LIFE Smooth seas do not make skillful sailors

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 • __________ (Androgens) • SNS >>> ADRENAL MEDULLA >>> _______ and __________ – Increase HR, Inc. BP, Dilated air passages – lungs, dec. GI function, vasoconstriction

Hormone Functions Mineralocorticoids – _____________ • Regulates electrolyte and H 2 O balance • Hypoadrenocorticism/ ____________ • Primarily Dogs • ____________________ Glucocorticoids • Promote_________________ • Suppress inflammation • Suppress immune system • Inhibit cartilage growth and development • Hyperadrenocorticism / _____________

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: 1. 2. 3. __________ inflammation __________ immune system __________ cartilage growth, development, and repair Causes: 1. 2. 3. ______________ (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 • signs are slow to develop and usually go unnoticed by owner Clinical Signs: 1. Some are similar to hypothyroidism 2. Dog >6 yr old (most are female) 3. PU/PD/PP 4. Pot bellied; obese 5. Muscle atrophy and weakness, lethargy, excess panting 6. Bilateral symmetric alopecia; pruritis; pyoderma (↓ immune response) 7. __________ (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: Dx Chemistry Panel 1. 2. 3. 4. ↑ _________, ____________, ________ ↓ BUN Lipemia ________ USG < 1. 015, proteinuria, hematuria, pyuria, bactiuria Urine cortisol/creatinine ratios (sample collected at home) 1. 2. Normal ratio=no Cushing’s Elevated ratio= _____ be Cushing’s ACTH Stimulation test 1. 2. 3. Normal patients show an increase of plasma cortisol Pituitary dependent disease (excess ACTH release) and Adrenal tumors: 6085% 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 1. 2. Inject low dose of steroid (should suppress ant. pit [ACTH]) Measure plasma cortisol at 0, 4, 8 h Interpretation: 1. 2. 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) 1. 2. Dosing: 0. 1 mg/kg IV Collect plasma cortisol at 0, 4, and 8 h Interpretation: 1. 2. 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— 1. 2. Specialized surgery; most vets would refer surgery Pituitary tumors are not surgically removed Medical treatment 1. 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 2030 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: 1. 2. 3. 4. 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 Parameter BUN Creatinine Sodium Potassium Na: K ratio (What is not normal? ) Value 81 mg/dl 2. 1 mg/dl 131 meq/L 6. 5 meq/L 20 Normal value 7 -27 mg/dl 0. 4 -1. 8 mg/dl 141 -156 meq/L 4. 0 -5. 6 meq/L 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) 1. 2. Normal saline IV (low _______ is hallmark finding of Addison’s) Glucorticoid replacement(cortisol will also be low) a. 3. Dexamethasone or Prednisone (IV or IM) Mineralocorcorticoid replacement a. b. __________ (fludrocortisone acetate)—po ___________-V (desoxycorticosterone pivalate) injection Chronic Management 1. Glucocorticoid replacement a. b. 2. Mineralocorcorticoid replacement a. b. 3. 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 1. 2. 3. 4. 5. 6. 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