Cushing's, Addison's and Pheochromocytoma Flashcards
85-95% of endogenous cushing’s dogs and cats are due to ____.
Pituitary-induced micro or macroadenoma
Cushing’s pathogenesis
XS ACTH made in pituitary –> adrenals –> hypercortisolemia (pituitary escape from negative inhibition)
Adrenal steroidogenesis
ACTH –> adrenal cortex –> aldosterone, cortisol and sex steroids.
Atypical cushing’s
normal cortisol levels, cushings symptoms caused by xs intermediate metabolites from steroidogenesis
What are the three zones of the adrenal cortex?
Glomerulosa
Fasciculata
Reticularis
What hormone is made in the zona glomerulosa?
aldosterone
What hormone is made in the zona fasciculata?
cortisol
What hormone is made in the zona reticularis?
ketosteroids and cortisol
Aldosterone has an effect on _____.
Na and K production in the body
Pathophysiologic effects of xs cotisol?
Muscle/bone/tendon - weakness
liver - glycogen deposition; steroid hepatopathy
gut - hyperacid secretions
immune system - suppressed, prone to secondary infection (silent UTIs)
kidney - PU/PD because ^GFR and renal plasma flow
Brain - hyperirritable. Dog: panting!
Bloodstream - mature neutrophilia, lymphopenia, eosinopenia, monocytosis, thrombocytosis, and increased RBCs
Lipid metabolism - increased cholesterol
Breed and age incidence of Hyperadrenocorticism?
toy and miniature breeds (poodles and dachshunds)
age: 3-13 range, avg 8 years old
main endogenous causes of Hyperadrenocorticism?
pituitary dependent (high ACTH, high cortisol) adrenal dependent (low ACTH, high cortisol)
exogenous cause of Hyperadrenocorticism?
iatrogenic - large doses of glucocorticoids (act like cortisol)
** must wean off these drugs because will have trouble making cortisol with removal of drug.
Physical features of Hyperadrenocorticism?
Panting (dogs)
PU/PD
pendulous abdomen (due to muscle weakness)
stria (stretch marks) from weakening/thinning of skin
truncal alopecia with hyperpigmentation
acne formation - keratin plugging of hair follicles
easily bruise
calcinosis cutis
cushings wrinkles
general muscle weakness- myotonia!
lethargy
polyphagia
testicular atrophy and hepatomegaly in the dog due to glycogen accumulation
hypercoagulable
Other: pulmonary calcification, prothrombotic tendency, hypertension, proteinuria, glomerulopathy (can be permanent)
Hyperadrenocorticism lab findings?
mature neutrophilia, eosinopenia, and lymphopenia
Polycythemia
high liver enzymes (hepatomegaly due to glycogen accumulation)
glucose (if also have DM)
+/- pyuria —> UTI
+/- hematuria
Proteinuric (glomerulopathy)
hypertension (glomerulopathy)
high cholesterol/TGs (lipemia)
high cortisol
adrenal/pulmonary calcification (gritty lungs on necropsy)
Cushing’s imaging
radiographs early phase pyeologram arteriography abdominal U/S pituitary CT/MR
If unilateral adrenal tumor is resected, the ipsilateral adrenal will be atrophied so expect _____ post-op.
adrenocortical insufficiency - supplement glucocorticoids
pituitary macroadenomas are hard to resect; try to remove whole pituitary which means will have _____ post-op.
diabetes insipidus (no renal ADH) or another hypoendocrinopathy
Cushing’s diagnosis
Urine cortisol/Cr ratio (if negative, rules out cushing's, if positive, could be something other than cushing's) ACTH stim test*** LDDT - low dose dex suppression HDDT Plasma ACTH - \$\$$ and time
Most common signs of cushing’s in a dog?
PU/PD, pendulous abdomen, and panting
ACTH stim test
hyperstimulation of ACTH (cortisol) is positive for cushings. (>20)
Doesn’t specify if pituitary or adrenal cushings, do LDDT/HDDT to determine which.
LDDT and HDDT
should suppress cortisol to <1.7
If suppresses but not below 1.7, then pituitary cushings.
If does not suppress at all, then adrenal tumor.
20% of PDH will not suppress HDDT
cushing’s treatment?
- surgical removal of hypothalamus or adrenal gland
- medical - OPDDD (dogs) and Trilostane (dogs and cats) suppress cortisol production. Lysodren and Metotane are OPDDD drugs.
- Iatrogenic - stop the steroids (taper off)
How to prove iatrogenic cushing’s?
hold off pred, do ACTH stim test –> no response
OPDDD drug interactions?
It is metabolized in the liver by cytochrome P450 so anything that affects this will affect its metabolism.
Phenobarbital makes OPDDD ineffective because enhances P450 metabolism
OPDDD cytotoxicity?
Adrenocorticolytic –> if destroy adrenal cortex, end up with Addison’s.
Lysodren _____ sometimes necessary
reloads
OPDDD side effects
drug toxicity - depression, weakness, vomiting, anorexia, and diarrhea –> stop use —> signs go away –> start again on lower dose
addison’s disease
pituitary tumor growth - nelson’s disease (micro–>macro), pituitary apoplexy (sudden death)
Trilostane
most popular drug for PDH
adrenal enlargement due to increased intermediate metabolites from steroid synthesis
Cushing cat is similar to the dog, but many are ______.
Diabetic, may require insulin, thin/friable skin
Cushing cat diagnostics are difficult because?
ACTH stim not sensitive, HDDT>ACTH stim
Most common cause of cushingoid dog?
Overtreatment with glucocorticoids
Pheochromocytoma incidence?
rare
50% benign 50% malignant
Pheochromocytoma arises from ____.
adrenal medulla
Pheochromocytoma signs usually due to _____.
catecholamine secretion or postcaval obstruction
Pheochromocytoma clinical signs?
Paroxysmal (periodic and severe) anxiety, mental depression, restlessness and panting. Also blanching, flushing, weakness and/or collapse.
Tachycardia +/- VPCs, tachyarrythmia or CHF
ascites –> post caval invasion by tumor
hyphema (blood in eye)
Pheochromocytoma ddx?
hypoglycemia
cardiac disease
cerebral dysfunction
hyperthyroidism
Pheochromocytoma dx?
history and physical exam! imaging (rads, U/S, CT) BP measurements strong index of suspicion - old dog with unexplained tachyarrhythmia elevated urinary normetanephrine
Pheochromocytoma treatment?
surgery
medicine: phenoxybenzamine (alpha blocker), regitine aka phentolamine (alpha blocker), propanolol (beta block)
If dog is hypertensive and tachyarrhythmic, do what?
ALPHA BLOCK BEFORE YOU BETA BLOCK
To increase surgery survival, you should?
Start phenoxybenzamine 2 weeks before to stabilize BP
Aldosteronoma more common in?
Cats»_space; dogs but overall it’s rare
Aldosteronoma is neoplasm of the?
zona glomerulosa of the adrenal cortex
Aldosteronoma clinical signs?
XS Na retention –> hypertension –> retinal hemorrhage and blindness
XS K excretion –> hypoK effects
PD/PU
Other causes of hypertension in a cat?
chronic renal insufficiency
hyperthyroidism
Addison’s is also called?
Hypoadrenocorticism
Cushing’s is also called?
Hyperadrenocoticism
Addison’s incidence?
Not common, mostly in dogs <5 years old
Causes of adrenocortical insufficiency?
iatrogenic - glucocorticoids induce atrophy infiltrative - cancer, mycoses infarction pituitary insufficiency OPDDD induced destruction Idiopathic Autoimmune destruction Cosyntropin - really rare
Sign that it is autoimmune?
adrenal cortex significanly diminished with lymphocytes and plasma cells invading on cytology
Relative adrenocortical insufficiency
septic patient has cytokines that can decrease glucocorticoid release from adrenals which leaves critically ill and dying patient with no glucs needed to maintain BP and live
atrophic zona fasciculata, what happens?
decreased cortisol –> decreased gluconeogenesis, decreased sensitivity to catecholamines, decreased water diuresis, decreased appetite, increased eosinophils and lymphocytes, decreased cerebration
atrophic zona glomeruloa, what happens?
decreased aldosterone –> excrete Na and retain K –> hyperK and low BP
Electrolyte markers for addison’s?
HyperK and HypoNa (together are really bad for heart)
Hypoadrenocorticism dx?
history and clinical findings
ECG changes
Addisonian crisis signs?
history of weight loss, lethargy, decreased appetite, and GI signs
presents weak or in collapse
mentally dull
bradycardia while hypotensive!! (<60 bpm)
weak femoral pulse
may clinically resemble acute uremic state
Addisonian crisis lab findings?
\+/- netropenia, eosiniphilia, and lymphocytosis hyperK hypoNa high BUN low bicarb \+/- hypocholesterolemia \+/-hypoalbuminemia \+/- hypercalcemia highly variable, not reliable for dx
Pseudoaddisons?
anything that causes low Na and high K
Renal dz
GI dz
DKA, HNKD
Chylothorax
Addison’s dx?
Na/K <20
ACTH Stim test*** gold standard
Cortisol:ACTH ratio
Aldosterone:Renin ratio
Plasma ACTH determination?
Primary addisons - ACTH high
Secondary Addison’s - ACTH low
When in crisis, need to treat immediately, what is the drug you go to first? Why?
Dexamethasone over pred because won’t interfere with cortisol assay
Simultaneous treatment and dx for addisonian crisis
- begin IV NaCl
- collect resting serum cortisol
- give ACTH
- give dex IV
- collect 2nd serum cortisol
Maintenance treatment for Addison’s
Florinef (both mineralocorticoid and glucocorticoid)
Prednisone
DOCP (only mineralocorticoid) - if OD, get hypoK
Atypical addison’s
chronic lethargy, weakness, poor appetite, weight loss
normal Na and K despite low aldosterone***
absent ACTH stim response
atypical Addison’s treatment?
because normal electrolyes, just give pred
Any medical or surgical stress to an Addisonian will warrant use of significant supplemental doses of ___.
glucocorticoids
causes of atypical addison’s
secondary adrenocortical insufficiency
immune destruction of z. fasciculata or glomerulosa