Cushing's Disease Flashcards
what are the functions of cortisol
anti-inflammatory and immunosuppressive
- increase BG
- promote vascular integrity
- promote GI mucosal integrity
- decrease bone formation
- aid in RBC production
pituitary dependent hypercortisolism (PDH) pathogenesis
pituitary micro or macroadenoma –> secretes ACTH –> overstimulation of adrenals –> bilateral adrenal hyperplasia –> excess cortisol production
PDH prevalence
most common cause of Cushing’s
most common in small dogs
PDH etiology
pituitary adenoma
majority are microadenomas
macroadenomas: either >1 cm OR growing out of the sella turcica
what is a sign that a well managed PDH dog has a pituitary macroadenoma
suddenly beomces inappetent, lethargic, disoriented, blind, etc
recommend workup for space occupying brain lesion (macroadenoma)
PDH adrenal morphology
bilateral hyperplasia
PDH ACTH levels
high to normal
(would expect 0 with high cortisol due to negative feedback)
adrenal dependent hypercortisolism (ADH) pathogenesis
functional adrenal tumor causing excess cortisol production –> suppression of CRH and ACTH from the hypothalamus + pituitary
ADH prevalence
less common than PDH
more common in large breed dogs
ADH etiology
adrenal adenoma
adrenal carcinoma
both are equally likely
criteria of malignancy:
1. > 2cm
2. local invasion
3. hemorrhage/necrosis
4. mineralization
ADH adrenal morphology
unilateral hypertrophy (tumor) + contralateral adrenal atrophy
ADH ACTH levels
low (should be 0)
caused by negative feedback from excess cortisol production
iatrogenic cushing’s
exogenous administration of glucocorticoids causes suppression of the HPA axis
iatrogenic cushing’s adrenal morphology
bilateral atrophy
iatrogenic cushing’s ACTH levels
low (should be 0)
negative feedback from exogenous glucocorticoids
most common clinical signs of cushing’s in dogs
- PU
- PD
- PP
- panting
- potbelly/pendulous abdomen
- alopecia
what are additional signs of cushing’s in dogs
- thin skin
- weakness (muscle atrophy)
- weight redistribution - often perceived as weight gain due to fat deposition in the abdomen w/ appendicular muscle loss
dermatologic changes associated with cushing’s disease
endocrine alopecia - bilaterally symmetric, truncal, non-pruritic alopecia
hyperpigmentation
calcinosis cutis
how is a diagnosis of cushing’s typically made
in the exam room - any further testing beyond clinical presentation is done to determine the type of cushing’s
iatrogenic can be ruled out with medication history
what are good screening tests for cushing’s
- history + PE
- minimum database
- UCCR
- ACTH stimulation test
- LDDS test
cbc changes with cushing’s
- stress leukogram
- mild polycythemia
- mild thrombocytosis
chem changes with cushing’s
- increased ALP (steroid isoenzyme)
- mild hyperglycemia
- hyperlipidemia (cholesterol + triglycerides)
- mild low BUN
UA changes with cushing’s
iso to hyposthenuria (due to secondary nephrogenic DI)
urine cortisol:creatinine ratio
good RULE OUT test for cushing’s - can NOT definitively diagnose
ideal to take a sample in a STRESS FREE environment at home (free catch)
acth stimulation test
best used for PDH > ADH
if < 2 –> addison’s
if 2-18 –> unlikely cushing’s (can’t rule out)
if > 20 –> cushing’s likely
why does PDH stim higher than ADH on an ACTH stim test
PDH: the ACTH will stimulate two hyperplastic glands to produce even more cortisol
ADH: only one adrenal is functional (tumor) and the other is non-productive due to atrophy, so ACTH stimulation will not result in much higher cortisol production
low dose dexamethasone suppression test (LDDS)
best for ADH > PDH
take 3 cortisol samples at times 0, 4, and 8 hours after low dose dex administration
how to evaluate LDDS results
- evaluate the 8 hr sample
- if < 1.4 –> normal
- if > 1.4 –> consistent w/ Cushing’s - use 4 hr sample to determine the type - evaluate the 4 hr sample
- if < 1.4 –> PDH
- if 4 or 8hr is < 50% baseline –> PDH
- if > 1.4 –> ADH or PDH
do adrenal tumors suppress during a LDDS test
no - ADH patients will not suppress cortisol production at any time point
tumors do NOT respond to negative feedback because ACTH is already low/zero (cannot get any lower)
therefore - any signs of suppression at the 4 or 8 hour time point rules out ADH
what tests are primarily used to differentiate ADH from PDH
- endogenous ACTH
- abdominal US
- HDDS test
- CT
- MRI
endogenous ACTH test
measures ACTH in the blood
must handle sample carefully - difficult test to run
if ACTH = 0 –> ADH
if ACTH > 0 –> PDH
what imaging is the best and most cost effective option to differentiate ADH and PDH
abdominal US
- if bilateral hyperplasia –> PDH
- if unilateral hypertrophy w/ contralateral atrophy –> ADH
- if bilateral atrophy –> iatrogenic
what is CT used for
pre-adrenalectomy surgical planning
assessment for macroadenoma
what is MRI used for
best choice for assessment of pituitary macroadenomas
what are the two medical therapy options for cushings
- trilostane (vetoryl)
- mitotane (lysodren)
trilostane (vetoryl) MOA
enzyme inhibitor
blocks an enzyme that is involved in converting cholesterol into cortisol in order to decrease cortisol production
best for ADH > PDH
trilostane pros
- reversible
- many tablet sizes for more accurate dosing (5, 10, 30, 60)
- FDA approved in dogs
trilostane cons
- monitoring can only be based on clinical signs, USH, water intake
- ACTH stimulation is NOT a reliable indicator of clinical monitoring
mitotane (lysodren) MOA
selective adrenal necrosis of the zona fasciculata + reticularis
best for PDH > ADH
mitotane pros
- ACTH stimulation test is VERY helpful for clinical monitoring
- highly effective drug for PDH
mitotane cons
- risk of irreversible adrenal necrosis leading to addison’s
- only ONE tablet size - more difficult to dose
- NOT FDA approved for dogs or cats
what are the two surgical options for cushing’s and what type are they used for
- adrenalectomy (ADH)
- hypophysectomy (PDH)
adrenalectomy
can be laparoscopic for non-invasive tumors
must be open laparotomy for invasive tumors
- greater risk of hemorrhage and post op complications
complications of adrenalectomy
poor healing
risk of pancreatitis
post op PTE
bilateral adrenalectomy may cause addison’s disease
hypophysectomy
transoral approach
less common in vet med in the US
will require lifelong glucocorticoids + levothyroxine due to lack of all anterior pituitary hormones after removal
when is radiation therapy useful
non resectable adrenal masses
pituitary macroadenomas
goal: resolve the space occupying effects of masses
differences in cushing’s disease in cats compared to dogs
- no elevated ALP (no steroid isoenzyme in cats)
- no calcinosis cutis
- no PU/PD/PP unless concurrent diabetes mellitus
what are the most common consequences of cushing’s (or exogenous steroid administration) in cats
- diabetes mellitus
- feline skin fragility syndrome
