resting cortisol values, esp. in horses (in which not only day but also season can significantly affect basal [cortisol]) |
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Term
| How is cortisol transported in the blood? |
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Definition
| almost all is bound to proteins (50% bound to albumin, 40% bound to transcortin), around 10-15% is free |
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Term
| What is the half life of cortisol in dogs? how does this compare to the half life of cortisol in cats? |
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Definition
| 1.5 h in dogs, less in cats |
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Term
| How is cortisol removed from circulation? |
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Definition
| Mostly by hepatocytes, but there can also be urinary excretion of cortisol and cortisol metabolites |
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Term
| What type of tube is ideal to collect or store a sample intended for ACTH measurement? |
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Definition
plastic, ACTH adheres to glass with prolonged contact
**it's also very labile and ideally should be run the day of collection, if not it should be frozen and dry-ice shipped |
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Term
| What is the gold standard assay for measuring cortisol? |
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Definition
RIA
**enzyme linked immunoassays are often commonly used
All of these assays may cross react with other glucocorticoids e.g. prednisone, so you must know if the patient has received corticosteroid therapy to interpret) |
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Term
| Which therapeutic glucocorticoid has poor cross-reactivity with cortisol immunoassays? |
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Definition
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Term
| Can you run urine on the same cortisol assay developed to measure plasma cortisol? |
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Definition
| yup (e.g. cortisol:creatinine ratio) |
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Term
| What is the most common cause of hyperadrenocorticism in dogs and cats? |
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Definition
Increased release of ACTH from PITUITARY ADENOMA
80-85% of dogs, 75-85% of cats |
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Term
| Describe the pathogenesis of hyperadrenocorticism (aka pituitary pars intermedia dysfunction) in horses |
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Definition
| hypothalamic degeneration results in decreased dopamine production --> loss of inhibition of melanotropes in the pituitary (pars intermedia) --> excess production of pro-opiomelanocortin which is processed into a variety of substances including ACTH |
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Term
| What non-pituitary/adrenal neoplasm in dogs has been associated with production of cortisol-like compounds that cause clinical hyperadrenocorticism? |
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Definition
| ovarian steroid cell tumor |
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Term
| What chemistry profile abnormalities are associated with hyperadrenocorticism? |
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Definition
| increased ALP (dogs), hyperglycemia, hypercholesterolemia, lipemia |
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Term
| How does ketoconazole affect [cortisol]? |
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Definition
| ketoconazole inhibits steroid biosynthesis --> decreased [coritsol] |
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Term
| How does trilostane decrease [cortisol]? |
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Definition
| trilostane inhibits 3beta-hydroxysteroid dehydrogenase, an enzyme that catalyzes an intermediate reaction in steroid synthesis |
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Term
| What chemistry profile abnormalities are associated with hypoadrenocorticism? |
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Definition
| hyponatremia, hypochloremia, hyperkalemia, hypercalcemia, hypoglycemia, azotemia |
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Term
| How should urine cortisol:cr ratio be used in the diagnosis of adrenal disease in dogs? |
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Definition
urine cortisol:creatinine ratio should be used to rule out hyperadrenocorticism, if dogs have results WRI
If results are increased, a confirmatory test must be run, because many false positives are observed (low positive predictive value, low diagnostic specificity) |
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Term
| What disease, other than hyperadrenocorticism, is frequently associated with markedly elevated urine cortisol:creatinine ratios in cats? |
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Definition
Hyperthyroidism, the mechanism is not clear but may reflect stress associated with the hyperthyroid state and should NOT be considered an indication of pathologic hyperadrenocorticism
**Just like in dogs, urine cortisol:creatinine ratio has poor positive predictive value for Cushings in cats |
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Term
| How would [ACTH] be expected to differ in dogs and cats with PDH vs. functional adrenal neoplasm? |
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Definition
PDH --> increased [ACTH], the tumor is producing
FAN --> decreased [ACTH] due to feedback inhibition of cortisol (produced by the tumor) on the pituitary and hypothalamus |
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Term
| In what season do horses have higher [coritsol]? |
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Definition
Highest in the fall-
[cortisol] is significantly higher in september compared to January and May |
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Term
| What is the main diagnostic use of measuring [ACTH]? |
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Definition
Diagnosing PPID in horses
**ACTH is relatively unstable and needs to be run immediately after collection or transferred to a plastic tube, frozen and dry-ice shipped |
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Term
| What cortisol:ACTH ratio would be expected in dogs with FAD vs PDH? |
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Definition
FAD: high cortisol:ACTH (functional adrenal tumor secrets cortisol which inhibits pituitary secretion of ACTH)
PDH: low cortisol:ACTH (functional pituitary tumor secretes ACTH, cortisol will also be increased but not to the same extent or only episodically)
**these ratios are not routinely used to distinguish FAD from PDH due to lack of published data on their diagnostic accuracy |
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Term
| What is the expected result of running a low or high dose dex suppression test in a healthy animal? |
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Definition
| injection of dexamethasone will suppress hypothalamic secretion of CRT --> decreased pituitary secretion of ACTH --> decreased [cortisol] at both 4 and 8h post injection (<50% baseline [cortisol]) |
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Term
| How can you confirm the presence of hyperadrenocorticism (PDH or FAD) using the low dose dexamethasone suppression test? |
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Definition
If the 8hr post injection [coritsol] is not suppressed, this is consistent with hyperadrenocorticism (could be FAD or PDH)
**dogs with non-adrenal illness may also have inadequate suppression (up to 56% may not suppress at 8h) <-- thats why the test should only be run in patients with suggestive clinical signs |
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Term
| How can the low dose dex suppression test distinguish between FAD and PDH? Can HDDST also distinguish? |
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Definition
LDDST can't always distinguish, but if the 4h post injection is suppressed and the 8h post injection is not suppressed, this escape pattern is highly suggestive of PDH (if concurrent supportive clinical signs)
**for HDDST if there is suppression at 4h [cortisol] this is consistent with PDH, but no suppression could be PDH or FAD |
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Term
| What is the best test to run to differentiated PDH from FAD? |
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Definition
high dose dex suppression test
*should only be run after hyperadrenocorticism is diagnosed (LDDST or ACTH stimulation test) |
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Term
| What test can be used to distinguish iatrogenic from PDH/FAN? |
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Definition
ACTH stimulation test
**iatrogenic cushings is associated with an inadequate response to ACTH (bilateral adrenal atrophy due to exogenous glucocorticoid administration) VS PDH/FAD usually have an exaggerated response to ACTH sim |
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Term
| What conditions are associated with an inadequate response to ACTH stimulation? |
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Definition
| iatrogenic cushings and hypoadrenocorticism |
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Term
| Why is the low dose dexamethasone suppression test not recommended in cats? |
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Definition
| 15-20% of healthy cats, and cays with non adrenal illness, don't have suppressed [cortisol] at 4 and 8h post with thise dose of dex. HDDST is recommended |
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Term
| What time intervals are recommended for assessing [cortisol] in cats after HDDST? |
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Definition
2, 4, 6, 8
Cats can escape the suppressive effect of dexamethasone faster than dogs and it might not be appreciated if only 4 and 8h samples are collected |
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Term
| How good is the ACTH stimulation test at diagnosing cats with Cushings? |
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Definition
| not that good, only 40-50% of cats with Cushings will have an exaggerated (>16 ug/dL) response to ACTH stimulation |
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Term
| What test is recommended for diagnosing Cushings (PPID) in horses? |
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Definition
| LDDST **Both healthy horses and horses with PPID can have exaggerated responses to ACTH administration (gel formulation). LDDST is a more discriminatory test, however, due to seasonal variation in [cortisol] inadequate suppression in healthy horses may be more likely if tested in september/fall |
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Term
| Describe how plasma [aldosterone] is related to [renin] |
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Definition
aldosterone production is stimulated by angiotensin III, which is derived from renin* via RAAS
**renin secretion in the kidney is stimulated by renal hypotension or decreased delivery of sodium to the distal tubules |
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Term
| What other hormone is often increased in dogs and cats with FAN? |
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Definition
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