Dana HardiskyRoss University

May 7, 2014Basic Science Advisor: Dr. John

RandolphClinical Advisor: Dr. Pedro Bento

o 6 year old female spayed Swiss Mountain Dog

o Mildly overconditioned (BCS 6 / 9)o Remaining physical examination

unremarkable

• 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

Parameter Value Reference Range

Hematocrit 38% 41 - 58 %

WBC 12.4 thou/uL 5.7 - 14.2 thou/uL

Seg Neutrophils 7.7 thou/uL 2.7 – 9.4 thou/uL

Lymphocytes 3.1 thou/uL 0.9 – 4.7 thou/uL

Eosinophils 1.2 thou/uL 0.1 – 2.1 thou/uL

Platelet Count 281 thou/uL 186 – 545 thou/uL

Parameter Value Reference Range

Sodium 146 mEq/L 142 – 150 mEq/L

Potassium 6.1 mEq/L 3.8 – 5.4 mEq/L

Chloride 110 mEq/L 105 – 116 mEq/L

BUN 30 mg/dL 10 – 32 mg/dL

Creatinine 1.6 mg/dL 0.6 – 1.4 mg/dL

Calcium 10.7 mg/dL 9.3 – 11.4 mg/dL

Cholesterol 99 mg/dL 138 – 332 mg/dL

Sodium Potassium Ratio = 24:1 Baseline Cortisol < 0.2 ug/dL (ref: 1.8 - 4 ug/dL)

Hyperkalemia DDx: Gastrointestinal disease, Renal disease,

Urinary obstruction, Acidosis, Hypoadrenocorticism

HypocholesterolemiaDDx: 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

Hyperkalemia DDx: Gastrointestinal disease, Renal disease,

Urinary obstruction, Acidosis, Hypoadrenocorticism

HypocholesterolemiaDDx: 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

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

Definitive Diagnosis – ACTH Stimulation Test: subnormal cortisol concentrations before and after administration of ACTH

Hyperkalemia, hyponatremia, Na:K< 27:1 orSubnormal aldosterone concentrations

Increased endogenous ACTH concentration

“The Great Pretender”Clinical Signs

o Anorexia, Lethargyo Vomiting, Diarrhea

Laboratory Findingso Hyperkalemia, hyponatremia,

hypochloremiao Azotemiao Non-regenerative anemiao Reverse stress leukogramo Hypercalcemiao Hypocholesterolemia

85% to 90% of adrenocortical tissue destroyed

Adrenal Cortex consists of: Zona Glomerulosa – secretes mineralocorticoids

Zona Fasciculata – secretes glucocorticoidsZona Reticularis – secretes sex hormones

Leads to deficiencies in mineralocorticoids and glucocorticoids •Mineralocorticoids (Aldosterone)

1) Body Water Homeostasis2) Enhances Sodium Reabsorption3) Enhances Potassium Secretion

•Glucocorticoids (Cortisol)1) Counteracts Stress2) Maintains Blood Pressure &

Water Balance 3) Gluconeogenesis & Lipolysis 4) Stabilizes Membranes &

Endothelium

•Immune-mediated mechanisms suspected •Other Rare Causes

Infiltrative Fungal Disease – Histoplasma, Blastomyces, Coccidioides, Cryptococcus

InfectionsNeoplasiaAmyloidosisTraumaCoagulopathy

•Autoimmune Polyglandular Syndrome Up to 5% Addisonian dogs have

concurrent endocrine-deficiency conditions

• Young to Middle Age Females • Breed Predilection

o Standard Poodleso Portuguese Water Dogso Nova Scotia Duck Tolling Retrievero Great Daneso West Highland White Terriers

www.bigskypoodles.comwww.aboutnovascotiaducktollingretriever.blogspot.com

Lifelong TherapyMineralocorticoid 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 ORFludrocortisone - 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

Current Therapy Protocol 44.7 kg dog

DOCP (1.1 mg/kg SC every 25 days) = $87.58Prednisone = $4.35 / monthTotal cost = $91. 93 /month

ORFludrocortisone (0.02 mg/kg/day ≈ 0.9 mg/day) 0.1 mg tab = $1.19 $10.71 /day or $321.30 /month

Consultations Fees: $ 286

Diagnostic Testing: $ 397.84

Medications: $ 525.94

Grand Total: $ 1,209.78

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.

Thank YouDr. RandolphDr. BentoFriends & Family