Endocrine2- Cushing's Dz
Card Set Information
Endocrine2- Cushing's Dz
Most cases of hypercortisolism occur due to...
bilateral adrenocortical hyperplasia due to ACTH-secreting adenoma of the pars distalis (second most common cause- adrenocortical neoplasia- independent of ACTH)
What are etiologies of hypercortisolism? (4)
pituitary-dependent HC, adrenocortical neoplasia, iatrogenic (long-term glucocorticoid txt), food-dependent HC (aberrant GI hormones)
Cushing's usually appears in _________ dogs of _______ breed.
middle aged to older; any
There is a characteristic appearance of cushing's dogs, and this is...
not always present with the disease.
Clinical signs of Cushing's are due to __(5)__ effects of ___________.
gluconeogenic, lipolytic, protein catabolic, anti-inflammatory, and immunosuppressive; glucocorticoid excess
What 5 clinical signs are common in Cushing's patients?
PU/PD****, polyphagia**, pendulous abdomen (redistribution of fat), muscle weakness, alopecia (dermatological changes)
What are dermatological signs associated with Cushing's? (7)
truncal alopecia, thin/dry/scaling skin, hyperpigmentation, easy bruising, comedones, pyoderma, calcinosis cutis
Describe calcinosis cutis.
calcium deposition in the dermis- rare but very suggestive of cushing's
What are clinical signs that are NOT associated with Cushing's? (rule it out) (10)
decreased appetite, vomiting, diarrhea, sneezing, coughing, pruritus, icterus, pain, seizures, bleeding
Complications that can occur due to Cushing's. (3)
hypertension, poor wound healing, pulmonary thromboembolism, proteinuria, urolithiasis, DM, gall bladder mucocoele
CBC results with Cushing's. (6)
stress leukogram- lymphopenia, eosinopenia, neutrophilia, monocytosis; increased PCV; thrombocytosis
Biochem panel results with Cushing's. (5)
mild hyperglycemia, high cholesterol, increased ALT, high bile acids, increased ALP (corticosteroid stereotype- only in DOGS)
Clinical signs of DM are ________ with Cushing's.
If corticosteroid ALP is not high in a dog, then...
rule out Cushing's (if it is high, it can be due to a number of diseases).
Is there any correlation b/w magnitude of increase in ALP and HC? If so, what correlation?
NO CORRELATION b/w magnitude of increase in ALP and likelihood of HC or severity of HC
Urinalysis findings with Cushing's. (2)
low USG, proeinuria
How should you collect urine for UA in a suspect Cushing's patient?
cysto- catheterization increases risk of infection
What can commonly be confusing in hormone laboratory findings in a Cushing's patients?
low T4- TSH is supressed; DO NOT confuse with hypothyroidism
Abdominal radiographs of a Cushing's patient shows... (2)
hepatomegaly, enlarged bladder
___(2)___ on radiograph should prompt suspicion of pulmonary thromboembolism in a Cushing's or suspect Cushing's patient.
Hypovascular lung fields and alveolar infiltrates
On abdominal US, _________________ in a dog with confirmed HC suggests pituitary-dependent HC.
bilaterally symmetrical enlargement of the adrenals with normal echogenicity
On abdominal US, _____________ in a dog with confirmed HC suggests adrenal-dependent HC.
non-symmetrical abnormalities: unilateral enlargement, distortion of shape, invasion into adjacent structures, and small contralateral gland
On abdominal US, ___________ in a dog with signs of HC suggests iatrogenic HC.
small adrenal glands
With Cushing's disease, there is an increased risk of ___________.
calcium-containing urinary calculi
With Cushing's, adrenal gland size is correlated to _________; most of the variation is in the _________.
Can non-adrenal illness cause enlarged adrenal glands?
: yes, with hypersomatotropism
What are the 2 types of tests used in the diagnosis of Cushing's?
Screening- is there excess cortisol?
Discriminatory- where is the excess cortisol coming from?
Is gathering the resting cortisol value useful in suspected Cushing's patients? Why?
No- dogs with Cushing's can have normal cortisol at any given moment due to episodic release of ACTH, and dogs of non-adrenal illness have have increased cortisol
The first and most important screening test for Cushing's?
history and physical exam
Any disease process can activate the ________ and increase _______.
HPA axis; cortisol
Avoid performing a Cushing's screening test if...
other serious illness is present- may get false positive
The ___________ is the screening test of choice unless iatrogenic HC is suspected.
The low dose dexamethasone suppression test is a ____________.
Describe the low dose dexamethasone suppression test.
measure plasma cortisol before and 4 and 8 hours after 0.01mg/kg dexamethasone
How do you interpret the low dose dexamethasone suppression test?
normal: plasma cortisol decreases to <10μg/dL 4 and 8 hours after shot; failure to suppress at the 8hr time point suggests HC (does not differentiate b/w etiologies)
With the LDDST, the ________ sample(s) is used for diagnosis of HC; the ________ sample(s) are useful for the discriminatory test.
8hr; 0 and 4hr
The ACTH stimulation test is a ___________.
Describe the ACTH stimulation test.
measure cortisol 1 hour after administration of synthetic ACTH (5μg/kg cosyntropin) to measure the maximal capacity to respond to ACTH
How do you interpret the results of the ACTH stimulation test?
above normal (post-ACTH cortisol>20μg/dL)- PDH, ADH, or severe illness
below normal (post-ACTH cortisol <5μg/dL)- iatrogenic, treated, addison's
The ACTH stim test is not ________ because...
sensitive; adrenal tumors may not always respond to ACTH; if negative, cannot rule out HC.
What is the only diagnostic test that can identify dogs with iatrogenic HC?
ACTH stimulation test
What is the test of choice for monitoring dogs being treated for HC?
ACTH stimulation test
What is used for diagnosis of "atypical Cushing's syndrome"? What is atypical cushing's syndrome?
17-hydroxyprogesterone measurement; cushing's-like signs caused by excess sex hormone
Why use the urine cortisol:cre ratio?
dividing cortisol by Cre corrects for urine being dilute or conc, its simple; use it when you want to rule out HC (esp. if you think it's unlikely)
What is that caveat to the urine cortisol:cre ratio?
very low specificity- can be used to rule out, but positive test needs further diagnostic proof to diagnose
What are the discriminatory tests used in HC patients? (3)
abdominal US, dexamethasone suppression test (
and maybe low dose combined), endogenous ACTH concentration
What are screening tests used in suspect HC patients? (3)
LDDST, ACTH stim test, urine cortisol:cre ratio
How do you perform the high dose dexamethasone suppression test?
0.1mg/kg dexamethasone; measure cortisol at 0,4,and 8 hrs
The discriminatory aspect of the dexamethasone suppression test is based on the principal that...
a dose of dexamethasone would sometimes suppress cortisol conc in dogs with PDH, but NEVER in dogs with ADH
If a dog fails to suppress cortisol with the dexamethasone suppression test, then...
you CANNOT draw any conclusions and must use other discriminatory tests.
What are the 4 criteria for suppression with the dexamethasone suppression test?
1. HD and LD
: 50% decrease in cortisol conc at 4hr
2. HD and LD
: 50% decrease in cortisol conc at 8hr
3. HD and LD
: cortisol conc <1.0μg/mL at 4hr
4. HD only
: cortisol conc <1.0μg/mL at 8hr
What are normal endogenous ACTH concentrations?
Endogenous ACTH is completely suppressed with ________, but it is measurable with ________.
With an adrenocortical tumor (ADH), eACTH value is __________.
With PDH, eACTH value is _________.
What is the downside to directly assaying eACTH?
it is VERY fragile and sample must be handled, frozen, and shipped appropriately, or you get artificially low results
What is the guiding principal of treatment of HC?
DO NOT treat a dog with HC that does not have clinical signs b/c they are impossible to monitor and there is questionable benefit
How should you handle a case of a dog with HC but no clinical signs?
monitor for and treat UTI, proteinuria, hypertension
What is the ideal treatment for HC? How is it usually treated?
: tumors that can be removed should be removed, especially those with malignancy potential
: medical txt due to cost of sx
Treatment methods for PDHC. (5)
hypophysectomy (expensive, difficult), Mitotane, Trilostane, ketoconazole, pituitary irradiation
How does the use of Mitotane compare for txt of PDHC and ADHC?
>80% PDHC dogs respond well; dogs with ADH are relatively refractory and can require higher doses
Mitotane causes selective necrosis of __(2)__.
zona fasiculata and reticularis
Mitotane should always be administered with ________ because...
food; better absorption
What is the dose for Mitotane for the induction period? How long should this period last?
30-50mg/kg/day divided b/w 2 doses for 7-10days
During the induction period of Mitotane, the owner MUST monitor __(2)__; changes warrant...
food and water intake; stopping txt immediately at any sign of decreased food or water intake; return for ACTH stim test the next day.
Mitotane toxicity usually occurs within ________ if it is going to occur; signs include...(6)
48hr; anorexia, vomiting, diarrhea, lethargy, weakness
How do you know if the induction phase of Mitotane was successful?
post-ACTH cortisol is 2-5μg/dL
What should you do if the induction phase of Mitotane was not successful?
mitotance at induction dose for an addition 3-5 days, repeat ACTH stim test until post-ACTH cortisol is 2-5μg/dL
What is the maintenance dose of Mitotane?
30-50mg/kg/week, divided into 2-3 doses over the course of the week
How do you monitor patients receiving Mitotane?
ACTH stim every 3 months, relapses common and require mini-induction phase
What is the dose that is used to intentionally overdose Mitotane and destroy the adrenal glands completely?
50-75 mg/kg/day divided into 2 doses for 25 days
Describe lifelong treatment of an animal in which you destroyed the adrenal glands with Mitotane.
glucocorticoids (physiologic doses of pred) and mineralocorticoids
How does Trilostane work?
competitive inhibitor of enzymes needed for conversion of pregnenolone to progesterone in the synthesis of corticosteroids
What is the starting dose for Trilostane?
1 mg/kg PO BID
How do you monitor patients being treated with Trilostane?
monitor clinical signs, ACTH stim 2-4 hours post pill 2 weeks after starting treatment/increasing dose-follow algorithm (covered on separate slides)
2 weeks after starting Trilostane, if dog is showing signs of cortisol deficiency of if post-ACTH cortisol is ________, you should...
<1.5μg/dL; discontinue treatment
2 weeks after starting Trilostane, if the dog is clinically doing well but post-ACTH cortisol is _________, you should...
<1.5μg/dL; discontinue treatment and start with a lower dose in a week.
2 weeks after starting Trilostane, if dog has no clinical signs and post-ACTH cortisol is >1.5μg/dL, you should...
continue at same dose and recheck in 2 weeks.
After 4 weeks of Trilostane txt, if clinical signs are not fully controlled, your options are...
if post-ACTH cortisol is high, increase dose; if post-ACTH cortisol is low, increase frequency
After 4 weeks of Trilostane txt, if clinical signs are significantly improved, there are 3 scenarios:
post-ACTH cortisol <1.5, discontinue for one week and start over with lower dose
post-ACTH cortisol 1.5-5.4, continue same dose and check in 3 months
post-ACTH cortisol >5.4, txt with same dose or increase dose
Everytime you change the dose of Trilostane, you should...
start over from step 1.
What are side effects of Trilostane? (5)
coagulation necrosis of adrenals, reversible hypoadrenocorticism, vomiting/diarrhea, unexplained hyperkalemia (w/ normal aldosterone), decreased Aldosterone
Compare the use of Trilostane to Mitotane. (5)
comparable clinical response, comparable cost, trilostane well-tolerated, trilostane no induction period, trilostane less reliable control of biochem abnormalities
Describe how ketoconazole is used to treat HC.
antifungal that interferes with steroid biosynthesis at high serum concs; not recommended
Pituitary irradiation causes _____________; it is recommended for _____________.
transient resolution of clinical signs; tumors>7mm
What are options for treatment of ADHC due to functional adrenal tumor? (3)
trilostane, mitotane, unilateral adrenalectomy
Before adrenalectomy, you should first...
rule out metastatic disease.
What are the risks associated with adrenalectomy? (4)
high risk of thromboembolism, high mortality, delayed wound healing, need supportive glucocorticoids postop b/c contralateral adrenal has been suppressed
What is the prognosis for adrenalectomy if the animal survives the post-op period and has no mets?
good- survival for several years
In general, prognosis for txt of HC is...
6-24 month survival; with therapy, clinical signs should regress in 3-5 months
With txt of HC, decrease in food intake, PU, and PD should occur within _______.
With txt of HC, muscle strength and resolution of abdominal distention may occur within _________.
With txt of HC, improvement of hair coat and resolution of hypertension and proteinuria and improvement in biochem occurs within ________.