SYS Path 2

Endocrine, dermatopath, urinary, c/r

What clinical signs are seen with canine hyperadrenocorticism

(in middle aged/older, 60% female dogs)

pu/pd

heat intolerance, panting

polyphagia

lethargy, muscle weakness

truncal alopecia, cutaneous hyperpigmentation

anestrus/testicular atrophy

Laboratory abnormalities for canine hyperadrenocorticism (CBC, Biochem, urinalysis)

CBC → stress leukogram (neutrophilia, monocytosis, lymphopenia, eosinopenia)

Biochemical profile → increased sALP, ALT, Cholesterol, abnormal bile acids

Urinalysis → USG <1.015, UTI with or without neutrophils

What percent of canine hyperadrenocoriticism develop secondary disease

10% develop diabetes mellitus, glucosuria

3 components of diagnostic testing for hyperadrenocoriticism

screening

confirming

differentiating

What is invoved in a screening test for canine hyperadrenocorticism

Looking at biochemistry sALP

Urince cortisol:creatinine ratio

What is involved with confirmatory tests when testing for canine hyperadrenocorticism

Low dose dexamethasone suppression test

ACTH stim test

What are some differentiating tests for canine hyperadrenocoriticism

LDDST

HDDST

Endogenous ACTH measurement

Imaging

What is the first test you would do if there is an animal with canine Hyper adrenocorticism compatible signs

Look into sALP activity (biochemistry) → it is frequently increased with HAC

If not increased ALP, the dog is very unlikely to have HAC

If increased, move into further testing

What screening test you use with an animal with canine HAC compatible signs and an increased sALP

Look into urine cortisol:creatinine ratio

More cortisol accumulates in urine of HAC: use a fasting urine sample collected at home → cannot be done with sick/stressed dogs, or dogs with renal disease

INCREASED value = >15 × 10^-6

normal dog = <10×10^-6

(HAC unlikely in a dog with a normal UC:CR)

What are the principles involved with a HAC confirmatory LDDST

(dexamethasone suppression test = >90% sensitivity)

In a normal dog, if you inject dexamethasone, ACTH will be suppressed

Less ACTH = less cortisol production

What are some normal values of a dog that has done an LDDST

0h = 30-300 nmol/L

4h = <40 nmol/L

8h = <40 nmol/L

ie → low cortisol at 4 and 8 h

What is often the result when a dog doing an LDDST has HAC

When they have HAC, cortisol is not decreased

There could be:

No suppression of cortisol

“Escape phenomenon” → suppressed at 4h, but not at 8h

90% of dogs with HAC have a cortisol of >40 nmol/L at 8h

In what situation can an LDDST diagnose and differentiate HAC

T4h <40, T8 >40 = pituitary tumour

OR

T4h <half, T8h >half of baseline value = pituitary tumour

What are the principles of using ACTH stimulation test for HAC

Give ACTH IV, wait 1h

A normal dog will secrete a predictable range of cortisol

HAC dog will hypersecrete cortisol: >600nmol/L of cortisol

Advantages and disadvantages of ACTH stim test

Advantages = can rule out iatrogenic HAC, these dogs will show no change in cortisol

Disadvantages =

• Does not distinguish between pituitary/adrenal origin HAC

• Sick/stressed dogs will hypersecrete cortisol

• 10% of truly HAC dogs will not actually respond

HDDST as a differentiating test for HAC, and interpretation

If LDDST does not work, a higher dose of dexamethasone may force cortisol suppress

If value is <40nmol/L OR by >half of the baseline value at 4 and/or 8h = pituitary tumour

What are issues with HDDST in differentiating HAD

30% of dogs with pituitary tumours do not suppress, with either LDDST/HDDST

• If that is true, measure ACTH, pursue DI

Features in using endogenous ACTH as an HAC differentiating test

A pituitary tumour dog will have a normal or increased ACTH

Adrenal tumours secrete cortisol, which shuts down ACTH production by pituitary → these dogs will have very low ACTH

What is the protocol for doing an endgenous ACTH as an HAC differentiating test, + results?

Once HAC has been confirmed, take an early morning plasma sample

Using silicone coated EDTA tube → spin down immediately, put plasma in plastic tube, freeze rapidly, ship on ice

Dogs with pituitary tumour = >18 pmol/L ACTH

Dogs with adrenal tumour = <4.4 pmol/L ACTH

Age of PPID vs. EMS in horses

pars pituitary intermedia dysfunction vs. equine metabolic syndrome

PPID easiest to diagnose in older horses

EMS in young to middle aged horses

Both associated with laminitis

2 PPID diganosis considerations for older horses

Affects young to middle aged horses as well, can create a diagnostic challenge

May occur in tandem with hyperinsulinemia/insulin dysregulation

EMS diagnosis considerations for young to middle aged horses

hyperinsulinemia → cut points needed! pregnancy, stress, pain can also be involved

Can also occur with PPID

Measuring plasma ACTH in horses with pars pituitary intermedia dysfunction

(specificity 94%)

Changes with seasons!

December to June = >10pmol/L

July to November = >20pmol/L

Equine metabolic syndrome and insulin as a test

EMS causes insulin resistance in young to middle aged horses

Measure serum insulin after giving glucose, should be an increased “resting” insulin

What causes ferret hyperadrenocorticism

Excessive sex steroid production (estrogen, androstenedione)

What are the clinical signs of ferret hyperadrenocorticism

Alopecia, pruitis

vulvar enlargement, return to male sexual behaviour

aggression

Stranguria

What are some lab findings for ferret hyperadrenocorticism

anemia/pancytopenia from estrogen toxicosis

How is ferret hyperadrenocorticism diagnosed

imaging

full panel sex hormones

What is the incidence of hypoadrenocorticism in dogs

0.5 in 1000 dogs → very rare

What is the common signalment for diagnosing hypoadrenocorticism

Female dogs more often

Often in young and middle aged (>5 years)

Mixed breed dogs most prevalent

What is a primary cause of hypoadrenocorticism

immune mediated destrution of adrenal cortices

What are common urinary test results in a dog with hypoadrenocorticism

(relates to lack of aldosterone)

Excess Na+ excretion and retention of K+/H+

Biochemical findings for hypoadrenocorticism

hyponatremia

hypovolemia, hypotension, pre-renal azotemia

(hypovolemic crisis = addisonian crisis)

What are the most common presenting complaints/clinical signs of hypoadrenocorticism

poor appetite/anorexia

lethargy/depression

thin

vomiting/regurgitation

What are some common physical exam findings for a hypoadrenocorticism, or dogs in hypovolemic crisis?

dehydration

shock/collapse

bradycardia

weak femoral pulse

hypothermia

What are the most common laboratory findings for hypoadrenocorticism

pre-renal azotemia (90%) → dehydration

mild to moderate, normocytic, normochronic non-regenerative anemia

No stress leukogram despite them being very sick

USG <1.030 despite dehydration

Increase in urea nitrogen, causing GI hemorrhage

hypoglycemia in 20-40% of cases (always measure glucose in suspected Addison’s dogs)

What are 2 ways to approach diagnosing hypoadrenocorticism

1. Look at electrolytes in biochem → serum Na:K <27 suggestive

2. ACTH stimulation test: administer ACTH, see if animal produces cortisol

• at 1h: <50 nmol/L (normal dog 250-600 nmol/L)

What are some features of feline hyperthyroidisim

Most common endocrine disorder in cats >8yo

Often from adenomas, 70% of which are bilateral

No breed or sex predilection

What are the clinical and physical exam findings for feline hyperthyroidism

weight loss

polyphagia

pu/pd

restlessness

palpable thyroid

hypertrophic cardiomyopathy

hypertension

Biochemistry findings for feline hyperthyroidism

Increased ALT (85%, mild to moderate)

Increased ALP (62%, mld to moderate)

Increased phosphate

Decreased albumin and creatinine

(Glomerular hyperfiltration → can mask renal diseas, SDMA)

3 parts to feline hyperthyroidism dianosis

Clinical signs

palpable thyroid nodule

measure tT4 (90% of which have increased tT4)

Goal of therapy for feline hyperthyroidism and CKD considerations

Improve the physical condition → monitor renal function, T4, monitor other organ systems

Treatment of hyperthyroidism → avoid iatrogenic hypothyroidism

Stage CKD carefully → BP, UPCR, record BCS and muscle condition

Canine hypothyroidism cause

is the most common canine endocrinopathy

primary hypothyroidism most comon (>95%) = lymphocytic thyroiditis, idiopathic thyroid atrophy

What are some common clinical signs for canine hypothyroidism

>1 year old

weight gain

lethargy/mentally dull/unwilling to exercise

dermatologic

endocrine alopecia

What are some common laboratory abnormalities with canine hypothyroidism

Anemia → mild normocytic, normochromic, non-regenerative

Fasting hypercholesterolemia (75%)

Fasting hypertrigylceridemia (88%)

2 parts to diagnosing canine hypothyroidism

1. Clinical suspicion

2. Thyroid panel

total t4, free t4, endogenous TSH, thyroglobulin autoantibody (TgAA)

Interpretation of canine thyroid panel results with

1. <10 tT4, low fT4, high TSH

2. low normal tT4, high TgAA OR low normal tT4, high TSH

1. primary hypothyroidism

2. repeat test in 6 months

What are some causes of euthyroid sick syndrome

1. non thyroidal illness may cause decreased t4 production by thyroid (body wants to redirect its energy elsewhere)

2. drugs may cause a decrease in tT4 (glucocorticoids, phenobarbitone, sulfonamides, furosemide)

Antidiuretic hormone and 2 types of diabetes insipidus

Can be: central diabetes insipidus (no ADH made), OR nephrogenic DI (no response to ADH)

Both result in: pu/pd, low USG

What are some clinical causes of nephrognic diabetes insipidus

Kidney does not respond to ADH because of =

Pyometra, pyelonephritis

hypercalcemia

cushings, glucocorticoids, acromegaly

addison’s, hypokalemia

hyperthyroidism

liver failure

How can you differentiate central from nephrogenic diabetes insipidus

resonse to desmopressin (a synthetic ADH)

What are the expeced results when administering desmopressin for nephrogenic diabetes insipidus and central diabetes insipidus

full nephrogenic DI → no change in post desmopressin USG, kidneys can’t respond

Full CDI → USG increases >50% of original value (generally >1.026)

What do pancreatic islet a cells and b cells secrete

alpha = glucagon

beta = insulin

Features of type 1 diabetes mellitus in dogs

Loss of beta cells (for any reason - genetic, immune mediated, etc)

Young to middle aged

Creates Insulin-dependent diabetes mellitus

Features of type 2 diabetes mellitus in cat

obesity → insulin resistance

From a loss of beta cell function = less insulin secreted

Also from insulin receptor defective function

non, or variably insulin dependent

What is the pathophysiology of insulin-dependent diabetes mellitus

Insulin deficiency from damaged b cells → tissues have suboptimal use of glucose, amino acids and fatty acids

Persistent hyperglycemia despite starving tissue

Persistent glucosuria once there is plasma glucose

Pu/pd (osmotic diuresis)

Polyphagia → lack of satiety response in hypothalamus

Weight loss → metabolism of protein and fat

Pathogenesis of type 2 diabetes mellitus in cats

(30-50% are non, or variably insulin dependent)

Obesity

Muscle and adipose tissue are insulin resistant → decreased affinity for insulin OR reduced insulin function in obesity

Chronic insulin over secretion, co-secreted with islet amyloid peptide (IAPP)

IAPP forms amyloid fibrils within islets, destroys beta cells

Detecting subclinical/pre-diabetic cats

Inject glucose, and see what insulin response occurs

Cats with insulin resistance will have a greater release of insulin and prolonged hyperglycemia

Is often months → years before becoming overtly diabetic

What is the common history and PE findings to diagnosing diabetes mellitus

Common signalment = female dogs, male cats

History = pu/pd, polyphagia, weight loss, blindness, dka

physical exam = hepatomegaly (from glycogen/fat deposition), neuropathy

what are some differentials for hyperglycemia

stress = especially in cats, can be epinephrine induced, may even have glucosuira

hyperadrenocorticism = cortisol antagonizes insulin

pancreatitis = though glucose usually <15 mmol/L

diestrus, pheochromocytoma, postprandial increases

growth hormone secretion in cats → acromegaly

Acromegaly/hypersomatotropism in cats

Pituitary tumour → increases release of growth hormone

Growth hormone → impairs glucose uptake (hyperglycemia), interferes with post-receptor signalling

growth hormone → liver gluconeogenesis, release of IGF-1

GH & IGF1 → cartilage and bone overgrowth (acromegaly)

What are the signs of hypersomatotropism in cats

acromegaly → enlarged flat bones, excess cartilage, polydypsia, polyphagia, hepatomegaly

15-25% of diabetic cats have overproduction of GH/IGF, thus hypersomatotropism

From a primary pituitary tumour, or secondary to diabetes mellitus

What are some common laboratory findings for diabetes mellitus

hyperglycemia and glucosuria

uti → bacteria eat glucose

increased liver enzymes

hyperlipidemia

(potentially pancreatitis, azotemia)

What are some specific tests that diagnose diabetes mellitus

IV glucose tolerance test → measures glucose and insulin over 2 h

Glycated proteins tests:

• Persistent hyperglycemia, glucose likes to attach to proteins

• Serum fructosamine, mainly albumin (glycemic control in previous 2-4 weeks)

• Hemoglobin

What is the pathophysiology of diabetic ketoacidosis

hyperglycemia → glucosuria → osmotic diuresis (water and electrolytes, dehydration)

Ketonemia → ketonuria

high anion gap metabolic acidosis from H+ accumulation

Nausea and vomiting → exacerbation of ketone production, dehydration, Cl loss

Increase in plasma osmolality (dehydration) → cellular dehydration → cerebral edema

H+/K+ switch, and K+ out in urine → whole body kypokalemia

What is an insulinoma

Tumour of pancreatic beta cells

Insulin production causes hypoglycemia, weakness/seizure

Malignant → metastasis common at diagnoses

How is an insulinoma diagnosed

a Fasting hypoglycemia of <3.3

Normal, or high insulin

Differentials for hypoglycemia

PSS

severe liver disease

hypoadrenocorticm

sepsis

hepatic or intestinal tumours secreting hypoglycemic substance

Insulinomas in ferrets

Is the most common tumour in ferrets

Clinical presentation is the same as dogs due to hypoglycemia

Not as malignant, surgery often curative

PTH affect on kidneys

increases reabsorption of Ca

increases excretion of P

increased production of active vitamin D

PTH affects on bone

increase osteoclast activity

increased calcium release

bone resorption

What does hyperparathyroidism do to PTH, and other consequences?

Excess PTH → excess Ca

Mineralization of renal tubular basement membrane → can cause dead tubular cells and kidney failure

GI abnormalities

Weak bones from calcium reabsorption → fibrous osteodystrophy (rubber jaw)

Autonomously secreting adenoma, of chief cells in parathyroid glands

• Rarely palpable in dogs, but if palpableconsider carcinoma

• Adenoma palpable in 50% of cats

Presenting signs → nonspecific, Pu/pd, weakness

How is hyperparathyroidism diagnosed

From a marked and persistent hypercalcemia

High normal or increased serum PTH concentration

Differential diagnoses for hypercalcemia

(PTH will be low-normal with any other cause of hypERcalcemia)

vit D toxicosis

osteolytic bone lesions

hypoadrenocorticism

Multiple myeloma

Neoplasia → PTH-rp production (rule out apocrine gland adenocarcinoma of anal sac)

Calcium balance and nutritional secondary hyperparathyroidism in reptiles

Will have a high P, and/or low Ca diet → causes secondary hyperparathyroidism

Causes = Ca removal from bones, fibrous osteodystrophy, pathologic fractures

What is the purpose of endocrine cells

synthesizes, stores, releases secretions (hormones) directly to blood vessels, reaches distant sites, hormones bind to receptors on target cells

2 types of hormones by target

Polypeptide: surface receptors on membrane

steroid: intracellular receptors

How are endocrine cells organized in the body

As dedicated endocrine glands → pituitary, thyroid, adrenal, parathyroid

As individual/aggregated cells with other organs → islets in pancreas, lung, skin, adipose tisse, etc.

Endocrine cells organized to: cords, packets, follicles that require close proximity to blood stream (separated by well-vascularized CT called stroma)

4 main types of endocrine pathologic processes

proliferation → hyperplasia (functional or non-functional; excess trophic hormone, disrupts negative feedback, idiopathic), neoplasia (benign vs. malignant, functional vs. non-functional)

atrophy → lack of trophic hormone, idiopathic, compression

inflammation → immune mediated > infectious

other → necrosis, degeneration, hypoplasia, vascular disturbance, etc.

What is functional endocrine neoplasia

producing an active hormone

distant effects → overproduces hormones in targeted tissue

Often see systemic effects

What is non-functional neoplasia

does not produce an active hormone

local effects, leading to compression or destruction of adjacent tissues

size matters more here than functional

Pituitary adenohypophysis

in the pars: distalis, intermedia, and tuberalis of the pituitary

can be in the form of cysts, neoplasia, inflammation

Pituitary neurohypophysis

in pars nervosa ONLY

causes diabetes insipidus

Pituitary cysts

Derived from different aspects of the pituitary gland (pars: distalis, intermedia, tuberalis)

Typically incidental unless they are large

What do larger pituitary cysts do

exerts pressure on other structures (like the optic chiasm, cranial nerves, etc)

• consequences depends on which structures are affected

can rupture, leading to inflammation and fibrosis

What are 4 major consequences of large or invasive cysts in the pituitary gland

Lack of secretions of pituitary hormones → atrophy and decreased functional adrenal cortex/thyroid gland, gonadal atrophy, failure to attain somatic maturation

Water metabolism distubrances → interferences with release/synthesis of ADH

Cranial nerve deficits

CNS dysfunction caused by extension to brain

Pituitary neoplasia features in 2 locations

Typically more solitary

More often adenoma > carcinomas

In the pars distalis → adenoma = more in dogs (dog = corticotroph, cat = somatotroph)

In the pars intermedia → melanotroph adenomas (horse = major pituitary neoplasm)

What are corticotrophs

functional pituitary neoplasia, adenoma

ACTH secreting

The pars distalis/pars intermedia produces ACTH → increases cortisol from adrenal gland

Causes a pituitary dependent hypercortisolism

Dogs

What are melanotrophs

In the pars intermedia, a functional pituitary adenoma

From POMC derived peptides

Causes pituitary pars intermedia dysfunction in horse

What are somatotrophs

GH secreting functional pituitary adenoma

Most common pituitary adenoma in cats (rare in other species)

Creates a large, indent hypothalamus that extends into the brain

Leads to hypersecretion of growth hormone, causes acromegaly

Can cause insulin resistant diabetes mellitus in cats (increased GH → down-regulation of insulin receptors)

What is acromegaly

From a pituitary somatotroph, often in cats

overgrowth of connective tissue, increased appositional growth of bone, coarsening of facial features

gingival hyperplasia, separating teeth, enlarged viscera

What are the features of pituitary involved inflammtion

Can be: Hypophysitis, or abscess

Can be from systemic disease → bacterial septicemia enters brain (common)

Can be from regional disease that extends to pituitary → suppurative meningitis, trauma, inne ear, tooth rot, sinuses

2 forms of diabetes insipidus

Hypophyseal form (in the pituitary) → inadequate ADH production from compression and destruction of the pars nervosa, infundibular stalk, or supraoptic nucleus in hypothalamus

• from cysts, neoplasia, granulomas, etc

Nephrogenic form → lack of response in target cells, can have a normal or high ADH

What are some pathologic processes involved with the adrenal gland

Inflammation (adrenalitis) → no hypofunction, unless it is immmune mediated

Hemorrhage

Hyperplasia/neoplasia

Atrophy (bilateral, unilateral)

2 causes of adrenalitis

Primary: Immune mediated hypoadrenocorticism, destruction of the adrenal glands

• lymphoplasmacytic, confined to the cortex

Secondary to systemic infection: from a high local concentration of anti-inflammatory steroids in the adrenal cortex to suppress local cell-mediated immunity, permitting growth of pathogens

What are some causes of adrenal gland hemorrhage

can be found in newborn animals

can be a stress response, toxemia, sepsis

• Toxemia/sepsis (inury to vasculature) causes a secondary infarct

Adrenal hyperplasia of the medulla

Can be diffuse or nodular

Most common in aged bulls or aged mares

Can precede the development of pheochromocytoma in bulls with C-cell tumours (C-cell tumours make calcitonin)

Adrenal hyperplasia of the cortex (2 types)

Nodular cortical hyperplasia → common in dogs, is often incidental and non-functional

Diffuse cortical hyperplasia (bilateral)

Pituitary vs. adrenal incidence of hyperadrenocorticism

Pituitary/functional corticotroph adenoma is 85% of cases

Adrenal (functional adrenal neoplasm) = 15%

3 main locations of adrenal neoplasia

neoplasia of the cortex, medulla, corticomedullary junction