Diseases of the exocrine pancreas Exocrine Pancreatic Insufficiency

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.

DISEASES OF THE ADRENAL GLANDS CUSHING’S DISEASE (Hyperadrenocorticism) ADDISON’S DISEASE (Hypoadrenocorticism)

Adrenal Glands

ADRENAL GLANDS mineralocorticoids Glucocorticoids Androgens epinephrine

Physiology Hypothalamus – Corticotropin realeasing factor (CRF) >>> Anterior Pituitary Gland – Adrenocorticotropic hormone (ACTH) >>> ADRENAL CORTEX Glucocorticoid hormone Mineralocorticoid hormone Sex hormones (Androgens) SNS >>> ADRENAL MEDULLA >>> Epinehrine and norepinephrine Increase HR, Inc. BP, Dilated air passages – lungs, dec. GI function, vasoconstriction

Hormone Functions Mineralocorticoids – Aldosterone Regulates electrolyte and H2O balance Hypoadrenocorticism/ Addison’s Primarily Dogs Life threatening Glucocorticoids Promote gluconeogenesis Suppress inflammation Suppress immune system Inhibit cartilage growth and development Hyperadrenocorticism / Cushing’s

Hyperadrenocorticism (Cushing’s 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: suppress inflammation suppress immune system inhibit cartilage growth, development, and repair Causes: Anterior pituitary lesion (pituitary-dependent disease) – 85% of cases Adrenal tumor (excess cortisol secretion independent of pituitary control) – 15-20% of cases Overmedication with glucocorticoids - Iatrogenic

Cushing’s Disease

Cushing’s Disease Bilaterally symmetrical alopecia, pot-belly, pyoderma

Cushing’s Disease Pot bellied PU/PD Muscle wasting Thin coat

Cushing’s Disease Clinical Signs: Some are similar to hypothyroidism signs are slow to develop and usually go unnoticed by owner Clinical Signs: Some are similar to hypothyroidism Dog >6 yr old (most are female) PU/PD/PP Pot bellied; obese Muscle atrophy and weakness, lethargy, excess panting Bilateral symmetric alopecia; pruritis; pyoderma (↓ immune response) Calcinosis cutis (firm plaques of Ca++ under skin) 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: Dx Chemistry Panel ↑ ALP, ALT, cholesterol, blood glucose ↓ BUN Lipemia Low USG < 1.015, proteinuria, hematuria, pyuria, bactiuria Urine cortisol/creatinine ratios (sample collected at home) Normal ratio=no Cushing’s Elevated ratio=may be Cushing’s ACTH Stimulation test Normal patients show an increase of plasma cortisol Pituitary dependent disease (excess ACTH release) and Adrenal tumors: 60-85% show EXAGGERATED cortisol response 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: Dx Low-Dose Dexamethasone Suppression Test Inject low dose of steroid (should suppress ant. pit [ACTH]) Measure plasma cortisol at 0, 4, 8 h Interpretation: Normal dogs will show decrease in plasma cortisol 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) Dosing: 0.1 mg/kg IV Collect plasma cortisol at 0, 4, and 8 h Interpretation: Pituitary dependent disease—70-75% will show decrease at 4 or 8 h Adrenal tumor—no change in plasma cortisol level (tumor is autonomous)

Cushing’s Disease: Rx Surgical removal— Medical treatment FAT - Specialized surgery; most vets would refer surgery Pituitary tumors are not surgically removed Medical treatment 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)

Hyperadrenocortism

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: lethargy, weakness, anorexia, wt loss Vomiting/Diarrhea PU/PD, dehydration 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 Panel Na: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= ↑ cortisol hypoadrenocorticism 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 value BUN 81 mg/dl 7-27 mg/dl Creatinine 2.1 mg/dl 0.4-1.8 mg/dl Sodium 131 meq/L 141-156 meq/L Potassium 6.5 meq/L 4.0-5.6 meq/L Na:K ratio 20 27-40

What is your Dx? ACTH Stimulation Test Results Value Normal Plasma Cortisol Pre-ACTH 0.2 2-6 Post-ACTH 0.3 6-18

Addison’s Disease: Rx Acute Crisis (may be life-threatening situation) Normal saline IV (low Na+ is hallmark finding of Addison’s) Glucorticoid replacement(cortisol will also be low) Dexamethasone or Prednisone (IV or IM) Mineralocorcorticoid replacement Florinef® (fludrocortisone acetate)—po Percortin-V (desoxycorticosterone pivalate) injection Chronic Management Glucocorticoid replacement Prednisone Prenisolone Florinef® (fludrocortisone acetate)—po daily (not cheap; 50¢/tab) Percortin-V (desoxycorticosterone pivalate)—inj ~monthly (expensive) Monitor electrolytes, BUN/Creatinine, clinical signs

Addison’s disease: Client info Mineralocorticoid deficiency is life-threatening Animal requires periodic blood tests Glucocorticoids needed in times of stress Always remind attending vet of pet’s condition Hormone replacement therapy continued for life of pet Prognosis: Good to excellent after stabilization and treatment

Hypoadrenocorticism Addison’s in crisis

References Alleice Summers, Common Diseases of Companion Animals http://www.aahanet.org/PublicDocuments/AAHADiabetesGuidelines.pdf http://www.vetmed.wsu.edu/cliented/diabetes.aspx http://www.sciencedirect.com/science/article/pii/S0378427408001732