Hyperadrenocorticism Flashcards
1
Q
describe cushing’s syndrome, hyperadrenocorticism (HAC), and hypercortisolemia
A
cushing’s syndrome: range of clinical syndromes caused by a chronic excess of glucocorticoid activity due to a variety of endogenous or exogenous steroid hormones
hyperadrenocorticism (HAC):
-general condition of increased adrenal activity
-autogenous production over rules negative feedback
hypercortisolemia:
-excessive glucocorticoid activity due to cortisol
-favored because precise and more clinically relevant
2
Q
describe the adrenal gland
A
- capsule: just there
- cortex: 3 zones
-zona glomerulosa: salt; mineralocorticoids (aldosterone)
-zone fasciculata: sugar; glucocorticoids (cortisol)
-zona reticularis: sex; sex hormones
- medulla:
-catecholamines
-epinephrine
-norepinephrine
3
Q
describe the roles of cortisol by organ/organ system
A
- liver:
-increase blood glucose
-increase neoglucogenesis
-increase glycogen storage
-potentiates glucagon and epinephrine effects - pancreas:
-decreases insulin secretion - muscle:
-increase proteolysis
-decrease glucose transport - adipose tissue:
-increase lipolysis and FFA release - bone:
-increase reabsorption - kidney:
-increase sodium reabsorption
-increase K and Ca secretion - vascular system:
-increase blood pressure
-increase reactivity to vasoactive agents - immune system:
-anti-inflammatory
-immunosuppressive
4
Q
describe the different forms of Cushing’s syndrome
A
- pituitary-dependent HAC:
-rogue cells in ant pit decide to ignore feedback and pump out ACTH, tell adrenals to keep producing cortisol (increase in endogenous ACTH)
-microadenoma (<1cm, most common form!)
-macroadenoma (>1cm), less common - adrenal-dependent HAC
-one of the adrenal glands decides to go crazy and ignore negative feedback, producing more cortisol
-other adrenal atrophies, so if you remove the malfunctioning gland, have to think of the consequences while the atrophied gland wakes up!
-50% benign, 50% malignant - atypical Cushing’s: caused by other steroid hormones
-iatrogenic
-ectopic
-food-dependent
5
Q
describe the signalment of HAC
A
- middle aged to older dogs
-90% are at least 9 years old at dx - breeds:
-poodles, dachshunds, boxers, terriers, schnauzers, labradors, maltese, beagles, GSD - large breeds likely more adrenal dependent
6
Q
describe common presenting history of HAC
A
common:
1. PU/PD/PP
2. panting: due to
-hepatomegaly and/or weakened thoracic wall muscles
less common:
-1. myotonia
2. pituitary macroadenoma: neuromuscular weakness, lethargy, depression, seizures, or CNS signs
7
Q
describe the physical exam of HAC
A
- hepatomegaly: due to glycogen accumulation
- muscle wasting
- unusual fat distribution
- alopecia
- thin, hyperpigmented skin
- comedones
- recurrent infections
- calcinosis cutis: if no exogenous steroids being given = giveaway for cushing’s!
- other considerations:
-hypertension
-poor wound healing
-ligamentous injury: CCL rupture
-calcium oxalate urolithiasis
-gallbladder mucocele
-thromboembolic disease (PTE)
8
Q
describe the CBC of HAC
A
stress leukogram (SSMILED):
-mature neutrophilia: demargination
-lymphopenia: lymphocyte lysis
+/- monocytosis, eosinopenia, erythrocytosis
-thrombocytosis
9
Q
describe the chemistry of HAC
A
- cholestatic hepatopathy in 85% of dogs (RARE IN CATS)
-increased ALKP due to glucocorticoid isoenzyme induction
-intrahepatic cholestasis (glycogen)
+/- mild ALT elevation - fasting hypercholesteremia
- fasting hyeprtriglyceridemia
- pseudohyperkalemia
-thrombocytosis
10
Q
describe the urinalysis of HAC
A
- low USG (<1.020) in more than 90% of dogs! due to
-secondary nephrogenic diabetes insipidus
-cortisol antagonizes ADH (most common mechanism of PU/PD) - proteinuria
- increase urine protein: creatinine ratio
- +/- active sediment: pyuria, hematuria, bacteria
-may see UTIs
11
Q
describe diagnostic sensitivity and specificity, NPV, and PPV
A
- sensitivity:
-ability to detect true positives
-used to minimize false negatives
-SNOUT: if a test is sensitive, a negative result rules OUT the disease
-used to screen for a disease/rule it out - specificity:
-ability to detect true negatives
-used to minimize false positives
-SPIN: if a test is specific, a positive result rules in the disease
-used to confirm a diagnosis - prevalence:
-comorbid disease impacts test performance
-PPV increases with prevalence
-discriminatory use improves diagnostic accuracy
-use tests when history, PE, and lab results are suggestive
12
Q
generally describe HAC diagnosis
A
- cortisol tests are not perfect and are prone to false positive results
-so AVOID testing when patient is stressed or sick - only test when clinical suspicion is high
-at least 2 clinical or laboratory abnormalities
-the more abnormalities, the stronger the indication
-exception: if dog has calcinosis cutis, test! - screening tests: used to rule out HAC
-urine cortisol creatinine ratio (UCCR) - diagnostic:
-low dose dexamethasone suppression test: LDDST
-ACTH stimulation test
-non-steroid hormone panel
13
Q
describe urine cortisol creatinine ratio
A
- 100% sensitivity = 0 false negatives so high negative predictive value
- use to RULE OUT HAC when LOW index of suspicion
-ex. only increased ALKP - wait 48 hours after clinic visit
-take morning urine sample for 3 days, take an equal amount from each sample = pooled UCCR - poor specificity and PPV
-canNOT use to diagnose HAS due to so many false positives
14
Q
describe the low dose dexamethasone suppression test
A
- give low dose dexamethasone IV to mimic negative feedback
-NO other tests or procedures should be performed during this test!! - highly sensitive:
-85-95% Sn = 5-15% false negatives
-MOSTLY trust a negative result - moderately specific:
-44-73% = lots of false positives
-low stress during test required because 50% of false positives occur if done when patient is sick or stressed - procedure: keep patient in a quiet area with min handling
-0hr: baseline blood sample
-give dexamethasone IV
-4hr: differentiation
-8hr: diagnostic - results:
-normal dog: suppressed below baseline for 24hr
-criteria for HAC:
–8hr cortisol >1.4 OR
–8hr cortisol >50% baseline - criteria for specifically pituitary dependent HAC
-8hr cortisol >1.4 or >50% baseline AND
-4hr cortisol <1.4 or 50% baseline
-suppress and escape inverse pattern
15
Q
describe pros and cons of low dose dexamethasone suppression test
A
pros:
1. easy to perform, dex is cheap
2. high Sn
3. may differentiate pituitary vs adrenal
cons:
1. requires 8hr time frame
2. lower Sp = more false positives
3. cannot diagnose iatrogenic disease
16
Q
describe the theory and procedure of the ACTH stimulation test
A
- giving synthetic ACTH mimics endogenous and stimulates the HPA axis which should stimulate adrenal glands to produce cortisol
-expect a supraphysiologic response in a patient with cushing’s - moderately sensitive:
-PDH: 80%
-ADH: 50-60% - moderately specific:
-if sick or stressed, use this instead of low dose dex suppression - procedure:
-0hr: baseline
-give ACTH IV
-1hr diagnostic OR
-0hr,
-give ACTH IM
-2hr diagnostic
17
Q
describe interpretation of ACTH stimulation test
A
- normal:
-goes from something, to more (usually use 17 as upper RI) - spontaneous HAC (PDH)
-something to MUCH MORE (up to 22 or above)
-if not above 22 but high than 17 = grey zone, go based on clinical suspicion - iatrogenic HAC via exogenous steroids:
-no/low response
18
Q
describe pros and cons of ACTH stim test
A
pros:
1. quick
2. best Sp of screening tests, few false positives
3. use is co-morbid disease present
4. the ONLY test that dx iatrogenic HAC
cons:
1. synthetic ACTH expensive and difficult to obtain
2. low Sn for adrenal disease
3. cannot differentiate pituitary from adrenal disease
19
Q
summarize HAC diagnostic tests
A
- UCCR:
-Sn: highest
-Sp: poor
-use: screening, rule OUT HAC - LDDST:
-Sn: high
-Sp: moderate
-use: 1st choice diagnostic, MAY differentiate PDH - ACTHST:
-Sn: moderate
-Sp: moderate
-use: 1st choice diagnostic if comorbid disease
20
Q
what tests can help differentiate pituitary versus adrenal HAC?
A
- LDDST
- abdominal ultrasound
- high dose dex suppression test (10x as high as lose dose)
- endogenous ACTH concentration
- pituitary imaging: MRI or CT
21
Q
describe high dose dexamethasone suppression test
A
- perform after a diagnostic test
-normal pituitary will look the same/be suppressed - can only diagnose PDH if suppression
-4 and/or 8hr < cutoff or <50% baseline cortisol - canNOT confirm functional adrenal tumor
22
Q
describe endogenous ACTH (eACTH) test
A
- perform after diagnostic test
- PDH = high
- ADH = low (CHECK SAMPLE TEMP)
-hormone is labile and requires rapid, special handling so esp if shipping to a lab, may be really tricky to submit diagnostic sample - also: overlap between pituitary and adrenal disease values, so approx 20% of results are inconclusive
23
Q
describe abdominal ultrasound to differentiate between PDH and ADH
A
- PDH: bilateral enlargement or normal (30%)
- ADH: ONE adrenal has mass/nodule and contralateral gland is small
-normal adrenal width: 4-7mm
- >2cm = likely neoplasia
- >4cm = likely malignant
24
Q
describe atypical HAC
A
- cushing’s syndrome caused by other steroid hormone excess
-excess intermediate steroid hormones in the adrenal can make a dog look cushinoid - controversial because some clinicians think dogs will become typical over time
- diagnosis:
-ACTH stimulation test, evaluate for excess steroid hormones (increase 2-3x fold upper RI)
-not specific because also increased in non-adrenal illness!
25
describe why management of canine hypercortisolemia
goal is to resolve clinical signs:
1. PU/PD/PP: resolve in days
2. abdominal distension, panting: within weeks
3. haircoat: within months
4. insulin resistance and diabetes mellitus; can help with increased risk
5. potentially prothrombotic state; treatment can resolve
6. if adrenal tumor = risk of hemoabdomen, treatment can resolve
7. pituitary macroadenoma: neurologic effects due to space-occupying, so treatment could resolve
26
describe medical management of canine hypercortisolemia
1. trilostane (vetoryl)
2. mitotane (lysodren): historic off label use
27
describe non-medical management of canine hypercortisolemia
REFER!
adrenal:
-adrenalectomy; ideal to manage for approx 4 weeks before
--vascular invasion and poor wound healing, prone to PTE so maybe do it laparascopically (AKA do NOT do in private practice bc #messy)
-contralateral gland atrophied!! so also need tapering glucocorticoid supplementation post-op
pituitary:
-RT for macroadenomas
-transsphenoidal hypophysectomy
28
describe use of trilostane
1. blocks 3-beta-hydroxysteroid dehydrogenase; goal is to reduce adrenal gland ability to respond to a pituitary signal or to produce cortisol on their own
2. not cheap BUT avoid compounded if possible! batch variability, questionable bioavailability, risk of inconsistent disease control (dose already hard to choose much less with inconsistent batches)
3. use: start and recheck 10-14d later to ensure not over-controlled; do NOT increase dose this early!
-assess clin signs and perform ACTH stim test (perform 4-6 hr post pill, want a positive delta cortisol, indicating an adrenal reserve)
4. monitoring at second recheck, after 30d:
-clinical signs still present and 1hr cortisol >5.0: increase dose and recheck in 10-14d
-clinical signs still present and 1hr cortisol <5.0: look for other causes of clinical signs
-no clinical signs and 1hr cortisol approx 5.0: controlled! yay!
-no clinical signs and 1hr cortisol >5.0: leave alone! controlled!
29
describe signs of iatrogenic hypocortisolism
1. depression, lethargy, collapse
2. anorexia (recently polyphagic so big difference!), V/D
3. PU/PD
4. need an ACTHST to diagnose:
-0 and 1hr cortisol often <1.0
-delta cortisol is low or negative
5. how to avoid:
-dispense glucocorticoids when start trilostane (dex preferred bc prednisone cross reacts with cortisol assay)
-owner gives one dose and brings to DVM/ER
-stop trilostane! supplement with glucocorticoids as needed, maybe take a drug holiday until clinical signs return and potentially re-start at a lower dose
30
describe feline HAC
REFER!
1. rare, most are PDH
2. clin signs:
-skin fragility!!
-bacterial or fungal infections
-diabetes mellitus: due to hypercortisolemia causing insulin resistance
3. testing:
-UCCR: screen, rule out
-LDDST: same as dogs
-ACTH: poor sensitivity in cats!
-diagnostic imaging: AUS, brain MRI, or CT
4. treatment:
-trilostane?
-adrenalectomy
-RT
-transsphenoidal hypophysectomy
31
describe HAC in ferrets
1. adrenal disease due to excess sex hormones
2. avg age 3-4 years
-due to de-sexing and lack of feedback
3. clin signs:
-pot-bellied. muscle wasting
-bilateral symmetrical alopecia with pruritis (rat tail)
-females: enlarged vulva
-males: prostatomegaly, sexual aggression
4. treatment:
-surgery
-repeated GnRH-agonist implants or depot injections
