Block 7 Flashcards
What is hyperadrenocorticism?
Cushings
Is canine or feline cushings common?
Canine
What does HAC mostly cause?
Hypercortisolemia
What can HAC also cause?
Technically refers to overproduction of any adrenocortical hormone
Sex hormones
Aldosterone
What are the layers of the cortex of the adrenal gland
Mineralcorticoids (salt)
Glucocorticoids (Sugar)
Androgens (Sex)
What are 2 mineralcorticoids?
Aldosterone and corticosterone
What are 2 glucocorticoids?
Cortisol and cortisone
What are 2 androgens?
Testosterone and estrogen
Where does steroid synthesis occur?
In adrenal cortex
What does steroid synthesis begin with?
Cholesterol
What are the 3 parts to the HPA axis?
Hypothalamus
Pituitary
Adrenal gland
What is the negative feedback on BOTH the pituitary and the hypothalamus?
Cortisol
What is released by the hypothalamus that stimulates the pituitary?
CRH (corticotropin releasing hormone)
What is released by the pituitary that stimulates the adrenal glands?
ACTH (corticotropin)
How many mechanisms of cortisol excess are there?
3
What are the 3 mechanisms?
Pituitary dependent HAC (PDH)
Adrenal dependent HAC (ADH)
Iatrogenic
What determines which mechanism it is?
Where the primary tumor is
What percent of HAC is PDH?
85%W
What type of tumor are most tumors?
Microadenomas
What size are macroadenomas?
> 1cm
What can macroadenomas cause?
Neurologic signs
What is the signalment of dogs with Cushings?
Middle to older age dogs
What percent of dogs are older than 6 yo?
100%
What percent of dogs are older than 9 yo?
90%
What percent of dogs with PDH are <20kg?
75%
What are the clinical symptoms of Cushings?
***PPPP
PU/PD
Polyphagia
Pot belly
Panting
What does cortisol cause to muscles?
Causes muscle weakness
What happens to the liver in HAC?
Enlarged liver
What causes the pot belly appearance of HAC?
Muscles of abdomen weaken and the liver enlarges so the liver falls into the abdominal space
What is another harmful result of muscle weakness in HAC dogs?
Potential for cranial cruciate tears
What are 4 dermatologic changes wth HAC?
Alopecia (non-pruritic)
Comedones
Hyperpigmentation
Calcinosis cutis
What is normally seen on CBC for HAC?
Stress leukogram
Thrombocytosis
What things are increased on chem for HAC?
ALP
ALT
GGT
Cholesterol
What crystals may you find on a UA?
Calcium oxalate or struvite
Why will T4 be low in a HAC patient?
Cortisol suppresses T4 so it will be low!
Dont diagnose hypothyroid!!
What are the 3 screening tests of HCR?
UCCR - urine cortisol:creatinine ratio
ACTH stim
Low-dose dex suppression
What is UCCR good for?
Ruling disease out!
Where should urine for UCCR be taken?
At home as to not stress the dog out and in the morning
What is the synthetic cortisol given in ACTH stim?
cosyntropin
What are steps to ACTH stim?
Give cosyntropin
Take ACTH cortisol 1 hour after
What result would not be in line with HAC?
<17 increase
What result is borderline increase for HAC?
17-22
What result is in line with HAC?
> 22
What can you not differentiate with a ACTH stim?
ADH vs PDH
How do you perform an LDDS?
Get a baseline cortisol
Administer dex
Obtain 4 hr levels
Obtain 8 hr levels
What is beneficial about LDDS?
It can differential between ADH and PDH
What do you look at first when reading an LDDS?
8 hr
Are there a lot of false negatives in LDDS?
No
What is a big con of LDDS?
Takes a long time
Are there a lot of false positives with LDDS?
Yes
What does LDDS test for?
PDH
What is another way besides LDDS to determine type of HAC?
Imagine (CT, US, MRI)
What is most important part of measuring the size of adrenal glands on ultrasound?
The thickness of the caudal poles?
Length doesn’t provide much information
What is normal adrenal size of dog?
4-5mm
If dog has cortisol-secreting adrenal mass, other adrenal gland should be small
Should endogenous ACTH be low or high in ADH dogs?
Low
How do you collect blood for endogenous ACTH measurement?
INTO CHILLED TUBE!
Cushings disease is a ______ disease
Clinical (clinical signs + clinicopathologic findings)
In feline HAC, what steroids are elevated?
Cortisol and aldosterone
What are 2 clinical signs that are different in cats than dogs with HAC?
Can come from poorly regulated diabetes mellitus
Cat skin can be very fragile
What test should not be used to screen feline Cushings?
ACTH stim
What test is considered the best screening test for feline Cushings?
LDDS test
What are 2 affects of the increased aldosterone?
Hypokalemia
Hypertension
What is the scoring system for Cushings and owners?
ALIVE score
Is higher or lower better for the ALIVE score?
lower the better
What should you do if there is a high blood pressure?
Fundic exam
What will you see on a cushing CBC?
Stress leukogram and thrombocytosis
What is a stress leukogram?
lymphopenia
Eosinopenia
monocytosis
neutrophilia
What causes the high potassium in Cushing chems?
The thromobocytosis
What will you see on the chem of Cushings?
Thrombocytosis
High ALT and ALP
Hypercholestrolemia
Hyperglycemia
What may you see on a Urinalysis for Cushings?
Low SG, high proteins
What is normal value for UPC (urine protein:creatinine)
<0.5
What might you see in the gallbladder of a Cushing dog?
Mucocele
What can HAC do to the liver?
Enlargement
What is the reference range for “not consistent with” in ACTH stim?
Post-ACTH cortisol <22
What type of HAC does LDDS test for?
PDH
What is SDMA a marker for?
Marker of GFR (kidney function)
What are 4 things that cause PUPD?
CKD
Cushings
Hepatic encephalopathy
pyometra
What is the cut off for LDDS at 8 hrs to be considered for HAC?
1.3
In a CBC, should cholesterol be high or low in HAC dogs?
Hypercholesterolemia
Describe liver findings of a dog with HAC
Heptomegaly
Hyperechoic liver
What is the threshold for diagnosis of HAC?
At least 3 consistent clinical signs and/or physical exam findings
At least 2 consistent clinpath findings
What is the definition of hypoadrenocorticism?
Decreased production of one or more adrenocortical hormone
What is the most common pathophysiology of Addison’s?
Primary immune mediated destruction of both adrenal glands
What is the more rare secondary pathophysiology of Addison’s?
Rare destruction of pituitary gland
What is typical Addison’s?
Glucocorticoid and mineralcorticoid deficiency
What is atypical Addison’s?
Just glucocorticoid deficiency
What age dogs get Addison’s?
Young to middle aged dogs
What is the median age of Addison’s?
4 years old
What is the sex predisposition of Addison’s?
Female (70%)
What are 2 breeds predisposed to heritable Addison’s?
Standard poodle and Portuguese water dog
What may trigger an Addison’s event?
A stressful event
What are some GI clinical signs of Addison’s?
Vomiting, diarrhea, anorexia, lethargy, weight loss
What are additional clinical signs of Addison’s?
Hypovolemic shock, collapse, NEVER PU/PD
What are some physical exam findings of Addison’s?
Weight loss, dehydration, abdominal pain, melena, bradycardia, hypotension
Does Addison’s have a stress leukogram?
NO!
***What is seen in the biochem?
Azotemia
Hypocholesterolemia
Hypoglycemia
Hypercalcemia
High globs, low albs
What occurs to liver enzymes with Addison’s?
Mild elevation
***In typical Addison’s, what additional chem values will you see?
Low bicarb
Hyponatermia
Hypochloremia
Hyperkalemia
What is a normal Na:K ratio?
27:1 - 40:1
What Na:K ratio is indicative (but not pathognomonic) of Addison’s?
<27:1
What occurs to lymphocytes in Addisons?
They are normally high!
What can cause the hyperkalemia to be an artifact?
Thrombocytosis may cause a pseudohyperkalemia
If measured using plsma, platelets have granules with Potassium so if blood is put in red top tube, you rely on platelets to activate and form clots. Once activated they will release potassium. With potassium, there is no clot so potassium is not released causing the pseudohyperkalemia!
Lymphocytes can also be artifactually high from younger animals (<6m), infectious disease, and neoplasia
What is the screening process to rule out Addison’s?
Basal or “resting” cortisol
Doesn’t rule it in but will rule it out
Proceed to ACTH stim test if the resting cortisol is lower than ____?
<2 (>2 its unlikely Addison’s)
How do you diagnose Addison’s?
ACTH stim?
How do you perform ACTH stim?
Give Cortrosyn
Measure 1-hour post cortisol
How do you diagnose ACTH stim?
If after an hour the ACTH-cortisol is still <2
Do cats get Addison’s?
NO (yes but very rare)
How do you determine typical vs atypical Addison’s?
Look at Na:K ratio
If already determined that K was WNL, the Na:K ratio will determine if it is typical or atypical Addison’s. What is typical, what is atypical?
Typical: <27 Na:K
Atypical: >27 Na:K
Can Addison’s cause Megaesophagus?
YES!!!
Is Pu/PD a sign of hypothyroidism?
NO!
What are 3 clinical signs of hypothyroidism?
Alopecia, pyoderma, and lethargy
What percent of dogs have primary hyperthyroidism?
> 95%
What is primary hypothyroidism caused by?
Lymphocytic plasmacytic thyroiditis or
idiopathic thyroid atrophy
What percent of the thyroid must be destroyed before clinical symptoms?
75%
What are 2 predisposed breeds for lymphocytic plasmacytic thyroiditis?
Beagles and borzois (BB)
Thyroid neoplasia is NOT a common cause of primary neoplasia
***Secondary hypothyroidism is very uncommon, what is most common cause of it?
Suppression of TSH by exogenous or endogenous glucocorticoids
What is the normal age range for hypothyroid dogs?
2-6 (middle to older dogs)
What breed of dog is hypothyroid rare in?
Toy breeds
German Shephards
What are 3 most common clinical findings of hypothyroid dogs?
Lethargy/inactivity
Weight gain w/o change in diet
Hyperkeratosis
What are the external physical exam findings “endocrine alopecia”?
Hyperkeratosis
Seborrhea (dandruff)
Thin hair
Rat tail
hyperpigmentation
What is a facial clinical sign?
“Tragic” facial expression due to myxedema (swelling of skin)
What is the main chem finding of hypothyroidism?
Hypercholesterolemia
What is the main cbc finding of hypothyroidism?
Non regenerative anemia
Hypothyroidism is a disease of clinical disorder. Patient needs clinical disorder and need something to improve to help monitor if there is improvement
What is sent to the pituitary from the hypothalamus?
TRH
What is sent to the thyroid from the pituitary?
TSH
What breed of dogs have lower T4 levels?
Sighthound
What is a Total T4 test used for?
To rule out hypothyroid (sensitive)
What is the most accurate thyroid test for diagnosis?
Free T4 ED (equilibrium dialysis)
What does the TSH test confirm?
Primary hypothyroidism
Should you use TSH test by itself?
NO!
What will be the result of the TSH test if its primary hypothyroidism?
High TSH and low T4
What does high autoantibodies suggest?
Primary hypothyroidism
What is the gold standard test for hypothyroidism?
TSH response test
With the TSH response test, prior treatment with T4 can fuck up results for 2 months after so do it right the first time
What results do you see with TSH response test if its hypothyroidism (administer TSH and check for response)
No response to TSH after 6 hours
Dogs get _____ Cats get ______
Dogs get hypothyroidism, cats get hyperthyroidism
What sex of cat gets hyperthyroidism more?
No sex predolection
What age cats get it more often?
Older cats
What is the #1 clinical sign of hyperthyroidism?
Weight loss
***What are other clinical signs of hyperthyroidism?
Polyphagia with weight loss
PU/PD
GI issues
Increased activity
People are often happy that their elderly cat is running around and acting like a kitten again
What is the apathetic form with hyperthyroidism?
Cat looks and feels ill
May be associated with concurrent disease
What clinical signs are there with apathetic form?
Lethargic, decreased activity and appetite, weakness
what are physical exam findings of hyperthyroid?
Thyroid slip
Thin
Poor hair coat
Systolic murmur
Tachycardia
Hyperactivity
Hypertension
What is an important step when you have a hyperthyroid cat with hypertension?
Fundic exam
What is a reliable screening test for Hyperthyroid/
Total T4
What are the 2 most reliable things seen on chem of hyperthyroid cats?
***Liver enzyme increase - ALT!
Azotemia
***What can be masked due to hypertension and increased GFR in old cats?
Kidney disease
What should you always run for hyperthyroid cats to unmask CKD?
UA (<1.035 is concerning)
What can you run to get an early detection that is not affected by muscle mass in hyperthyroidism?
SDMA
What is the best test to look for masked CKD (SDMA or USG)?
USG <1.035
You should use both the USG and SDMA values to increase the likelihood that you are correctly diagnosing masked CKD
What may be seen on CBC for hyperthyroid cats?
Increased PCV and MCV
What may be seen on radiographs of a cat with hyperthyroidism?
Cardiomegaly
What is the best test to use for diagnosing hyperthyroidism?
increasing T4 with baseline
What is most affected by illness severity?
T4
What is a radiological approach to diagnosis?
Nuclear scintigraphy
What are the thyroids compared to in nuclear scintigraphy?
The salivary gland
What ratio indicates hyperthyroid in nuclear scintigraphy?
> 2:1 with the salivary glands
What will happen in normal physiology with administration of T3?
A decrease in TT4
What happens if you administer T3 to a hyperthyroid cat?
TT4 will remain the same “T3 suppression test”
What 4 drugs have the potential to affect thyroid function?
Glucocorticoids
Phenobarbitals
Sulfonamides
NSAIDs
What is a functional pituitary neoplasm
Tumor that causes an overproduction of hormones
What is a nonfunctional pituitary neoplasm?
Tumor that doesnt cause a release of hormones
What 2 domestic species most frequently devlope pituitary neoplasms?
Dogs and horses
What are the clinical signs of PPID primarily caused by?
Compression of normal pituitary/hypothalamus
For horses it is the pituitary adenoma of the pars ______
Intermedia
For dogs it is the pituitary adenoma of the pars _____
distalis
What is the ACTH secreting adenoma/
Pars distalis
What is adenoma of the pars distalis called?
Canine cushings
What is adenoma of the pars intermedia called in horses?
Equine cushings
In rats with an adenoma of the pars distalis, what hormone is increased?
Prolactin
What does the increased prolactin levels in the rat cause?
Potential for increased mammary neoplasias
Of the adrenal gland, what is the negative feedback to the pituitary gland?
Glucocorticoids
An adenoma in the pituitary may increase the ACTH secretion causing an increase in glucocorticoids and will not respond to the negative feedback
What is nodular hyperplasia
Masses in the adrenal cortex that doesnt cause disease
What is adrenal cortical hyperplasia?
Unlike nodular hyperplasia, this is diffuse thickening and always due to ACTH-secreting pituitary tumor
What are teh most ACTH responsive regions of the adrenal cortex?
Zona fasiculata and zona reticularis
What is the malignant tumor of the adrenal cortex?
Adrenal carcinoma
Where may the adrenal carcinoma invade?
Vena cava
What percent of ferrets will develop an adrenal-associated endocrinopathy?
70%
Spay/neuter of ferrets disrupt negative feedback of GnRH which increases luteinizing hormone, causing a stimulation of sex-steroid producing adrenal cells with overproduction
What hormones are increased in ferrets with adrenal disease?
GnRH and luteinizing hormone
What region of the adrenal gland is overproduced?
Hyperestrogenism
What are the clinical signs of ferret adrenal disease?
Alopecia
Enlarged vulva and mammary hyperplasia
Urinary obstruction, prostatic hyperplasia
What does paraganglioma mean?
Umbrella term for tumors derived from neural crest cells
Adrenal medulla is derived from neural crest cells which is different from the adrenal cortex!!!
What are tumors derived from teh adrenal medullary called?
Pheochromocytomas
What type of tumor is formed from alpha cells?
Glucagonoma
What type of tumor is formed from beta cells?
Insulinoma
What is the most common islet-origin tumor?
Insulinoma
Do insulinomas tend to be carcinomas?
Yes
What is caused by the increase in insulin produced by the insulinoma?
Hypoglycemia
What is a clinical sign of the insulinoma that causes hypoglycemia?
seizures
Ferrets will also get adenomas of the endocrine pancreas
What is likely a major cause of diabetes mellitus in dogs and cats?
pancreatic hypofunction
What causes the pancreatic hypofunction?
Secondary loss of beta cells by recurrent pancreatitis/chronic pancreatitis
What are 3 secondary lesions associated with diabetes mellitus?
Cachexia
Cataract
hepatic lipidosis
What is a common cause of islet degeneration in cats?
Islet amyloidosis
What percent of cats have islet amyloidosis?
20%
What percent of DM cats have islet amyloidosis?
60%
What species is islet amyloidosis most common in?
Cats
What is uniform, bilateral enlargement of thyroid gland called?
Goiter
What may cause goiter?
Excess iodine
Iodine deficiency
Goitrogenic compound plants
Who usually has goiter?
Fetuses/young food animals and horses that are born with it
Why do the young have goiter?
Dam either is grazing on goitrogenic plants
Dam has iodine deficient diet
Iodine excess
What plants are goitrogenic?
Brassicaceae family
What does fetal goiter cause?
Abortion, stillbirth, prolonged gestation, dystocia, neonatal death
Why would a dam have iodine excess?
Mares eating dry seaweed
High iodine in fetal circulation interferes with thyroid hormone synthesis <T3. T4 deficiency -> goiter
After correction of the iodine in goiter, what is it called?
Colloid goiter
What are the 4 major players of calcium-regulating hormones?
PTH, calcitriol, calcitonin, FGF23
What is another name for vitamin D3?
Cholecalciferol
What is the active form of cholecalciferol?
calcitriol
What is the role of vitamin D in the intestin?
Facilitates intestinal absorption of calcium (calcium binding protein)
Inhibits PTH synthesis and secretion
When is PTH released?
When there is low calcium
What is needed to activate vitamin D?
UV light (sheep more susceptible because fiber)
What is rickets?
Defective vitamin D metabolism at sites of endochondral ossification
What is osteomalacia?
Defective vitamin D metabolism at site of skeletal remodeling
What causes rickets and osteomalacia?
Dietary deficiency in either vitamin D or phosphorus
Where do the lesions most commonly occur for rickets?
Sites of rapid growth
What are 3 reasons for primary hyperparathyroidism?
Parathyroid nodular hyperplasia, adenoma, carcinoma
What are 2 reasons that may cause secondary hyperparathyroidism?
Chronic renal disease and dietary imbalances
CKD causes hyperparathyroidism because the decreased GFR causes an increased blood phosphate. The increased phosphate causes an increased FGF23, decreased calcitriol production. Chief cell hyperplasia is a result and increases PTH production
What is the primary cause of fibrous osteodystrophy?
Nutritional secondary hypercalcemia
What is fibrous osteodystrophy?
Osteoclastic resorption of bone causing swelling, pliability, and fractured bone
What are the 3 hypercalcemias secondary to neoplasia?
Humoral hypercalcemia of malignancy (HHM)
Metastasis to bone
Hematologic malignancies localized to bone
What does PTHrP stand for?
Parathyroid hormone-related protein
What does elevated PTHrP indicate?
Elevated values indicate neoplasia
What 3 things is elevated PTHrP indicative of?
Apocrine gland adrenocarcinoma of the anal sac
T cell lymphoma
Multiple myeloma
PTHrP has a very similar affect on the body as PTHrP
What is the most common pituitary tumor in dogs?
Corticotrophs
What is the most common pituitary tumor in cats?
Somatotrophs
Can pituitary tumors be defined as carcinomas through histo alone?
No, only by metastasis
What is the most common form of spontaneous hyperadrenocorticism?
Canine pituitary-dependent hyperadernocortisism (85%)
HAC due to the pituitary gland will cause BILATERAL adrenal hyperplasia
Are clinical signs the same if its adenoma vs adenocarcinoma?
YES!
_______% of dogs have pituitary tumors not visible on CT or MRI
40-50%
How is pituitary enlargement diagnosed on CT/MRI?
Pituitary height:brain ratio
What is the threshold ratio consistent with enlargment?
> 0.31
What is the mean age for feline pituitary-dependent HAC?
10years
What is the most common tumor in feline HAC?
Adenomas
How do cats present with HAC compared to dogs?
Sicker
Feline patients presenting with HAC, what is it not uncommon to see as well?
Insulin-resistant diabetes mellitus
What is seen on blood work for HAC??
Elevated ALP, ALT, hypercholesterolemia, azotemia, and low USG
Concurrent hyperglycemia, glycosuria
What percent of adrenocarcinomas invade the renal vena cava?
20%
What percent of adrenocortical carcinomas are metastatic?
50%
What 2 spots do the adrenocortical carcinomas usually invade?
Liver
Lungs
What can be a side effect and presenting complaint of invasion into the vena cava?
Hemoabdomen
What is a go-to method for extent and invasion of a tumor?
CT
What is the adrenal medullary tumor of the chromaffin cells?
Pheochromocytoma
What do pheochromocytoma (chromaffin cells) secrete?
Catecholamines
What is the metastatic rate of pheochromocytomas?
40%
What are the common sites for metastasis of pheochromocytomas?
Liver, spleen, regional LN, and bone
What is the vascular invasion rate of pheochromocytoma?
80%
What is the best diagnostic approach for pheochromocytomas?
Abdominal ultrasound and CT
Plasma and urine catecholamine level
Histology: Chromogrenin A
What are the 4 subgroups of thyroid tumors?
Follicular, compound, papillary, anaplastic
What are the 2 most common subgroups of thyroid tumors in dogs?
Follicular and compound
Are thyroid tumors usually benign or malignant?
Malignant
What is an increasing risk factor for malignant thyroid tumor?
Bilateral involvement
What is a syndrome related to the face that can be caused by thyroid tumors?
Horner’s syndrome
What locations are the most likely area to metastasize to?
Lungs or retropharyngeal lymph nodes
What are the top 2 diagnostic approaches for thyroid tumors?
CT
Ultrasound guided FNA
What should you be aware with ultrasound guided FNA?
High vascular structure!
What is an insulinoma?
Neoplasia of beta cells
What does an insulinoma cause?
Upregulation of insulin
What are the clinical signs of insulinomas?
Seizures
Collapse
Weakness
What is serum test that will help confirm insulinoma?
Low blood glucose paired high insulin
What is diabetes mellitus characterized by?
Hyperglycemia that results from defects in insulin secretion or insulin sensitivity in target tissues or both
What is type I diabetes diabetes mellitus a result of?
Beta cell loss or destruction
What is type II diabetes mellitus a result of?
Abnormal beta cell function
What type of diabetes mellitus do dogs get?
Type I
What type of diabetes mellitus do cats get?
Type II
What is the threshold for cortical blood glucose in dogs?
180
What is the threshold for cortical blood glucose in cats?
280
***What are the 3 clinical signs of diabetes mellitus?
PU/PD
Polyphagia
Weight loss
What is the pathophys of glucosuria in diabetes mellitus?
As blood glucose concentrations rise, there is too much glucose in the blood for the glomerular ultrafiltrate to resorb
What causes the polyuria in diabetes patients?
Glycosuria creates an osmotic diuresis drawing urine into the tubules
What causes polyphagia and weight loss?
The lack of insulin in diabetes causes little uptake of glucose into cells which is required to trigger satiety so body continuously wants to eat. Without peripheral tissue utilization, body loses a lot of glucose via urine
What type of diabetes is unexpected weight loss more common?
Type I
What is a common breed to get diabetes?
Miniature schnauzers
In dogs, which sex is more likely to get DM?
Females
What is a common presenting complain of DM?
Acute blindness
In cats, which sex is more likely to get DM?
Neutered males
What is an eye issue that may make you suspicious of diabetes?
Acute cataracts
What is seen on CBC with DM?
No much
What is seen on UA with DM?
Glucosuria
Proteinuria
Bacteriuria
What is seen on chem with DM?
Hyperglycemia, Increased ALT and ALP, hypercholesterolemia
Why do you see mildly increased liver values on chem?
The decreased insulin causes lipid mobilization which causes the liver to become inflamed and release some enzymes
How do you document persistence of DM?
Fructosamine
What is considered hypoglycemic?
BG less than 60
What is Whipple’s triad of hypoglycemia?
Consistent clinical signs
Hypoglycemia
Response to treatment
What do you expect to see in the chem of a dog with an insulinoma?
hypoglycemia
What are the 4 main suspects of true insulin resistance
Bacterial infection
Organ failure
Pancreatitis
Concurrent endrocrinopathies (Cushing/Addisons)
What is another iatrogenic cause of “insulin resistance”
Owners just not giving insulin correctly
What is the Somogyi phenomenon?
Counter regulatory pattern of insulin induced hypoglycemia followed by hyperglycemia phase
What causes insulin-induced hyperglycemia?
Too much insulin that stresses the animal and causes a counter-regulatory release of stress hormones
What is acromegaly?
excessive release of GH
What causes acromegaly?
Pituitary adenoma
What does acromegaly cause?
Insulin resistance
IGF-1 release and bony and soft tissue overgrowth
Are cats with acromegaly always diabetic?
YES!
What is a clinical sign that is not seen in cats with acromegaly despite uncontrolled DM?
Weight loss
What are the 2 diagnostics for acromegaly/
Measure of IGF-1
Brain imaging to confirm
Will high IGF-1 always mean acromegaly?
No, there is some variation but will almost always mean that diabetes is not under control
What will DM cause when screening for HAC?
False positives
How do you test a HAC with DM?
Glucosuria, increased blood glucose, fructosamine
What are the 3 ketone bodies?
Acetoacetate, BHB, acetone
What causes sickness from DKA?
Ketones cause a high anion gap metabolic acidosis
What are the common things seen on UA for DKA?
Ketones, uremic toxins, lactic acid, or salicylates
How do you calculate anion gap?
(Na+K) - (Cl + HCO3)
What must always be asked when a patient undergoes DKA?
Why did it
Why do diabetics get DKA?
Lower insulin allows lipolysis, increasing availability of fatty acids.
What are clinical signs of a dog in DKA?
Vomiting, dehydration, severe illness
What things will be seen on diagnostics for DKA?
D - hyperglycemia / glycosuria
K - ketonemia / ketonurea
A - acidosis
What specifically are you looking for in the urine of a DKA animal for diagnostics?
Acetone
What comes from somatotropic cells in the anterior pituitary?
GH
What contains receptors for GH to release IGF-1?
Liver
GH has effects that can be characterized into which 2 categories?
Anabolic
Catabolic
What does the catabolic affect do?
Increases insulin resistance
What does the anabolic affect do?
IGF-1 leads to bone, fibrous, etc. growth
What is the one difference in diabetes that acromegaly cats will present with?
Weight gain instead of loss
Acromegaly cats can also present with some neurological signs
So I know a previous answer to this was brain imaging and IGF but this is different… What is a one time measurement that can be used to diagnose acromegaly?
IGF-1
Why does GH need to be measured at multiple time points with acromegaly?
There can be GH spikes
What does MED stand for?
Multiple endocrine diseases
What is the test of choice when you have multiple endocrinopathies present?
ACTH stim
Which 2 diseasese have similar mechanisms?
Diabetes mellitus
Hypothyroidism
What are essentially the same thing for large animals in terms of ketones?
Ketosis and pregnancy toxemia?W
Who gets pregnancy toxemia and when?
Small ruminants before partuition
Who gets ketosis and when?
Cattle after parturition
What can be a consequence of chronic ketosis or pregnancy toxemia?
Hepatic lipidosis
What is the transition period?
3w before and 3w after
What are 3 things that change for ruminants in transition period?
Feed, social structure, daily routine
When is peak milk production for a cow?
4-6 weeks
When is peak feed consumption?
7-8 weeks
“Lake gestation fetus steals space from rumen”
What happens when there is a negative energy balance during transition period?
Mobilize NEFAs
What is the site of gluconeogenesis and ketone production?
Liver
What is the primary NEFA?
BHB
What is primary ketosis?
Lactation energy demands are too high
What is secondary ketosis?
Decreased feed consumption
Which ketosis type has a higher risk for hepatic liposis?
Type II
What is type I ketosis?
Peak lactation / high production cow
What is type II ketosis?
Early lactation, overweight cow in dry period
What do NEFAs and BHB increase activation of?
Pro-inflammatory (NF-KB)
When is peak incidence of hyperketonemia?
5 days in milk
What is the gold standard for determining ketosis?
Blood BHB
What is the clinic threshold for ketosis?
> 3
What are the 3 tests you can run to measure ketosis?
Urine
Blood
Milk
What is the median time of resolution of ketosis?
5 days
What is the prognosis of pregnancy toxemia?
Poor
pregnancy toxemia can occur in beef cows
When does pregnancy toxemia occur?
Final 4-6 weeks of pregnancy
Why dont small ruminants eat more in late gestation?
Increased uterus makes it physically unable to consume more
What inhibits the normal circulation of the kreb cycle?
Oxaloacetate
What is a common clinical department of pregnancy toxemia?
Nervous system
What is gold standard diagnostic for pregnancy toxemia?
BHB
What is clinical pregnancy toxemia BHB levels?
> 2.6
What are the 2 scenarios in which you may see a sudden drop in BHB?
Treatment is working
Lamb/kid dies
What is a large contributing factor to hepatic lipidosis?
Overconditioned in dry period
All high producing dairy cows have some degree of increased fat in liver
What is mortality of hepatic lipidosis/
> 25%
What is the gold standard to diagnose hepatic lipidosis?
Liver biopsy
What hormones do camelids produce a lot more of than other domestic species?
T3 and T4
Is normal blood glucose higher in camelids than ruminants?
YES! Like 2x higher
Camelids have a _______ insulin production?
Low
Camelids are very sensitive to insuline diseases becuase of their low production
NEFAs, BHB, and triglycerides should all be ________ in fed state?
LOW
With hyperlipidemia in camelids, unlike cattle, what level of BHBs will you see in camelids?
Low
Are clinical changes severe or mild in camelids with hyperlipidemia?
More severe
What is a large contributing factor to ketosis in camelids?
Stress
Since camelids release very low insulin, stress will cause cortisol release causing increased levels of gluconeogenesis and thus glucose resulting in hyperglycemia
Camelids are known as the what of large animals?
Cats
*** What 5 effects do NEFAs have?
Pro-inflammatory
Cytotoxic
Inhibit hepatic glycogen storage
Inhibit glucose uptake
Increase insulin resistance
What 2 things may cause hepatic lipidosis in camelids?
Hypoglycemia
Hyperglycemia
“Feast or famine”
What level of BHBs are indicative of hepatic lipidosis in camelids/
> 2.5
What is the blood glucose renal threshold?
> 200
What is the main clinical sign of hyperglycemia in camelids?
PU/PD
Is diabetes mellitus rare in camelids?
YES
What are the clinical signs of diabetes mellitus in camels?
PU/PD
Ocular changes
Ulcerative foot lesions
How much total calcium is lost in 24 hours during partuition?
46-48g
What 3 things contribute to the loss of calcium during partuition?
Maintenance
Fetal skeleton
Milk/colostrum
What are 4 risk factors for milk fever?
Older cows
Periparturient diseases
Breed
Alkalosis
What are the 3 diet risk factors for milk fever?
High cations, low magnesium, high phosphorus
What does a high cation diet cause?
Alkalinizing effect
What is a non-lactating cause of hypocalcemia?
Oxalate-containing plants
/What is stage I hypocalcemia?
Tremors, head open, tongue extended
What is stage II hypocalcemia/
Sternal recumbancy, still able to stand, hypothermia, S curve neck
What is stage III hypocalcemia?
Flaccid muscles, lateral recumbancy, bloat
Dogs and cows act differnetly with calcium… Dogs: lower ionized calcium causes acetylcholine release causing inctact muscles resulting in hyperthermia and tetany. Cows: lower ionized calcium causes acetylcholine release inhibiting muscles and causing hypothermia and flaccid paralysis.
What is the key role in immune cell signaling and activation?
Calcium
What are 3 risk factors of hypocalcemia in small ruminants?
Older
Multiple fetuses
High milk production
What 2 things cause the release of PTH?
Low Ca and Low Mg
What does PTH do to phosphorus?
Decreases levels
What are 4 risk factors for low vitamin D?
Fall born
Dark coat
Heavy fleece
Rapid growth
Why does hyperphosphatemia occur a lot?
Poor diets high in phosphorus low in calcium
What does hyperphosphatemia do to the parathyroid gland?
hyperplasia
What is hypocalcemia of pigs called?
Eclampsia
How much is too much calcium to give to a hypocalcemic cow?
1-2 bottles
What is almost always associated with hypervitaminosis?
Hypercalcemia and hyperphosphatemia
What is the difference between hyperlipidemia and hyperlipemia
Hyperlipemia is a disease state
What is hyperlipemia?
Hypertriglyceridemia in horses
What is the level typically resulting in hyperlipemia?
> 500
What are 3 risk factors of hyperlipemia?
Late gestation
Lactation
Heavy work
Hyperlipemia is increased triglyceridemia that results in disease most commonly caused by increased metabolic demands and mobilization of lipids
What are predisposed breeds to hyperlipemia?
Small, stocky thangs OR overweight horses brought into negative energy balance
What is hormone sensitive lipase sensitive to?
Insulin
What are the 3 main tissues responsive to insulin?
Muscle
Liver
Fat
What is a nearly pathogneumonic lesion of hyperlipemia?
Plaque of ventral edema
***Assume hyperlipemia is present in any ill equid of a predisposed species and test for it in others
What may you see to diagnose hyperlipemia in serum?
Increased triglycerides in serum
What special stains should be done to diagnose hepatic lipidosis?
Oil Red O
PAS
What effect does lipid have on total protein?
Lipid causes an increased tp on refractometer
Hyperlipidemia causes errors in clinical chemistry assessments via several mechanisms (pseudohyponatremia, pseudohypokalemia, pseudohypochloridemia)
What is the complete inability to sweat when physiologically appropriate?
Anhidrosis
What is the insufficient sweat under same conditions?
Hypohidrosis
What is a clinical sign of anhidrosis?
Tachycardiac
Exercise intolerance
Hyperthermia
What is the diagnosis for anhidrosis?
Intradermal sweat test
Is hypocalcemia or hypercalcemia more common?
Hypercalcemia
____________ hypoparathyroidism and ____________ hyperparathyroidism cause hypocalcemia
Primary, secondary
What are the 5 top differential for hypoparathyroidisim?
Hypoparathyroidism
Eclampsia
Malabsorption
Pancreatitis
Nutritional hyperparathyroidism
What level should PTH be when total calcium/ionized calcium is low?
PTH should be above reference interval
What is the most common reason for primary hypoparathyroidism?
Immune-mediated
What are classic signs of hypoPTH?
Facial rubbing
Tremors
Seizures
If calcium is low, which direction is phosphorus usually?
high
What 2 tests do you need to make the definitive diagnostic for hypoPTH?
Paired PTH and ionized calcium
What is eclampsia?
Puerperal tetany
What increases likelihood of a dog getting eclampsia
Small dogs with large litters (first 3 weeks of lactation)
What are 2 causes of secondary hyperparathyroidism?
Renal and nutritional
Can you differentiate secondayr and primary hypocalcemia on a paired inionzed and PTH panel alone?
NO!
Chronic kidney disease may wash out all of the Calcium in the body causing a cycle of resorption of bone leading to demineralization of the body
With low calcium, what other values do you see?
High phosphorus and low vitamin D
What significant values do you see in CKD?
Low vitamin D
What nutrients will cause secondary hyperparathyroidism?
Diets low in Ca
Diets low in Vit D
Diets high in P
What is the ration of Ca:P that is bad?
Ca:P < 1
What is the orthopedic sign seen with nutritional hyperPTH?
Fibrous osteodystrophy
What are the clinical signs of nutritional hypoPTH?
Orthopedic issues (lameness, limb deformities)
Who do you see nutritional hypoPTH in the most?
Young growing animals
Can serum Ca and P be normla in a nutritional hypoPTH animal?
YES!!
What is another name for PPID?
Equine cushings
PPID’s pathophysiology is similar to what human disease?
Parkinson’s
What part of the pituitary do humans not really have?
Pars intermedia
Where is the lesion causing PPID?
Pars intermedia
What does PPID stand for?
Pituitary pars intermedia dysfunction
Where is ACTH made?
Pars distalis
When is ACTH secreted normally?
In the fall for a winter coat
What occurs with PPID?
The ACTH signals are constantly sent
What are the retained hairs from PPID called?
Guard hairs
What are 6 main clinical signs of PPID?
Hypertrichosis
Weight loss/muscle loss
Laminitis
Secondary infection (endoparasites)
PU/PD
Hyperhidrosis
What clinical sign is associated with the weight loss?
Dropped abdomen
Is PPID primarily cortisol driven?
No
Some other clinical signs to think about: Regional adiposity (supraorbital fossae, delayed wound healing, seizure / neuro issues)
What is the only risk factor for PPID?
Age
What is considered (but not that accurate) gold standard for PPID?
Histopathology of Pars intermedia
What is the recommendation for diagnosing PPID?
Use multiple diagnostic tests
What are the 2 current tests to be used for diagnosing PPID?
endogenous ACTH
TRH - Stimulation test
When is the e-ACTH test most sensitive?
Fall!
When is teh TRH stim test most senestive?
Fall!
How do you do the TRH stim test?
Get 1mL baseline blood sample, give TRH, measure ATCH at 10 min and 30 min
What do owners usually report as laminitis associated with green pasture?
Seasonal lameness
Why does green pasture cause laminitis/
Acute increase in carbs triggering inflammatory cytokines
What are the 3 risk factors of EMS?
Obesity
Insulin dysregulation
History or current lameness
Where is the regional fat for EMS usually found?
Neck and tail head
What is laminitis?
Disease/disruption of the digital lamellae
What are cases with rotation or distal displacement of the coffin bone?
Founder
***Who is predisposed to EMS?
Ponies
Donkeys
Mules
(Gaited Horses)
American Saddlebreds
Tennessee Walking Horses
Morgans
Paso Finos
Arabians
What are the 3 current tests for EMS?
Basal insulin and glucose concentration
Oral sugar test
IV insulin tolerance test
You need to do all 3 tests for diagnosis. If just one tests positive, EMS is likely
Most hypocalcemic disorders are ______
acute
Most hypercalcemic disorders are ______
chronic
What does sepsis do to calcium?
Hypocalcemic
What is the cause of primary hypothyroidism in horses?
Idiological
What kind of calcium do striated muscles need?
Intracellular Ca
What kind of calcium do neurons and smooth muscle need?
Extracellular Ca
What are types of secondary hypoparathyroidism?
Sepsis, low magnesium
What is a clinical sign of hypocalcemia associated with breathing?
Synchronous diaphragmatic flutter
What causes impaired thyroid gland dysfunction?
Cytokines
Why does diarrhea cause hypocalcemia?
Lost in intestines
Acidosis or alkalosis leads to signs of hypocalcemia?
Alkalosis
Acidosis or alkalosis falsely elevated Ca?
Acidosis
Why do horses with anterior enteritis get hypocalcemic?
Horses lose Cl- and replaced by HCO3 causing alkalosis -> hypocalcemia
What is a C-cell adenoma?
Adenoma of the thyroid gland
Non-functional C-cell adenomas are majority compared to functional c-cell adenomas
What do functional C-cell adenomas secrete?
Calcitonin
What are 4 causes of hypercalcemic disorders in horses?
Hyperparathyroidism
Chronic renal failure
Vitamin D intoxication
Cancer - HHM
What are the 3 reasons that hypercalcemia causes PU/PD
High Ca blocks electrolyte and water reabsorption, inducing diuresis
High Ca blocks the actions of antidiuretic hormone (ADH)
High Ca acts like Lasix blocking electrolyte reabsorption
What are 2 causes of secondary hyperparathyroidism?
Renal disease
Nutritional
What are 3 reasons a horse can have hypervitaminosis D
Iatrogenic
toxic plants
Rodenticides
Increased vitamin D equals….?
Increased Ca, increased P
How can you tell if a horse has vitamin D toxicity?
Both high Ca and P
What is hypercalcemia of malignancy?
HHM
What are the laboratory findigns of HHM?
Hypercalcemia, Hypophosphatemia, high PTHrP, low PTH
Chronic renal failure can cause hypercalcemia
What cause hypercalcemia in chronic renal failure?
Less renal Ca excretion
What is the main cause (most common) of hypercalcemia in horses?
Chronic renal failure
Hypocalcemia and hypomagnesemia are frequent in critically ill horses
What panel do you run for PTH and calcium?
Malignancy panel
What is the average age of dogs with primary hyperparathyroidism?
10 years old
*****Why are hypercalcemic animals PuPD?
Calcium interferes with antidiuretic hormone (ADH) hypercalcemia also causes nephrogenic diabetes inspidus (NDI)
What should you think if you see mild to moderate hypercalcemia in a young cat?
Idiopathic hypercalcemia
What are the 3 causes of hypercalcemia with cancer?
Humoral hypercalcemia with cancer (PTHrP)
Cancer in the bone marrow
Tumor metastasis to bone
Which disases are hte most common causes of hypercalcemia in cats?
Neoplasia, renal disease, hyperparathyroidism, Addison’s disease
Which diseases are the most common causes of hypercalcemia in dogs?
Neoplasia, renal disease, urolithiasis
What are 3 humoral hypercalcemia of malignancy?
Lymphoma
Anal sac adenocarcinoma
Squamous cell carcinoma
What are 2 cancers of bone marrow?
Lymphoma
Multiple myeloma
What are 2 solid tumors of the bone?
Mammary carcinomas
Squamous cell carcinoma
Does osteosarcoma induce hypercalcemia?
NO!!!
