Hyperadrenocorticism Flashcards
HPA Axis
- Remember it and make sure you can draw it out
Hyperadrenocorticism Definition
- Constellation of clinical signs/abnormalities resulting from chronic glucocorticoid exposure
What is the primary cause of Cushing’s if not iatrogenic?
- due to a TUMOR in either
1. Pituitary gland (PDH)
2. Adrenal gland(s) (ADH)
Iatrogenic Cushing’s
- Due to exogenous exposure
What type of tumor is most common in dogs with Cushing’s?
- Pituitary (PDH)
- 80-85% of dogs
Are most pituitary tumors in Cushing’s benign or malignant?
- Benign
85% are <1cm microadenomas - > 1 cm would be a macroadenoma
What breed size (small/toy vs medium/large) is more likely to have a PDH?
- 75% of small and toy breeds have PDH
- <20kg
What percentage of dogs will have an adrenal dependent Cushing’s?
- 15%
What is the breakdown for benign adenoma vs carcinoma in adrenal dependent Cushing’s?
- 50/50 for benign adenomas vs carcinomas
Breed distribution for adrenal dependent hyperadrenocorticism
- Affects large breed dogs more frequently (50% > 20kg)
- MORE LIKELY to have a adrenal than a shih tzu, but most common is still pituitary dependent in large breeds
Typical age in Cushing’s
- Tend to be middle to older age
Typical sex in Cushing’s
- Predisposition towards females
Most common presenting complaints in Cushing’s
- PU/PD
- Polyphagia
- Panting
- Dermatologic problems (e.g. alopecia)**
- Secondary infections (e.g. UTI)
- Respiratory
- Musculoskeletal
- General
- Macroadenoma (neurologic)
Dermatologic Manifestations of Cushing’s
- Calcinosis cutis**
- Truncal alopecia (common signs)**
- Symmetrical, non-pruritic unless secondary infection
- Thin skin
- Recurrent pyodermas
- Adult onset demodicosis
- Cutaneous hyperpigmentation
- Difficulty of skin wounds to heal
Calcinosis Cutis
- Deposits of calcium in the skin
- Firm plaques that may be ulcerated or irritated
What is the most common presenting complaint for hyperadrenocorticism?
- PU/PD (80-91% of cases)
- May no longer be housebroken
What is the pathophysiology of PU/PD in Cushing’s?
- Blocks action of ADH at the collecting tubules
What should you do with the urine sample for Cushing’s?
- CULTURE THE URINE
- (1) Dilute urine and (2) Poor immune response predispose to UTI
What is the most common musculoskeletal complaint with Cushing’s?
- > 80% of cases have abdominal distention
- Fat redistribution, increased liver size, weakness of abdominal muscles
Other musculoskeletal signs with Cushing’s
- Generalized weakness
- Muscle wasting (protein catabolism)
- Collagen breakdown
Respiratory signs of Cushing’s
- Panting (diaphragm is weakened and liver is enlarged)
- If severe dyspnea seen, suspect pulmonary thromboembolism (PTE) (hypercoagulable from the clots)
Other fairly common clinical signs with Cushing’s?
- Polyphagia (90% or more of cases)
- Lethargy
- Diabetes mellitus
- Obesity (if weight loss occurs, suspect diabetes mellitus or macroadenoma)
Macroadenoma signs
- Neurologic signs
- Inappetance/anorexia (most common)*
- Dullness (most common)*
- Disorientation
- Circling
- Ataxia
- Behavior Changes
Common changes on CBC for Cushing’s
- Stress leukogram
- Thrombocytosis (not well understood)
Biochemistry panel common changes for Cushing’s
- Increased ALP (moderate to marked)
- Increased ALT (mild - swollen hepatocytes swell and accumulate glycogen; crowd other cells and either cause hypoxia or bile damage )
- Increased cholesterol (variable)
- Elevated fasting blood glucose (mild)
What are the most common findings on chemistry in Cushing’s?
- Increased ALP and cholesterol are most constant findings and seen in >90% of dogs with Cushing’s
Urinalysis changes with Cushing’s and Pathophysiology
- Isothenuria (1.007-1.012 due to cortisol interfering with ADH at the distal tubules)
- Proteinuria (due to glomerular scerlosis)
- Urinary tract infections common (should perform culture and sensitivity even with quiet sediment)
Most common findings on abdominal films with Cushing’s disease
- Hepatomegaly
Potential findings on thoracic films in patients with Cushing’s
- Rarely, metastasis from adrenal adenocarcinoma
What tests are involved in ruling Cushing’s in or out?
- Urine cortisol to creatinine ratio
- ACTH stimulation test
- Low dose dexamethasone suppression test
Pros of urine cortisol/creatinine ratio
- Easy to perform
- inexpensive
- high sensitivity (75-100%)
Cons of urine cortisol/creatinine ratio
- Can’t be performed during hospital visit
- Not specific (<20%)
Urine C/C Ratio test protocol
- have owner bring first morning urine as the stress of the visit to the hospital will increase cortisol
Interpretation of a positive UCCR test
- Could be Cushing’s, but could be a number of other diseases that aren’t Cushing’s either
Interpretation of a negative UCCR test
- Probably not Cushing’s
ACTH stim test principle
- Evaluates maximal stimulation of adrenocortical reserve
Speed of ACTH stim test
Fast (1 hr)
Sensitivity of ACTH stim test
- Good (60-85%)
Specificity of ACTH stim test
- Good (85-90%)
- Less affected by non-adrenal illness
What is the disease that only the ACTH stim test can test for?
- Iatrogenic Cushing’s
Price of ACTH stim test
Expensive
Can ACTH stim test differentiate between PDH and ADH?
- No
Post cortisol value >21 µg/dL in ACTH Stim Test
- generally considered diagnostic in an animal with appropriate clinical signs and no concurrent illness
- SUPPORTIVE
ACTH Stim test with PDH
- Tumor producing high amounts of ACTH
- Consistently high ACTH has the adrenal glands ramped up and producing more cortisol than normal dogs
- Give ACTH: adrenal glands respond by releasing all of the cortisol that they have saved up
- In most dogs, cortisol levels will increase beyond the reference ranges
ACTH stim test with ADH
- Adrenal tumor cells produce cortisol erratically and are not necessarily responsive to exogenous ACTH
- Cortisol may be elevated with an adrenal tumor but a normal result does not rule out ADH
Iatrogenic Cushing’s result
- Cushing’s like signs and blood abnormalities due to administration of exogenous steroids
- Atrophy of the adrenal glands leading to lack of endogenous steroid production
- Inability of adrenal glands to respond to ACTH
- Your ACTH stim test would be low
- It should look like <2 and <2 µg/dL for both pre-and post
Low dose Dexamethasone Suppression test Normal individual
- Dexamethasone suppresses ACTH and decreases cortisol release from adrenals
Price of LDDST
- less than ACTH
Sensitivity of LDDST
- Good (90-95%)
Specificity of LDDST
- Fair (50%)
- More affected by non-adrenal illness
Can LDDST differentiate between PDH and ADH?
Yes
Length of LDDST
- 8 hrs
LDDST and Iatrogenic Cushing’s
- Cannot diagnose it
Protocol for LDDST
- Check baseline cortisol
- Administer dexamethasone
- Check cortisol at 4 hours and 8 hours post
- 8 hr time point is used for diagnosis of Cushing’s; 4 hr time point is used for differentiation
Result if LDDST is >1.4µg/dL at 8 hr time point?
- This is consistent with Cushing’s
- overwhelming your negative feedback
LDDST PDH response
- Tumor cells may briefly suppress in response to dexamethasone (4 hr)
- They will then usually recover and go back to their ways and return to producing large amounts of ACTH (8 hours)
- This is called an escape
ACTH stim and LDDST diagrams *(Just a reminder, not an actual flash card)
- This is your reminder to look at the diagrams for the tests because they are quite helpful!
LDDST ADH response
- Producing cortisol erratically independent of pituitary
- High amount of cortisol produced by the tumor causes negative feedback on the pituitary thus little ACTH is produced
- Cortisol will stay high with no suppression at any time point
LDDST Interpretation with suppression 4 hrs and escape at 8 hrs?
- Diagnostic for PDH
- 65% of dogs with PDH will show this pattern
LDDST Interpretation with lack of suppression at 4 hrs
- Does not differentiate between PDH and ADH
- Need further differentiating tests
HDDST (High Dose Dexamethasone Suppression) Procedure
- Same as LDDST only with a higher dexamethasone dose
Purpose of HDDST
- More likely to show the suppression and escape pattern for PDH than LDDST
- Still need LDDST as a screening test
HDDST pattern with PDH
- Suppression at 4 hours and escape at 8 hrs
- 75% of PDH will show this
HDDST pattern with ADH
- Never suppress
Interpretation of HDDST test without suppression?
- Does not differentiate between PDH and ADH
- Further differentiating tests needed
Ability of Endogenous ACTH test to diagnose:
- ) ADH
- ) PDH
- ) Can diagnose ADH
2. ) Cannot diagnose PDH
Speed of Endogenous ACTH
- Send out test - delayed results
Endogenous ACTH Sample Handling
- Special sample handling required to prevent false results
Endogenous ACTH results with adrenal tumor
- ACTH suppressed due to negative feedback so levels are low
- Poor sample handling can lead to rapid degradation of ACTH in blood which can falsely lower
Endogenous ACTH results with pituitary tumor
- Secretion of ACTH is variable, but ACTH usually normal or high
Further testing to support Hyperadrenocorticism
- Abdominal ultrasound
Abdominal ultrasound benefits for Cushing’s
- Superior to radiographs
- Evaluate size and shape of both adrenals
- Helps to differentiate between PDH and adrenal tumors, as well as evaluate for metastasis
- Evaluate liver and look for causes of cholestasis
What imaging is recommended in cases of PDH?
- CT/MRI
- Evaluate pituitary tumor and look for macroadenoma
What imaging is recommended if owners want to pursue adrenalectomy for ADH?
- Evaluate adrenal glands and tumor for surgical planning
Cost of CT/MRI
$$$$$
Differentials for Adrenal Tumor (4 main ones plus mets)
- Functional adenoma - producing cortisol
- Nonfunctional adenoma (incidentaloma)
- Cortical adenocarcinoma (functional or not)
- Pheochromocytoma - medullary tumor producing catecholamines
- Other - metastasis (pulmonary, mammary, prostatic, gastric, pancreatic, carcinoma, melanoma, lymphoma, etc.)
How can you determine of the adrenal tumor is producing cortisol?
- Endogenous ACTH
- Measures baseline levels of ACTH being produced by the pituitary gland
- Should be quite low with ADH
Differentiating ADH and PDH and normal dogs with endogenous ACTH
- Minimal overlap between PDH and ADH
- Significant overlap between PDH and normal
- Minimal overlap between ADH and normal
What are the primary categories of treatment options for PDH?
- Medical management with drugs
- Medical management with irradiation
- Surgery
What drugs are used for treatment of PDH?
- Mitotane
- Trilostane
- Selegiline and ketoconazole not recommended anymore
What type of surgery is performed to treat PDH?
- Hypophysectomy
Mitotane overview
- Chemotherapeutic agent
- Adrenolytic - destroys adrenal tissue
Mitotane monitoring
- Monitor with ACTH stim testing
Trilostane overview
- Synthetic steroid analog and enzyme inhibitor that prevents formation of cortisol
Reversibility of trilostane vs mitotane
- Trilostane is reversible with dose dependent side effects
- Mitotane is not reversible
Monitoring for trilostane
- Monitor with ACTH stim testing and electrolytes
Radiation for PDH duration of effectiveness
- variable
Radiation for PDH onset of effect
- can take awhile
- up to months
Radiation for PDH Cost
- Expensive
- 3 weeks ~$3500
Radiation for PDH Availability
Limited
Surgery for PDH
- Hypophysectomy (removing the pituitary)
What do you need to supplement if you do a hypophysectomy?
- Other hormones (e.g. thyroid, vasopressin)
Availability and cost of hypophysectomy
- HIGHLY technical surgery
- Very limited availability
- Very expensive
Efficacy of trilostane vs mitotane for PDH
- Similar survival times (14-16 months)
- No major difference in efficacy
- Both drugs control clinical signs
Adverse effects of trilostane vs mitotane for PDH
- Rate of side effects and severity of side effects may be higher with mitotane
- Mitotane up to 40%
- Trilostane up to 63% (usually mild)
Trilostane benefits for PDH
- Generally considered more user friendly
Mitotane benefits for PDH
- Less expensive overall in most cases
- Requires less frequent dosing
Monitoring in trilostane vs mitotane
- Both require significant monitoring especially early on
Options of treatment for ADH
- Medical vs surgical
Medical treatment for ADH
- Trilostane or Mitotane
- No major difference in efficacy, and both control clinical signs
Surgical treatment for ADH
- adrenalectomy
- potential to be curative (whenever possible, they want to go in)
Prognosis for Cushing’s: Degree of ALP elevations in terms of severity of disease or response to treatment
- Does not reflect severity
Prognosis for Cushing’s: Pituitary microadenoma
- good long term prognosis
Prognosis for Cushing’s: Pituitary macroadenoma
- Poor without treatment, can be fair with effective treatment
Prognosis for Cushing’s: Adrenal tumors
- Good to poor depending on the type and treatment performed
