Small Ani. Med- Endocrine 3

wilsbach's version from 2016-05-01 16:27

hyperA ctd

Question Answer
**SCREENING test for hyperA?can look at electrolytes! but also Urine cortisol/creatinine ratio <--good for R/O not good for dx
explain what you use the urine cortisol:creatinine ratio for?Basically look if the ratio is low (low cortisol) then they do NOT have cushings (it is a SeNsitive test bc you can trust the Negative) but if it has elevated cortisol, it could be from anything- so it is not specific. So good for ruling out cushings.
Diagnostic vs differentiation tests for hyperADIAGNOSTIC: ACTH stim test, LOW-dose dexamethasone (always start low and work ur way up). DIFFERENTIATION: High-Dose Dexamethasone suppression test, Endogenous ACTH concentration
how can you use your CBC/chem to help with screening for hyperA?not elevated alp or stress leuko-- not inclined to think Cushings
what test can you also monitor therapy with?ACTH stimulation test
there are the two diagnostic tests: ACTH stim and low-dose dexamethasone suppression test. how do you know which to choose when?in a HEALTHY DOG, the low dose dex suppression test is the most sensitive and specific. the sensitivity and specificity drop though as they get sicker. So in the sick pt you choose ACTH stim instead bc less affected by other things.
what does the High-Dose Dexamethasone suppression test differentiate?pituitary from adrenal tumor.
in what way is the low dose test partially a differentiation test?can tell you there is hyperA, and can also tell you, IN SOME CASES WITH SOME PATTERNS, can tell if it's pituitary. Wont be able to tell if adrenal tho. (more on this later)
DO NOT CONFUSE Endogenous ACTH concentration WITH ACTH STIM.stim is GIVING a high dose of ACTH and seeing what cortisol does. Endogenous is measuring the amount of ACTH in the body
how would you describe the adrenals on US in a pituitary dependant hyperA?They will BOTH be plump-- more "pear" shaped than peanut shaped. (in adrenal tumor one will be HUGE and tumory and the other will be super tiny)
how do you do urine cortisol:crt ratio?Remember, can only rule OUT cushings. very easy: have Owner bring in first morning urine (first pee of morning bc hormonal cycle related to sleep and also very concentrated).
**what is the only test that can dx IATROGENIC HYPERA?ACTH STIM TEST!
explain the ACTH Stimulation Test (what is normal/abnormal)**DIAGNOSTIC TEST** Administer synthetic ACTH (IV cosyntropin) and evaluate cortisol. NORMAL POST-ACTH STIM should be <500mmol/L (so normal animal, normal amount of cortisol is released- so goes from like 50 to somewhere under 500). If they are hyperA, they will have a post-stim that is >500mmol/L Because they either have two plump adrenal glands bc pituitary tumor, or they have one huge one from adrenal tumor. So they just have lots more tissue making cortisol, so they can release more at once. This is also the ONLY TEST THAT CAN DIAGNOSE IATROGENIC hyperA. Think about it: Iatrogenic bc you are giving lots of exogenous steroids so there is a turned off feedback loop. so adrenal glands are small bc they haven't had to make anything since it's all exogenous. So if you then give a huge ACTH dose- the adrenal glands do NOTHING or not enough. (iatrogenic- start low and stay low). on stim test will look hypo but physically look like cushing dog bc we have been giving them too many steroids. So if it looks like cushings but gets low numbers on the ACTH stim, you know it's iatrogenic.
why use dexmethasone for these tests instead of pred?bc when you measure the cortisol, dex doesnt interfere with that measurement, it is different enough. But pred will interfere.
when do you not bother doing a low-dose dexmethasone? Why?When they are sick! the LDDST has great seNsitivity (better than acth stim) but it isnt very specific and gets LESS specific when they are sick so dont bother with this test when theyre sick.
explain the Low-Dose Dexamethasone Suppression Test (what is normal/abnormal)You give a LOW dose of dexmethasone (0.01mg/kg) and then measure their cortisol levels at time 0, 4hr, and 8hr. So ideally, you give a low dose of dex, it goes to the brain, tells the brain to turn off CRH and ACTH, which would cause the cortisol to go down. AND IT SHOULD STAY DOWN FOR 12 HOURS BECAUSE THAT IS THE HALF LIFE OF THE DEX. Which means if you have a normal dog, at 0hr it is the baseline number, and whatever that number is, it's important, because at 4 hours it has to drop by MORE THAN HALF. It drops, and that much, bc the neg feedback has kicked in. If it has not dropped more than half, it isn't being suppressed adequately, which means they have hyperA. If if DID drop more than half, at 8 hours it should STILL BE LOW in the healthy dog. So if you look at the 8 hour mark, if it has shot back up (escaped suppression).... you know they HAVE HyperA. So look at 8hr first. Then 4 can tell you a little bit about what type they have. So if you start at 0, and then at 4 hours it goes down MORE THAN HALF-- AND IT ESCAPES? that is pituitary dependant. But if it DIDN'T, you cannot say it is an adrenal tumor
what does it mean on your low dose dexamethasone suppression test if... you start at baseline, at 4h it has dropped MORE than half the original baseline number, and then at 8 hour it stays down (reference ranges meaning it is <40nmol/L or <2ug/dL)...what does this mean?NORMAL ANIMAL.
what does it mean on your low dose dexamethasone suppression test if.... you start at baseline, at 4h it has dropped MORE than half the original baseline number, and then at 8 hour it has gone back UP (reference ranges meaning it is >40nmol/L or >2ug/dL)...what does this mean?pituitary dependant hyperadrenocorticism
what does it mean on your low dose dexamethasone suppression test if.... you start at baseline, at 4h it has dropped LESS than half of the original baseline number (so like from "10" to "6" or something) and then at 8 hour it has gone back UP (reference ranges meaning it is >40nmol/L or >2ug/dL)...what does this mean?means it is EITHER PDH OR AT-- because this test can only differentiate a PDH, not an AT (bc some pituitary will never suppress, etc)-- the reason we know if it goes more than 50% suppressed, and then escapes, that that is def a PDH is because they are usually microadenomas and we can kinda bully them around a bit-- can overwhelm them and turn off stim, but within 4 hours are back to secreting ACTH.
WHAT IS UP WITH THIS DOG? HAS HYPERADRENOCORTISISM!! because it did not suppress more than 50% (went from 10 to 6, should have gone below 5)
explain the high-dose dexamethasone suppression test**DIFFERENTIATION TEST-- ONLY DO AFTER DX TEST (LDDST or ACTH stim)** So got a result where we know its hyperA but dont know if PDH or AT. Give a high dose (0.1-1mg/kg) of dex, to see if we can REALLY suppress that pituitary tumor-- and then it escapes. If we get that pattern, we know it's PDH (but REMEMBER 20% of PDH WILL NEVER SUPPRESS- so still not a perfect test). So this basically will tell you if the grey area PDHs are PDHs (except for that 20% that will never suppress). If you are concerned about AT, you MUST IMAGE (And this is important bc how you treat PDH vs AT is v different)
explain Endogenous ACTH Concentration test and what the results mean.take a single serum sample and send to a special lab- NOTE: eACTH is not a stable molecule. Must add aprotinin to prevent breakdown. eACTH normal to high= PDH. eACTH low= AT. 10-15% chance of ‘gray’ zone results
what will radiographs of hyperA show?Hepatomegaly (bc steroid hepatopathy hepatocytes become markedly distended with cytosolic glycogen with or without discrete membrane bound lipid inclusions...and only ALP might be high too, bc steroid isoenzyme). Might also see soft tissue mineralization. If it is AT hyperA, you might be able to see the mass or adrenal mineralization (Ca is being mobilized from the bone and deposits in strange places, this includes calcinosis cutis.)
things you can look at with US with hyperAPDH: both are PLUMP (more pear than peanut). AT: one is huge, the other one you prolly cant find. Can also see if there are liver metastasis (50% of AT are malig) or caval invasion
drug of choice for hyperA?TRILOSTANE.
remember that no matter what, cushings is a...TUMOR
why might cushings pt go blind?IF MACROADENOMA OF PITUITARY-- CAN PUSH ON OPTIC CHIASM bc its right in that area.
sx is the treatment of choice for which hyperA?AT!
Is it possible to remove the pituitary if its PDH?(neurohypophysis aka posterior and adenohypophysis aka anterior) actually. yes. Think about in the adult dog (avg age cushings is 8yr), what it is doing: so there isnt growth hormone. but if its an adult its ok. there are sex hormones (FSH/LH)-- many pts spayed already. thyroid homone-- make them hypothyroid- put them on cheap and easy pill (L thyroxin), oxytocin (milk letdown? prolly not a big deal). and then ADH/vasopressin. can be temporary central diabetes insipidus- but its just stored there- its made in hypothalamus- so its just released somewhere else. but in baby will make a difference.
when might you use radiation therapy for hyperA?pituitary dependant
what are the 4 possible drugs for tx hyperA?Mitotane(Lysodren), Trilostane(Vetoryl), Ketoconazole (she doesnt like this-- can cause bad liver probs and they might already have a steroid hepatopathy), Selegeline(L-Deprenyl-- this is a dementia drug, she says its not a very successful tx)
mitotane vs methimazoleMITOTANE IS FOR HYPERA. METHIAZOLE IS FOR HYPERT (crazy cats on meth)
how does mitotane work? SEs?Selectively destroys zonae fasciculata and reticularis. SEs of vomiting, anorexia-- can affect aldosterone, if not careful might have hyperadrenocortisism
explain how you start and continue a mitotane regimen for PDHbefore you start giving them drugs.... start on Mon, cut food down by a quarter. Want them starving (esp bc with cushings theyre already polyphagic). Bc then on FRIDAY start with a LOADING DOSE which is a higher dose. Now we wanna make sure they dont get hypOA because that can actually kill them. So we want them starving because if they should be hungry bc they arent getting enough food, but they ARENT hungry, we know not to give the pill that day. So we give loading dose maximum of 8 days or until response is noted (not wanting to eat). Response being signs of hypOA such as: Decreased appetite, vomiting, diarrhea, listlessness, water intake <60ml/kg/d. loading dose or until response is noted, then do an ACTH stim and see where they are and if their levels are normal (<500). If still elevated, continue loading dose. But make sure on day 8 you stim them anyway, even if they aren't showing signs, because you do NOT want to overdo it. If normal (<500)-- start on maintenance dose. Once on maintenance, you should recheck with ACTH stim at 1mo, 3mo, 6mo or if any changes in bh or CSs occur (its a tumor-- CSs can totally come back). IF DURING LOADING OR MAINTENANCE DOSE you see any weird things that make you think HYPOarenocortisism, such as vomiting, STOP MITOTANE AND GIVE THEM ER PRED. Would rather have a messed up procol than an addisonian crisis which can acually kill them (cushings is more annoying than it is deadly)
explain mitotane regimen for ATREMEMBER-- TOC IS SX FOR AT-- but if there is metastasis or some reason you cant do sx, then consider mitotane... give them a MASSIVE loading dose to try to murder tumor. and then maintenance is also pretty high. Monitor for signs of addison's!
why will you never have control of your diabetes if you have cushings?bc glucocorticoids (cortisol) are an ANTI-INSULIN HORMONE.
explain mitotane regimen when they have diabetes too?Give mitotane loading, but also giving physiological doses of pred at the same time (just enough for them to live)
MOA of trilostane? Competitively inhibits 3- β hydroxysteroid dehydrogenase--> Inhibit cortisol and aldosterone synthesis
Is mitotane reversible? is trilostane?Not mitotane, my trilostane IS because it is just inhibiting the enzyme for cortisol and aldosterone (small amount can have idiopathic adrenal necrosis)
SEs of trilostane?Lethargy, Vomiting, Hypoadrenocorticism, Death (rare se), Idiopathic adrenal necrosis
what are trilostane protocols like?many variations, most dogs respond best to 2x/d. Monitor with ACTH stim in 14 days, and 4-6hours post pill.... **CHECK SERUM ELECTROLYTES, ESP Na+K bc can inhibit aldosterone too. Adjust doses based on your ACTH stim. Once stable, check q3-6mo
If you are going to heavy on the trilostane, which electrolyte will go up and why?trilostane can also inhibit aldosterone, so there is the possibility to K+ INC-- CHECK TO MAKE SURE THIS ISNT HAPPENING (remember, normally aldosterone is the sodium saver and so if it isnt saving Na, it's saving K))