1. Dana Hardisky Ross University May 7, 2014 Basic Science Advisor: Dr. John Randolph Clinical Advisor: Dr. Pedro Bento

2. o 6 year old female spayed Swiss Mountain Dog o Mildly overconditioned (BCS 6 / 9) o Remaining physical examination unremarkable

3. December 11, 2012 - CUHA Emergency Vomiting, Diarrhea, and Poor Appetite January 15, 2013 – CUHA CPS Poor Appetite and Hematochezia Baseline T4 consistent with HYPOTHYROIDISM January 31, 2014 – CUHA CPS Lethargy and Poor Appetite Complete Blood Count, Serum Biochemistry Profile Baseline Cortisol Concentration February 07, 2014 – CUHA SAIM Further evaluation of dog including laboratory abnormalities

4. ParameterValueReference Range Hematocrit38%41 - 58 % WBC12.4 thou/uL5.7 - 14.2 thou/uL Seg Neutrophils7.7 thou/uL2.7 – 9.4 thou/uL Lymphocytes3.1 thou/uL0.9 – 4.7 thou/uL Eosinophils1.2 thou/uL0.1 – 2.1 thou/uL Platelet Count281 thou/uL186 – 545 thou/uL

5. ParameterValueReference Range Sodium146 mEq/L142 – 150 mEq/L Potassium6.1 mEq/L3.8 – 5.4 mEq/L Chloride110 mEq/L105 – 116 mEq/L BUN30 mg/dL10 – 32 mg/dL Creatinine1.6 mg/dL0.6 – 1.4 mg/dL Calcium10.7 mg/dL9.3 – 11.4 mg/dL Cholesterol99 mg/dL138 – 332 mg/dL Sodium Potassium Ratio = 24:1 Baseline Cortisol < 0.2 ug/dL (ref: 1.8 - 4 ug/dL)

6. Hyperkalemia DDx: Gastrointestinal disease, Renal disease, Urinary obstruction, Acidosis, Hypoadrenocorticism Hypocholesterolemia DDx: Gastrointestinal disease, Hypoadrenocorticism, Liver disease Waxing and Waning Gastrointestinal Signs DDx: Dietary indiscretion, Gastrointestinal Disease, Pancreatitis, Liver disease, Hypoadrenocorticism Lethargy DDx: Endless ……. Low Baseline Cortisol DDx: Hypoadrenocorticism, Normal variation

7. Hyperkalemia DDx: Gastrointestinal disease, Renal disease, Urinary obstruction, Acidosis, Hypoadrenocorticism Hypocholesterolemia DDx: Gastrointestinal disease, Hypoadrenocorticism, Liver disease Waxing and Waning Gastrointestinal Signs DDx: Dietary indiscretion, Gastrointestinal Disease, Pancreatitis, Liver disease, Hypoadrenocorticism Lethargy DDx: Endless ……. Low Baseline Cortisol DDx: Hypoadrenocorticism, Normal variation

8. Electrolyte Panel Hyperkalemia 5.6 mEq/L (ref: 3.8 – 5.4 mEq/L) ACTH Stimulation Test Cortisol pre–ACTH < 0.2 ug/dL (ref: 1.8 – 4 ug/dL) Cortisol post–ACTH < 0.2 ug/dL (ref: 6 – 16 ug/dL) Endogenous ACTH Concentration ACTH 322 pg/mL (ref: 0 – 25 pg/mL) Definitive Diagnosis: Addison’s Disease

9. Definitive Diagnosis – ACTH Stimulation Test: subnormal cortisol concentrations before and after administration of ACTH Hyperkalemia, hyponatremia, Na:K< 27:1 or Subnormal aldosterone concentrations Increased endogenous ACTH concentration

10. “The Great Pretender” Clinical Signs o Anorexia, Lethargy o Vomiting, Diarrhea Laboratory Findings o Hyperkalemia, hyponatremia, hypochloremia o Azotemia o Non-regenerative anemia o Reverse stress leukogram o Hypercalcemia o Hypocholesterolemia

11. 85% to 90% of adrenocortical tissue destroyed Adrenal Cortex consists of: Zona Glomerulosa – secretes mineralocorticoids Zona Fasciculata – secretes glucocorticoids Zona Reticularis – secretes sex hormones

12. Leads to deficiencies in mineralocorticoids and glucocorticoids Mineralocorticoids (Aldosterone) 1) Body Water Homeostasis 2) Enhances Sodium Reabsorption 3) Enhances Potassium Secretion Glucocorticoids (Cortisol) 1) Counteracts Stress 2) Maintains Blood Pressure & Water Balance 3) Gluconeogenesis & Lipolysis 4) Stabilizes Membranes & Endothelium

13. Immune-mediated mechanisms suspected Other Rare Causes Infiltrative Fungal Disease – Histoplasma, Blastomyces, Coccidioides, Cryptococcus Infections Neoplasia Amyloidosis Trauma Coagulopathy Autoimmune Polyglandular Syndrome Up to 5% Addisonian dogs have concurrent endocrine-deficiency conditions

14. Young to Middle Age Females Breed Predilection o Standard Poodles o Portuguese Water Dogs o Nova Scotia Duck Tolling Retriever o Great Danes o West Highland White Terriers www.bigskypoodles.com www.aboutnovascotiaducktollingretriever.blogspot.com

15. Lifelong Therapy Mineralocorticoid Replacement Therapy Desoxycorticosterone pivalate (DOCP) 1-2.2 mg/kg IM or SC every 25 days – adjust dose based on electrolyte concentrations at 12 & 25 days OR Fludrocortisone - starting dose 0.02 mg/kg/day PO (also contains glucocorticoid) Glucocorticoid Replacement Therapy Prednisone 0.1-0.2 mg/kg/day PO animalendocrine.blogspot.com

16. Current Therapy Protocol 44.7 kg dog DOCP (1.1 mg/kg SC every 25 days) = $87.58 Prednisone = $4.35 / month Total cost = $91. 93 /month OR Fludrocortisone (0.02 mg/kg/day ≈ 0.9 mg/day) 0.1 mg tab = $1.19 $10.71 /day or $321.30 /month

17. Consultations Fees: $ 286 Diagnostic Testing: $ 397.84 Medications: $ 525.94 Grand Total: $ 1,209.78

18. Baumstark ME, Sieber-Ruckstuhl NS, Muller M, et al. Evaluation of aldosterone concentrations in dogs with hypoadrenocorticism. J Vet Intern Med 2014;28:154-159. DiBartola, SP. “Fluid Therapy in Endocrine and Metabolic Disorders.” In: Fluid, Electrolyte, and Acid – Base Disorders in Small Animal Practice. St Louis: Elsevier Saunders, 2012; 500- 511. Feldman, E and Nelson R. “Hypoadrenocorticism.” In: Canine and Feline Endocrinology and Reproduction. St. Louis: Elsevier Saunders, 2004; 394-438. Kintzer PP, Peterson ME. Treatment and long-term follow up of 205 dogs with hypoadrenocorticism. J Vet Intern Med 1997; 11: 43-49. Klein SC, Peterson ME. Canine hypoadrenocorticism: Part I. Can Vet J 2010;51:63-69. Klein SC, Peterson ME. Canine hypoadrenocorticism: Part II. Can Vet J 2010;51:179-184. McGonigle KM, Randolph JF, Center SA, et al. Mineralocorticoid before glucocorticoid deficiency in a dog with primary hypoadrenocorticism and hypothyroidism. J Am Anim Hosp Assoc 2013;49:54-57. Mitchell AL, Pearce SH. Autoimmune Addison disease : pathophysiology and genetic complexity. Nat Rev Endocrinol 2012;8:306-316. Oberbauer AM, Bell JS, Belanger JM, et al. Genetic evaluation of Addison's disease in the Portuguese Water dog. BMC Vet Res 2006;2:15-22. Short AD, Boag A, Catchpole B, et al. A candidate gene analysis of canine hypoadrenocortisciem in 3 dog breeds. J Hereditary 2013;104: 807-820.

19. Thank You Dr. Randolph Dr. Bento Friends & Family