ATTITUDE“The people who get on in this world are the people who get up and look for the circumstances they want, and if they

can’t find them, make them.”-George Bernard Shaw

ENDOCRINE SYSTEM DISEASES

‘CRINE’ – to secrete

Endocrine System Diseases

Main trigger: Hypothalamus

Review of the basics• Endocrine ____________- basic units of the

endocrine system.– Secrete hormones ___________ into the

bloodstream.• Circulate throughout body and produce effects when

attach to receptors in or outside of cells.– __________ glands.

• Exocrine glands- units that secrete their products onto epithelial surfaces through tiny tubes called _____________.

Hormones• ___________ messengers produced by endocrine

glands and secreted directly into blood vessels. • Produce effects when find their receptors in or on

cells.– Each body cell has specific receptors to certain

hormones (___________).– If body does not have receptor, hormone will pass by. – Only certain hormones can _______ to receptors and

when it occurs, then it changes the activity of the cell.

Hormones

Control of Hormone Secretion• “Negative Feedback System”

– Endocrine glands will be stimulated to produce more hormone when it drops below a certain amount in the body.

– If hormone is of adequate levels, gland will either slow or stop production of the hormone which is called negative feedback.

• Direct Stimulation of Nervous System– Secretion of some hormones is stimulated by sympathetic nerve

impulses when an animal feels threatened. • Fight or flight response from sympathetic nervous

system

DISEASES OF THE THYROID GLAND

HYPERTHYROIDISMHYPOTHYROIDISM

Hypothyroidism

Thyroid Gland• Gland not usually palpable• Located at ventral cervical region along lateral margins of

trachea• Hormones produced

– T3 (___________________) and T4 (_____________________), iodine containing hormones.

• Produced by follicular cells– ______________ – Causes Calcium deposition in bone which

decreases blood Calcium concentrations• Produced by parafollicular cells

Hypothyroidism

• Definition: clinical state associated with ____________________ which causes low cell metabolism in most tissues of the body

• Primary acquired – 90% of dogs– Caused by ________________or

_________________________– Also by iodine deficiency, neoplasia, infection

• Secondary acquired- RARE– Anterior Pituitary dysfunction or destruction from neoplasia

– leads to ↓TSH• Congenital Hypothyroidism-RARE

– Cretinism (newborns)

Hypothyroidism

• MOST COMMON ENDOCRINE DISEASE IN____________; rare in cats– Breeds: Golden Retriever, Doberman, Irish Setter,

Schnauzer, Cocker Spaniel, Dachshund, others• 4-10 yrs of age• Females• Greyhounds and Scottish deerhounds

physiologically have lower T4 (thyroxine)

Hypothyroidism• Clinical Signs - COMMON

– __________________________________– Skin changes

• Bilaterally symmetric truncal alopecia (which other disease has this clinical sign? )

• ______________________ neck, axillae, and other areas of friction

• Seborrhea• Superficial pyoderma• Dry, lusterless haircoat• Hyperpigmentation

– Cold intolerance (why?)– Lethargy/sleeping– Exercise intolerance

Hypothyroidism

Hypothyroidism

Hypothyroidism

Hypothyroidism

Hypothyroidism

• Clinical signs/Bloodwork – Less common– ___________________– generalized weakness, ataxia, facial

paralysis/paresis, seizures (secondary to cerebral atherosclerosis)– _______________– Constipation, Regurgitation caused by

megaesophagus– Bloodwork abnormalities –_____________lipidemia is most

common, gross lipemia ( milky appearance to the serum), ____________________cholesterolemia (80%), anemia (mild non-regenrative)

– Eye – hyperlipidemia => corneal lipidosis and anterior uveitis

*Virtually all body systems are affected, clinical signs aregenerally non-specific

Hypothyroidism: DIAGNOSIS• Blood Tests

– Hypothyroid dogs have lowered level of T4– Test total T4(TT4), +/- T3 levels– Free T4: Free T4 is thyroxine that is not protein bound

(ED is most accurate test for fT4 measurement)– Basal TSH concentration

• Measures TSH in blood, should be used in conjunction with other tests and clinical signs

*ED = equilibrium dialysis

Hypothyroidism: Considerations

• Remember sick animals and animals on certain medications (anti-epileptics, glucocorticoids) may have depressed T4 levels. (_________________)– Wait and re-test after treatment of underlying cause

if clinical signs persist. • Greyhounds have low T4 levels naturally

diagnose based on clinical signs as well as test results; treat if clinically evident.

Hypothyroidism

• Treatment– Thyroid supplement – _________________

• Oral, synthetic levothyroxine (0.02 mg/kg BID)• Daily administration (after cs resolves consider

SID)– Steady state levels – 4/8 wks (1st 6-8 months)

• Test levels and adjust dose until T4 normal – Want to test 4-6 hours after dose is given (when serum

levels are highest)

Thyroid replacement hormone (levothyroxine sodium)

Hypothyroidism

• Client Education– Supplement for ________________– Daily dosing required– Overdose => hyperthyroidism

• Regular rechecks are recommended including bloodwork.• PU/PD; nervousness, weight loss, panting, weakness, inc.

appetite– Vet may recommend a reduced fat diet until body

weight is satisfactory and T4 levels are normal.

Hyperthyroidism

Definition: Pathologic, sustained, high overall metabolism caused by high circulating concentrations of thyroid hormones

• Most common Endocrine disease in ____________ (one of the big 3 diseases of older cats)– Very rare in dogs

• Pathophysiology– Autonomously ___________________________, no

physiologic controls (functional thyroid adenoma)– Secrete _______ and ____________

Hyperthyroidism in cats

Hyperthyroidism

• Clinical Signs– Multi-systemic: reflects increase in metabolism

• _________________• __________________• Vomiting/diarrhea• _____________________• Tachypnea/dyspnea• Hyperactivity• Aggression

Hyperthyroidism

• Clinical signs cont’d– ____________________(thickening of LV

and heart muscle)– Hypertension– Poor body condition– Thickened nails– Unkempt appearance– ______________________ gland 70% -

bilateral

Hyperthyroid cat

Middle age to older cats Blindness with retinal detachmentWt loss Palpable enlarged Thyroid glandPolyphagia AggressiveTachycardia unkempt haircoat

Hyperthyroid cat: Goiter

Hyperthyroidism

• Diagnosis– Palpate enlarged thyroid gland– Elevated T4, FT4– X-rays for associated heart disease

Hyperthyroidism: Scintigraphy

Normal catNormal uptake in salivary glandsand thyroid glands

Hyperthyroid catUnilateral thyroid adenoma

Hyperthyroidism: Scintigraphy

Hyperthyroid catBilateral thyroid adenoma

Hyperthyroid catEctopic (intrathoracic)thyroid adenoma

Hyperthyroid catFunctional thyroid carcinoma(represents regional metastasis)

Hyperthyroidism• Treatment

– ______________________ (Tapazole) – anti-thyroid drug – block incorporation of iodine into thyroglobulin.

– Monitor: q 2-3 weeks• COMMON AND PRACTICAL FOR CLIENTS

– Radioiodine treatment – I131 • Effective • Emitted radiation destroys functioning follicular cells• ______________________________________________

– Surgical removal of gland• May cause hypothyroidism• May result in hypocalcemia due to hypoparathyroidism

Hyperthyroidism: Medical Rx

METHIMAZOLE

ORAL DRUG, BUT CAN BE FORMULATED INTO A TRANSDERMAL OINTMENT

Hyperthyroidism• Complications

– Renal disease/failure unveiled when thyroid levels controlled• 2-3 months after medication started

– Occasionally tapazole will no longer be effective usually after 2-3 years of treatment

• Prognosis – Excellent if uncomplicated– If labs show ___________________ prior to treatment, prognosis

more guarded

Hyperthyroidism: Client Info• Cause of disease is unknown• Surgery or Radiation are only cures • Cat may become hypothyroid following Rx –

usually not clinically significant and supplementation can be initiated if necessary

• Following Tapazole, Blood pressure and kidney values should be checked routinely

EDUCATIONEducation is learning what you didn’t

even know you didn’t know.-Daniel J. Boorstin

DISEASES OF THE PARATHYROID GLANDS

HYPERPARATHYROIDISMHYPOPARATHYROIDISM

Thyroid/Parathyroid glands

1=normal thyroid gland2 and 3=parathyroid gland4=enlarged thyroid gland

Parathyroid gland

• Secretion: Parathyroid hormone (PTH, Parathormone)

• Function: ↑ plasma Ca2+ concentration– 1. ↑ osteoclast activity– 2. ↑ Ca++ absorption from GI tract– 3. ↑ Ca++ reabsorption from kidney tubules

• Hyperparathyroidism →hypercalcemia• Hypoparathyroidism →hypocalcemia

Hyperparathyroidism

• Causes:– 1º hyperparathyroidism—adenoma or carcinoma– 2º hyperparathyroidism—poor diet; low Ca intake

• Clinical signs:– Many animals show no clinical signs– signs occur as organ dysfunction occurs

• urinary/renal calculi (high plasma Ca++)• cardiac arrhythmias, tremors (Ca++ necessary

for normal muscle contraction• Anorexia, vomiting, constipation• weakness

Hyperparathyroidism

Dx:• Routine chemistry panel

– ↑ blood Calcium (normal: ~8-10 mg/dl))– +/- ↓ blood Phosphorus (normal: ~2-6 mg/dl)

• PTH assay– normal PTH: dogs ~20 pg/ml, cats ~17 pg/ml– In a normal animal: if blood Ca++ is high, PTH is low (neg feedback)– 1º Hyperparathyroidism: Ca++ high, PTH elevated

• Ultrasound of neck – enlarged glands, abdomen - uroliths

Hyperparathyroidism

Tx:1. Surgical removal of diseased parathyroid (generally 4 lobes are imbedded in thyroid gland)

Other options:2. Ultrasound-guided chemical (ethanol) 3. Ultrasound-guided heat (laser) ablation

Post-Op Care:1. Hospitalize for 1 wk; ↓PTH may predispose animal to hypocalcemia2. Calcium therapy (oral tabs, liquid)3. Vit D supplements (promotes Ca intestinal absorption)

Hyperparathyroidism

Client Info1. Most hyperparathyroid animals show no

signs when first diagnosed2. Run yearly chem panels on all normal, older

animals

Hypercalcemia: Other causes

• Causes– Neoplasia (lymphoma, perianal gland

tumors)– Renal failure– Hypoadenocorticism– Vitamin D rodenticide– Drugs or artifacts (ex lipemia)

• Clinical signs vary with cause– PU/PD, anorexia, lethargy, vomiting,

weakness, stupor/coma (severe), uroliths

Hypercalcemia

• Tests– Elevated serum calcium levels– Low to low-normal phosphorus concentrations

Hypercalcemia

• Treatment– Fluids: 0.9% NaCl

• No Ca2+ containing fluids– Diuretics (furosemide)– Steroids

• Complications– Irreversible renal failure– Soft tissue calcifications

HypocalcemiaCauses:1. Parathyroid disease

a. Inadvertent removal of parathyroid during thyroidectomy (most common causeb. 1º Hypoparathyroidism (uncommon in animals)

2. Chronic renal failure—a. may cause ↑ serum P, which can result in ↓ serum Ca (Ca:P inverse relation)b. Vit D normally activated in kidneyc. Protein-losing nephropathy results in loss of albumin-bound Ca

3. Puerperal Tetany (Eclampsia)—late gestation thru post-partum perioda. Improper prenatal nutritionb. Heavy lactationc. Inappropriate Ca++ supplementation

http://www.thepetcenter.com/gen/eclampsia.html#The_video

Hypocalcemia

Clinical Signs:1. Restlessness, muscle tremors, tonic-clonic contractions,

seizures 2. Tachycardia with excitement; bradycardia in severe cases

(Ca++ is necessary for proper muscle contractions)3. Hyperthermia4. Stiffness, ataxic

Hypocalcemia

Dx:Total serum <6.5 mg/dl

Tx:1. IV infusion of 10% Ca gluconate solution (monitor

HR and rhythm during infusion)2. Diazepam (IV) to control seizures3. Oral supplements of Ca (tabs, caps, syrup)4. Improve nutrition

Hypocalcemia

Client info:1. Well-balanced diet; increase volume as

pregnancy progresses2. Signs in pregnant animal is emergency; call

vet immediately3. May recur with subsequent pregnancies4. Early weaning is recommended

LIFE“Nobody can go back and start a new beginning, but anyone can start today

and make a new ending.”-Maria Robinson

DISEASES OF THE PANCREAS

DIABETES MELLITUSINSULINOMA

EXOCRINE PANCREATIC INSUFFICIENCY

Review of pancreas functions

• Long flat organ near duodenum and stomach

• Exocrine function (the majority of the pancreas):– Digestive enzymes

• Endocrine function – islets of Langerhans– Alpha cells => glucagon– Beta cells => insulin– Delta cells => somatostatin

Pancreas

Pancreas: beta cells

Review

• Insulin – Moves glucose into cells to be used for energy– Decreases blood glucose

• Glucagon– Raises blood glucose

• Stimulates liver to release glucose• Stimulates gluconeogenesis

– Other hormones from other glands perform similar functions (hyperglycemic effect)

• Growth hormone• Glucocorticoids

Insulin/Glucagon Balance

Endocrine Pancreas

• Hyperglycemia– Definition: Excessively high blood glucose

levels• Normal in dogs: 60-120 mg/dl• Normal in cats: 70 -150 mg/dl

Diabetes Mellitus

• Definition: Disorder of carbohydrate, fat and protein metabolism caused by an absolute or relative insulin deficiency

• Type I – Insulin Dependent DM – very low or absent insulin secretory ability

• Type II – Non insulin dependent DM (insulin insensitivity) – inadequate or delayed insulin secretion relative to the needs of the patient

Diabetes mellitusIncidence:

Dogs: ~100% Type I (Insulin dependent)Cats: ~ 50% Type I and 50% Type II

-non-insulin dependent catscan sometimes be managed withdiet and drug therapy

Causes: Chronic pancreatitisImmune-mediated disease -beta cell destruction

Predisposing/risk factors:Cushing’s DiseaseAcromegalyObesityGenetic predispositionDrugs (steroids)

Diabetes mellitus• Age/sex:

– Dogs: 4-14 yrs, females 2x more likely to be affected

– Cats: all ages, but 75% are 8-13yrs, neutered males most affected

• Breeds: Poodles, Schnauzers, Keeshonds, Cairn Terriers, Dachshunds, Cockers, Beagles

DM

• Pathophysiology– Insulin deficiency => impaired ability to use glucose from

carbohydrates, fats and proteins– Impaired glucose utilization + gluconeogenesis => hyperglycemia– Clinical signs develop when:

• Exceeds capacity of renal tubular cells to reabsorb• Dogs – BG > 180-220 mg/dl• Cats - BG > 200-280 mg/dl

– Glycosuria develops• Osmotic diuresis• Polyuria/polydipsia

DM• SYSTEMS AFFECTED:

– Endocrine/metabolic: electrolyte depletion and metabolic acidosis

– Hepatic: liver failure 2° to hepatic lipidosis (mobilization of free fatty acids to liver leads to hepatic lipidosis and ketogenesis)

– Ophthalmic: cataracts (dogs) from glaucoma

– Renal/urologic: UTI, osmotic diuresis– Nervous: peripheral neuropathy in cats– Musculoskeletal: Compensatory weight

loss

Diabetes Mellitus

• Clinical Signs:– Polyuria– Polydipsia– Polyphagia– Weight loss– Dehydration– Cataract formation-dogs– Plantigrade stance-cats

Plantigrade postureDiabetic neuropathy

Diabetes in Cats:Plantigrade posture

Diabetes: Cataracts

Increase in sugar (sorbitol) in lens causes an influxof water, which breaks down the lens fibers

Diabetic Ketoacidosis

2 metabolic crises: ↑ lipolysis in adipose tissue → fatty acids →ketone bodies →ketoacidosis →coma (insulin normally inhibits lipolysis)↑ hepatic gluconeogenesis (in spite of high plasma glucose levels)

(insulin normally inhibits gluconeogenesis)

Diabetic Ketoacidosis

• Definition: True medical emergency secondary to absolute or relative insulin deficiency causing hyperglycemia, ketonemia, metabolic acidosis, dehydration and electrolyte depletion

• DM causes increased lipolysis => ketone production and acidosis

Diabetic Ketoacidosis• Diagnosed with ketones in urine or ketones in blood

– Can use urine dip stick with serum.

• Clinical Signs– All of the DM signs – Depression– Weakness– Tachypnea– Vomiting– Odor of acetone on breath

Diabetic Ketoacidosis

• IV fluids to rehydrate 0.9% NaCl – K (potassium) supplement

• Regular insulin to slowly decrease BG • Monitor BG q 2-3 hrs• When BG close to normal and patient

stable switch to longer acting insulin

DM• DIAGNOSIS:

– CBC: normal– Biochemistry panel:

• Glucose > 200 mg/dl (dogs), >250 (cats)– UA

• Glycosuria!!!!• Ketonuria• USG – low

– Electrolytes may be low due to osmotic diuresis– Blood gases (if ketoacidotic)– Fructosamine levels – mean glucose level for last 2-3 weeks

(dogs)• Ideal to test for regulation checks

DM Rx: INSULIN AND DIET!!!Table 1. Traditional insulin outline.

Duration/onset category

Insulin types Concentration

Rapid acting Regular (Humulin R) U-100 (100 units/ml)

Intermediate acting NPH (Humulin N) U-100

Lente (Vetsulin® by Intervet) NO LONGERAVAILABLE*

U-40 (40 units/ml)

Long acting PZI (Idexx) U-40

Ultralente NO LONGERAVAILABLE*

U-100

Glargine insulin analog U-100

Diabetes: Insulin therapy

DM: Insulin therapy

• INSULIN– Beef-origin insulin is biologically similar to cat

insulin– Porcine-origin insulin is biologically similar to

dog insulin– Dogs and cats have responded well to human

insulin products• INSULIN ADMINISTRATION:

– ALWAYS USE THE APPROPRIATE INSULIN SYRINGE! (U-40 vs. U-100)

• Insulin is given in units (insulin syringes are labeled in units, not mL)

DM: dietary management• DIET

– DOGS: high fiber, complex carbohydrate diets• Slows digestion, reduces the post-prandial glucose spike,

promotes weight loss, reduces risk of pancreatitis• Hill’s R/D or W/D

– CATS: high protein, low carbohydrate diets• Cats use protein as their primary source of energy – blood

glucose is maintained primarily through liver metabolism of fats and proteins

• Purina DM, Hill’s M/D• Often a diet change in cats can dramatically reduce or

eliminate the need for insulin– This is particularly true for type II

DM

• Oral hypoglycemicso Sulfonylureas – Glipizide

oDirect stimulation of insulin secretion from the pancreasoAlpha-Glucosidase Inhibitors – Acarbose

oDelays digestion of complex carbohydrates and delays absorption of glucose from the intestinal tract.

Diabetes Mellitus: Monitoring

Find an ear vein Prick the ear to get Place drop of blood blood sample on green tip; readout in

a few seconds

Diabetes Rx: Urine glucose

Diabetes monitoring: Urine glucose

DM: monitoring

DM• Client Education

– Lifelong insulin replacement therapy– Insulin administered by injection– Refrigerate insulin, mix gently (no bubbles), single use syringes– Cataracts common, permanent– Consistent diet and exercise– Recheck BG or curve regularly or fructosamine levels– Progressive– If animal does not eat- NO INSULIN

Endocrine Pancreas• Hypoglycemia

– Definition: Low blood glucose levels– Causes

• Neonatal and juvenile• Septicemia• Neoplasia• Starvation• Iatrogenic – insulin overdose• Portosystemic shunt• Many others

Insulin Shock

Causes:1. Insulin overdose (misread syringe)2. Too much exercise3. AnorexiaSigns:Weakness, incoordination, seizures, coma

Insulin Shock

Prevention1. Consistent diet (type and amount)/consistent

exercise (less insulin with exercise)2. Monitor urine/blood glucose at same time each

day3. Feed 1/3 with insulin; the rest 8-10 h later (at

insulin peak)4. Have sugar supply handy

Insulinoma

• CAUSE: tumor of beta cells, secreting an excess of insulin• SIGNS: prolonged hypoglycemia→weakness, ataxia, muscle

fasciculations, posterior paresis, brain damage, seizures, coma, death,

Insulinoma: Dx• Chem Panel

– ↓blood glucose– Simultaneous glucose and insulin tests

Low glucose, High insulin => insulinoma

• Observations– Symptoms occur after fasting or exercise– when symptomatic, blood glucose<50 mg/dl– symptoms corrected with sugar administration

Insulinoma: RxSurgical Rx: removal of tumorMedical Rx: Acute, at home: administer glucose (Karo); keep animal quiet, seek vet careAcute, in Hosp adm. glucose (50% Dextrose)Chronic care feed 3-6 small meals/day (high protein, low fat)

limited exerciseglucocorticooid therapy (antagonizes insulin effect at cellular level)Diazoxide (↓insulin secretion, tissue use of glucose, ↑blood glucose)Octreotide (Sandostatin) injections—inhibits synthesis and release of insulin by both normal and neoplastic beta cells

Insulinoma: Client info• 1. Usually, by the time insulinoma is diagnosed, metastasis has occurred

so prognosis is poor• 2. With proper medical therapy, survival may be 12-24 mo• 3. Always limit exercise and excitement• 4. Feed multiple, small meals throughout day; keep sugar source close

during exercise• 5. Karo syrup on mm provides for rapid absorption of glucose into

blood stream• 6. Avoid placing hand into dog’s mouth during seizure to avoid being

bitten

Exocrine Pancreas Insufficiency (EPI)

• Inability to process nutrients efficiently due to lack of production of enzymes from pancreas.– Pancreatic acinar atrophy

• Found most commonly in German Shepherds and Rough Collies through a recessive gene.– In cats, EPI is primarily the result of chronic

pancreatitis

Diagnosis of EPI

• Not usually evident until 85-90% of pancreas is unable to secrete enzymes.– Weight loss although no change in diet or appetite

(appetite often increases)– Persistent tarry diarrhea.– Flatulence– Poor haircoat

Testing and treatment for EPI• TLI (trypsin-like immunoreactivity)

– Detects trypsin and trypsinogen– Usually want below 2.5 in dogs to be diagnostic

• Canine 5.7-45.2• Feline 12-82

• Treatment includes enzymatic supplement– Viokase powder– Raw ox or pig pancreas

Client considerations

• Usually life long treatment.• Can be very expensive.• Can be well controlled. • Should not breed animal that has EPI.

LIFE“Smooth seas do not make skillful

sailors.”-African proverb

DISEASES OF THE ADRENAL GLANDS

CUSHING’S DISEASE(Hyperadrenocorticism)

ADDISON’S DISEASE(Hypoadrenocorticism)

Adrenal Glands

ADRENAL GLANDS

mineralocorticoids

Glucocorticoids

Androgens

epinephrine

Hyperadrenocorticism (Cushings Disease)

• Definition: Disorder caused by deleterious effects of high circulating cortisol concentrations on multiple organ systems

• Systems affected:– Renal– Skin– Cardiovascular– Respiratory– Endocrine/metabolic– Musculoskeletal– Nervous– Reproductive

Cushing’s Disease

Effects of excess glucocorticoids:1. suppress inflammation2. suppress immune system3. inhibit cartilage growth, development,

and repairCauses: 1. Anterior pituitary lesion (pituitary-dependent disease) – 85% of

cases2. Adrenal tumor (excess cortisol secretion independent of pituitary

control) – 15-20% of cases3. Overmedication with glucocorticoids - Iatrogenic

Cushing’s Disease

Cushing’s Disease

Bilaterally symmetrical alopecia, pot-belly, pyoderma

Cushing’s Disease

Pot belliedPU/PDMuscle wastingThin coat

Cushing’s Disease• signs are slow to develop and usually go unnoticed by owner

Clinical Signs:1. Some are similar to hypothyroidism2. Dog >6 yr old (most are female)3. PU/PD/PP4. Pot bellied; obese5. Muscle atrophy and weakness, lethargy, excess

panting6. Bilateral symmetric alopecia; pruritis; pyoderma (↓

immune response)7. Calcinosis cutis (firm plaques of Ca++ under skin)8. Abnormal gonadal function (lack of estrus; soft,

small testicles)

Cushing’s Disease: Calcinosis cutis

Commonly seen on the dorsal midline, ventral abdomen and inguinal region. Skin is usually thin and atrophic

Cushing’s Disease: DxChemistry Panel1. ↑ ALP, ALT, cholesterol, blood glucose2. ↓ BUN3. Lipemia4. Low USG < 1.015, proteinuria, hematuria, pyuria, bactiuria

Urine cortisol/creatinine ratios (sample collected at home)1. Normal ratio=no Cushing’s2. Elevated ratio=may be Cushing’s

ACTH Stimulation test1. Normal patients show an increase of plasma cortisol2. Pituitary dependent disease (excess ACTH release) and Adrenal tumors: 60-

85% show EXAGGERATED cortisol response3. Does not differentiate between Pit disease and Adrenal tumor

ACTH Stimulation for Hyperadrenocorticism

• Take a pre blood sample.• Inject ACTH stimulation gel or liquid

– Verify amounts with lab as there is difference between amount to be injected with gel and liquid.

• Wait two hours and take a post sample

Cushing’s Disease: DxLow-Dose Dexamethasone Suppression Test1. Inject low dose of steroid (should suppress ant. pit [ACTH])2. Measure plasma cortisol at 0, 4, 8 h

Interpretation:1. Normal dogs will show decrease in plasma cortisol2. Pituitary tumor and adrenal tumor will not show any effect at 8 h

(cortisol will still be high)

Cushing’s Disease: Dx

High-Dose Dexamethasone Suppression Test (used to differentiate between Pit Dis and Adrenal tumor)

1. Dosing: 0.1 mg/kg IV2. Collect plasma cortisol at 0, 4, and 8 h

Interpretation:1. Pituitary dependent disease—70-75% will show decrease at 4 or

8 h2. Adrenal tumor—no change in plasma cortisol level (tumor is

autonomous)

Cushing’s Disease: RxSurgical removal—1. FAT - Specialized surgery; most vets would refer surgery2. Pituitary tumors are not surgically removed

Medical treatment1. Lysodren (o,p,DDD)—necrosis of z fasiculata (middle), z reticularis

(deep)-repeat ACTH stimulation q 7-10 d until cortisol normal-like chemotherapy-excess dose affects z glomerulus (Addison’s Dis)

Cushing’s Disease: Rx

2. trilostane (Vetoryl®)—less side-effects than o,p,DDD-interfers with cortisol production (doesn’t kill cells)-FDA approved

Cushing’s Disease: Client info• Serious disease; life-long treatment• Periodic monitoring required• Addison’s disease may result• Prognosis: average life expectancy is 20-

30 mo on therapy with frequent recurrence of clinical symptoms – varies with cause (pit vs adrenal, tumors)

HARD TIMES“In the depths of winter, I finally

learned that within me there lay an invincible summer.”

-Albert Camus

Addison’s Disease (Hypoadrenocorticism)

• Definition: Disorder caused by deficient production of glucocorticoids (cortisol) or mineralocorticoids (aldosterone) or both

• Secondary disease caused by chronic administration of corticosteroids

Addison’s Disease (Hypoadrenocorticism)

• Not as common as Cushing’s Disease; rarely seen in cats• Deficiency of Glucocorticoids and Mineralocordicoids• Clinical signs due to Mineralocorticoid (Aldosterone) deficiency

Clinical Signs:1. lethargy, weakness, anorexia, wt loss2. Vomiting/Diarrhea3. PU/PD, dehydration4. Bradycardia

Addison’s Disease

• Pathophysiology– Decreased aldosterone => Increased K and

decreased Na– => decreased volume => azotemia,

hypotension, dehydration, weakness, depression

– Hyper K => heart (bradycardia)– Glucocorticoid deficiency => vomiting,

diarrhea, melena, lethargy, wt loss, hypoglycemia (less common than expected)

Addison’s Disease: Dx

Chem PanelNa:K ratio <25:1 !!!(normal=27:1 to 40:1)↑ BUN, Creatinine, Ca++ ↓ blood glucose, albumin (less common

ACTH Stimulation test (definitive test)normal dog= ↑ cortisolhypoadrenocorticism dog= low, unchanged cortisol level

Endogenous ACTH will be increased (1º hypoadrenocorticism; lack of neg feedback)

What is your Dx?

Chem Panel (What is not normal?)

Parameter Value Normal valueBUN 81 mg/dl 7-27 mg/dlCreatinine 2.1 mg/dl 0.4-1.8 mg/dlSodium 131 meq/L 141-156 meq/LPotassium 6.5 meq/L 4.0-5.6 meq/LNa:K ratio 20 27-40

What is your Dx?

ACTH Stimulation Test ResultsValue Normal

Plasma CortisolPre-ACTH 0.2 2-6

Post-ACTH 0.3 6-18

Addison’s Disease: RxAcute Crisis (may be life-threatening situation)1. Normal saline IV (low Na+ is hallmark finding of Addison’s)2. Glucorticoid replacement(cortisol will also be low)

a. Dexamethasone or Prednisone (IV or IM)3. Mineralocorcorticoid replacement

a. Florinef® (fludrocortisone acetate)—po b. Percortin-V (desoxycorticosterone pivalate) injection

Chronic Management1. Glucocorticoid replacement

a. Prednisone b. Prenisolone

2. Mineralocorcorticoid replacementa. Florinef® (fludrocortisone acetate)—po daily (not cheap; 50¢/tab)b. Percortin-V (desoxycorticosterone pivalate)—inj ~monthly (expensive)

3. Monitor electrolytes, BUN/Creatinine, clinical signs

Addison’s disease: Client info1. Mineralocorticoid deficiency is life-threatening2. Animal requires periodic blood tests3. Glucocorticoids needed in times of stress4. Always remind attending vet of pet’s condition5. Hormone replacement therapy continued for life of

pet6. Prognosis: Good to excellent after stabilization and

treatment