Clin Path: Endocrine DZs

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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?

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