Canine Hyperadrenocorticism Flashcards
What is the key enzyme that is present in the zone fasciculata and reticularis that is not present in the glomerulosa that synthesis cortisol?
17-alpha-hydroxylase
What are the 2 form of canine hyperadrenocorticism? Which form is more common?
Pituitary vs adrenal dependent
PDH is more common (80-85%) & 90% have a detectable pituitary tumour
Other than CRH, what else can stimulate ACTH secretion?
- dopamine
- cytokines (IL-1, IL-6, TNF-alpha)
- leptin
- AVP
- Angiotensin II
What inhibits CRH secretion?
- glucocorticoids (negative feedback loop) = dominant one
What are the 2 theories of PDH in dogs?
- Hypothalamic theory (not widely accepted)
- excessive CRH secretion and vasopressin + defective cortisol receptor - Pituitary (monoclonal) - accepted and supported
- single somatic mutation of a corticotroph leading to tumour
Can cytology ddx between adrenal adenoma vs carcinoma?
No
What are some features that would be more consistent with an adrenal carcinoma?
- > 2cm
- vascular invasion
- broken through the capsule
- down regulation of ACTH receptor
What are some common urinary signs of dogs with hyperadrenocorticism?
- PU/PD
- UTI
- overflow incontinence
Steroid can interfere with ADH, leading to PU
The dilute urine, urine retention and immunosuppression = increased risk of UTI
What are some common non-urinary signs of dogs with hyperadrenocorticism?
- polyphagia
- 5-10% develop diabetes mellitus
- pot-bellied appearance –> combination of weakened muscle, hepatomegaly and large urinary bladder, redistribution of peripheral fat to mesentery
- muscle weakness = catabolic effect of glucocorticoids
- excessive panting –> decreased pulmonary compliance, pulmonary hypertension, respiratory muscle weakness, or direct effect of glucocorticoids on the respiration centre
- pulmonary thromboembolism = rare complication
What are some CNS of dogs with hyperadrenocorticism?
Due to pituitary macroadenoma (10-25% dogs with PDH)
- most common signs = moderate to severe lethargy
- others: aimless wandering, decrease appetite/ anorexia, stupor, circling, ataxia, change in behaviour, seizures
What are some uncommon signs of dogs with hyperadrenocorticism?
- Cushing’s psuedomyotonia –> stiff gait, dog “hops”
- ligament laxity (plantigrade stance)
- facial nerve paralysis, anestrus, testicle atrophy, thromboembolism due to hypercoagulopathy (FAT can invade in the phrenicoabdominal vein, caudal vena cava, or both)
What are some common physical exam abnormalities noted for dogs with hyperadrenocorticism?
Common:
- pot belly
- bilateral symmetrical alopecia
- thin skin, hyperpigmentation
- comedone
- pyoderma
What’s the pathogenesis of calcinosis cutis?
Calcinosis cutis = irregular plagues in/under skin. Mostly in the dorsal neck/ midline, ventral abdomen, inguinal regions or temporalis region
- due to gluconeogenic and protein catabolic mechanisms of glucocorticoids –> rearrangement of protein structures –> formation of organic matrix that attracts and binds Ca2+, forming apatite crystals
How does HAC effect sexually intact dogs?
Less common signs
- testicular atrophy and anestrous
- due to glucocorticoid negative feedback on the synthesis and secretion of FSH and LH
Can HAC dogs be acutely ill?
Yes!
- severe lethargy, weakness, pale mucus membranes, pain
- may be due to rupture of the adrenal mass
What are some CBC changes typically noted for dogs with HAC?
- lymphopenia
- eosinopenia (bone marrow sequestration)
- monocytosis, neutrophilia (steroid-enhanced capillary margination)
- thrombocytosis, mild erythrocytosis (direct bone marrow stimulation or ventilation response)
What are is the common biochem change for dogs with HAC?
Most common (85-95%) = marked increase in ALP
- ALT: mild to moderate increase
- Cholesterol/ triglycerides: mild to moderate increase, seen in > 50% of HAC dogs
How does HAC influence blood sugar level?
- mild hyperglycemia: due to the gluconeogenic nature, and decreased peripheral glucose utilization by interfering insulin action at a cellular level (receptor/ post receptor) level
- abdominal fat and adipokines also play a role in insulin resistance
How does HAC influence other biochemical parameters?
- BUN decreased in 30-50% of dogs, due to diuresis
- phosphorus and calcium can also be decreased due to increased urinary excretion –> secondary hyperparathyroidism possible
- Azotemia = uncommon
- bile acids may be elevated in up to 30% of patients
How does HAC influence coagulation?
dogs with HAC = hypercoagulable
- increases in pro-coagulants (II, V, VII, IX, X, XII) and decreased antithrombin
- TEG changes
- shortened PT, higher fibrinogen concentration
What kind of U/A changes are noted with HAC?
- low USG, commonly < 1.012
- proteinuria, UPCR 1-6, >0.5 in 70%; >1 in 45%
- UTI, occult possible, should culture
How does HAC influence thyroid function test?
- can be low (T4, fT4)
- due to hypothalamic-pituitary suppression from excessive corticosteroids
What changes on CXR can be noted for dogs with HAC?
- want to rule out metastatic disease
- look for PTE (alveolar infiltrates)
- commonly have interstitial lung pattern
- sometimes mineralized bronchi/ tracheal rings
What changes on abdominal radiographs can be noted for dogs with HAC?
- enlarged liver and bladder
- dystrophic mineralization
- mineralization of adrenal nodule does not correlate to malignancy
What are some common AUS findings for dogs with pituitary dependent hyperadrenocorticism?
in PDH
- adrenal glands should be bilaterally enlarged –> size (breed dependent)
- signs of metastasis
- can use ultrasound to assess vascular invasion
- can also look for sequelae of HAC – gallbladder mucocele, uroliths
- 25% PDH will have normal adrenal glands
- adenomegaly does not equal HAC
What are some common AUS findings for dogs with functional adrenal tumour?
in FAT
- single gland is enlarged, irregular, invading/ compressing on adjacent structures
- ddx: pheochromocytoma, aldosteronoma, metastatic mass, non-functional adrenal tumour
What’s the utilities of CT/MRI for dogs with HAC?
Use if PDH is suspected - macroadenoma = >1cm pituitary gland
- based on neurological signs (66% will have a pituitary tumour)
- but >70% of dogs with PDH won’t have neurological signs
- CT can miss 56% of dogs with PDH (ie normal pituitary size)
What’s the utilities of CT/MRI for the abdmomen?
- can identify adrenal incidentaloma (most are non-function, benign)
- CT/MRI are both good –> assess vascular invasion, tissue invasion, metastasis
What’s the utilities of urine cortisol to creatinine ratio (UCCR) test for dogs suspected of having HAC?
- high sensitivity, low specificity
- good for ruling out HAC
- if >100 (normal <10), 90% = PDH
What’s the utilities of ACTH stim for dogs suspected of having HAC?
- only test to differentiate between true HAC vs iatrogenic HAC
- less affected by non-adrenal illness
- does not differentiate between PDH or FAT
- has 60% sensitivity for FAT, 85% sensitivity for PDH, with overall specificity of 85-90%
- may be good for dogs with atypical / occult Cushing’s
What’s the utilities of low dose dexamethasone suppression test (LDDST) for dogs suspected of having HAC?
- it’s the test of choice
- sensitivity 90-95% of PDH, virtually 100% for FAT
- specificity is only 40-50%, esp if patient has non-adrenal illness
- pre, 4 and 8h post samples
- if escaped pattern “V” pattern noted at 4th hour = PDH
- if less than 50% of baseline $ 4h = PDH
- failure to suppress but >50% of baseline = HAC, but can’t differentiate between PDH and FAT
How does UCCR/LDDST combo work?
The owner collects urine for 2 consecutive days as baseline @ 8am
- after the 2nd collection, give dexamethasone 0.01mg/kg PO
- collect urine again @ 2 & 4pm
- dogs with HAC would not suppress
What are the 3 criteria to qualify for PDH wit LDDST?
- 4h cortisol < 1.4mcg/dL
- 4h cortisol <50% basal
- 8h cortisol <50% of basal, but > 1mcg/dL
- 65% of dogs of PDH will fit one of the 3 criteria
- none of the dogs with FAT will fit those requirements
What’s the utilities of high dose dexamethasone suppression test (HDDST) for dogs suspected of having HAC?
- it’s good for the 10% of patients that failed to suppress on LDDST
- if that was the case, other differentiating test, such as head imaging or endogenous ACTH test would be better than HDDST
How does UCCR/HDDST combo work?
- 3 consecutive morning urine samples
- dexamethasone 0.1mg/kg PO q8h given right after the 2nd urine sample
- if baseline UCCR is increased = HAC
- if 3rd sample is <50% of baseline = PDH
What’s the utilities of eACTH for dogs suspected of having HAC?
- should only be used once HAC is confirmed to differentiate between PDH vs FAT
- eACTH is normal or increased in PDH
- eACTH is low in FAT or iatrogenic HAC
- expensive and difficult to process samples
How can AUS ddx PDH vs FAT?
- PDH: both adrenal gland will be enlarged
- however, some can be normal, some can be asymmetrical
- FAT: usually one enlarged gland
- examining the smaller gland thickness: <5mm = tumour, > 5mm = hyperplasia
How is CT/MRI helpful in HAC dogs?
- CT/MRI cannot replace endocrine testing
- changes in height will be noted first (expands dorsally)
- 50-60% of dogs with PDH can be detected on CT
- 50% of non-neurological dogs with HAC with a pituitary mass identified on MRI
How does mitotane work?
It inhibits 3-Beta-hydorxysteorid dehydrogenase (3 beta HSD), which is required to convert pregnenolone to progesterone, thus inhibiting cortisol synthesis
- it also inhibits aldosterone (minor)
How often should trilostane be givien?
- historically high dose once a day (up to 50mg/kg/day)
- now, BID should be considered (0.5-1mg/kg BID)
- BID may have better control and long term outcome
How is effectiveness of trilostane monitored?
improved in PU and lethargy should be noted in 7-10 days
- derm issues may take longer
- ACTH stim can be done to assess treatment
What’s the recurrence rate of trans-sphenoid hypophysecotmy?
25%
What’s the risk of side effects with mitotane? What are they?
60%
- anorexia, weakness, vomiting, diarrhea, and lethargy
What’s the best medical treatment for FAT?
trilostane
