Addison's, Conn's & Cushing's: Understanding Adrenal Disorders in Pets

Two small glands sitting just in front of your pet's kidneys quietly run an enormous share of their day-to-day biology—blood pressure, salt balance, stress response, and metabolism. When those glands make too little hormone, too much of one hormone, or too much of another, three very different diseases can result: Addison's disease, Conn's syndrome, and Cushing's disease. Despite living in the same small organ, they could hardly behave more differently.

This article walks through what each condition actually does inside the body, who tends to get it, how we catch it, and — because this is usually the question owners care about most — what recovery realistically looks like.

Figure 1. The adrenal cortex is arranged in concentric layers, each dedicated to a different hormone: the outer zona glomerulosa makes aldosterone, the middle zona fasciculata makes cortisol, and the inner zona reticularis makes sex-steroid precursors, while the central medulla makes adrenaline. Disease in any one layer produces a distinct clinical picture (Bugbee et al., 2023).

The adrenal cortex is governed by two separate feedback loops, and almost everything about these three diseases falls out of which loop is disrupted and in which direction.

The first is the hypothalamic–pituitary–adrenal (HPA) axis: the hypothalamus releases corticotropin-releasing hormone (CRH), which tells the pituitary gland to release adrenocorticotropic hormone (ACTH), which in turn tells the adrenal cortex’s zona fasciculata to release cortisol. Rising cortisol then signals back to the hypothalamus and pituitary to switch the whole cascade off—a classic negative feedback loop (Bugbee et al., 2023). Cushing’s disease is what happens when this loop gets stuck in the “on” position.

The second is the renin–angiotensin–aldosterone system (RAAS), which runs independently of the brain. A drop in blood pressure or blood volume triggers the kidney to release renin, which converts liver-derived angiotensinogen into angiotensin I; angiotensin-converting enzyme (ACE) then converts this to angiotensin II, which stimulates the adrenal cortex’s zona glomerulosa to release aldosterone (Djajadiningrat-Laanen et al., 2011). Aldosterone tells the kidney to retain sodium and excrete potassium, which restores blood volume and pressure. Conn’s syndrome is this loop running out of control, independent of the kidney’s actual needs.

Addison’s disease is different again: it is a loss of adrenal cortical tissue itself, usually through immune-mediated destruction, so both loops lose their downstream organ, and cortisol and aldosterone fall together (Klein & Peterson, 2010a).

Notice the electrolyte pattern: Addison’s and Conn’s sit at almost opposite ends of the same sodium–potassium axis, while Cushing’s tends to leave electrolytes closer to normal because cortisol has only weak mineralocorticoid activity of its own (AAHA/Bugbee et al., 2023). The figure below makes that mirror-image relationship visible.

Addison’s disease has earned the nickname “the great pretender” because its early signs—intermittent vomiting, poor appetite, and lethargy that comes and goes—look exactly like a dozen more common problems (Klein & Peterson, 2010a).

Figure 3. Adrenal insufficiency is classified by where the HPA axis breaks down. In primary disease (typical Addison’s), the adrenal cortex itself is destroyed, and both cortisol and aldosterone fall while ACTH rises in compensation. In secondary disease, the pituitary fails to release ACTH, so cortisol falls, but aldosterone — controlled separately by RAAS — is preserved. Atypical Addison’s in dogs behaves similarly to the secondary pattern, with normal electrolytes despite low cortisol (Klein & Peterson, 2010a).

In the great majority of canine cases, the body’s own immune system gradually destroys the adrenal cortex, and clinical signs only appear once roughly 85–90% of the tissue is lost (Klein & Peterson, 2010a). Because both cortisol and aldosterone fall together, affected dogs lose the ability to retain sodium and excrete potassium, and they lose cortisol’s role in maintaining blood pressure and vascular tone under stress.

Figure 4. A healthy adrenal cortex (left) versus the shrunken, fibrotic gland typical of immune-mediated adrenalitis (right). This structural loss is why Addison’s is not reversible — management replaces the missing hormones rather than restoring the tissue that made them (Klein & Peterson, 2010a).

Genetic studies point to a strongly heritable, autoimmune basis in several breeds. A pedigree analysis of Nova Scotia Duck Tolling Retrievers estimated the heritability of hypoadrenocorticism in the breed at 0.98, consistent with a major autosomal-recessive gene effect (Hughes et al., 2007). Standard Poodles, Portuguese Water Dogs, Bearded Collies, West Highland White Terriers, and Great Danes are also well documented as over-represented (Hughes et al., 2007; Klein & Peterson, 2010a).

A resting cortisol concentration can rule the disease out if high enough, but confirmation requires an ACTH stimulation test: cortisol is measured before and after synthetic ACTH is given, and Addisonian dogs show little to no rise (Klein & Peterson, 2010b). Once confirmed, lifelong treatment combines a mineralocorticoid—typically monthly desoxycorticosterone pivalate (DOCP) injections—with a low daily dose of oral glucocorticoid, most often prednisolone (Klein & Peterson, 2010b).

Dogs presenting in crisis typically stabilise with aggressive IV fluids and corticosteroids within 24–48 hours. Once a maintenance dose is established, the long-term outlook is excellent: With consistent monitoring, Addisonian dogs generally have a normal life expectancy and a good quality of life (Klein & Peterson, 2010b).

Conn’s syndrome is essentially a feline disease. It is driven by a small, usually benign adrenal tumour (or, less commonly, bilateral hyperplasia) that secretes aldosterone independently of the RAAS signals that would normally control it (Ash et al., 2005).

Figure 5. The renin–angiotensin–aldosterone system (RAAS) normally responds to low blood volume: the kidney releases renin, the liver’s angiotensinogen is converted stepwise to angiotensin II, and the adrenal cortex releases aldosterone to retain sodium. In Conn’s syndrome, an autonomous adrenal tumour secretes aldosterone regardless of what the kidney is signalling (Djajadiningrat-Laanen et al., 2011).

Unrestrained aldosterone drives two things at once: relentless potassium loss in the urine and sodium/water retention that raises systemic blood pressure. In the original case series that defined the disease in cats, the two presenting patterns were hypokalaemic polymyopathy (profound muscle weakness) in the majority of cats and sudden blindness from hypertensive retinal detachment in the rest (Ash et al., 2005).

A markedly elevated aldosterone-to-renin ratio, alongside hypokalaemia and hypertension, supports the diagnosis; adrenal ultrasound helps confirm a unilateral mass and distinguish surgical from medical candidates (Djajadiningrat-Laanen et al., 2011). Medical management centres on potassium supplementation and an aldosterone antagonist or calcium channel blocker to control blood pressure; where the tumour is unilateral and the cat is a surgical candidate, adrenalectomy can be curative (Ash et al., 2005).

Potassium supplementation and blood pressure control typically improve muscle strength within days. Medically managed cats often do well for one to three years, with long-term outcome closely tied to how well hypertension is controlled to protect the kidneys; surgically cured cats generally have a longer, more favourable outlook (Ash et al., 2005; Djajadiningrat-Laanen et al., 2011).

Cushing’s disease behaves almost like the mirror image of Addison’s: instead of the HPA axis switching off, it gets stuck switched on. It is one of the most common canine endocrinopathies, and it is slow — developing over months to years rather than announcing itself acutely (Behrend et al., 2013).

Figure 6. The HPA axis in health: CRH from the hypothalamus stimulates pituitary ACTH release, which in turn drives adrenal cortisol production; rising cortisol then suppresses further CRH and ACTH release. In pituitary-dependent Cushing’s disease (≈80–85% of canine cases), a small pituitary tumour secretes ACTH regardless of cortisol’s feedback signal, driving both adrenal glands to overproduce cortisol (Behrend et al., 2013).

Pituitary-dependent Cushing’s (PDH) accounts for the large majority of cases and is caused by a small, usually benign, ACTH-secreting pituitary tumour. Adrenal-dependent Cushing’s (ADH), seen in the remaining cases, arises from a cortisol-secreting tumour of one adrenal gland itself and tends to occur more often in larger-breed dogs, whereas PDH is more often reported in small breeds (Merck Veterinary Manual).

Chronic cortisol excess also suppresses the immune system and thins the skin, so recurrent skin or urinary infections, symmetrical hair loss, and fragile, slow-healing skin are common (Merck Veterinary Manual).

The 2012 ACVIM consensus statement recommends testing only when compatible clinical signs are present, since no single test is perfectly accurate; the low-dose dexamethasone suppression test (LDDST) is the preferred first-line screening test, sometimes followed by abdominal imaging to distinguish PDH from ADH (Behrend et al., 2013). Oral trilostane, which reversibly inhibits cortisol synthesis, is the most widely used medical treatment (Merck Veterinary Manual).

Most owners notice a marked drop in thirst, appetite, and urination within two to four weeks of starting trilostane, with visible coat and skin improvement typically following over two to three months. Cushing’s is managed rather than cured; because it is predominantly a disease of older dogs, overall survival is often shaped as much by concurrent age-related disease as by the endocrinopathy itself, but quality of life on treatment is usually very good (Behrend et al., 2013; Merck Veterinary Manual).

Any dog or cat can, in principle, develop an adrenal disorder, but genetics and age clearly load the dice.