Canine hypoadrenocorticism, also known as Addison’s disease, results from inadequate production of adrenal hormones. An Addisonian crisis is a life-threatening complication requiring aggressive treatment.
Immune-mediated destruction of the adrenal cortex remains the most common cause of primary hypoadrenocorticism in dogs. A small number of dogs suffer from iatrogenic primary Addison’s disease. Secondary hypoadrenocorticism occurs when the pituitary fails to secrete ACTH, so these patients are deficient only in cortisol. Iatrogenic secondary hypoadrenocorticism can result from administration of exogenous glucocorticoids. Glucocorticoids should be tapered and never withdrawn abruptly for this reason.
As the name suggests, the mineralocorticoids regulate the mineral balance, or in other words, electrolyte regulation. Specifically, aldosterone is integral in the handling of sodium, chloride and water resorption, as well as potassium excretion. Clinical signs of mineralocorticoid deficiency consequently are polyuria/polydipsia, hypovolemia, cardiac arrhythmia, bradycardia, dehydration, mental depression, nausea, hypotension, and weakness.
Glucocorticoids are essential for times of stress and survival in a starvation situation. Specifically, cortisol promotes gluconeogenesis and glycogenolysis, and antagonizes insulin’s glucose lowering effect (increases insulin resistance). Clinical signs of glucocorticoid deficiency include weight loss, lethargy, vomiting, diarrhea, impaired mentation, anorexia, weakness, and trembling.
Understanding the Consequences of Deficiency
Aldosterone is responsible for the retention of Na and water, as well as the excretion of K. The lack of aldosterone will interfere with this system and total body stores of Na become depleted quickly, resulting in massive total body water loss and an accumulation of dangerous levels of potassium.
Serum chloride levels often parallel sodium loss and hypochloremia is commonly found as well. The loss of extracellular fluid compromises cardiac output leading to decreased renal perfusion. Prerenal azotemia ensues with inappropriately dilute urine.
Aldosterone also enhances the renal excretion of hydrogen ions (H+). A buildup of hydrogen will lower the blood pH, leading to a metabolic acidosis. Hypoperfusion will contribute to a build-up of lactic acid as lactate is a product of anaerobic metabolism, further contributing to the acidosis. Severe metabolic acidosis can have deleterious effects on cardiovascular system, hepatic, and renal functioning, making it a major threat to survival. The loss of bicarbonate (HCO3-) through small bowel diarrhea can also contribute to the development of metabolic acidosis.
The pituitary secretes corticotropin-releasing hormone (CRH) which stimulates the release of ACTH. In response, the adrenals release cortisol. Cortisol is one of the most important substances, aside from ATP and oxygen, that maintain physiologic homeostasis. Cortisol has multiple effects on vascular integrity and stimulates erythropoiesis. This can manifest as “lack of a stress leukogram”, with eosinophilia, hypocholesterolemia, and hypoglycemia.
The dog with chronic Addison’s will commonly have waxing and waning gastrointestinal symptoms with a history of anorexia and periodic lethargy. They may present with any number of physical signs from bright and healthful looking, to obtunded and flat. In contrast, dogs presenting in an acute Addisonian crisis are far more evidently ill. Presentations are associated with hypovolemic shock.
Addisonian patients generally will have a deficiency of both mineralocorticoids and glucocorticoids. A subset of dogs that are considered “atypical” and exhibit only signs associated with glucocorticoid deficiency because they can maintain normal electrolyte balance.
A low sodium: potassium ratio of less than 27:1 is the hallmark of this disease, however there is only one definitive diagnostic test for Addison’s disease. Testing involves measuring the serum cortisol level before, and one hour after a synthetic adrenocorticotropic hormone (ACTH) (Cosyntropin, Cortrosyn) injection. The introduction of ACTH should stimulate a cortisol release in a dog with functioning adrenal glands. An inadequate adrenal response will result in a post injection cortisol level that has not deviated far from the baseline level.
Exogenous glucocorticoids will mimic the physiologic response and are contraindicated prior to testing except for dexamethasone, which will not cross-react with the test. If your clinic is unable to perform an ACTH stimulation test and your patient would benefit from the use of steroids, dexamethasone would be ideal for this reason as it would not delay treatment.
Treating The Addisonian Crisis
Survival of a patient in crisis depends on a quick diagnosis, expedient treatment, and the ability to respond to the effects of electrolyte derangements. Aimed at the careful correction of the hypovolemia and hypotension, emergency stabilization involves restoring adequate circulating volume and tissue perfusion. Additionally, correction of the metabolic acidosis will begin almost immediately as fluid therapy is initiated through dilution and diuresis.
Hyponatremia results in hypo-osmolality of plasma which will induce a shift of water from the extracellular space to the intracellular space. In severe cases, this can lead to cell swelling and lysis. In the central nervous system (CNS) this can mean cerebral edema. The severity of signs, as well as the rate of correction is determined by the onset of the derangement. Patients with acute development of hyponatremia should be treated with intravenous administration of balanced electrolyte solution, such as normal saline. Profound or chronic hyponatremia has the potential to be markedly more detrimental, though these patients may have no signs because the CNS has been compensating as the brain’s tonicity slowly dropped. Too rapid elevation of sodium can result in cerebral myelinolysis, a condition that causes damage to areas of the brain due to the way the cells adapt to prevent brain swelling. Therefore, increases should be no faster than 0.5mEq/L/hr. This may be achieved using a 0.45% saline solution. Failure to allow sufficient time for the brain to respond can put the brain at risk for osmotic demyelination, a syndrome characterized by sudden deterioration, days after therapy.
Hyperkalemia warrants immediate electrocardiogram evaluation because of potassium’s effect on the cardiac myocyte. Increased plasma K concentrations will affect myocardial excitability and in severe cases, the myocyte becomes unable to depolarize and bradycardia develops. This will ultimately slow conduction and result in fatal cardiac arrhythmias. Mild hyperkalemia causes increased positive or negatively deflected T wave amplitude (peaked T waves) while moderate hyperkalemia causes bradycardia and a flattening of the P wave, also known as atrial standstill. Severe hyperkalemia is associated with prolongation of the PR interval and bradycardia.
Hyperphosphatemia is common in these patients as phosphate ions shift similarly to potassium. As with most electrolyte derangements, resolution is generally achieved through correction of the underlying cause, in this case, hypoperfusion, decreased glomerular filtration rate and metabolic acidosis.
With the help of glucocorticoid replacement and mineralocorticoid supplementation for the duration of their lives, these patients can return to health and lead a full life.
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- Spence, S., Gunn, E. and Ramsey, I. (2018), Diagnosis and treatment of canine hypoadrenocorticism. In Practice, 40: 281-290.
- Camilo, C.P., Cardoso, M.J.L., De Marchi, P.N., Ricci, F.G. and Romeiro, M.S. (2020) Canine Hypoadrenocorticism: A Bibliographic Review. Open Journal of Veterinary Medicine, 10, 164-172.