Hyperadrenocorticism Flashcards
OBJ: Understand adrenal gland functional anatomy and regulation
OBJ: Know the common clinical signs of hyperadrenocorticism (HAC)
- PU/PD
- normal to increased appetite
- panting, restless, anxiety
- Cushingoid body type
- pendulous distended abdomen
- muscle wasting
- thin coat
- multiple dermatologic lesions
- thin skin
- comedones
OBJ: Understand the two most common types of HAC (PDH and ADH)
- Pituitary Dependent Hyperadrenocorticism
- Pituitary
- Adenoma
- 85% of cases
- bilateral enlargement of adrenal size due to hyperplasia
- Adrenal Dependent Hyperadrenocorticism
- adrenal gland
- adenoma or adenocarcinoma
- 15% of cases
- Unilateral enlargement
- contralateral atrophy
OBJ: Understand common screening and differentiating test for HAC
- Screening
- UCCR
- LDDST
- ACTH
- Differentiating
- Adrenal US
- Endogenous ACTH measurement
- HDDST
OBJ: Know treatment options for PDH and ADH
- PDH
- hypophysectomy
- Medical management
- anti-adrenal therapy
- pituitary therapy
- Radiation
- ADH
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OBJ: Review/Understand Pertinent aspects of feline HAC
- PDH
- hypophysectomy
- Medical management
- anti-adrenal therapy
- pituitary therapy
- Radiation
- ADH
- Adrenalectomy
- Anti-adrenal therapy
- Trilostane
- Lysodren
- Ketoconazole
- Anipryl
How is cortisol secretion regulated?
- Regulated through the Hypothalamic Pituitary Adrenal Axis (HPAA)
- See Image
- ACTH secretion is pulsatile
- Influenced by:
- Feeding
- Physiologic / environmental stress
- Pain
- Trauma
- Hypoxia
- Pyrogens
- Cold exposure
- Surgery
- Influenced by:
What is the difference between PDH and ADH?
What is the common signalment of hyperadrenocorticism in dogs?
- Any breed
- Median age of diagnosis is 10-11yr
What are the clinical signs of Hyperadrenocorticism?
- Dogs with HAC generally feel and act well
- PU/PD - almost all dogs with HAC
- Appetite normal to increased
- Panting, restlessness, anxiety
- ‘Cushingoid’ body type
- pendulous and distended abdomen
- muscle wasting
- thin coat
- multiple dermatologic lesions
- thin skin
- comedones
What neurologic signs are common in hyperadrenocorticism dogs?
- signs caused by macroadenoma (10-15% PDH cases)
- Anorexia
- behavioral changes
- disorientation
- blindness
What Cardiovascular effects are common in hyperadrenocorticism dogs?
- Hypertension
- Thromboembolism (hypercoagulable)
What musculoskeletal problems are common in hyperadrenocorticism dogs?
- Poor body condition
- muscle loss
- cruciate rupture
- myopathy
What reproductive signs are common in hyperadrenocorticism dogs?
- decrease in testicular androgen production in males
- Anestrus in females
What findings are common on diagnostic imaging in dogs with hyperadrenocorticism
- Hepatomegaly
- Adrenal tumor
- Focal calcification
- Lung mineralization
What CBC findings are common in hyperadrenocorticism dogs?
- Anemia is uncommon
- Stress leukogram - neutrophilia, lymphopenia
- Thrombocytosis
What Serum Chemistry findings are common in hyperadrenocorticism dogs?
- Elevated liver enzymes (ALP > ALT)
- ALP - GC induced isoenzyme
- ALT - vacuolar hepatopathy
- Hypercholesterolemia
- Hyperglycemia (mild)
What urinalysis findings are common in hyperadrenocorticism dogs?
- Low urine specific gravity <1.020
- Proteinuria
How is hyperadrenocorticism diagnosted?
- 2 step approach
- Screening tests - confirm adrenal hypersecretion
- Urine cortisol:creatinine ratio (UCCR)
- Low does dexamethasone suppression test (LDDST)
- ACTH stimulation test
- Differentiating tests - distinguish PDH and ADH
- Adrenal US (or other dx imaging)
- endogenous ACTH measurement
- High dose dexamethasone suppression test (HDDST)
- Screening tests - confirm adrenal hypersecretion
What do the results of a Urine Cortisol : Creatinine Ratio (UCCR) test mean?
- Dogs with HAC have elevated urine cortisol:creatinine ratio
- normal results rule out HAC - high specificity
- Abnormal result require confirmation with another screening test
What do the results of a Low Dose Dexamethasone Suppression Test (LDDS) mean?
- Effective screening test
- can be a differentiating test
- dogs with HAC have elevated 8-hr cortisol
- Stress / Nonadrenal illness = False +
What do the results of a ACTH stimulation Test mean?
- Generally considered more Specific than LDDS
- Dogs with HAC have elevated post-ACTH cortisol
- Cannot distinguish between PDH and AT
What Hyperadrenocorticism screening test is a good choice if non-adrenal illness is suspected?
ACTH Stimulation test
What do the results of a High Dose Dexamethasone Suppression Test (HDDST) mean?
- Suppression = PDH
- 70% of PDH cases suppress - can differentiate from AT
- 30% of PDH cases do not suppress
- No Suppression = AT
What doe the results of an Endogenous ACTH Test (eACTH) mean?
- Low = AT
- High = PDH
- Diagnostic in >80% of dogs (>95% when re-tested)
Compare and contrast Hyperadrenocorticism tests
What imaging techniques are useful for diagnosing PDH?
- CT, MRI, and US
- Pituitary tumor (macroadenoma or smaller)
- only 50% of PDH have detectable ass
- Bilateral adrenal hypertrophy (uniform / nodular)
- normal and abnormal glands overlap in size
- Pituitary tumor (macroadenoma or smaller)
What imaging techniques are useful for diagnosing ADH?
- US, CT
- Unilateral adrenal enlargement (usually nodular change)
- Atrophy of contra-lateral gland
- Not every adrenal mass is functional - possible misdiagnosis if functional testing is not done
What are the treatment options for PDH?
- Hypophysectomy
- Surgical
- removal/destruction of adenoma
- Difficult
- Surgical
- Medical Management
- Anti-adrenal therapy
- Pituitary Therapy
- Radiation
- Reserved for macroadenoma
- Slows tumor growth
- less effect on abnormal hormone production
What is an Adrenalectomy?
- Preferred treatment for ADH
- Pre-op imaging - asses metastasis and local invasion
- May require pre-surgical stabilization
- Peri- and post-operative complications
- Hemorrhage
- Thromboembolism
- Adrenal insufficiency
- Prognosis
- good is tumor is benign and easily removed
- malignant tumors = less favorable prognosis
What medications are available to treat hyperadrenocorticism?
- Trilostane
- Lysodren
- Ketoconazole
- Anipryl
How does Trilostane work to treat HAC?
- Inhibits synthesis for adrenal cortical steroids
- Reversible inhibitor of 3B-hydroxysteroid dehydrogenase
What is the dose of Trilostane? Adverse effects?
- 2 - 4 mg/kg/day (divided BID)
- Incremental increase as needed
- Minimal Adverse Effects:
- Transient vomiting, diarrhea and lethargy
- Rarely, hypoadrenocorticism may develop
- Acute adrenal necrosis (rare
How can trilostane therapy be monitored for effectiveness?
-
ACTH stimulation test
- 10 - 14 days after starting
- 2 weeks after dose increase
- q3 months for the long term
- Target post-ACTH of 1.45 - 5.4 ug/dl
- up to 9.1 ug/dl is acceptable if clinical signs are controlled
-
Post-dose cortisol concentration
- sample 4 - 6 hr post-dose.
- Cortisol ≥ 1.3 ug/dl excludes excessive suppression
- ≤ 2.9 excludes grossly inadequate control
-
Pre-dose Cortisol
- pre-trilostane cortisol of 1.4 - 5 ug/dl correlates with effective control of clinical signs but not with post-ACTH stim cortisol concentrations
How does Lysodren work to control HAC?
- “mitotane”
- Adrenocorticolytic that acts by destruction of functional adrenal tissue
- Occasionally used as alternative to trilostane
How does Ketoconazole work to control HAC?
- Reversible inhibition of adrenal steroidogenesis (primarily glucocorticoids)
How does Anipryl control HAC?
- “selegiline’ ‘L-deprenyl’
- Monoamine oxidase inhibitor (MAO) - reduces ACTH production
What is the Prognosis of HAC?
- PDH
- goal - improved quality of life
- CNS signs carry guarded prognosis
- ADH
- Benign adrenal tumors - good/excellent prognosis if removed
- Malignant tumors - guarded to poor prognosis due to local tissue invasion
Do cats suffer from hyperadrenocorticism?
- Considered uncommon to rare
- >80% have PDH
- ~50% have microscopic pituitary tumors
- Iatrogenic - less common than dogs
- Differentials include DM and acromegaly
- >80% have PDH
What is the common signalment of cats with HAC?
- Middle age or older (average - 10 yr)
- Higher incidence in females (70%)
- 80% of cats have insulin resistance and diabetes
What are the common clinical signs of Feline HAC?
- PU/PD
- polyphagia
- Diabetes that is “difficult to regulate”
- weight loss / failure to gain weight
- Lethargy; look ill
- Skin fragility
- alopecia
- failure to groom
- pendulous abdomen
What laboratory findings are common with Feline HAC?
- Limited Database
- CBC - no consistent abnormalities
- Serum chemistry
- hyperglycemia
- ALP not increased
- cats lack GC - induced ALP isoform
- Urinalysis
- Spec Gravity usually <1.020
- Glucosuria
How is Feline HAC diagnosed?
- Screening test - same as Canine HAC
- ACTH stimulation test
- LDDS Test
- use 0.1 mg/kg (vs 0.01 mg/kg in dog)
- UCCR
- Differential testing - same as Canine HAC
- HDDS test
- Use 1.0mg/kg (0.1mg/kg in the dogs)
- Abdominal ultrasound
- Endogenous ACTH levels
- HDDS test
What is the treatment for Feline ADH?
- Surgery best option if metastatic disease/invasion absent
What is the treatment for Feline PDH?
- Treatment of choice is controversial
- Surgery - Bilaeteral adrenalectomy
- Hypophysectomy
- Radiation Therapy
- Medical Therapy
- mitotane - cats more resistant
- Trilostane - limited information
- Ketoconazole - cats more resistant
What is the prognosis for Feline HAC?
guarded to poor
