Boretti Felicitas S, Harburger Livia, Riond Barbara, Neubert Elisabeth, Hofmann-Lehmann Regina, Unterer Stefan, Dennler Matthias, Sieber-Ruckstuhl Nadja S
Clinic for Small Animal Internal Medicine, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
Clinical Laboratory, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland.
BMC Vet Res. 2025 Jul 22;21(1):480. doi: 10.1186/s12917-025-04876-9.
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.
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.
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.
长期给予糖皮质激素可抑制下丘脑 - 垂体 - 肾上腺（HPA）轴，增加停药后肾上腺功能不全的风险，且恢复时间难以预测。本研究通过促肾上腺皮质激素（ACTH）刺激试验、ACTH动态监测和肾上腺超声检查，评估了一种超过200天的泼尼松龙给药方案对犬HPA轴的影响，从而对该方案进行标准化评估。4只健康的比格犬从第1天至181天每天口服泼尼松龙（第1 - 150天的中位剂量：2mg/kg；第151 - 181天的中位剂量：0.25mg/kg）。从第182天至208天，隔天给予泼尼松龙（中位剂量：0.25mg/kg），并于第209天停药。
所有犬在高剂量泼尼松龙给药150天后均出现皮质醇增多症的临床症状。ACTH刺激试验表明，高剂量给药150天后皮质醇反应降低，尽管只有1只犬的皮质醇水平低于138nmol/L。出乎意料的是，内源性ACTH浓度在第150天显著升高，但到第183天已恢复至基线水平。ACTH曲线显示出短暂的抑制，每次泼尼松龙给药后6小时内水平下降，12小时后反弹至基线。超声检查显示，到第150天时肾上腺明显缩小，双侧肾上腺尾极的最大直径均减小（左侧：15% - 42%；右侧：13% - 26%）。到第211天时，与第150天相比，肾上腺大小显著重新增大。
长期每天一次高剂量给予泼尼松龙会导致犬出现明显的临床皮质醇增多症和显著的肾上腺萎缩；然而，尽管有这些结构变化，大多数犬仍保留正常的功能储备。ACTH的快速恢复正常以及皮质醇反应性仅轻度降低表明，每天一次给药可能允许有足够的停药间隔时间来维持近乎完整的HPA功能。尽管如此，由于缺乏每日两次给药的比较组，限制了关于给药频率在预防严重HPA轴抑制中作用的任何确定性结论。
