Clin Path: Endocrine DZs

STUDY
PLAY
DM
Hyperglycemia + ketonuria + glucosuria =
Dogs (IDDM)
Immune-mediated destruction of Beta cells in pancreas most common cause of DM in:
Cats
Amyloidosis in pancreas most common cause of DM in:
Samogyi overswing
Insulin induced post-hypoglycemic hyperglycemia
Fructosamine (red top)
Test for DM
Except cats with hyperthyroid
Glycated hemoglobin (EDTA)
Test to indicate average glucose concentration in RBC over their lifespan
Unspayed
What female dogs will have insulin resistance?
Insulin resistance
What will these ednocrinopathies do to insulin?
Cushings (Glucocorticoids)
HyperT4 (Thyroid hormones)
Pheochromocytoma (Catecholamines)
Hyperpituitarism (GH, GnRH/Progestins)
Glucagonoma
Heinz
______ bodies in CATS with
DM
HyperT4
LSA
DM
DX?
Inc ALT, AST, ALP, GGT secondary to hepatic lipidosis
Heinz bodies (cat)
>150 glucose (dogs)
Pre-renal azotemia
HYPER K
HYPO Na, Cl, Phos (hemolysis -> anemia)
Proximal duodenal obstruction
DX?
Cattle
Glucose 250-1000! (Stress also contributes)
Normal insulin
(Shock or dehydration will decrease glucose)
Abomasal volulus
DX?
Cattle
Lower glucose than PDO 100-200
Horses
In what species is glucose more prognostic?
300
In a HORSE, if glucose is >_____ that indicates a poor prognosis
Pregnancy
Stress
Physiologic causes of insulin resistance in horses (2):
Laminits
Equids likely to develop ______ with insulin resistance
Glucocorticoids!
PHARM Q: What drugs can cause laminitis?
Equine Metabolic
What syndrome?
Horses with chronic insulin resistance
W/O PPID
Obese (regional adiposity)
In EMS what will their weight status be?
hyperTG
hyperLeptinemia
hyperTension (LAMINITIS)
What 3 components of EMS will be HYPER__emia?
Addisons
HypoT4
2 metabolic DZs that causes hypoglycemia:
Hypo (glycemia)
Hyper or hypo glycemia:
Ketosis in CATTLE
Pregnancy toxemia in SHEEP
Neonatal ____glycemia in PIGS
Insulinoma
DX?
Hypoglycemia (mild to severe)
Severe increase in insulin
Grey (Flouride oxalate)
Tube used for Glucose analysis
TRH, TSH, T3/fT4/T4
Hypothalamus secretes ______ to pituitary who secretes ____ to thyroid who secretes ____
Primary
Primary, secondary or tertiary?
T3, T4, fT4 deficiency, HIGH TSH
Secondary
Primary, secondary or tertiary?
TSH deficiency
Tertiary
Primary, secondary or tertiary?
TRH deficiency
Primary
Most common cause of Hypothyroidism in DOGS -
Primary, secondary or tertiary?
TSH (normal) rT3 (increased)
In a euthyroid sick animal (low total T4), what hormone is NORMAL compared to true thyroid sick animals (HIGH TSH)?
What hormone is INCREASED?
Lymphocytic thyroiditis (immune-mediated)
Most common cause of primary hypothyroidism in DOGS
TgAA
Hypothyroidism is caused by autoantibody ______ towards T4 or T3
Idiopathic follicular atrophy
Neoplasia (carcinoma, scc)
Congenital (defective synthesis or iodine deficiency)
3 other causes of hypothyroid, besides immune mediated:
Estrus
In an unspayed bitch, when are T4 levels decreased?
TgAA (can detect as early as 1 year old)
What test should you run before breeding 1-5 year old females to test for thyroid abnormalities?
free T4 (measured by equilibrium dialysis)
Gold standard test for hypothyroidism:
Secondary
If a GSH has pituitary dwarfism, causing hypothyroid and addisons, what category hypythyroid is this? Primary, secondary or tertiary?
Hypothyroidism
C/S:
Decreased appetite, Weight gain!
Bradycardic
Non-pruritic bilateral alopecia
Myxedema, pyoderma
Cold
Infertile
Seizures, coma
Weakness, mm. wasting
Hypothyroidism
CBC:
Mild normocytic, normochromic non-reg anemia
Target cells (leptocytes - abn lipid met)
Inc WBC - pyoderma
Hypothyroidism
CHEM:
HYPERcholesterolemia
Inc CK (mm. atrophy)
Mild/mod inc ALT, AST, ALP
Proteinuria (glomerulonephritis, lymphocytic thyroiditis)
Free T4*
Total T4
Endogenous TSH
TgAA
4 tests for hypothyroid
Cushings
DM
Euthyroid sick animals will have
NORMAL TSH
Low T4 (transient)
Endocrine DZs associated are (2) _________
Antiepileptic drugs (Barbituates, Benzodiazapines)
Steroids
What drugs can cause Euthyroid sickness (2)? Some include NSAIDs, Sulfur, penicillin, furosemide
Greyhounds
What breed dog normally has LOW T4?
(At least) 4 weeks (ideal:6-8 weeks)
How long should you wait to test an animal's T4 levels after you stops it's thyroid medications?
Euthyroid sick
DX?
Low T4
High rT3
normal TSH
T4
Endogenous TSH
In a serum sample (red top) what 2 tests can you request to DX hypothyroidism>
Hypothyroidism
DX?
Low T4
Low fT4
High TSH
Levothyroxine
PHARM Q: Drug used to TX hypothyroidism in all species?
No, T4/fT4
Can you DX hypothyroid using endogenous cTSH alone? If not, what do you use it with?
TSH stim
What test evaluates the thyroid gland's response to exogenous TSH
5 weeks (thyroid drugs) 4 weeks (other drugs)
Before doing a TSH stim test, how long must you have weaned the animal off thyroid drugs before testing? How about other drugs?
No (normal dogs will increase T4 by 2x)
Will hypothyroid dogs respond to the TSH stim test?
Increased
In early hypothyroid cases, what are the levels of T4, fT4 and T3? Increased, normal or decreased?
TgAA
cTSH
In early hypothyroid cases, what other tests (2) can you use to help DX?
No
Will an animal respond to a TSH stim test if it has primary hypothyroidism?
Goiter
What is different about hypothyroidism in Large animals?
No, retest (later day)
If you take a sample from a horse and you get low T4 levels, is this DXtic for hypothyroidism? If not, what should you do next?
CATS
What species more likely will have functional, bilateral thyroid adenomas?
Hyperthyroidism
C/S:
Polyphagic, but Weight loss!
Tachyarrythmia, HCM!! (reversible)
Poor coat
Swelling neck
Panting, hypersensitivity (nervous)
Stress intolerance
PU/PD

Less common - V/D/Fever/Ventroflexion of neck (thiamine def, hypokalemia), ataxia (mm. weakness)
Hyperthyroidism
CBC:
Stress leuk
Heinz bodies (LSA, DM will have this too)
Hyperthyroidism
CHEM:
HYPOcholesterolemia
Mild/mod inc ALP and/or AST
Mild inc ALT (hepatotoxic, ishemia)
Hepatic lipidosis (anorexic) in ALP
DM or stress
1006-1060, GFR, renal, ADH
PU/PU in hyperthyroidism:
Azotemia with a USG from _____ - _____
Increased T4 causes and increase in _____
Increased GFR = hyperfiltration, which may mask _______ disease.
Decreased USG due to increased medullary flow
Thyroid hormones also will inhibit _____
No, (Serum) Total T4
If a hyperthyroid cat has a USG below 1035, can you say this is renal or prerenal? If not, what other tests should you run?
Free T4 (ED)
Best test for hyper and hypothyroid?
~4 weeks
If an animal tests positive for hyperthyroidism using total T4, but you also suspect a concurrent non-thyroid DZ, when should you retest?
T3 (suppression test)
What is a SUPPRESSION test you can use to DX hyperthyroid?
Little to none
If an animal has hyperthyroidism, what effect will a T3 stim have on it?
Owner compliance (check if correctly dosing when doing a T3 suppression stim)
When is the ONLY time you would measure T3?
Plain (red top)
What tube should you collect blood for a T3 suppression stim?
Methimazol
PHARM Q: Drug used to TX hyperthyroidism in CATS?
CRH, ACTH, Cortisol (stress response)
The hypothalamus secretes ______ which causes a release of ______ at the pituitary, which causes secretion of ______ at the adrenal glands.
Secondary (PDA)
Is the most common cause of Cushings primary (adrenal cortical adenoma) or secondary (Pituitary dependent HyperA)?
Ovarian sertoli cell tumor
Non-endocrine tumors (lung)
Iatrogenic (drugs)
Other causes of hypercortisolemia (2)
Glycogen, hepatopathy, ALP, bile acids
What happens IN THE LIVER when cortisol is high?
Deposition of ________
Steroid ________
Induction of enzyme: _______ (DOGS)
Increase in ______ ______
catabolism, gluco(neogenesis) and lipolysis
What happens in TISSUES when cortisol is high?
Overall tissue _________ via
____neogenesis and ________.
ADH
In Cushings animals PU/PD due to inhibition of ______
Low (T4, T3)
What thyroid levels do Cushings patients have? AKA Euthyroid sick syndrome!
DM, insulin
Cushings can result in another endocrine disease called _____ due to ______ resistance in CATS (sometimes dogs)
PDA (ADA -> SX)
In DOGS Cushings has to be distinguished b/w PDA and ADA, becuase _____ can be treated medically.
SX
In CATS with Cushings, most cases are treated with ____
Regular Insulin (IV)
PHARM Q: Drug used to TX Insulin dependent Ketotic DM =
NPH
Lente
Ultralente
Protamine zinc
PHARM Q: Drugs (4) used to TX Insulin dependent DM (no ketosis) =
Sulfonylureas (MOA = stimulate Beta cells to secrete insulin)
PHARM Q: Drug used to TX insulin resistant DM =
Mitotane (Ketoconazole can also be used)
PHARM Q: Drug of choice to TX Pituitary Dependent Cushings =
Selective destruction of adrenal cortex
PHARM Q: MOA of Mitotane
Pergolide mesylate
PHARM Q: Drug used to TX PPID in HORSES =
Binds and stimulates DOPAMINE receptors in pars intermedia
PHARM Q: MOA of Pergolide mesylate
Sweating
Hirsutism
2 common signs of PPID in HORSES:
Cushings (Dog)
C/S:
CYSTITIS AND RECURRENT UTI
HYPERTENSION
-Truncal obesity/alopecia, Pot Belly, abdominal distention
-Polyphagia
-PU/PD (ADH suppression)
-Muscle weakness (abd. distension)/wasting
-Thin skin (opposite hypoT4)
-Comedomes
-Pyoderma (immunosuppression and thin skin)
-Polypenia (weak resp muscles)
-Neuro signs (PDA)
-Pulmonary thromboembolism
Emphysematous cystitis (E. Coli proliferate and produce gas bubbles in wall)
PATH II Q: What is commonly seen with DM patents in the u. bladder?
Anestrus, testicular
What reproductive changes could you see in Cushings patients?
______ due to gonadotropin suppression (females)
______ atrophy (males)
CATS (But, severe thinning of skin - wounds by grooming)
What species with Cushings may not show any signs at all?
Cushings
CBC: (Dogs)
POLYCYTHEMIA
STRESS LEUKOGRAM
Left shift if pyoderma
Inc PCV, nRBC without regeneration
Cushings
CHEM:
INCREASED ALP (5-45x normal)
HYPERglycemia (CATS - IRDM)
UTI without PYURIA (immunosuppressed)
LOW Urea (PU/PD)
USG - Hyposthenuric, Isosthenuric (ADH suppression)
Dexamethasone (.1% cortisol)
What is the steroid of choice to test for Cushings?
Cushings (DM increased)
Using a serum fructosamine test, which will have a normal level of fructosamine, Cushings or DM?
2-4 weeks
How long should you GRADUALLY wean an animal off of cortisol based drugs before testing for Cushings?
Urinary cortisol:creatinine ratio (UCCR)
ACTH stim
Name 2 SCREENING tests for Cushings (Can't use to confirm Cushings)
Increase
What will stress, PU/PD and Cushings do to a UCCR?
Cushings
Which UCCR will be very high, stress, PU/PD and Cushings?
High (high true positives), low (lots of false + --> a lot of things can look like Cushings)
UCCR has a ____ sensitivity, but _____ specificity.
morning
How do you avoid stress when taking a UCCR?
Sample urine in the _____ (time of day) 2 days after the vet visit
Out
A low/normal UCCR will rule in or out Cushings?
Increase
The UCCR can rule in DM, DI, Pyometra, hypercalcemia, renal/liver failure by showing an ________ (increase or decrease).
ACTH stim
LDDS (Low dose dex suppression)
What 2 adjunctive tests asses the hypothalamic-pituitary-adrenal gland axis?
10
If results in dogs are not definitive of Cushings, you can do UCCR over ___ consecutive days
ACTH stim
What is the ONLY SCREENING TEST that can be used to (DX)
1. Iatrogenic Cushings
2. Addison's
3. Treatment assesment using Mitotane / Trilosane
LDDS
Which test is more sensitive, ACTH or LLDS?
maximally, adrenal, cortisol
The goal of a ACTH stim is to ________ stimulate the _______ cortex to make as much ________ as possible
Sensitivity
ACTH stim will not 100% diagnose an animal with PDA (84%), ADA (51%) or iatrogenic CUSHINGS (14%). This is b/c it has a lower ________ than LDDS.
Phenobarbitone
Drugs such as __________ and glucocorticoids can elevate the post ACTH value and well as increase liver enzymes (ALP).
ACTH (Pituitary neg. feedback)
What will a LDDS suppress?
decrease
Normal animals will ____ the amount of cortisol produced when given Dex
high
CUSHINGS patients (All ADA and most PDA) are resistant to negative feedback of Dex, so ______ levels remain high when you give Dex.
Illness
Chronic Stress
What, besides Cushings, can also override the negative feedback of Dex?
False negatives
If the LDDS is more sensitive than ACTH stim, it will have less ____ _____
PDA
If an animal responds by a decrease in cortisol 4 hours hours after given Dex this could mean they're healthy or have ______
Specificity
There is a high false positive rate when using LDDS because lots of things like stress won't allow the animal to suppress (keep cortisol low). This means LDDS has a low _________
8
You can say it's probably Cushings when the __hr value is above the cutoff.
1.45,
50 baseline
50% baseline
What are the 3 critiera used to help distinguish between PDA from ADA?
1. 4hr plasma cortisol <____microg/dl
2. 4hr plasma cortisol <______%of _______
3. 8hr plasma cortisol >______ or 1.45
No (Only 60-65% will - Some won't even suppress AT ALL)
Will ALL PDA suppress below 1.45mircog/dl at 4 hours?
No suppression (at 4 or 8hr)
What is expected of ADA Cushings using the LDDS?
Oral-LDDS (test urine instead of plasma)
If IV-LDDS and UCCR inconclusive, what other method could you use?
HDDS (10x Dex dose)
After a DX of Cushings has been made with ACTH or LDDS, how else can you confirm a PDA or ADA? What discriminatory test can you use?
Ultrasound
What is a more sensitive diagnostic test you can utilize to DX ADA?
Unilateral
If Cushings, how would you know it's an adrenal carcinoma aka ADA? ______ enlargment.
Bilateral
If Cushings, how would you know it's a pituitary adenoma aka PDA/ _____ enlargement.
PDA
Using a HDDS test, if you have suppression at 4hr and 8hr, what can you definitively diagnose?
NEITHER!!!! (15% of PDA won't suppress at all)
Using a HDDS test, if you don't have any suppression at all at 4hr and 8 hr, which form can you DEFINITIVELY diagnose?
Endogenous ACTH
What is another, relatively not available unfortunately, test to distinguish between PDA and ADA?
High (It's an ACTH secreting tumor!)
Using endogenous ACTH, what will the levels of ACTH be if PDA?
Low (Suppresses pituitary)
Using endogenous ACTH, what will the levels of ACTH be if ADA?
Plastic EDTA tube (spin down and freeze plasma ASAP)
What tube should you use to collect blood for an endogenous ACTH assay?
ACTH stim
Occult HyperA - "Alopecia X"
Syndrome diagnosed with a _____ ___ test to measure sex hormones and aldosterone
19hr dex suppression test
What test can be used to DX PPID in a HORSE?
Primary
What is the most common cause of Addisons, primary (detroyed adrenals) or secondary (pituitary deficiency of ACTH)?
Mitotane!
What drug can cause Addisons?
Trichuris vulpis (whip worm)
What parasite mimic's Addisons on a CBC/Chem profile?
HYPO Na, Cl
HYPER K
What are the main (3) electrolyte imbalances with Addisons?
Secondary (ACTH does not affect Aldosterone!)
Which form of Addison's DOES NOT have electrolyte imbalance?
Addisons
C/S:
Episodic frequency of dec mineralocorticoid signs =
-Weight loss
-Weak pulse and BRADYCARDIA (High K)
-DEPRESSION & WEAKNESS
-DECREASED GLUCOCORTICOID
-Dehydration or HYPOTENSION
-PU/PD due to ELECTROLYTE imbalances
-V/D
-Shivering, shaking, shock. collapse
-Hyperpigmentation
-Stress intolerance
FALSE! (Hypo Na,Cl - med washout)
T/F: PU/PD in Addisonians is due to an inhibition in ADH?
Addisons
CBC:
-Hemoconcentration
-Mild, non-regenerative anemia (~MASKED)
-High Lymphocytes and Eosinophils
=REVERSE STRESS LEUKOGRAM, even when very sick
Addisons
CHEM:
-HYPER K, Phos, HYPER Ca (n = iCa)
-HYPO Na, Cl
-Metabolic acidosis (Dec HCO3)
*Na:K <15*
-Dehydration CAN MASK electrolyte LOWs
-Hypovolemia dec GFR
-Dec GFR -> PRERENAL AZOTEMIA
-Gastric hemorrhage increases UREA
-USG <1.025; med washout
<25
What is the Na:K likely to be in:
Addisons
Uroabdomen
CRF
GI DZ (Whips, Salmonella)
Chylothorax
Severe metabolic acidosis
CHF
Breeds: Shiba inu, Shar Pei
Young horses
Clotting process releases K (Lots of platelets)
Basal cortisol
ACTH stim
Endogenous ACTH
3 Tests used for Addisons:
Basal cortisol
What is the only endocrine test that you only have to take a blood sample for once to make a diagnosis?
ACTH stim
What is the gold standard test for Addisons?
double, 2
What is diagnostic for Addisons using a ACTH stim?
Failure of cortisol to _______ from baseline or increase >___microg/dl
No, Endogenous ACTH
Does an ACTH stim DX between primary or secondary Addisons? If not, what can?
HIGH (Pituitary senses low electrolytes and is trying to tell the adrenals to make glucocorticoids! Also, there is no negative feedback coming from the adrenals)
Primary Addisons will have _____ ACTH using an endogenous assay.
Low (Pituitary ACTH deficiency - secondary Addisons)
Secondary Addisons will have _____ ACTH using an endogenous assay.
Low, Iatrogenic cushings
Using an ACTH stim test, post cortisol levels will be _____ for Addisons & ________ _______
PTH, calcitriol
What 2 hormones increase Ca when it is too low?
Calcitonin
What hormone decreases Ca when it is too high?
Calcitonin
What hormone is made my parafollicular C cells in the THYROIDgland that decreases Ca by inhibiting osteolysis and stimulates Ca excretion in the kidneys?
Increase, decrease
What will PTH do if Ca is low?
___ Ca ; ____ Phos
decreases
When calcium increases, PTH _____
Increase
Decrease
Bone
Vitamin D
Actions of PTH:
___ renal absorption of Ca
___ renal absorption of Phos
Reabsorb Ca from _____
Activate _____ _ in the kidney
D
What vitamin promotes Ca absorption from the GIT
Adenoma
Hyperplasia
Primary hyperthyroidism is RARE. It can be due to parathyroid ______, ______, functional PTcarcinoma or autnomous over-secretion of PTH
Older dogs
Usually hyperPT occurs in ____ _____ than cats.
inhibits ADH
Why are hyperPT animals PU/PD. Hypercalcemia _______ _____
Calculi
Why do animals who are hyperPT get UTI?
Urinary ______ build up, causing blockage and stasis.
Hyperparathyroidism
C/S:
Lethargy
Depression
Weak
Anorexic
Muscle wasting
Shivering, twitching, seizures
Bradycardia
Osteopenia (bone loss)
Hyperparathyroidism
CHEM:
-Mild to marked hypercalcemia
-Low to normal phosphorus
-PTH high or wnl (non-hyperPT low)
-Isosthenuria (1007-1017)

If renal damage:
-Azotemia (mineralization)
-Casts
-Ca oxylate dihydrate crystals
Hypercalcemia
What will calcium be in a HORSE with Chronic renal failure?
CATS
What species will you see an idiopathic hypercalcemia in?
Hypoparathyroidism
C/S:
Muscle twitching
Weakness
Tetany
PARESIS in RUMINANTS
Hypoparathyroidism
CHEM:
Hypocalcemia
+/-Hyperphosphatemia
Mild hyperglycemia (Ca needed for insulin release)
PTH assay (serum - special handling)
Test for hypoparathyroidism
Increase it
What will cholecalciferol toxicity do to Ca?
PTHrp
What will you see in neoplasia regarding PTH?
LSA
Apocrine gland adenocarcinoma of the anal sac
(Also gastric squamous cell carcinomas)
Name 2 neoplasims thats secrete PTHrp:
Hypocalcemia (2* nutritional hypoparathyroidism)
What will bran DZ in HORSES cause?
Apparent hypocalcemia (Ca is ALB bound)
What can a low albumin cause?
EDTA, binds ca
What tube should you not use to Ca tests? Why?
Levothyroxine sodium (IV - warm)
PHARM Q: TX MYXEDEMA in hyperthyroid patients: