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

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

Adrenal Glands

ADRENAL GLANDS mineralocorticoids Glucocorticoids Androgens Epinephrine Norepinephrine

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

Hormone Functions Regulates electrolyte and H2O balance Hypoadrenocorticism/ _______________________ Primarily Dogs ________________________________________ Mineralocorticoids – __________________________ Promote__________________________________ Suppress inflammation Suppress immune system Inhibit cartilage growth and development Hyperadrenocorticism / __________________________ Glucocorticoids

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

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 -________________

Cushing’s Disease

Cushing’s Disease ____________________________, 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) ___________________ (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 ↑ _________, _______________, _________________, _______________ ↓ 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

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

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)

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

Cushing’s Disease: Rx _____________________ removal— Medical treatment 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 (_____________________)

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 _________________ production of glucocorticoids (cortisol) or mineralocorticoids (aldosterone) or both Secondary disease caused by chronic administration of _______________________

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 _________________________________________

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)

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)

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 _____________ 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 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