What distinguishes pituitary-dependent Cushing's from adrenal-dependent disease in dogs clinically?

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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. 23 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%. 38 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. 6 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. 3 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. 3 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. 5 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%. 12 The previously used general cutoff of 7.5 mm overestimates normal size in small-breed dogs. 12 Adrenal asymmetry is present in approximately 20% of PDH cases, so symmetric enlargement is supportive but not required. 5 A unilateral adrenal mass with contralateral atrophy points toward ADH, though concurrent pituitary and adrenal lesions occur in 5