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

Adrenal Glands

ADRENAL GLANDS mineralocorticoids Glucocorticoids Androgens epinephrine

Physiology Anterior Pituitary Gland releases Adrenocorticotropic hormone (ACTH) ACTH acts on the ADRENAL CORTEX Glucocorticoid hormone Mineralocorticoid hormone Sex hormones (Androgens) Sympathetic Nervous System stimulates the Adrenal medulla > Epinephrine and norepinephrine FIGHT OR FLIGHT RESPONSE ACTIVATED Increase HR, Inc. BP, Dilated air passages, dec. GI function, vasoconstriction

Hormone Functions *** Regulates electrolyte and H2O balance Associated with Hypoadrenocorticism/ Addison’s Primarily dogs A decrease is life threatening Mineralocorticoids – Aldosterone Promote gluconeogenesis Suppress inflammation Suppress immune system Inhibit cartilage growth and development Associated with Hyperadrenocorticism / Cushing’s Glucocorticoids

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 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 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 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: Dx Chemistry Panel Urinalysis ↑ ALP, ALT, blood glucose Urinalysis Low USG < 1.015 due to PU/PD Urine cortisol/creatinine ratios Normal ratio=no Cushing’s Elevated ratio=may be Cushing’s (high levels of cortisol in the urine)

ACTH Stimulation for Hyperadrenocorticism 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 Pituitary tumor and Adrenal tumor ACTH Stimulation Test Procedure Take a baseline blood sample to detect cortisol levels Inject ACTH stimulation gel or liquid Wait two hours and take a post sample to look for a rise in cortisol

Cushing’s Disease: Dx Low-Dose Dexamethasone Suppression Test Draw a blood sample to determine baseline cortisol levels Inject low dose of steroid (goal is to suppress ant. pit [ACTH]) Measure plasma cortisol at 4 & 8 hr later Interpretation: Normal dogs will show decrease in plasma cortisol A Cushingoid animal will not show any decrease of cortisol at 8 hr

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Cushing’s Disease: Dx High-Dose Dexamethasone Suppression Test (used to differentiate between Pit Dis and Adrenal tumor) Collect plasma cortisol at 0, 4, and 8 h Interpretation: Pituitary dependent disease—70-75% will show decrease of cortisol at 4 or 8 h Adrenal tumor—no decrease in plasma cortisol level because tumor is autonomous

Cushing’s Disease: Rx Surgical removal Medical treatment Adrenal tumor - Specialized surgery; most vets would refer surgery Pituitary tumors are not surgically removed Medical treatment Lysodren (mitotane)—necrosis of zona fasiculata, zona reticularis repeat ACTH stimulation q 7-10 d until cortisol normal excess dose affects zona glomerulosa (Addison’s Dis)

Cushing’s Disease: Rx Medical management Vetoryl®(trilostane): less side-effects than mitotane interferes with cortisol production (doesn’t kill cells)

Cushing’s Disease: Client info Serious disease; life-long treatment Periodic monitoring required Addison’s disease may result from treatment Prognosis: average life expectancy is 20-30 mo on therapy with frequent recurrence of clinical symptoms

Addison’s Disease (Hypoadrenocorticism) Definition: Disorder caused by deficient production of glucocorticoids (cortisol) or mineralocorticoids (aldosterone) or both Iatrogenic disease caused by chronic administration of corticosteroids followed by sudden cessation

Addison’s Disease (Hypoadrenocorticism) Clinical Signs: lethargy, weakness, anorexia, wt. loss Vomiting/Diarrhea PU/PD, dehydration Bradycardia

Addison’s Disease Pathophysiology Decreased aldosterone => decreased retention of Na=> decreased blood volume =>hypotension, dehydration, azotemia Hyperkalemia affects the heart => bradycardia Glucocorticoid deficiency => vomiting, diarrhea, melena, lethargy, wt. loss, hypoglycemia

Addison’s Disease: Dx Chemistry Panel Na:K ratio <25:1!(normal=27:1 to 40:1) ACTH Stimulation test (definitive test) normal dog= ↑ cortisol hypoadrenocorticism dog= low, unchanged cortisol level Test Endogenous ACTH - will be increased due to lack of neg. feedback

Addison’s Disease Example 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

Addison’s Disease 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 Glucocorticoid replacement cortisol will also be low Dexamethasone or Prednisone IV or IM Mineralocorcorticoid replacement Florinef® (fludrocortisone acetate) - PO Percortin-V (desoxycorticosterone pivalate) injection

Addison’s disease: Rx Chronic Management Glucocorticoid replacement Prednisone Mineralocorcorticoid replacement Florinef® (fludrocortisone acetate) - PO daily Percortin-V (desoxycorticosterone pivalate) – inj. given ~monthly Monitor electrolytes, BUN/Creatinine, clinical signs

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

References Alleice Summers, Common Diseases of Companion Animals http://www.aahanet.org/PublicDocuments/AAHADiabetesGui delines.pdf http://www.vetmed.wsu.edu/cliented/diabetes.aspx http://www.sciencedirect.com/science/article/pii/S037842740 8001732