Hypoadrenocorticism can be classified as either primary or secondary.​​

The primary form of the condition, otherwise known as Addison’s disease, occurs as a result of destruction of the adrenocortical tissue itself. In most cases, this destruction appears to be immune mediated in origin. Rarer causes of destruction of the adrenal cortex include drug therapy with mitotane or trilostane, creating disease purposefully in order to treat another condition (i.e. by performing a bilateral adrenalectomy) and infectious / infiltrative disease.​​

Secondary hypoadrenocorticism occurs due to suppression of stimulatory hormone. Therefore, there is a deficiency in glucocorticoid due to a lack of production of ACTH. This can occur naturally, after surgery or can occur due to abrupt cessation of pharmaceuticals with glucocorticoid action.  More uncommonly, there can be state of secondary mineralocorticoid deficiency due to a lack of renin. ​

The adrenal gland itself is split into a cortex and a medulla. The cortex compromises approximately 75% of the adrenal gland itself and more specifically is split into three regions: the innermost is the zona reticularis; next is the zona fasciculata; and the outer region is termed the zona glomerulosa (Figure 1). It is these three zones that are responsible for producing a range of steroid hormones. ​

Figure 1- Diagram showing the architecture of the adrenal gland

Aldosterone is the principle mineralocorticoid hormone and is produced by the zona glomerulosa. Its release is, in part, regulated by both the renin-angiotensin system (Figure 2) and its major function is to control blood volumes by the regulation of body electrolytes. Dogs with a deficiency in aldosterone have low sodium and/or increased potassium levels alongside low blood volume. Clinically, this can manifest as dehydration, gastrointestinal signs, bradycardia and muscle weakness. 

Cortisol is the main glucocorticoid hormone secreted by the zona reticularis and fasciculata. Its release is under the control of ACTH secreted from the anterior pituitary, which in turn is controlled by CRH release from the hypothalamus (Figure 2). ​​​

Cortisol can be thought of as the hormone which protects the body against the long term effects of stress. Clinically, a deficiency in cortisol leads to weight loss, lack of appetite, anaemia and low blood sugar levels.

Figure 2 - Diagram depicting the regulation of Aldosterone and Cortisol

Although almost any dog, from a puppy to a geriatric patient, has the potential to be diagnosed with hAC, clues can be gained by assessment of signalment.

Primary hypoadrenocorticism is commonly diagnosed in younger to middle aged dogs and bitches appear more commonly affected by males. Breed is also thought to play a role, specific predispositions include:

• Standard Poodles
• Bearded Collies
• Nova Scotia Duck Tolling Retrievers
• Portuguese Water Spaniels
• Leonbergers
• Great Danes
• West Highland White Terriers
• Rottweilers
• Wheaten Terriers

Analysis into the mode of heritability of hAC appears to point to a genetic predilection in many of these breeds.

Dogs with hAC may present with a non-specific history of vague clinical signs which respond well to non-specific treatment

In particular, a clinician’s index of suspicion should be raised if a patient has responded very positively to intra-venous fluid therapy. However, due to the lack of specificity of clinical signs, hypoadrenocorticism can be easily confused with other, more common, diseases. This has led to hAC being given the colloquial nickname of ‘The Great Pretender’. Diseases which may present in a similar way to hAC include acute renal failure, acute pancreatitis, infectious enteritis and hepatitis to name a few (Table 2). ​ ​