9/8/2016

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Addison’s Disease

Stanley I. Rubin, DVM, MSDiplomate ACVIMClinical Professor

Department of Veterinary Clinical Medicine

Disclosures

• Consulting, AVL Laboratories, St. Louis, MO

Ringo

• Signalment: 2 ½ year old, MC, Gt Dane• History:

– Listlessness– Decreased appetite– Wt loss (10 lbs)– Diarrhea X24 hrs– Pu/PD

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Physical Examination

• BCS 4/9, Wt 110 lbs (50 kg)• Vital signs: HR 132, RR 24, Temp

101.7• Otherwise NAF

Ringo – Differential Diagnoses

Pu/Pd

• Kidney dz• Hyperadrenocorticism• DM/DKA• Pyometra• Hypercalemia• Liver dz• Hypoadrenocorticism• Hypokalemia• Drugs• Psychogenic

Diarrhea• Primary GI

– Dietary indiscretion/toxins

– Infectious– Obstruction/FB/Intusscep

tion– Acute pancreatitis– IBD– Neoplasia

• Secondary GI/Systemic– Uremia– Hypoadrenocorticism– Hypercalcemia– Liver dz

Ringo – Diagnostic Plan

• CBC• Serum biochemistry• Urine analysis

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Ringo

• Laboratory– Na+ 135mEq/L (141-152)– K+ 5.4 mEq/L (3.9-5.5)– Chloride 105 mEq/L (107-118)– BUN 32 mg/dl (6 – 30)– Creatinine 1.4 mg/dl (0.5-1.5)– Cholesterol 101 mg/dl (129-297)– Glucose 69 mg/dl (68-126)

Ringo• Laboratory

– WBC 13.8 (5.5 – 16.9)– Neutrophils 6.9 (3 – 11.5)– Lymphocytes 5.7 (1 - 4.8)– Hematocrit 56.8 (35 – 52)

Most Significant Abnormalities

• Hyponatremia/Hypochloremia• Abnormal Na/K ratio (25:1)• Mild azotemia/Non-concentrated urine• Non-stress leukogram• Hemoconcentration

• Next steps?

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Ringo – Next Steps

• Resting cortisol < 27.6 nmol/L• Cortisol (1 hr post ACTH) < 27.6 nmol/L

Ringo• Diagnosis: Hypoadrenocorticism• Rx:

– DOCP 110 mg– Prednisone 12.5 mg/day (0.25

mg/kg/day)

• Recheck – Wk 4– Doing well at home, appetite is normal– Gained 3.6 kg

Beau

• Signalment: 8 month, MC, Labradoodle

• History:– Presented to ER on

day 1– 5-day history of

anorexia– Vomiting– Rx: IV fluids,

ondansetron, doxycycline

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Beau

• History:– Declined after discharge– Represented to ER on day 5– Vomited that day

Physical Examination

• QAR• BCS 3/9, Wt 42 lbs (19.2 kg)• Vital signs: HR 120, RR 40, Temp

100.1• Otherwise NAF

Beau

• Laboratory (Nova ®)– Na+ 131mEq/L (144-151)– K+ 6.7 mEq/L (3.7-4.9)– Chloride 105 mEq/L (107-118)– BUN 25 mg/dl (9 – 24)– Creatinine 1.4 mg/dl (0.7-1.2)– Calcium, ionized 1.48 (1.17-1.37)

• Received IV fluids

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Beau• Laboratory

– WBC 20.28 (5.5 – 16.9)– Neutrophils 14.95 (3 – 11.5)– Lymphocytes 3.94 (1 - 4.8)– Hematocrit 52.9 (35 – 52)

Beau

Hypoadrenocorticism

• Failure of adrenal glands to secrete normal quantities of corticosteroids to support normal homeostasis

• Big reserve > 85% of mass must be lost before c/s• Most common is primary adrenal failure dt

deficiency of both glucocorticoids and mineralocorticoids

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Normal Function

• Adrenal medulla – catecholamines• Adrenal cortex – mineralocorticoids,

androgens and cortisol• Synthesis and secretion of cortisol –

hypothalamic pituitary axis• CRF from hypothalamus stimulates secretion of

ACTH from pituitary• ACTH stimulates secretion of cortisol• Cortisol has negative feedback on CRF and

ACTH release

Normal Function

• Aldosterone secretion regulated by renin-angiotensin axis, plasma [K+]

• Increased plasma K+ and angiotensin II stimulate aldo release from adrenal

• Glucocorticoids– Stimulate hepatic gluconeogenesis and

glycogenolysis– Important in maintaining vascular reactivity to

catecholamines– Maintain normal BP– Counteract effects of stress

Normal Function• Mineralocorticoids

– Increase absorption of Na+ and secretion of K+ from the kidney, sweat glands, salivary glands and intestinal epithelial cells

– Conserve Na+ and maintain vascular volume

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Etiopathogenesis

• Most dogs classified as idiopathic• Immune-mediated adrenalitis• May be concurrent with other endocrine

disorders such as hypothyroidism, dm and hypoparathyroidism

• Unusual causes– Granulomatous destruction– Hemorrhagic infarction– Necrosis– Metastatic neoplasia

• Lysodren, trilostane

Signalment

• 70% of affected dogs are female• Median age of onset for all breeds – 4

years (4 months to 14 yrs)• Inherited in Standard Poodle, Portuguese

Water Dog, Nova Scotia Duck Tolling Retriever, Bearded Collie

• Increased risk in many breeds, eg. Great Dane

Most Commonly Diagnosed Breeds

• Mixed 24%• Toy or miniature poodle 10%• Labrador retriever 9%• Rottweiler 9%• Standard poodle 8%• German Shepherd dog 6%• Doberman Pinscher 4%• Golden Retriever 4%• West Highland White Terrier 4%• Great Dane 3%

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• 30-40% of dog population insured in Sweden• 534 dogs diagnosed with Addison's• 64% female• Breeds at highest risk: Standard poodle,

Bearded Collie, Portuguese Water Dog, Cairn Terrier and Cocker Spaniel

• Decreased risk in German Shepherd Dog and Dachshund

• Female dogs 1.85 X greater risk than males

History• Acute illness• Gradual in onset, waxing/waning c/s• Illness may be triggered by stressful event• Vague signs

– Anorexia, vomiting/diarrhea, lethargy, weakness, wt loss

– Pu/Pd– Abdominal pain– Dehydration, hypovolemic shock,

collapse

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History• Vague signs

– Less common: seizures, episodic muscle cramping, GI hemorrhage

• Many owners unaware of what constitutes a “normal” pet

• Some dogs have been ill much of their lives

• Periods of good health often followed by nonspecific veterinary care

Physical Findings

• Often vague/nonspecific• Poor body condition• Lethargy, weakness,

hypothermia, • Weak pulses, prolonged CRT,

signs of shock

Laboratory Findings

• Classic findings– Hyponatremia/hyperkalemia– Non-regenerative anemia– Lymphocytosis

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Hematologic Abnormalities• Non-regenerative anemia; may be masked

by hemoconcentration• Eosinophilia; normal eosinophil count in

stressed or ill dog• Lymphocytosis; normal or increased

counts in ill or stressed dog• Above changes only seen in 10-30% of

dogs• Absence of stress leukogram – 90% of

cases• Upside down CBC

Serum Chemistry

• Hyperkalemia• Hyponatremia• Mild metabolic acidosis• Azotemia with USG < 1.030 (60% of

dogs)• Hypercalcemia• Hypoglycemia• Hypoalbuminemia

Na+/K+ Ratio

• A “red flag”• A tool for gaining suspicion of dogs

with adrenal insufficiency• Normal > 27:1• Values < 27:1 consistent with

primary hypoadrenocorticism

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Abnormal Na +/K+ Ratio

• Intestinal parasitism; trichuris/ancylostoma

• Perforated duodenal ulcers• Salmonellosis• Diabetes mellitus• Pleural effusion• Artifact: Akita, hemolysis, marked

leukocytosis, thrombocytosis

Imaging

• Microcardia• Small cranial lobar pulmonary artery• Narrow caudal vena cava• Microhepatica• Megaesophagus• Adrenal glands small or cannot be id’d

Endocrine Studies

• Basal/resting cortisol – Some normal dogs will have low

baseline cortisol yet have normal response to ACTH

– [cortisol] < 55 nmol/L (2 µg/dL) are suggestive of but not diagnostic for hypoadrenocorticism

– A baseline [cortisol] > 55 nmol/L (2 µg/dL) does not support diagnosis of hypoadrenocorticism

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Endocrine Studies

• ACTH stimulation test– Gold Standard– Need to confirm diagnosis – life long treatment– Baseline and 1 hr post ACTH– Most dogs – resting & post-ACTH < 1 ug/dl

(

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Maintenance Therapy

• Glucocorticoid replacement– DOCP lacks glucocorticoid activity– Physiologic dose of prednisone (0.1 –

0.25 mg/kg)– Gradually taper to lowest dose that

prevents signs of hypoadrenocorticism– May only need EOD

Maintenance Therapy

• Glucocorticoid replacement– Avoid excess supplementation– 50% of dogs given fludrocortisone

require glucocorticoid therapy– > 90% of dogs given DOCP require

glucocorticoid therapy– Owner should have prednisone to give

to dog in time of stress , 0.25 – 0.5 mg/kg twice a day

DOCP

• Desoxycorticosterone pivalate

• Only FDA approved drug• Some consider it treatment

of choice• 2.2 mg/kg every 25 days• Interval may be increased

to every 30 days or longer

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DOCP

• Recheck at 12 & 25 days after first 2 or 3 DOCP injections

• Increase dose if dog has hyponatremia or hyperkalemia

• Shorten interval if day 12 profile is normal but abnormal at day 25

Fludrocortisone

• Florinef® and generics• 0.02 mg/kg PO once daily

or divided• Initially reassess

electrolyte every 1 – 2 wks• Goal is to reestablish

normal Na+ and K+ concentrations

• Some report that dose requirement increases over time

Fludrocortisone

• Wide range in doses required to control electrolyte concentrations

• Dog may develop Pu/Pd and urinary incontinence

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Recheck Visits

• Some recommend weekly after first start fludrocortisone

• Some recommend every 12 and 25 days with DOCP

• Expectation is that dog feels “well”• Consider amount of glucocorticoid

supplementation

Aypical Hypoadrenocorticism

• Signs of glucocorticoid deficiency• Serum electrolytes normal• Deficiency could adrenocortical

(Most common) or pituitary (impaired secretion of ACTH)

• May be early sign of failure and mineralocorticoid deficiency wks or months later

Aypical Hypoadrenocorticism

• Diagnosis– Vague GI c/s: lethargy, anorexia, vomiting,

diarrhea, wt loss– Normal routine blood tests– Abnormal ACTH stimulation test– Need to periodically check electrolytes

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Questions?

• References available on request