Canine Pituitary & Adrenal Diseases Flashcards
What are the 2 forms of naturally occurring Cushing’s syndrome? Which one is most common?
- ACTH-dependent - pituitary hypercorticism, commonly caused by a tumor (PDH)**
- ACTH-independent - adrenal hypercorticism, commonly caused by a tumor (ADH)
What is the most common cause of iatrogenic Cushing’s syndrome?
exogenous excess of cortisol, commonly caused by too high doses or chronic glucocorticoid administration
- betamethasone
- dexamethasone
- prednisone
What are the 2 pituitary tumors that cause Cushing’s syndrome? Which one is most common?
- microadenoma**
- macroadenoma - >1 cm, large enough to cause neurological signs
What are the chances that adrenal tumors that cause Cushing’s are benign vs. malignant?
50/50
- malignant tends to invade vessels and metastasize (surgical removal!)
What is the most common signalment of dogs with Cushing’s syndrome?
middle-aged to older Poodles, Dachshunds, Beagles, Boxers, Boston Terriers, and Bichons
- no sex predisposition
What are the 5 signs associated with the classic Cushingoid dog?
- PU/PD - cortisol decreases ADH action at kidneys
- polyphagia
- panting
- potbelly appearance - hepatomegaly + weak abdominal muscles (muscle weakness = exercist intolerance)
- alopecia
What are the most common cutaneous manifestations of Cushing’s?
- hyperpigmentation
- thin skin
- rat tail
- comedones
- bruising
- calcinosis cutis
What are 2 additional signs of Cushing’s?
- hepatomegaly
- recurrent infections
How is the cardiovascular system affected by Cushing’s?
- hypertension
- hypercoagulability (PTE, not as common)
Most common signs of Cushing’s:
What findings are commonly seen on CBC, biochem, and UA in Cushingoid dogs?
increased cortisol = stress leukogram (neutrophilia, lymphopenia)
increased ALP caused by isoenzyme production (C-ALP) in 90% of dogs
concentration varies, byt hyposthenuria is common + proteinuria
What is the difference between screening and differentiation adrenal testing for Cushing’s?
SCREENING - presence of hyperadrenocorticism (yes/no)
DIFFERENTIATION - type of hyperadrenocorticism (PDH/can’t tell)
What 3 adrenal tests are used for Cushing’s?
- LDDST
- ACTH stimulation
- urine cortisol:creatinine ratio
How is LDDST performed?
- take a pre cortisol sample
- give dexamethasone injection
- measure cortisol at 4 and 8 hrs later
What is the sensitivity and specificity of LDDST like?
sensitivity = ~95% (great at screening)
specificity = low - false positive associated with non-adrenal illness
What is expected in normal and Cushingoid dogs in response to LDDST?
NORMAL - dexamethasone injection should suppress ACTH secretion from the pituitary and a decrease in cortisol by 8 hrs
CUSHINGOID - dexamethasone has no effect on the pituitary or adrenal gland because the tumors will continue to secrete ACTH and cortisol, causing high cortisol level by 8 hrs
How is the LDDST interpreted?
8 hr sample confirms hyperadrenocorticism - if high, Cushing is present; if suppressed, there is no hyperadrenocorticism
can differentiate PDH:
- suppressed at 4 hrs
- 4 or 8 hr results are <50% baseline, indicating relative suppression
Is this patient Cushingoid? Can it be differentiated?
YES - 8 hr sample is above RI
YES, PDH - 4 hr sample is not suppressed, but 4 and 8 hr samples are <50% of baseline = relative suppression
Is this patient Cushingoid? Can it be differentiated?
NO - 8 hr sample within RI
Is this patient Cushingoid? Can it be differentiated?
YES - 8 hr sample is above RI
YES, PDH - 4 hr sample is suppressed
How is an ACTH stimulation test performed?
- collect a pre cortisol sample
- inject ACTH (Cortrosyn) and take a sample 1 hr later (elevated if Cushingoid)
In what 4 ways does the ACTH stim test compare to LDDST?
85% sensitivity and specificity
- 15% of Cushingoid dogs will not have high cortisol, if signs are there, perform a LDDST
- higher specificity makes it less affected by non-adrenal illness
- only test able to diagnose iatrogenic and spontaneous hyperadrenocorticism (cannot differentiate other types)
- only takes an hour, better for a time crunch
How do normal dogs react to ACTH stim test? PDH? ADH? Iatrogenic?
in response to ACTH, the adrenal gland will produce cortisol within an expected RI
bilaterally enlarged adrenal glands - exaggerated post cortisol levels above RI
doesn’t tend to work as well in these dogs, but unilarerally enlarged adrenal glands - exaggerated post cortisol levels above RI (not seen, do LDDST)
atrophied glands will not secrete cortisol, even if stimulated by ACTH
Are these dogs Cushingoid? They all present with signs of Cushing’s and have no other adrenal illness identified.
- borderline high - likely yes, try a LDDST to be sure
- YES - 1 hr sample above RI
- YES - iatrogenic!
How is a urine cortisol:creatinine ratio performed?
collect urine at home, then measure cortisol and creatinine in urine - Cushingoid dogs have excess urinary cortisol excretion
- high sensitivity, poor specificity (false positives!)
- able to r/o Cushing’s with low results
What imaging can be done to diagnose Cushing’s?
- abdominal ultrasound - expect enlarged adrenals; unilateral (with contralateral atrophy) = ADH, bilateral = PDH
- CT/MRI - pituitary macroadenoma (neuro signs)
What are the 2 medical treatment options for Cushing’s?
- Trilostane (Vetoryl)* - reversible inhibitor of 3-beta-hydroxysteroid dehydrogenase, which stops cortisol synthesis
- Mitotane (Lysodren) - irreversible destruction of zona fasciculata and reticularis, which stops cortisol synthesis
How is the dosage of Mitotane developed for Cushingoid dogs?
irreversible destruction to adrenal cortex
- begin with a loading dose
- wait for decrease in polyphagia and polydipsia, depending on owner observation
- continue with a maintenance dose to avoid developing Addison’s disease
When is surgical management recommended with Cushingoid dogs?
as a whole, medical management is safest and most commonly recommended
- PDH = med > sx
- ADH = surgical removal of unilateral tumor, avoids malignant metastasis into vena cava (thrombosis, embolism)
How is medical treatment of Cushing’s monitored?
use ACTH stim test with a goal of 1.5-5 and up to 9 if signs are controlled (with reference to no longer being clinical)
- 2 week follow-up to ensure hypoadrenocorticism is occuring
- another 2 week follow-up to see if it is controlled and if dosage changes are required
- every 4 week follow-ups
- periodic follow-ups
What are the 3 main adverse effects associated with medical treatment of Cushing’s?
- cortisol deficiency - anorexia, vomiting, diarrhea
- aldosterone deficiency - hyponatremia, hyperkalemia, collapse, hypovolemia (decreased Na = decreased water withing ECF)
- direct GI effects (cortisol responsible for GIT mucosa health) - anorexia, vomiting diarrhea
What is prognosis of PDH Cushing’s like?
MICROADENOMA - lifelong medical treatment with good prognosis, median 2 years with death not due to hyperadrenocorticism
MACROADENOMA - fair to good with radiation treatment and better without neurological signs at outset
What is prognosis of ADH Cushing’s like?
ADENOMA - excellent with surgery
CARCINOMA - fair to poor
What is atypical hyperadrenocorticism? How is it diagnosed? Treated?
patient has signs consistent with hyperadrenocorticism, but ACTH and LDDST are normal thought to be caused by increased sex hormones
Tennessee panel - ACTH stim with sex hormone measurement
same as typical HAC - Trilostane, monitor with ACTH stim
What clinical signs are associated with sex hormone-secreting adrenal tumors?
- as expected estradiol and androgen levels (if testosterone increased in cats = barbs on penis)
- increased PROGESTERONE = cortisol-like signs - anorexia, vomiting, diarrhea
What is the most common presentation, clinical pathology, and treatment used for Cushing’s?
panting and alopecia common, fragile skin that does not tear
- elevated ALP (90%) due to steroid-induced ALP form
- stress leukogram
- 10% diabetic
mitotane, trilostane, sx for unilater AT
What is the pathophysiology of pituitary dwarfism?
deficient pituitary gland causes decrease in GH, TSH, prolactin, and gonadotropins
When do clinical signs of pituitary dwarfism appear? What signs are most common?
3-5 m/o
- proportionate dwarfism
- retention of puppy coat
- alopecia, hyperpigmentation
- weakness, ataxia
What are 2 ways of diagnosing pituitary dwarfism? How is it treated?
- genetic test for LHX3 gene (GSDs)
- decreased IGF-1 (no tests available in the US for GH)
hormone supplementation - thyroid, GH
