hyperadrenocorticotism Flashcards
1
Q
etiology for hyperadrenocorticotism
A
- Bilateral adrenocortical hyperplasia (80-85%)
- ACTH secreting adenoma of pars distalis
- PDH –Pituitary Dependent Hyperadrenocorticism
- Adrenocortical neoplasia (15-20%)
- ADH –Adrenal Dependent Hyperadrenocorticism
- Iatrogenic
- Exogenous steroids
2
Q
causes of pituitary dependent hyperadrenocortism
A
-
Microadenoma
- Most (85%) pituitary tumors are microadenomas
- < 1 cm in diameter
- Clinical signs are due to excessive ACTH production
-
Macroadenoma
- Up to 15% of pituitary tumors may be macroadenomas
- > 1 cm in diameter
- Clinical signs are due to excessive ACTH production AND signs associated with mass effects of tumor
3
Q
eitiology for adrenal dependent hyperadrenacorticotism
A
50% are benign (adenoma)
50% are malignant (adenocarcinoma)
Often large, more invasive (vena cava)
Can potentially metastasize (lungs, liver, etc.)
More common in large breed dogs
4
Q
signalment for hyperadrenocortism
A
- Middle-aged to older dogs
- Most are > 9 years of age
- No strong sex predilection
- Any breed or mixed breed dogs
- PDH -often affects smaller dogs
- ADH –often affects larger dogs (exception: PDH in Boxers)
5
Q
history for hyperadrenocorcotism
A
- Generally considered “healthy” by the owner
- Clinical signs due to effects of excess glucocorticoids
- Gluconeogenic
- Lipolytic
- Protein catabolic
- Anti-inflammatory
- Immunosuppressive
- The P’s
- Polyuria and polydipsia (80% of cases)
- Polyphagia (90% of cases)
- Panting
- Decreased exercise tolerance
Lethargy
6
Q
what do u feel on pe of a hyperadrenocorticotism dog
A
- Abdominal enlargement (80%)
- Muscle weakness
- Hepatomegaly
- Hepatocyte vacuolation due to glycogen accumulation
- Almost all have some dermatologic signs
- Bilaterally symmetric truncal alopecia
- Thin, dry, scaling skin
- Hyperpigmentation
- Easy bruising (e.g. after venipuncture)
Comedones - Calcinosis cutis
- Calcium deposition in the dermis
- Uncommon but very suggestive of hyperadrenocorticism
- Pyoderma
- Increased susceptibility to infection
7
Q
other findings of hyperadrenocorcocotism
A
- Hypertension (> 50% of cases)
- Poor wound healing
- Pulmonary thromboembolism
8
Q
cbc findings of hyperadrenocorcocotism
A
- Stress leukogram
- Leukocytosis due to neutrophilia
- Monocytosis
- Lymphopenia, eosinopenia (80% of cases)
- Mild to moderate erythrocytosis
- Thrombocytosis (cause unknown)
9
Q
chemistry profile for hyperadrenococotism
A
- Mild hyperglycemia (50% of cases)
- Glucocorticoids increase hepatic gluconeogenesis and decrease peripheral uptake of glucose
- Increased ALP (90% of cases)
- CIALP unique to the dog
- Sensitive but not specific
- Hypercholesterolemia (75% of cases)
- Increased ALT –mild to moderate (50% of cases)
10
Q
urinalysis findings of hyperadrenocoticotism
A
- Low urine specific gravity (80% of cases)
- < 1.015 to 1.020
- Bacteriuria in 50% of cases but pyuria < 20% of cases
- Avoid catheterization for urine collection
- Increased risk of infection; use cystocentesis
- Proteinuria (can have mildly increased UPC)
11
Q
abdominal rads findings for hyperadrenocorticotism
A
- Hepatomegaly (80-90% of cases)
- Enlarged bladder (due to polyuria)
- Approximately 50% of adrenocortical tumors calcified
- Increased risk of calcium-containing urinary calculi (calcium oxalate or calcium phosphate)
12
Q
discuss resting cortisol levels as a dx for hyperadrenocorticotism
A
- Not valuable because many dogs with hyperadrenocorticism have normal cortisol concentrations at any given moment due to the episodic secretion of ACTH
13
Q
screening tests for hyperadrenocoticotism
A
- ACTH Stimulation Test
- Low Dose Dexamethasone Suppression Test (LDDST)
- Urine Cortisol/Creatinine Ratio (UCCR)
14
Q
ACTH stimulation test
A
- Normal resting cortisol
- 1-5 μg/dL; normal post-ACTH cortisol: 5-22 μg/dL
- Dogs with hyperadrenocorticism
- Exaggerated response to ACTH
- Post-ACTH cortisol > 22 μg/dL)
- Very sensitive (approximately 95%)
- Reasonably specific (approximately 90%)
15
Q
advantages of ACTH stimulation test
A
- Cheaper than LDDST and takes less time
- Only test to identify iatrogenic hyperadrenocorticism
- Test of choice to monitor dogs being treated with mitotane or trilostane
16
Q
disadvantages of ACTH stimulation test
A
Stress of non-adrenal illness can cause abnormal test results
17
Q
how does LDDST test work
A
- Measure plasma cortisol before and 4 and 8 hours after 0.01 mg/kg/IV dexamethasone
- Normal dogs
- Plasma cortisol decreases to < 1.4 μg/dL 4 and 8 hours after dexamethasone
- Failure to suppress suggests Cushing’s syndrome
- Very sensitive (approximately 95%)
- Not very specific (approximately 70%)
18
Q
adv. of urine cortisol/crea. ratio
A
Easy (have owners get free catch from dog at home)
19
Q
disadvantages of urine cortisol/creat. ratio
A
- Extremely low specificity (20-40%) despite very high sensitivity (> 90%)
- Used primarily when you don’t think the animal has Cushing’s and you want to quickly rule it out
- Not helpful at all in ruling in Cushing’s
- If positive, must perform ACTH stim or LDDST
20
Q
PDH vs. ADH……does it really matter?
A
PDH vs. ADH……does it really matter?
21
Q
disadvantages of HDDST
A
- Previously used as a discriminatory test
- Based on principle that a high dose (0.1 mg/kg/IV) of dexamethasone would suppress cortisol in dogs with PDH but not ADH
- Unfortunately, 40-50% of dogs with PDH also fail to suppress with HDDST
- Thus suppression indicates PDH but NO conclusion can be drawn if dog fails to suppress
22
Q
disadvantages of radioimmnoassay in ACTH
A
- Previously used as a discriminatory test
- Based on principle that a high dose (0.1 mg/kg/IV) of dexamethasone would suppress cortisol in dogs with PDH but not ADH
- Unfortunately, 40-50% of dogs with PDH also fail to suppress with HDDST
- Thus suppression indicates PDH but NO conclusion can be drawn if dog fails to suppress
23
Q
what would u see on US in a patient with PDH vs ADH
A
- Most practical test
-
PDH
- Bilateral symmetrical enlargement
- Glands retain their normal “peanut” shape
- Normal echogenicity
-
ADH
- Unilateral enlargement with distortion of shape
24
Q
words of wisdom for abd. Us in hyperadrenocorticotism
A
- Don’t use as a screening test
- Dogs with non-adrenal illness can have enlarged adrenal glands
- Dogs with hyperadrenocorticism may have normal adrenal glands
- Not all identified adrenal masses are functional (e.g. non-functional adenoma, pheochromocytoma)
- Contralateral adrenal gland in dogs with ADH is not necessarily small on ultrasound examination as might be expected
25
guiding principles for tx hypeadrenocoticotism
* DO NOTtreat a dog with hyperadrenocorticism that has NO clinical signs
* In other words…..no clinical signs…..NO TX!!!
* High ALP does NOTequal hyperadrenocorticism
* Hyperadrenocorticism is a CLINICAL diagnosis!!!!!
26
discuss adv. and disd. of unilateral adrenalectomy in the tx of adh
* Preoperative thoracic radiographs to rule out metastatic disease
* Very difficult (best left to specialist surgeons)
* High risk of thromboembolism and high mortality 24-48 hours postoperatively
* Delayed wound healing
* Contralateral adrenal suppressed
* Dog must be supported with glucocorticoids intra-and post-operatively
* Potentially good prognosis (adenoma better than carcinoma)
27
disadvantages of Hypophysectomy
* **for pdh**
* Difficult technique
* Requires specialist surgeon
* Not routinely performed in dogs in USA
* Due to loss of pituitary hormones
* Must replace glucocorticoids, T4, and ADH post-op
* DI often is transient
* Lifelong glucocorticoid and T4 support is needed
28
Medical Adrenalectomy
* **for PDH**
* Intentional over dosage of mitotane to completely destroy adrenal glands
* Hypoadrenocorticism is created
* Dog must be supported with glucocorticoids and mineralocorticoids for life
* Indications
* Extremely refractory cases of PDH
29
discuss ketakonazole in the txment of PDH
* Anti-fungal drug
* Inhibits biosynthesis of steroids
* Adverse effects
* Anorexia, increased liver enzymes, icterus
* NOTrecommended for routine treatment of hyperadrenocorticism
30
discuss mitotanein txment of PDH
* Lysodren®
* Most common treatment for PDH in USA
* Selective necrosis of zona fasiculata, zona reticularis
* Dogs with ADH are refractory to tx
31
discuss induction of mitotane
* Mitotane -PDH
* Induction
*
* Owner must monitor appetite and water intake carefully to identify endpoint
* Stop treatment if decreased appetite or water intake and return for ACTH stimulation test
* Stop after 10-14 days regardless (maybe even 7 days?)
* Repeat ACTH stimulation test
32
discuss mitotane toxicity
* Direct toxicity of mitotane
* Anorexia, vomiting, diarrhea, lethargy, weakness
* Must be differentiated from development of actual hypoadrenocorticism by ACTH stimulation if these signs develop
* Mitotane-induced hypoadrenocorticism may be transient or permanent
33
successful induction of mitotane
* Both pre-and post-ACTH cortisol concentrations should be 1-5 μg/dL
* Decreased responsiveness of adrenal glands to ACTH
* Most importantly: control of clinical signs
34
what should u do If post-ACTH cortisol \> 5 μg/dL after mitotane induction
* Administer mitotane for an additional 3-5 days
* “Mini-induction”
* Repeat ACTH to determine that both pre-and post-ACTH cortisol concentrations are 1-5 μg/dL
35
discuss mitotane maintainance
* in PH we keep on adjusting the drug
* Relapses are not unusual and require “mini-inductions” of 3-5 days of mitotane followed by return to maintenance
36
response of dogs to mitotane tx
* Overall good clinical response to mitotane
* 80% of dogs with PDH respond well
* Survival of 2 years or more (geriatric dogs)
37
advantages of trilostane tx
* Can be used for both PDH and ADH
* drug of choice if u decide nt to send the dog to sx wen they hav adrenal mass
* no induction dose
38
px with trilostane tx
* Good clinical response in 80% of treated dogs with survival times of 2-3 years
* Control of biochemical abnormalities (e.g., ALP, cholesterol) is less reliable than control of clinical signs (e.g. PU, PD, polyphagia)
39
advantages of trilostane
* Well-tolerated
* Useful in dogs with other serious medical problems
* Effects are reversible
* No induction phase
40
disad. of trilostane
* Expensive
* Rare cases of adrenal necrosis
41
disad. of raditherapy for PDH
* Only available at selected institutions
* May see substantial reduction in size of pituitary tumor but only transient resolution of clinical signs
* Usually recommended for tumors \> 7 mm
* So-called “macroadenomas” are ≥ 10 mm
42
complications for hypercorticotism tx
Hypertension
Proteinuria (related to hypertension or PLN or both?)
Thromboembolism
Susceptibility to infections (e.g., UTI)
Urolithiasis (e.g., calcium oxalate, calcium phosphate)
Concurrent diabetes mellitus in 5% of dogs with hyperadrenocorticism
43
px for PDH
Depends on size and rate of growth of pituitary tumor
44
px for ADH
* Depends on local invasion or distant metastasis
* Adenomas have better prognosis than carcinomas
45
px for hyperadrenocorticotism
* With treatment, clinical signs regress in 3-5 months
* Polyphagia, polydipsia, polyuria within 10 days
* Muscle strength returns and abdominal distension improves within weeks
* Improvement in hair coat and resolution of hypertension and proteinuria over months (some don’t resolve?)
* Improvement in biochemistry (e.g. SAP, cholesterol) over months
46
hyperadrenocorticosm in cats
* Rare but increasingly reported
* Older cats
* Usually presented for DM that is difficult to control
* Insulin resistant DM
* Fragile, thin skin!!!
* Weakness, weight loss, polyuria, polydipsia
* PU/PD due to concurrent DM
* Glucocorticoids do NOT usually cause PU/PD in cat
* Ocular abnormalities (mydriasis, blindness, retinal detachment) associated with hypertension
47
lab findings for hyperadrenocorticotism in cats
Hypokalemia, hypernatremia, metabolic alkalosis, increased creatine kinase (due to hypokalemic myopathy), dilute urine
Very high aldosterone (\> 1000 pg/L; normal, 200-400 pg/L)
Caused by aldosterone-secreting adrenal adenoma or adenocarcinoma
48
tx and px for hyperthyroidism in cats
* Tumors identified on abdominal ultrasound (1-3 cm diameter)
* **Surgical remova**l is difficult (adherence to caudal vena cava) **but treatment of choice for adenomas**
* Palliative management
* Spironolactone (aldosterone antagonist)
* Potassium supplementation
* Long-term survival (up to 3 years) reported
