Effects of long-term high-dose prednisolone in Beagle dogs on structural and functional responses of the HPA Axis.

Abstract

BACKGROUND: Long-term glucocorticoid administration can suppress the hypothalamic-pituitary-adrenal (HPA) axis, increasing the risk of adrenal insufficiency upon withdrawal, with an unpredictable recovery timeline. This study provides a standardized evaluation of a > 200-day prednisolone administration regimen in dogs by assessing its effect on HPA axis through adrenocorticotropic hormone (ACTH) stimulation tests, ACTH dynamics monitoring, and adrenal ultrasonography. Four healthy Beagle dogs received once-daily oral prednisolone from days 1–181 (median dose: 2 mg/kg for days 1–150; median dose: 0.25 mg/kg for days 151–181). From days 182–208, prednisolone (median dose: 0.25 mg/kg) was given on alternate days before discontinuation on day 209. RESULTS: All dogs developed clinical signs of hypercortisolism after 150 days of high-dose prednisolone administration. The ACTH stimulation test indicated a reduced cortisol response after 150 days of high-dose administration, though only one dog exhibited cortisol levels below 138 nmol/L. Unexpectedly, endogenous ACTH concentrations were significantly increased on day 150 but had returned to baseline levels by day 183. ACTH curves showed a short-lived suppression, with levels declining within 6 h of each prednisolone dose and rebounding to baseline by 12 h. Ultrasonography revealed significant adrenal downsizing by day 150, with a reduction in the maximal diameter of the caudal pole of both adrenal glands (left: 15–42%, right: 13–26%). By day 211, adrenal size had significantly re-increased compared to day 150. CONCLUSIONS: Prolonged, once-daily high-dose prednisolone administration caused overt clinical hypercortisolism and pronounced adrenal shrinkage in dogs; however, most retained a normal functional reserve despite these structural changes. The rapid normalization of ACTH and only mild reduction in cortisol responsiveness indicate that once-daily dosing may allow sufficient off-drug intervals to maintain near-intact HPA function. Nevertheless, the absence of a twice-daily comparison group limits any definitive conclusions about the role of dosing frequency in preventing severe HPA axis suppression.