Utility of the ACTH/cortisol ratio for differentiating pituitary microadenomas from macroadenomas in dogs with pituitary-dependent hypercortisolism

No simple, blood-based biomarker to estimate tumor size in dogs with pituitary-dependent hypercortisolism (PDH) has been evaluated.

Determine whether the adrenocorticotropic hormone (ACTH)/cortisol ratio differentiates pituitary microadenomas from macroadenomas in dogs with PDH and correlates with pituitary size.

Seventy privately-owned dogs with PDH (microadenomas, n = 30; macroadenomas, n = 40).

Retrospective multicenter observational study. Endogenous ACTH and cortisol concentrations obtained at the same time point before treatment were used to calculate the ACTH/cortisol ratio. Pituitary tumor size was classified using the pituitary-to-brain (P/B) ratio. Diagnostic performance was evaluated using receiver operating characteristic analysis and multivariable logistic regression.

Dogs with macroadenomas had significantly higher ACTH/cortisol ratios than dogs with microadenomas (median, 9.12; IQR, 6.46-14.28 vs median, 4.90; IQR, 3.08-8.10; P < .001). The ratio showed moderate discrimination for differentiating macroadenomas from microadenomas with an area under the curve of 0.77 (95% CI, 0.66-0.89; P < .001). A cutoff >5.69 yielded 85% sensitivity and 60% specificity (positive likelihood ratio 2.13), whereas a higher ratio >11.74 achieved 90% specificity and 35% sensitivity (positive likelihood ratio 3.50). The ACTH/cortisol ratio showed moderate positive correlation with pituitary size (Spearman's ρ = 0.48; 95% CI, 0.26-0.64; P < .001) and remained independently associated with macroadenoma classification in multivariable analysis (OR, 1.19; 95% CI, 1.05-1.40).

The ACTH/cortisol ratio is associated with pituitary tumor size in dogs with PDH and may support clinical risk stratification, particularly when advanced imaging is unavailable.