The recommended differentiation workup combines the low-dose dexamethasone suppression test (LDDST), endogenous ACTH concentration, and abdominal ultrasonography, with computed tomography (CT) reserved for surgical planning or suspected macroadenoma.AAHA Clinical G…+1
The LDDST is the first-line test and serves dual purpose — it both confirms hyperadrenocorticism (HAC) and differentiates pituitary-dependent hyperadrenocorticism (PDH) from adrenal-dependent hyperadrenocorticism (ADH) in many cases.MSD Vet Manuals+1 A decrease of ≥50% in plasma cortisol concentration or urinary corticoid-to-creatinine ratio (UCCR) after dexamethasone administration is consistent with PDH.Journal of Vete… Resistance to suppression occurs in approximately 25% of PDH dogs on the high-dose dexamethasone suppression test (HDDST), limiting its reliability as a sole differentiating test.Journal of Vete…
Endogenous ACTH concentration is a key differentiating test. In PDH, inappropriate and unregulated ACTH secretion causes intermittent elevation in plasma ACTH concentration, whereas in ADH, autonomous cortisol secretion suppresses ACTH via negative feedback at the hypothalamic-pituitary axis.Journal of Vete… The corticotropin-releasing hormone test (CRHT) offers an alternative approach: at a cutoff of 26.3 pg/mL for endogenous ACTH concentration (EAC), sensitivity is 90.62% and specificity is 87.50%; at a cutoff of 54.5 pg/mL for post-stimulation ACTH concentration (PAC), sensitivity is 100% and specificity is 66.67%.Journal of Vete… The 95% reference interval for EAC in healthy dogs is 5.00–79.8 pg/mL, and for PAC is 1.92–153.42 pg/mL.Journal of Vete…
Abdominal ultrasonography is a standard component of the differentiation workup. Bilateral adrenal enlargement supports PDH, while a unilateral adrenal mass with contralateral atrophy supports ADH.Journal of Vete… The sensitivity of ultrasonography to detect adrenomegaly in dogs with HAC is 95.6% when weight-adjusted reference intervals are applied.Veterinary Reco… Weight-adjusted upper limits for left adrenal gland thickness in healthy dogs are: 5.1 mm (2.5–5 kg), 5.5 mm (>5–10 kg), 6.4 mm (>10–20 kg), and 7.3 mm (>20–40 kg); for the right adrenal gland: 5.3 mm (2.5–5 kg), 6.8 mm (>5–10 kg), 7.5 mm (>10–20 kg), and 8.7 mm (>20–40 kg).Veterinary Reco… In small breed dogs (<10 kg specifically), a cut-off adrenal width of 6.0 mm differentiates normal glands from adrenal hyperplasia with sensitivity of 75% and specificity of 94%.Journal of Vete… Importantly, 43% of dogs with PDH have adrenal glands within normal limits on ultrasound, so a normal measurement does not exclude PDH.Journal of Vete…
Equivocal adrenal asymmetry (EAA) on ultrasound is common and does not resolve the PDH vs. ADH question — EAA occurs in 39.6% of dogs with HAC, and 56% of HAC dogs have ultrasound findings clearly consistent with either PDH or ADH.Veterinary Reco… In these cases, endogenous ACTH concentration is the most useful next step.Journal of Vete…
CT imaging is indicated in specific scenarios rather than as a routine differentiating test. Pituitary CT is appropriate when a macroadenoma is suspected or when the owner would pursue radiation therapy or hypophysectomy.AAHA Clinical G… Abdominal CT is pursued before adrenalectomy in dogs with confirmed ADH, and thoracic imaging is important in adrenocortical tumor cases to evaluate for metastases.AAHA Clinical G…+1 Concurrent pituitary and adrenal lesions can occur, and abdominal ultrasonography alone may yield an incomplete diagnosis if pituitary size and ACTH secretion are not assessed.Journal of Vete…
Endocrine testing should not be performed within 2 weeks of short-acting glucocorticoid administration (oral, otic, or ophthalmic) or within 4 weeks of long-acting glucocorticoids.AAHA Clinical G…
| Test | Protocol/Cutoff | Diagnostic Performance | Key Caveat |
|---|---|---|---|
| LDDST | ≥50% cortisol suppression after dexamethasone | First-line; confirms HAC and differentiates PDH vs. ADH in many cases | ~25% of PDH dogs resist suppression on HDDSTJournal of Vete… |
| Endogenous ACTH (EAC via CRHT) | Cutoff 26.3 pg/mL | Sensitivity 90.62%, specificity 87.50% for PDH vs. ADHJournal of Vete… | Reference interval in healthy dogs: 5.00–79.8 pg/mLJournal of Vete… |
| Post-stimulation ACTH (PAC via CRHT) | Cutoff 54.5 pg/mL | Sensitivity 100%, specificity 66.67% for PDH vs. ADHJournal of Vete… | Reference interval in healthy dogs: 1.92–153.42 pg/mLJournal of Vete… |
| Abdominal ultrasound (weight-adjusted) | See weight-category cutoffs above | Sensitivity 95.6% for adrenomegaly in HACVeterinary Reco… | 43% of PDH dogs have normal adrenal size; EAA in 39.6% of HAC dogsVeterinary Reco…+1 |
| Abdominal CT | Pre-adrenalectomy in ADH | Method of choice for metastasis evaluation in adrenocortical tumorsJournal of Vete… | Also detects concurrent pituitary lesions missed by ultrasound aloneJournal of Vete… |
| Pituitary CT/MRI | When macroadenoma suspected or radiation/hypophysectomy plannedAAHA Clinical G… | Evaluates pituitary size and brain compression | Not required if owner declines surgical/radiation optionsAAHA Clinical G… |
Would you like to review the treatment options for confirmed PDH, including trilostane dosing protocols versus hypophysectomy candidacy criteria?