Hyperadrenocorticism Flashcards
1
Q
HPA Axis
A
- Remember it and make sure you can draw it out
2
Q
Hyperadrenocorticism Definition
A
- Constellation of clinical signs/abnormalities resulting from chronic glucocorticoid exposure
3
Q
What is the primary cause of Cushing’s if not iatrogenic?
A
- due to a TUMOR in either
1. Pituitary gland (PDH)
2. Adrenal gland(s) (ADH)
4
Q
Iatrogenic Cushing’s
A
- Due to exogenous exposure
5
Q
What type of tumor is most common in dogs with Cushing’s?
A
- Pituitary (PDH)
- 80-85% of dogs
6
Q
Are most pituitary tumors in Cushing’s benign or malignant?
A
- Benign
85% are <1cm microadenomas - > 1 cm would be a macroadenoma
7
Q
What breed size (small/toy vs medium/large) is more likely to have a PDH?
A
- 75% of small and toy breeds have PDH
- <20kg
8
Q
What percentage of dogs will have an adrenal dependent Cushing’s?
A
- 15%
9
Q
What is the breakdown for benign adenoma vs carcinoma in adrenal dependent Cushing’s?
A
- 50/50 for benign adenomas vs carcinomas
10
Q
Breed distribution for adrenal dependent hyperadrenocorticism
A
- 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
11
Q
Typical age in Cushing’s
A
- Tend to be middle to older age
12
Q
Typical sex in Cushing’s
A
- Predisposition towards females
13
Q
Most common presenting complaints in Cushing’s
A
- PU/PD
- Polyphagia
- Panting
- Dermatologic problems (e.g. alopecia)**
- Secondary infections (e.g. UTI)
- Respiratory
- Musculoskeletal
- General
- Macroadenoma (neurologic)
14
Q
Dermatologic Manifestations of Cushing’s
A
- 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
15
Q
Calcinosis Cutis
A
- Deposits of calcium in the skin
- Firm plaques that may be ulcerated or irritated
16
Q
What is the most common presenting complaint for hyperadrenocorticism?
A
- PU/PD (80-91% of cases)
- May no longer be housebroken
17
Q
What is the pathophysiology of PU/PD in Cushing’s?
A
- Blocks action of ADH at the collecting tubules
18
Q
What should you do with the urine sample for Cushing’s?
A
- CULTURE THE URINE
- (1) Dilute urine and (2) Poor immune response predispose to UTI
19
Q
What is the most common musculoskeletal complaint with Cushing’s?
A
- > 80% of cases have abdominal distention
- Fat redistribution, increased liver size, weakness of abdominal muscles
20
Q
Other musculoskeletal signs with Cushing’s
A
- Generalized weakness
- Muscle wasting (protein catabolism)
- Collagen breakdown
21
Q
Respiratory signs of Cushing’s
A
- Panting (diaphragm is weakened and liver is enlarged)
- If severe dyspnea seen, suspect pulmonary thromboembolism (PTE) (hypercoagulable from the clots)
22
Q
Other fairly common clinical signs with Cushing’s?
A
- Polyphagia (90% or more of cases)
- Lethargy
- Diabetes mellitus
- Obesity (if weight loss occurs, suspect diabetes mellitus or macroadenoma)
23
Q
Macroadenoma signs
A
- Neurologic signs
- Inappetance/anorexia (most common)*
- Dullness (most common)*
- Disorientation
- Circling
- Ataxia
- Behavior Changes
24
Q
Common changes on CBC for Cushing’s
A
- Stress leukogram
- Thrombocytosis (not well understood)
25
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)
26
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
27
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)
28
Most common findings on abdominal films with Cushing's disease
- Hepatomegaly
29
Potential findings on thoracic films in patients with Cushing's
- Rarely, metastasis from adrenal adenocarcinoma
30
What tests are involved in ruling Cushing's in or out?
1. Urine cortisol to creatinine ratio
2. ACTH stimulation test
3. Low dose dexamethasone suppression test
31
Pros of urine cortisol/creatinine ratio
- Easy to perform
- inexpensive
- high sensitivity (75-100%)
32
Cons of urine cortisol/creatinine ratio
- Can't be performed during hospital visit
| - Not specific (<20%)
33
Urine C/C Ratio test protocol
- have owner bring first morning urine as the stress of the visit to the hospital will increase cortisol
34
Interpretation of a positive UCCR test
- Could be Cushing's, but could be a number of other diseases that aren't Cushing's either
35
Interpretation of a negative UCCR test
- Probably not Cushing's
36
ACTH stim test principle
- Evaluates maximal stimulation of adrenocortical reserve
37
Speed of ACTH stim test
Fast (1 hr)
38
Sensitivity of ACTH stim test
- Good (60-85%)
39
Specificity of ACTH stim test
- Good (85-90%)
| - Less affected by non-adrenal illness
40
What is the disease that only the ACTH stim test can test for?
- Iatrogenic Cushing's
41
Price of ACTH stim test
Expensive
42
Can ACTH stim test differentiate between PDH and ADH?
- No
43
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
44
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
45
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
46
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
47
Low dose Dexamethasone Suppression test Normal individual
- Dexamethasone suppresses ACTH and decreases cortisol release from adrenals
48
Price of LDDST
- less than ACTH
49
Sensitivity of LDDST
- Good (90-95%)
50
Specificity of LDDST
- Fair (50%)
| - More affected by non-adrenal illness
51
Can LDDST differentiate between PDH and ADH?
Yes
52
Length of LDDST
- 8 hrs
53
LDDST and Iatrogenic Cushing's
- Cannot diagnose it
54
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
55
Result if LDDST is >1.4µg/dL at 8 hr time point?
- This is consistent with Cushing's
| - overwhelming your negative feedback
56
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
57
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!
58
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
59
LDDST Interpretation with suppression 4 hrs and escape at 8 hrs?
- Diagnostic for PDH
| - 65% of dogs with PDH will show this pattern
60
LDDST Interpretation with lack of suppression at 4 hrs
- Does not differentiate between PDH and ADH
| - Need further differentiating tests
61
HDDST (High Dose Dexamethasone Suppression) Procedure
- Same as LDDST only with a higher dexamethasone dose
62
Purpose of HDDST
- More likely to show the suppression and escape pattern for PDH than LDDST
- Still need LDDST as a screening test
63
HDDST pattern with PDH
- Suppression at 4 hours and escape at 8 hrs
| - 75% of PDH will show this
64
HDDST pattern with ADH
- Never suppress
65
Interpretation of HDDST test without suppression?
- Does not differentiate between PDH and ADH
| - Further differentiating tests needed
66
Ability of Endogenous ACTH test to diagnose:
1. ) ADH
2. ) PDH
1. ) Can diagnose ADH
| 2. ) Cannot diagnose PDH
67
Speed of Endogenous ACTH
- Send out test - delayed results
68
Endogenous ACTH Sample Handling
- Special sample handling required to prevent false results
69
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
70
Endogenous ACTH results with pituitary tumor
- Secretion of ACTH is variable, but ACTH usually normal or high
71
Further testing to support Hyperadrenocorticism
- Abdominal ultrasound
72
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
73
What imaging is recommended in cases of PDH?
- CT/MRI
| - Evaluate pituitary tumor and look for macroadenoma
74
What imaging is recommended if owners want to pursue adrenalectomy for ADH?
- Evaluate adrenal glands and tumor for surgical planning
75
Cost of CT/MRI
$$$$$
76
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.)
77
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
78
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
79
What are the primary categories of treatment options for PDH?
1. Medical management with drugs
2. Medical management with irradiation
3. Surgery
80
What drugs are used for treatment of PDH?
1. Mitotane
2. Trilostane
- Selegiline and ketoconazole not recommended anymore
81
What type of surgery is performed to treat PDH?
- Hypophysectomy
82
Mitotane overview
- Chemotherapeutic agent
| - Adrenolytic - destroys adrenal tissue
83
Mitotane monitoring
- Monitor with ACTH stim testing
84
Trilostane overview
- Synthetic steroid analog and enzyme inhibitor that prevents formation of cortisol
85
Reversibility of trilostane vs mitotane
- Trilostane is reversible with dose dependent side effects
| - Mitotane is not reversible
86
Monitoring for trilostane
- Monitor with ACTH stim testing and electrolytes
87
Radiation for PDH duration of effectiveness
- variable
88
Radiation for PDH onset of effect
- can take awhile
| - up to months
89
Radiation for PDH Cost
- Expensive
| - 3 weeks ~$3500
90
Radiation for PDH Availability
Limited
91
Surgery for PDH
- Hypophysectomy (removing the pituitary)
92
What do you need to supplement if you do a hypophysectomy?
- Other hormones (e.g. thyroid, vasopressin)
93
Availability and cost of hypophysectomy
- HIGHLY technical surgery
- Very limited availability
- Very expensive
94
Efficacy of trilostane vs mitotane for PDH
- Similar survival times (14-16 months)
- No major difference in efficacy
- Both drugs control clinical signs
95
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)
96
Trilostane benefits for PDH
- Generally considered more user friendly
97
Mitotane benefits for PDH
- Less expensive overall in most cases
| - Requires less frequent dosing
98
Monitoring in trilostane vs mitotane
- Both require significant monitoring especially early on
99
Options of treatment for ADH
- Medical vs surgical
100
Medical treatment for ADH
- Trilostane or Mitotane
| - No major difference in efficacy, and both control clinical signs
101
Surgical treatment for ADH
- adrenalectomy
| - potential to be curative (whenever possible, they want to go in)
102
Prognosis for Cushing's: Degree of ALP elevations in terms of severity of disease or response to treatment
- - Does not reflect severity
103
Prognosis for Cushing's: Pituitary microadenoma
- good long term prognosis
104
Prognosis for Cushing's: Pituitary macroadenoma
- Poor without treatment, can be fair with effective treatment
105
Prognosis for Cushing's: Adrenal tumors
- Good to poor depending on the type and treatment performed
