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Basics

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BASICS

Overview!!navigator!!

  • Synonymous with hypoadrenocorticism and “adrenal exhaustion”
  • Characterized by glucocorticoid (i.e. cortisol) and/or mineralocorticoid (i.e. aldosterone) deficiency caused by adrenal cortex destruction (primary AI), ACTH deficiency (secondary AI), or suppression of the HPA axis by exogenous steroid or ACTH administration
  • May be permanent, complete AI (“Addison disease,” rare), or transient, “relative” AI secondary to concurrent critical illness (RAI/CIRCI)

Systems Affected

  • Endocrine
  • Cardiovascular
  • Renal
  • Musculoskeletal
  • Gastrointestinal
  • Behavioral
  • Immune

Signalment!!navigator!!

Any age, sex, and breed. RAI/CIRCI is most common in neonatal foals, especially premature foals.

Signs!!navigator!!

  • Acute RAI/CIRCI—signs of septic shock, including fever or hypothermia, hyperemic mucous membranes, weakness, hypotension, hemoconcentration, cardiovascular collapse, and death
  • Chronic cases—depression, anorexia, weight loss, poor hair coat, exercise intolerance, polyuria/polydipsia, mild abdominal pain, salt craving, and diarrhea

Causes and Risk Factors!!navigator!!

  • Chronic administration of glucocorticoids, exogenous ACTH, or anabolic steroids
  • HPA axis immaturity attributable to prematurity in neonatal foals
  • HPA axis suppression and/or adrenal hemorrhage and necrosis subsequent to systemic inflammatory response or sepsis/septic shock

Diagnosis

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DIAGNOSIS

Differential Diagnosis!!navigator!!

Renal failure, colitis, primary cardiovascular disease.

CBC/Biochemistry/Urinalysis!!navigator!!

  • Acute RAI/CIRCI—hemoconcentration, leukopenia (neutropenia), and hypoglycemia. If mineralocorticoid secretion is also affected, hyponatremia, hypochloremia, hyperkalemia, and decreased sodium–potassium ratio (reference range >27) may be seen, but this is uncommon
  • Chronic cases—mineralocorticoid secretion is generally maintained, so serum electrolytes are usually within normal limits

Other Laboratory Tests!!navigator!!

  • Measure baseline plasma ACTH and cortisol concentrations. AI should be considered in ill or stressed animals with ACTH and cortisol concentrations below reference intervals, though this is not a sensitive test for AI
  • ACTH stimulation testing—administer synthetic ACTH (1 μg/kg IV or IM, 100 μg IV for a neonatal foal). Measure serum cortisol before and 90–120 min after ACTH. An increase <2–4-fold is consistent with AI
  • With insufficient aldosterone secretion, fractional excretion of sodium (reference range <1%) is increased despite a normal or low serum sodium concentration

Imaging!!navigator!!

N/A

Other Diagnostic Procedures!!navigator!!

N/A

Treatment

TREATMENT

  • Complete rest and avoidance of stress, particularly surgery, infection, and trauma
  • Fluid, dextrose, and electrolyte support
  • Treat the underlying primary cause
  • If mineralocorticoid insufficiency, provide sodium supplementation (e.g. salt) and avoid potassium supplementation

Medications

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MEDICATIONS

Drug(s) of Choice!!navigator!!

  • Glucocorticoid and, if necessary, mineralocorticoid replacement at physiologic doses equivalent to daily corticosteroid production rates
  • For acute RAI/CIRCI in foals, low-dose hydrocortisone (1.3 mg/kg/day IV divided every 4–6 h) is recommended. This dose may also be effective in adult horses with RAI/CIRCI and acute AI, though it has not been well studied to date
  • Avoid long-term or high-dose steroid supplementation as this can prolong HPA axis suppression. In acute RAI/CIRCI, a tapering course of hydrocortisone over 3–7 days is recommended
  • For longer term therapy in adult horses with chronic AI, the maintenance dose of prednisolone is approximately 25 mg/day. However, exposure to stress dramatically increases corticosteroid requirements. During periods of stress, increase the dose by 2–10-fold and divide into 2 or 3 daily doses
  • Mineralocorticoid replacement with fludrocortisone may be considered

Contraindications/Possible Interactions!!navigator!!

N/A

Follow-up

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FOLLOW-UP

Patient Monitoring!!navigator!!

  • Monitor electrolytes, renal function, acid–base balance, blood glucose, and blood pressure
  • Once the animal is stable, HPA axis recovery can be documented by repeating ACTH stimulation test

Prevention/Avoidance!!navigator!!

Avoid excessive use of exogenous glucocorticoids, ACTH, and anabolic steroids.

Possible Complications!!navigator!!

Excessive glucocorticoid administration, especially with long-acting forms (e.g. triamcinolone), increases susceptibility to infections and may induce insulin dysregulation, which could increase the risk of laminitis.

Expected Course and Prognosis!!navigator!!

N/A

Miscellaneous

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MISCELLANEOUS

Associated Conditions!!navigator!!

N/A

Age-Related Factors!!navigator!!

N/A

Zoonotic Potential!!navigator!!

N/A

Pregnancy/Fertility/Breeding!!navigator!!

N/A

Abbreviations!!navigator!!

  • AI = adrenal insufficiency
  • ACTH = adrenocorticotropin hormone
  • CIRCI = critical illness-related corticosteroid insufficiency
  • HPA = hypothalamic–pituitary–adrenal
  • RAI = relative adrenal insufficiency

Suggested Reading

Hart KA. Adrenal glands. In: Smith BP, ed. Large Animal Internal Medicine, 5e. St. Louis, MO: Elsevier Mosby, 2015:12281233.

Author(s)

Author: Kelsey A. Hart

Consulting Editor: Michel Lévy and Heidi Banse

Acknowledgment: The author and editors acknowledge the prior contribution of Laurent Couëtil.