Utility of the ACTH/cortisol ratio for differentiating pituitary microadenomas from macroadenomas in dogs with pituitary-dependent hypercortisolism.
4 affiliations
- 1Small Animal Practice, Paphos 8300, Cyprus.
- 2Animal House Veterinary Clinic, Capoterra 09012, Italy.
- 3Joint Department of Veterinary Medicine, Faculty of Applied Biological Science, Gifu University, Gifu 501-1193, Japan.
- 4Department of Veterinary Medical Science, University of Bologna, Ozzano dell'Emilia, Bologna 40064, Italy.
Abstract
Background
No simple, blood-based biomarker to estimate tumor size in dogs with pituitary-dependent hypercortisolism (PDH) has been evaluated.Hypothesis/objectives
Determine whether the adrenocorticotropic hormone (ACTH)/cortisol ratio differentiates pituitary microadenomas from macroadenomas in dogs with PDH and correlates with pituitary size.Animals
Seventy privately-owned dogs with PDH (microadenomas, n = 30; macroadenomas, n = 40).Methods
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.Results
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).Conclusions and clinical importance
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.
Related
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- ACTH-independent hypercortisolism across the cardiometabolic spectrum
- Case Report: A case study on bilateral macronodular adrenocortical disease: ACTH-independent hypercortisolism with refractory diabetes and hypertension
- Diabetes in Cushing’s disease: age, hypercortisolism, central adiposity, and β-cell stress as determinants of glycaemia
BibTeX
@article{stylianou2026utility,
title = {{Utility of the ACTH/cortisol ratio for differentiating pituitary microadenomas from macroadenomas in dogs with pituitary-dependent hypercortisolism.}},
author = {George Stylianou and Federico Vassallo and Naohito Nishii and Alessia Diana and Antonio M Tardo and Francesca Del Baldo and Federico Fracassi},
journal = {Journal of veterinary internal medicine},
year = {2026},
month = sep,
doi = {10.1093/jvimsj/aalag269},
url = {https://europepmc.org/article/MED/42955823},
note = {CC BY},
}
RIS
TY - JOUR
TI - Utility of the ACTH/cortisol ratio for differentiating pituitary microadenomas from macroadenomas in dogs with pituitary-dependent hypercortisolism.
AU - George Stylianou
AU - Federico Vassallo
AU - Naohito Nishii
AU - Alessia Diana
AU - Antonio M Tardo
AU - Francesca Del Baldo
AU - Federico Fracassi
PY - 2026
DA - 2026/09/01
JO - Journal of veterinary internal medicine
DO - 10.1093/jvimsj/aalag269
UR - https://europepmc.org/article/MED/42955823
AB - Background No simple, blood-based biomarker to estimate tumor size in dogs with pituitary-dependent hypercortisolism (PDH) has been evaluated.Hypothesis/objectives Determine whether the adrenocorticotropic hormone (ACTH)/cortisol ratio differentiates pituitary microadenomas from macroadenomas in dogs with PDH and correlates with pituitary size.Animals Seventy privately-owned dogs with PDH (microadenomas, n = 30; macroadenomas, n = 40).Methods 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.Results 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).Conclusions and clinical importance 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.
SN - 0891-6640
SN - 1939-1676
ER -