Overview

Cushing's disease results from chronic cortisol excess, causing multisystemic effects. Pituitary-dependent hyperadrenocorticism (PDH) — 85% of cases — is caused by a pituitary corticotroph adenoma secreting excess ACTH, which chronically stimulates both adrenal glands. Adrenal-dependent hyperadrenocorticism — 15% of cases — from a cortisol-secreting adrenal adenoma or carcinoma (unilateral) or bilateral adrenal hyperplasia (rare). The clinical presentation is classic: PU/PD, polyphagia, pot-bellied appearance, bilateral flank alopecia, and calcinosis cutis. Diagnosis requires endocrine function testing. Treatment is medical (trilostane preferred, mitotane alternative) for PDH. Adrenal tumors may be surgical candidates with pre-operative medical stabilization.

Common Clinical Signs

Polyuria and polydipsia (PU/PD) — often the presenting complaint Polyphagia Pot-bellied appearance (hepatomegaly, abdominal muscle laxity) Bilateral symmetrical alopecia (flank, rump, ventral abdomen) Calcinosis cutis (mineral deposits in skin — raised, firm plaques) Muscle wastage (hindquarters especially) Lethargy Recurrent pyoderma and urinary tract infections Thin, fragile skin; easy bruising Panting (respiratory signs from tracheal cartilage softening)

Diagnostic Approach

Diagnostic Test Interpretation
Hematology / Chemistry Panel Stress leukogram (mature neutrophilia, lymphopenia, eosinopenia). Elevated ALP (alkaline phosphatase) — highly sensitive for Cushing's in dogs. Elevated ALT and cholesterol. Hyperglycemia (usually mild). Low BUN (polyuria). These changes are supportive but not diagnostic alone.
Urinalysis Dilute urine (USG often <1.015 despite PU/PD). Concurrent proteinuria and bacteriuria (UTIs are common in Cushing's dogs due to immunosuppression — often subclinical). Culture recommended even without obvious signs.
ACTH Stimulation Test Baseline cortisol measured, then cosyntropin (synthetic ACTH) administered IM/IV at 5 µg/kg, and cortisol re-measured 1 hour later. PDH: exaggerated post-stimulation cortisol response. Adrenal tumor: minimal response (adrenal cortex autonomous, doesn't respond to external ACTH). ~80% sensitivity for PDH; less sensitive for adrenal-dependent. Used to monitor trilostane therapy.
Low-Dose Dexamethasone Suppression Test (LDDST) Gold standard screening test. Dexamethasone (0.015 mg/kg IV) given at T=0, cortisol measured at T=0, T=4h, T=8h. Normal: cortisol suppresses at 4h and stays suppressed at 8h. Cushing's: cortisol fails to suppress at 4h. Can also differentiate PDH (suppresses at 8h in ~65% of PDH cases) from adrenal-dependent. ~95% sensitivity for PDH. Requires 8 hours of hospitalization.
Abdominal Ultrasound Bilateral adrenal gland enlargement in PDH. Unilateral adrenal mass in adrenal-dependent disease. Used to differentiate PDH from adrenal-dependent before selecting treatment. Adrenal glands >1.0 cm thick suggest PDH; unilateral mass >2 cm with contralateral atrophy suggests adrenal tumor.
Endogenous ACTH Best test for differentiating PDH from adrenal-dependent. Low ACTH = adrenal-dependent (negative feedback suppressed pituitary). Normal/High ACTH = PDH. Must be run on EDTA plasma, transported refrigerated, measured before any steroid supplementation.

Differential Diagnoses

  • Diabetes mellitus — PU/PD is a shared sign. Cushing's dogs may have stress hyperglycemia but diabetes causes weight loss, not polyphagia. Blood glucose and fructosamine differentiate.
  • Chronic kidney disease — PU/PD in older dogs. CKD causes azotaemia, isosthenuria that persists despite dehydration. Cushing's has elevated ALP, no azotaemia in early stages. Creatinine and SDMA differentiate.
  • Urinary tract infection — PU/PD can occur. UTIs cause dysuria and pollakiuria rather than true PU/PD. Urinalysis and culture differentiate. Cushing's predisposes to UTI.
  • Hypothyroidism — Alopecia and lethargy are shared but hypothyroidism does not cause PU/PD. Low T4/elevated TSH on thyroid panel differentiates.
  • Exogenous corticosteroid administration (iatrogenic Cushing's) — Identical clinical signs from steroid injections or oral steroid medication. History of steroid use (creams, ear drops, injections) is key.

Treatment

Trilostane (Vetoryl) is the preferred treatment: inhibits 3-β-hydroxysteroid dehydrogenase, blocking cortisol synthesis. Dosed at 2.2-6.6 mg/kg/day PO, started at 2.2-5 mg/kg/day. Monitor with ACTH stimulation at 10-14 days post-start and then every 3 months. Target: clinical improvement + post-ACTH cortisol of 2-5 µg/dL. Mitotane (Lysodren) is an adrenolytic alternative: destroys the zona fasciculata and reticularis. Loading dose then maintenance. Requires careful monitoring for hypoadrenocorticism as a side effect. Selegiline (Anipryl) is a dopamine agonist used for PDH only — less effective than trilostane. Adrenalectomy for unilateral adrenal tumors requires pre-operative trilostane to control cortisol before surgery.