Forms of the disease and dogs at risk
Guzman Ramos and colleagues state that immune-mediated destruction is the most common cause of primary disease. Neoplasia, granulomatous or infectious disease, infarcts and drugs such as trilostane or mitotane are reported less often [1]. Secondary disease comes from loss of pituitary ACTH, and the review notes that prior glucocorticoid or progestin use can cause it temporarily [1].
Classification has historically split cases into "typical" disease, with electrolyte changes, and "atypical" disease, with cortisol deficiency alone [1][2]. The 2022 review reports that the European Society for Veterinary Endocrinology's ALIVE project proposed replacing these with "hyponatraemic and/or hyperkalaemic primary hypoadrenocorticism" and "eunatraemic, eukalaemic primary or secondary hypoadrenocorticism" [1]. Its authors caution that normal electrolytes can coexist with aldosterone deficiency, and the NC State authors cite evidence supporting the same point [1][4].
On signalment, the 2022 review places glucocorticoid-only cases at a slightly older age, typically 6 to 8 years. It also reports odds 1.85 to 2.6 times higher in females in the general dog population, though not all breed-specific studies found this [1]. It lists a strong heritable component in standard poodles, Portuguese water dogs, Nova Scotia duck tolling retrievers, soft coated wheaten terriers and bearded collies [1]. Lathan and Thompson describe iatrogenic disease mainly in dogs treated with trilostane or mitotane for hyperadrenocorticism [2].
Clinical presentation
Guzman Ramos and colleagues compiled pooled case series, and their main hypoadrenocorticism group included some cases not differentiated from glucocorticoid deficiency alone. In that group, lethargy was reported in 84.6% (495 of 585 dogs), anorexia in 79.7%, vomiting in 71.8% and diarrhoea in 41.7% [1]. The review advises that suspicion should rise when waxing and waning gastrointestinal signs respond quickly to fluids or glucocorticoids, or worsen with stress [1]. The Merck Veterinary Manual notes that the condition is often referred to as "the great imitator" [3].
In a hypovolaemic dog, the review notes that an absent compensatory tachycardia, or a bradycardia, should prompt consideration of the disease because hyperkalaemia can blunt the heart rate response [1]. One study cited there found a median systolic pressure of 90 mmHg in 53 affected dogs, compared with 140 mmHg in 110 dogs with other illness [1]. Lathan and Thompson report bradycardia in 17% of dogs [2].
Both reviews say that dogs without electrolyte changes tend to go undiagnosed longer [1][2]. Lathan and Thompson add that some of these dogs come to attention only through hypoalbuminaemia or hypocholesterolaemia [2].
Laboratory and imaging findings
| Finding | Hypoadrenocorticism group | "Atypical" disease |
|---|
| Hyperkalaemia | 87.2% | 0% |
| Hyponatraemia | 80.1% | 2.6% |
| Increased urea | 81.7% | 16.4% |
| Hypocholesterolaemia | 13.0% | 72.5% |
| Hypoalbuminaemia | 10.3% | 74.2% |
| Hypoglycaemia | 15.9% | 31.3% |
Figures are pooled from published case series by the 2022 review. The authors note that mineralocorticoid status was usually inferred rather than measured [1].
Both reviews describe the missing stress leukogram in a sick dog as a clue, while noting that eosinophilia and lymphocytosis appear in only a minority of cases [1][2]. Azotaemia with urine specific gravity below 1.030 can make an Addisonian dog look like a case of acute kidney injury. Lathan and Thompson write that clinicians "must consider HOAC in every suspected AKI patient" [2].
On the sodium to potassium ratio, the Merck Veterinary Manual says values below 27 suggest the disease "but are not pathognomonic" [3]. Lathan and Thompson go further. They write that "the utility of the ratio is questionable" and that any hyponatraemic or hyperkalaemic dog should be considered a suspect [2].
For imaging, one study cited in the 2022 review found that a maximal left adrenal thickness under 2.8 mm was highly suggestive. The authors warn, however, that body weight affects adrenal size and a single cut-off cannot fit all dogs [1].
Confirming the diagnosis and testing pitfalls
All three clinical sources treat the ACTH stimulation test as the confirmatory test [1][2][3]. Lathan and Thompson describe giving 5 ug/kg (up to 250 ug/dog) of synthetic ACTH IV, with cortisol measured before and one hour after. They require a post-ACTH cortisol "<2 ug/dL (55 nmol/L)" for diagnosis [2]. The 2022 review adds that doses as low as 1 ug/kg may be enough, and that IV dosing is preferred because absorption may lag in dehydrated dogs [1]. It treats post-ACTH values between 55 and 220 nmol/L as equivocal. It cites a follow-up study in which such dogs were unlikely to develop the disease over a median of 2 years [1].
According to the 2022 review, basal cortisol at or below 55 nmol/L has a sensitivity of 99.4% to 100% but a specificity of only 63.3% to 78.2%, so it serves to screen and exclude rather than to confirm [1].
Testing pitfalls named in the sources include:
- Prednisone and methylprednisolone cross-react with cortisol assays, while dexamethasone does not, according to Lathan and Thompson [2].
- The 2022 review reports that in healthy beagles, a single IV dose of 0.1 mg/kg dexamethasone altered ACTH stimulation results for up to 3 days, though stimulation was still adequate to exclude disease [1].
- Lathan and Thompson do not recommend compounded ACTH gel because of inconsistent results [2].
- The test confirms cortisol deficiency only and does not separate primary, secondary and iatrogenic disease [1][2].
The 2022 review reports a prospective study of 23 affected dogs, 79 dogs with mimicking diseases and 30 healthy dogs. In that study, a cortisol to endogenous ACTH ratio of 0.01 or lower showed 100% sensitivity and 99% specificity [1]. Endogenous ACTH is labile and needs special handling [1]. Lathan and Thompson note that the ranges of the ratio differed significantly between studies and that more investigation is needed before clinical use [2]. Endogenous ACTH also distinguishes primary from central disease, and pre- and post-ACTH aldosterone can identify mineralocorticoid deficiency in dogs with normal electrolytes [1].
Managing the Addisonian crisis
Lathan and Thompson list the initial goals as correcting hypovolaemia, hypotension, hyperkalaemia with its arrhythmias, hypoglycaemia and acidosis [2]. They describe 0.9% NaCl as the historical fluid choice, with some clinicians preferring Normosol-R, Plasma-Lyte A or lactated Ringer's solution [2]. Because rapid correction risks myelinolysis, they state that sodium should not rise by more than 0.5 mEq/kg/h or by more than 12 mEq/L per 24 hours, and that hypertonic saline should not be used [2].
| Drug | Lathan and Thompson [2] | Merck Veterinary Manual [3] |
|---|
| 10% calcium gluconate | 0.5-1.0 mL/kg slowly over 15 minutes with ECG monitoring | 1 mL/kg, IV, over 10 minutes |
| Regular insulin | 0.2-0.5 U/kg IV, followed by 1-2 g dextrose per unit | Dextrose with or without regular insulin, no dose stated |
| Dexamethasone sodium phosphate | 0.25 mg/kg IV | 0.1 mg/kg, IV, every 12 hours, tapering when appropriate |
Both sources favour dexamethasone because it does not interfere with a subsequent ACTH stimulation test [2][3]. Lathan and Thompson describe calcium gluconate as cardioprotective without lowering potassium, and they place glucocorticoid supplementation after the life-threatening problems are addressed [2]. They report that most patients improve within hours and are usually discharged in 3 to 5 days [2].
Long-term management and monitoring
Mineralocorticoids
Lathan and Thompson cite a 2014 study in which DOCP suppressed plasma renin activity more effectively than fludrocortisone [2]. They note that the labeled DOCP dose is 2.2 mg/kg, that published series found lower doses effective, and that the authors routinely begin at 1.5 mg/kg [2]. The Merck Veterinary Manual lists 2.2 mg/kg IM every 25 days, with a lower starting dosage of 1.1-1.5 mg/kg IM as an option [3]. Lathan and Thompson recheck electrolytes at 14 days to judge the dose and at 25 days to judge the interval, then every 3 to 6 months once the dose is stable [2].
In the NC State cohort, the median starting DOCP dose was 2.11 mg/kg and the median last documented dose was 1.88 mg/kg, with a median last interval of 28 days [4]. For fludrocortisone, Lathan and Thompson give a starting dose of 0.01-0.02 mg/kg/day and report that 12 of 37 dogs needed twice-daily dosing to control electrolytes [2].
Glucocorticoids
Lathan and Thompson give a physiological prednisone dose of 0.1-0.25 mg/kg/d, adjusted on clinical signs, with the dose usually doubled around stressful events [2]. They state that an ACTH stimulation test "is never repeated in patients with primary HOAC" [2]. The Merck Veterinary Manual lists polyuria, polydipsia, panting and polyphagia among signs of overtreatment [3].
For dogs without electrolyte changes, Lathan and Thompson recommend electrolyte rechecks at 1 and 3 months after diagnosis and every 6 months afterward, since mineralocorticoid deficiency can develop later [2].
Prognosis and client communication
The NC State study was a retrospective cohort of 141 dogs from a single referral hospital, with 66 included in the survival analysis [4]. Median survival after diagnosis was 5.7 years for dogs with electrolyte changes and 5.6 years for those without, a difference that was not significant [4]. Each additional year of age at diagnosis was associated with a 0.4-year decrease in median survival [4]. Dogs with iatrogenic disease had a median survival of 0.6 years after diagnosis, which the authors attribute to the older age of dogs treated for hyperadrenocorticism [4]. The authors list owner reporting, small sample size and a referral population as limitations [4].
Of 25 deaths with a known cause, neoplasia was the most common. Three deaths were attributed to hypoadrenocorticism, including one dog euthanised after a crisis that followed a missed DOCP dose [4]. Owners of 42 of 58 dogs reported polyuria, polydipsia or polyphagia, though the authors note that the questionnaire's wording may have overestimated these [4].
Lathan and Thompson stress that owners must not stretch the DOCP interval without veterinary advice, because this "often results in Addisonian crisis" [2]. They add that a crisis is significantly more expensive to treat than a single DOCP injection. They also describe doubling prednisone during stressful situations and rechecking electrolytes regularly [2].
