LIFE

1. LIFE “Smooth seas do not make skillful sailors.” -African proverb

2. DISEASES OF THE ADRENAL GLANDS CUSHING’S DISEASE (__________________________) ADDISON’S DISEASE (__________________________)

3. Adrenal Glands

4. ADRENAL GLANDS mineralocorticoids Glucocorticoids Androgens Epinephrine Norepinephrine

5. Physiology • Hypothalamus – Corticotropin realeasing factor (CRF) >>> ____________________________________________________________________(ACTH) • >>> ADRENAL CORTEX • _________________ hormone • __________________ hormone • ___________________ (Androgens) • SNS >>> ADRENAL MEDULLA >>> _____________ and ____________________ • Increase HR, Inc. BP, Dilated air passages – lungs, dec. GI function, vasoconstriction

6. Hormone Functions

7. Hyperadrenocorticism (Cushings Disease) • Definition: Disorder caused by deleterious effects of ________________________ circulating cortisol concentrations on multiple organ systems • Systems affected: Pansystemic disease • Renal • Skin • Cardiovascular • Respiratory • Endocrine/metabolic • Musculoskeletal • Nervous • Reproductive

8. Cushing’s Disease Effects of excess glucocorticoids: • ____________________ inflammation • ____________________ immune system • ___________________ cartilage growth, development, and repair Causes: • ___________________________ (pituitary-dependent disease) – 85% of cases • ____________________________ (excess cortisol secretion independent of pituitary control) – 15-20% of cases • Overmedication with glucocorticoids -________________

9. Cushing’s Disease

10. Cushing’s Disease ____________________________, pot-belly, pyoderma

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

12. Cushing’s Disease • 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) • ___________________ (firm plaques of Ca++ under skin) • Abnormal gonadal function (lack of estrus; soft, small testicles)

13. Cushing’s Disease: Calcinosis cutis Commonly seen on the dorsal midline, ventral abdomen and inguinal region. Skin is usually thin and atrophic

14. Cushing’s Disease: Dx Chemistry Panel • ↑ _________, _______________, _________________, _______________ • ↓ BUN • Lipemia • ________________ USG < 1.015, proteinuria, hematuria, pyuria, bactiuria Urine cortisol/creatinine ratios (sample collected at home) • Normal ratio=no Cushing’s • Elevated ratio= __________ 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 ____________________________ cortisol response • Does _______________________ differentiate between Pit disease and Adrenal tumor

15. 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

16. 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 ________________ in plasma cortisol • Pituitary tumor and adrenal tumor will not show any effect at 8 h (cortisol will still be __________________)

17. Cushing’s Disease: Dx High-Dose Dexamethasone Suppression Test (used to ______________________ 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 __________________ at 4 or 8 h • Adrenal tumor—__________________ change in plasma cortisol level (tumor is autonomous)

18. Cushing’s Disease ACTH stimulation: Exaggerated response Low dose dex Normal: reduce Pit/Adr tumor: high High dose dex Pit: Decrease 4, 8 hrs Adrenal: No change

19. Cushing’s Disease: Rx _____________________ removal— • 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 (_____________________)

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

21. 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)

22. HARD TIMES “In the depths of winter, I finally learned that within me there lay an invincible summer.” -Albert Camus

23. Addison’s Disease (Hypoadrenocorticism) • Definition: Disorder caused by _________________ production of glucocorticoids (cortisol) or mineralocorticoids (aldosterone) or both • Secondary disease caused by chronic administration of _______________________

24. 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 (____________________) deficiency Clinical Signs: • lethargy, weakness, anorexia, wt loss • Vomiting/Diarrhea • PU/PD, dehydration • _________________________________________

25. Addison’s Disease • Pathophysiology • Decreased aldosterone => Increased ____ and decreased _________________ • => decreased volume =>_______________, hypotension, dehydration, weakness, depression • Hyper K => heart (____________________) • Glucocorticoid deficiency => vomiting, diarrhea, melena, lethargy, wt loss, hypoglycemia (less common than expected)

26. Addison’s Disease: Dx Chem Panel Na:K ratio <___________________ !!!(normal=27:1 to 40:1) ↑ BUN, Creatinine, Ca++ ↓ blood glucose, albumin (less common) ACTH Stimulation test (________________________ test) normal dog= ↑ cortisol hypoadrenocorticism dog= _______________ , unchanged cortisol level Endogenous ACTH will be increased (1º hypoadrenocorticism; lack of neg feedback)

27. 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

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

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

30. 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