Hypoadrenocorticism (Addison's disease)

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• Apparently uncommon but probably underdiagnosed.
• Cause : insufficient mineralocorticoid and glucocorticoid production.
• Signs : vomiting/diarrhea, muscle tremor, weakness, lethargy, collapse.
• Diagnosis : electrocardiography, biochemistry, hormone assay.
• Treatment : hormonal supplementation (mineralocorticoids and glucocorticoids).
• Prognosis : excellent once controlled.

Print out owner factsheet on Addison's disease (hypoadrenocortisicism)  to give to your client.

• Vomiting (may be intermittent over period of months of acute crisis).
• Lethargy.
• Depression.

• Diarrhea (may be hemorrhagic).
• Anorexia.

• Weight loss.
• Weakness/collapse.

• Circulatory collapse, protracted vomiting.

• Young to middle-aged (mean 5 years).

• Female (male:female ratio 1:2).

• Standard Poodle - possibly hereditary .
• Bearded Collie - possibly hereditary .

• Rottweilers .
• West Highland White Terriers .

Pathogenesis

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• Impaired adrenal cortical function.
• Usually idiopathic.
• May be auto-immune.
• Other possible causes:
  • Necrosis.
  • Hemorrhage.
  • Tumor.
  • Amyloidosis.

• Iatrogenic: bilateral excision.
• Mitotane treatment  hypoadrenocorticism.

• Withdrawal of high-level, prolonged corticosteroid treatment (glucocorticoid insufficiency).

• Reduced ability to conserve sodium and chloride and excrete potassium.
• If sodium loss increased, eg vomiting/diarrhea or intake reduced, eg anorexia  depletion total body salt stores  volume depletion.
• Reduced renal perfusion  increased hyperkalemia  reduced myocardial excitability.

• Reduced glucogenesis + fat metabolism may  hypoglycemia.
• In 1° adrenal insufficiency  increased ACTH secretion from pituitary  impaired tolerance to stress.

• Cases of Addison's disease without typical electrolyte changes are increasingly being reported.
• Diagnosis in these cases is particularly difficult and clinical signs include lethargy, severe gastrointestinal disease (often hemorrhage) and megaesophagus.
• In many cases signs associated with hypocortisolemia are apparent initially and with time electrolyte abnormalities develop.
• However, in some cases animals have been monitored for several years with no development of electrolyte abnormalities.

• May have insidious onset over months to years with waxing and waning illness.
• Often present in acute crisis with circulatory collapse.

Diagnosis

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• Vomiting/diarrhea.
• Weakness/intermittent collapse .

• Collapse.

• Lethargy/depression.
• Anorexia, intermittent vomiting and diarrhea (may be hemorrhagic).
• Weight loss.
• Weakness (usually episodic).
• Waxing and waning illness (43%).
• Shaking/muscle tremor (24%).
• Polyuria (24%).
• Hematemesis.
• Abdominal pain.

• Rapidly progressive, life-threatening:
  • Hypovolemia.
  • Bradycardia.
  • Collapse.
  • Shock.

Chronic

• Weakness.
• Hypothermia.
• Dehydration.
• Bradycardia, weak femoral pulse.
• Restlessness/shaking/shivering.
• Abdominal pain, gastrointestinal hemorrhage.

• Hemoconcentration in crisis (increased PCV, increased [plasma protein]).
• Chronic form: non-regenerative anemia  (which may be masked by hemoconcentration).
• Severe anemia if gastrointestinal hemorrhage.
• Occasionally lymphocytosis and eosinophilia .
  Lack of stress leukogram may  suspicion of hypoadrenocorticism in sick animal.

• Decreased [sodium] (81%)  : <135 mmol/l.
• Increased [potassium] (96%) .
• Na:K ratio <27:1.
• Decreased chloride .
  Serum electrolytes may be normal if dog evaluated when clinical signs minimal.
• Increased [urea]; normal excretory index (prerenal failure).
• Mild to moderate acidosis.
• Increased [calcium] .
• Hypoglycemia .

• SG: less than 1.030 (due to impaired concentrating mechanism) in presence of azotemia.
• Raised liver enzymes (30%) and mild hyperbilirubinemia (20%).

• See also thoracic radiography .
• Microcardia: due to dehydration and hypovolemia.
• Esophageal dilation: due to severe muscle weakness.

• See also ECG .
• Impaired conduction [potassium].
• Guidelines:
  • 5.5 mmol/l - peaking of the T wave, shortening of the Q-T interval.
  • 6.5 mmol/l - increased QRS duration.
  • 7.0 mmol/l - P wave amplitude decreased, P-R interval prolonged.
  • 8.0 mmol/l - P wave absent, severe bradycardia.

Other

• ACTH stimulation test (definitive) .
• Plasma [cortisol] low initially and no response to ACTH.
• Aldosterone release can also be measured via ACTH stimulation test .
• Normal cortisol concentrations:
  • Pre-ACTH 50-200 nmol/l.
  • Post-ACTH 200-500 nmol/l.

• ACTH assay .
  Endogenous ACTH concentrations are high because no negative feedback from cortisol occurs.

Aldosterone to renin (ARR) or cortisol to ACTH ratio (CAR)

• One study has shown that these ratios can be used for diagnosis of hypoadrenocorticism.
• Calculation of the ratios eliminates the overlap that occurs between [cortisol] and [ACTH] in healthy and hypoadrenocorticoid dogs.
• CAR normal 1.1-2.6 (hypoadrenocorticoid dogs 0.003-0.17).
• ARR normal 0.1-1.5 (hypoadrenocorticoid dogs 0.002-0.08).
  Special care is needed in collecting sample for ACTH assay and aldosterone and renin assays can only be performed in highly specialized laboratories.

• Clinical signs.
• Laboratory results.

• ACTH stimulation test.

• Artifactual hyperkalemia; Akita  may have high [potassium] in RBCs, hemolysis of sample.

• Gastrointestinal disease.
• Chronic blood loss.
• Acute renal failure .
• Repeated drainage of chylous and non-chylous pleural effusions .
• Lymphangiosarcoma.
• Whipworms.

Treatment

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• Rapid infusion of 0.9% saline (60 ml/kg/h) for 2 hours and then reduce infusion rate.
• Intravenous glucocorticoids:
  • Hydrocortisone sodium succinate (5 mg/kg TID) .
  • Prednisolone sodium succinate (5 mg/kg) .
  • Dexamethasone sodium phosphate (0.5-1 mg/kg)  then 0.05-0.1 mg/kg q2-6h BID until oral glucocorticoids can be given.
    Perform ACTH stimulation test before administering glucocorticoids (except dexamethasone)
• Intravenous glucose (with saline) if hypoglycemic.
• Continue IV fluids until electrolytes stabilized and animal eating again.

Chronic
Either Fludrocortisone acetate (0.1-0.5 mg/animal/day PO) .
Or Desoxycorticosterone pivalate   (mineralocorticoid) IM/SC (2.2 mg/kg q25-30 days). Also requires glucocorticoid replacement .

• Table salt added to food daily: 0.5 teaspoon until sodium levels restored to normal.
• Prednisolone: (0.1-0.2 mg/kg daily) initially at times of stress .
• Water ad lib.

• Usually show rapid response to therapy (within 1-2 hours).
• ECG: changes resolving.
• [Sodium] and [potassium] concentrations: normalizing.
• Uremia resolving.
  Rehydration may unmask severe anemia.

• Lifelong therapy.
• Regular monitoring of Na:K ratio.
• Increased dose of glucocorticoid during periods of stress.

Sequelae

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• Excellent once adrenal crisis is controlled.

• Initial therapy and monitoring not sufficiently aggressive.
• Not supplying glucocorticoid replacement  with mineralocorticoid therapy .
• Owner not realizing importance of:
  • Lifelong therapy.
  • Regular monitoring.
  • Need to increase glucocorticoid dose during stress.

Sources

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• Recent references from PubMed.
• Javadi S, Galac S, Boer P, Robben J H, Teske E & Kooistra H S (2006) Aldosterone-to-renin and cortisol-to-adrenocorticotropic hormone ratios in healthy dogs and dogs with primary hypoadrenocorticism. J Vet Intern Med 20 , 556-561 PubMed.
• Schaer M, Halling K B, Collins K E & Grant D C (2001) Combined hyponatremia and hyperkalemia mimicking acute hypoadrenocorticism in three pregnant dogs. JAVMA 218 , 897-900 PubMed.
• Syme H M & Scott-Moncrieff J C (1998) Chronic hypoglycemia in a hunting dog due to secondary hypoadrenocorticism. JSAP 39 , 348-351.
• Kintzer P P & Peterson M E (1997) Treatment and longterm follow-up of 205 dogs with hypoadrenocorticism. JVIM 111 , 43-49.
• Lifton S J, King L G & Zerbe C A (1996) Glucocorticoid deficient hypoadrenocorticism in dogs - 18 cases (1986-1995). JAVMA 12 , 2076-2081.
• Peterson M E, Kintzer P P & Kass P H (1996) Pretreatment clinical and laboratory findings in dogs with hypoadrenocorticism - 225 cases (1979-1993). JAVMA 208 , 85-91.
• Sadek D S & Schaer M (1996) Atypical Addison's disease in the dog - a retrospective survey of 14 cases. JAAHA 32 , 159-163.
• Schaer M & Chen C L (1983) A clinical survey of 48 dogs with adrenocortical hypofunction. JAAHA 19 , 443-452.

• Feldman E C & Nelson R W (1996) In: Canine and Feline Endocrinology and Reproduction.Philadelphia: W B Saunders.
• Herrtage M E (1990) The adrenal glands. In: Manual of Small Animal Endocrinology.Cheltenham: British Small Animal Veterinary Association.
• Feldman E C & Peterson M E (1984) Hypoadrenocorticism. Vet Clin N Am 14 , pp 751.

• Dr David Bruyette DVM DipACVIM , VCA West Los Angeles, 1818 South Sepulveda Boulevard, Los Angeles, CA 90025, USA.

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