Clinically, pituitary-dependent hyperadrenocorticism (PDH) and adrenal-dependent hyperadrenocorticism (ADH) are indistinguishable on physical examination and history alone — the clinical signs of chronic glucocorticoid excess (polyuria, polydipsia, polyphagia, pot-bellied appearance, excessive panting, dermatopathy, and muscle weakness or wasting) are identical regardless of whether the source is pituitary or adrenal. MSD Vet Manuals+1
The epidemiological split is the first differentiating factor to apply. PDH accounts for 80–85% of naturally occurring Cushing's syndrome in dogs, with ADH comprising the remaining 15–20%. AAHA Clinical G…+1 This prior probability alone makes PDH the working diagnosis in any new case before testing begins.
The low-dose dexamethasone suppression test (LDDST) is the screening test of choice and provides the first opportunity to differentiate the two forms. MSD Vet Manuals Partial suppression at 4 hours (cortisol <1.4 mcg/dL) or escape at 8 hours, or any cortisol concentration falling below 50% of baseline at either the 4- or 8-hour sample, is consistent with PDH. AAHA Clinical G… Up to 35% of dogs with PDH will not fulfill at least one of these suppression criteria, so failure to observe suppression on the LDDST does not confirm ADH. AAHA Clinical G…
Abdominal ultrasonography is the primary imaging tool for differentiation. Bilaterally symmetric adrenal enlargement is the characteristic finding in PDH, reflecting bilateral cortical hyperplasia driven by excess ACTH. Frontiers in Ve… In dogs with PDH weighing less than 10 kg, a maximum adrenal gland width cutoff of 6.0 mm distinguishes normal adrenal glands from adrenal hyperplasia with a sensitivity of 75% and specificity of 94%. Journal of Vete… The previously used general cutoff of 7.5 mm overestimates normal size in small-breed dogs. Journal of Vete… Adrenal asymmetry is present in approximately 20% of PDH cases, so symmetric enlargement is supportive but not required. Frontiers in Ve… A unilateral adrenal mass with contralateral atrophy points toward ADH, though concurrent pituitary and adrenal lesions occur in 5% of all dogs with hypercortisolism and in 10% of dexamethasone-resistant dogs, which can complicate interpretation. Journal of Vete…
Endogenous ACTH concentration is the most direct biochemical differentiator. Suppressed plasma ACTH is consistent with ADH (autonomous cortisol production suppressing pituitary output), while elevated or inappropriately normal ACTH supports PDH. AAHA Clinical G… When the LDDST does not achieve differentiation, the 2023 AAHA guidelines recommend pursuing abdominal ultrasound and/or endogenous ACTH concentration. AAHA Clinical G…
The thyrotropin-releasing hormone (TRH) stimulation test should not be used to differentiate PDH from ADH in dogs. TRH administration increases plasma cortisol in both PDH-affected and clinically normal dogs without a significant rise in ACTH in either group, likely due to direct TRH receptor stimulation on adrenocortical cells rather than a pituitary-mediated effect. Veterinary Quar…
| Feature | PDH | ADH |
|---|---|---|
| Prevalence | 80–85% of cases AAHA Clinical G…+1 | 15–20% of cases AAHA Clinical G…+1 |
| Clinical signs | Identical to ADH MSD Vet Manuals+1 | Identical to PDH MSD Vet Manuals+1 |
| LDDST suppression | Partial suppression or escape pattern supportive AAHA Clinical G… | Failure to suppress; 35% of PDH also fails AAHA Clinical G… |
| Adrenal ultrasound | Bilateral symmetric enlargement; asymmetry in ~20% Frontiers in Ve… | Unilateral mass ± contralateral atrophy Journal of Vete… |
| Adrenal width cutoff (small breeds <10 kg) | >6.0 mm: Se 75%, Sp 94% for hyperplasia Journal of Vete… | Unilateral mass typically >6.0 mm Journal of Vete… |
| Endogenous ACTH | Elevated or inappropriately normal AAHA Clinical G… | Suppressed AAHA Clinical G… |
| Concurrent pituitary + adrenal lesions | — | 10% of dexamethasone-resistant dogs Journal of Vete… |
| TRH stimulation test | Not useful — cortisol rises in both PDH and normals Veterinary Quar… | Not useful Veterinary Quar… |
Would you like to go through the treatment options for confirmed PDH — specifically the comparison between trilostane, mitotane, and hypophysectomy?