Tizianel Irene, Lizzul Laura, Mondin Alessandro, Voltan Giacomo, Mazzeo Pierluigi, Scaroni Carla, Barbot Mattia, Ceccato Filippo
Department of Medicine-DIMED, University of Padova, Padova, Italy.
Endocrinology Unit, Department of Medicine DIMED, University Hospital of Padova, Via Ospedale Civile, 105, Padova, 35128, Italy.
J Endocrinol Invest. 2025 Mar 26. doi: 10.1007/s40618-025-02572-x.
Cushing's disease (CD) is associated with phenotypic traits and comorbidities that may persist after the normalization of cortisol levels. Medical therapy is usually given in recurrent or persistent CD after transsphenoidal surgery. We aimed to investigate the impact of long-term normalization of daily cortisol secretion on clinical picture and cardiometabolic comorbidities, comparing surgical remission to medical treatment.
Monocentric retrospective study, two- and five-years observation. Sixty CD patients, with sustained normal 24-h urinary free cortisol (UFC) levels, divided group 1 (surgical remission, n = 36) and group 2 (medical remission, n = 24).
Patients were different after achieving eucortisolism with surgery or medical treatment. Phenotypic traits: round face, dorsocervical fat pad, and bruisability persisted more prominently in the group 2, however abdominal obesity and muscle weakness persisted in both groups, especially in those patients with increased late-night salivary cortisol (LNSC).
greater improvement was observed in group 1 (-31% vs. -5%, p = 0.04). Diabetes: less prevalent in group 1 after 2 years (2/36 vs. 9/24, p = 0.002), with a corresponding reduction in glucose-lowering treatments and persistence of impaired LNSC in diabetic patients (p < 0.001). Dyslipidemia: remained widespread in both groups, with minimal improvement over time (-22% in surgical and - 6% in medical cohort).
Surgical remission leads to faster and sustained improvements in clinical phenotype. However, obesity, arterial hypertension, and dyslipidemia do not completely revert in five years, especially during medical treatment. Most comorbidities persist despite UFC normalization, due to impaired LNSC: the recovery of cortisol rhythms confirms the remission of hypercortisolism.
库欣病（CD）与表型特征及合并症相关，这些特征和合并症在皮质醇水平恢复正常后仍可能持续存在。经蝶窦手术后复发或持续性CD通常采用药物治疗。我们旨在研究每日皮质醇分泌长期恢复正常对临床表现和心脏代谢合并症的影响，比较手术缓解与药物治疗的效果。
单中心回顾性研究，进行两年和五年观察。60例CD患者，24小时尿游离皮质醇（UFC）水平持续正常，分为第1组（手术缓解，n = 36）和第2组（药物缓解，n = 24）。
通过手术或药物治疗实现皮质醇正常分泌后，患者情况有所不同。表型特征：第2组中圆脸、颈背脂肪垫和易瘀斑更为明显地持续存在，然而两组中腹部肥胖和肌肉无力均持续存在，尤其是那些午夜唾液皮质醇（LNSC）升高的患者。
第1组改善更明显（-31% 对 -5%，p = 0.04）。糖尿病：两年后第1组中患病率较低（2/36对9/24，p = 0.002），降糖治疗相应减少，糖尿病患者中LNSC受损持续存在（p < 0.001）。血脂异常：两组中仍普遍存在，随时间改善甚微（手术组-22%，药物组-6%）。
手术缓解可使临床表型更快且持续改善。然而，肥胖、动脉高血压和血脂异常在五年内并未完全恢复，尤其是药物治疗期间。尽管UFC恢复正常，但由于LNSC受损，大多数合并症仍持续存在：皮质醇节律的恢复证实了高皮质醇血症的缓解。
