Addison's is called "the great pretender" for a reason. It walks in looking like gastroenteritis, kidney disease, or just a sick dog that needs fluids. It feels better in the hospital, goes home, and comes back worse two weeks later. The NAVLE loves this condition because it punishes the test-taker who pattern-matches to the most obvious diagnosis without thinking through the whole picture.
Three numbers run this case: the Na:K ratio, the post-ACTH cortisol, and the heart rate. Get those three right and you'll nail every Addison's question on the board.
Why the Adrenal Cortex Fails
Primary hypoadrenocorticism means the adrenal cortex itself is destroyed — immune-mediated adrenalitis accounts for over 90% of cases. All three cortical zones go down: glomerulosa, fasciculata, reticularis. That means you lose both aldosterone and cortisol simultaneously. Secondary hypoadrenocorticism, by contrast, comes from inadequate ACTH from the pituitary. The zona glomerulosa is spared because aldosterone is regulated by the RAAS, not ACTH — so electrolytes stay normal in secondary disease.
The cortical zones from outer to inner: Glomerulosa → Fasciculata → Reticularis. Salt, Sugar, Sex. GFR. That's the mnemonic, and it's worth knowing because the exam occasionally tests which zone produces what.
Who Gets It
Young to middle-aged females, median age around 3–4 years. About 70% of diagnosed dogs are female. Standard Poodles have a confirmed heritability of 0.75 with an 8.6% breed incidence — that's not just predisposition, that's a real genetic disease in that population. Nova Scotia Duck Tolling Retrievers have heritability of 0.98. Portuguese Water Dogs and Bearded Collies are also on the list.
For the NAVLE, the signalment shortcut is: young, spayed female, predisposed breed (Standard Poodle or NSDTR especially), with a history that keeps cycling.
What the Electrolytes Are Doing and Why
Without aldosterone, the kidneys can't retain sodium or excrete potassium. Sodium washes out, potassium accumulates. The resulting hyponatremia drives water loss and hypovolemia. The hyperkalemia slows the heart — which is exactly the opposite of what you'd expect in a hypovolemic, shocky patient.
The Na:K ratio below 27 (normal is 27–40) is the classic lab marker. But it's not pathognomonic — you need to know the mimics cold.
| Parameter | Finding | Prevalence | Mechanism |
|---|---|---|---|
| Sodium | Decreased | 80–90% | Renal sodium wasting (no aldosterone) |
| Potassium | Increased | 80–95% | Impaired renal excretion |
| Na:K Ratio | <27 | 70–80% | Combined sodium loss + potassium retention |
| BUN/Creatinine | Increased | 65–90% | Prerenal azotemia from hypovolemia |
| Glucose | Decreased | 25–30% | Impaired gluconeogenesis (no cortisol) |
| Eosinophilia | Elevated eosinophils | 20–25% | Loss of cortisol-mediated suppression |
The azotemia-plus-dilute-urine combination regularly fools clinicians into calling it AKI. The differentiator: Addisonian azotemia resolves rapidly with IV fluid therapy. True renal failure does not.
The Atypical Form: Normal Electrolytes, Real Disease
Up to 30% of dogs with hypoadrenocorticism present with completely normal sodium and potassium. This is atypical Addison's — glucocorticoid deficiency only, no mineralocorticoid loss. It presents as vague lethargy, GI signs, and weight loss without the dramatic electrolyte picture. The Na:K ratio is normal. The CBC has no stress leukogram. The ACTH stim still diagnoses it.
Atypical Addison's can progress to the typical form over time as the zona glomerulosa eventually gets destroyed. Secondary hypoadrenocorticism also causes glucocorticoid-only deficiency for the same anatomic reason — the zona glomerulosa runs on RAAS, not ACTH, so it survives pituitary dysfunction.
Addison's vs. Cushing's: The Comparison the Board Loves
Cortisol: Too little
Aldosterone: Too little (typical form)
Sodium: Low
Potassium: High
Heart rate: Paradoxical bradycardia
Body condition: Thin, weak
Stress leukogram: Absent
Diagnostic test: ACTH stim (low post-ACTH cortisol)
Signalment: Young female, poodles
Cortisol: Too much
Aldosterone: Normal
Sodium: Normal
Potassium: Normal
Heart rate: Normal or elevated
Body condition: Pot belly, muscle wasting
Stress leukogram: Present
Diagnostic test: LDDS test or ACTH stim (high cortisol)
Signalment: Middle-aged to older, Poodles, Dachshunds
ECG Changes from Hyperkalemia
Hyperkalemia depolarizes cardiac muscle and disrupts conduction. The changes progress in a predictable sequence — and the board will test whether you know the order.
| Potassium (mEq/L) | ECG Changes |
|---|---|
| 5.6–6.5 (Mild) | Peaked, narrow-based ("tented") T waves; bradycardia |
| 6.6–7.5 (Moderate) | Wide QRS; decreased R wave amplitude; prolonged PR interval |
| 7.0–8.5 (Severe) | Absent P waves; atrial standstill |
| >8.5 (Critical) | Sine wave pattern → ventricular fibrillation → asystole |
Mnemonic: "Potassium PEAKS the T, then FLATTENS the P, then WIDENS the QRS." The sine wave pattern at the end is a terminal finding — if you're seeing that, the patient is in serious trouble.
The ACTH Stimulation Test
This is the gold standard for Addison's diagnosis. No other test confirms it. The protocol is straightforward:
1. Collect baseline serum cortisol. 2. Give synthetic ACTH (cosyntropin) at 5 mcg/kg IV. 3. Collect post-ACTH cortisol at 1 hour.
| Post-ACTH Cortisol | Interpretation | Action |
|---|---|---|
| <2 mcg/dL | Diagnostic — "flatline" | Initiate treatment |
| 2–8 mcg/dL | Indeterminate | Repeat in 2–4 weeks |
| >8 mcg/dL | Normal | Explore other differentials |
Baseline cortisol >2 mcg/dL effectively rules out hypoadrenocorticism. A flatline response — cortisol barely moves after ACTH — is the signature finding of a destroyed adrenal cortex.
Acute Crisis Management
An Addisonian crisis is a cardiovascular emergency. The patient is volume-depleted, hyperkalemic, and possibly hypoglycemic. Treatment priorities in order: fix hypovolemia, address life-threatening hyperkalemia, replace glucocorticoids.
0.9% NaCl (normal saline) — fluid of choice. Corrects hypovolemia and hyponatremia simultaneously. Shock dose: 60–90 mL/kg/hr in dogs (give to effect, monitor carefully). Lactated Ringer's is avoided because it contains potassium.
If ECG changes present or K >7.0 mEq/L:
- 10% Calcium Gluconate 0.5–1.0 mL/kg IV slow over 10–15 min — cardioprotective, does NOT lower potassium level
- Dextrose (50%) 0.5–1.0 mL/kg IV diluted — stimulates endogenous insulin, drives K intracellularly
- Regular Insulin 0.1–0.25 U/kg IV + dextrose — drives K intracellularly faster
Dexamethasone SP 0.1–0.5 mg/kg IV — does not interfere with ACTH stim test. Give this first if testing is still pending. Transition to prednisone once patient is eating and stable.
Long-Term Maintenance
Typical Addison's requires both mineralocorticoid and glucocorticoid replacement for life. The mineralocorticoid choice is where the board questions live.
| Drug | Dose | Route/Frequency | Key Point |
|---|---|---|---|
| DOCP (desoxycorticosterone pivalate) | 1.1–1.5 mg/kg | SC every 25–30 days | Pure mineralocorticoid; must give prednisone separately |
| Fludrocortisone | 0.02 mg/kg/day | PO q12–24h | Has some glucocorticoid activity; may reduce prednisone need |
| Prednisone | 0.1–0.22 mg/kg/day | PO q24h | Required with DOCP; increase 2–5x during stress ("stress dosing") |
DOCP is now the preferred mineralocorticoid. The old starting dose of 2.2 mg/kg was too high — current evidence supports starting at 1.1–1.5 mg/kg. Fludrocortisone is an alternative that replaces both mineralocorticoids and glucocorticoids in one pill, which some owners prefer, though the daily oral dosing is a compliance consideration.
Prognosis with treatment is excellent. Median survival exceeds 4.7 years, with most dogs dying from unrelated causes. The disease is manageable — the challenge is diagnosing it in the first place.