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

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: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

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)

signs are slow to develop and usually go unnoticed by owner

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: Dx

Low-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)

• 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: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 replacementa. 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 info

1. 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

• 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