Department of Internal Medicine and Clinical Nutrition, Institute of Medicine at Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden.
Department of Endocrinology, Sahlgrenska University Hospital, Göteborg, Sweden.
J Clin Endocrinol Metab. 2019 Jun 1;104(6):2375-2384. doi: 10.1210/jc.2018-02524.
Whether patients with Cushing disease (CD) in remission have increased mortality is still debatable.
To study overall and disease-specific mortality and predictive factors in an unselected nationwide cohort of patients with CD.
DESIGN, PATIENTS, AND METHODS: A retrospective study of patients diagnosed with CD, identified in the Swedish National Patient Registry between 1987 and 2013. Medical records were systematically reviewed to verify the diagnosis. Standardized mortality ratios (SMRs) with 95% CIs were calculated and Cox regression models were used to identify predictors of mortality.
Of 502 identified patients with CD (n = 387 women; 77%), 419 (83%) were confirmed to be in remission. Mean age at diagnosis was 43 (SD, 16) years and median follow-up was 13 (interquartile range, 6 to 23) years. The observed number of deaths was 133 vs 54 expected, resulting in an overall SMR of 2.5 (95% CI, 2.1 to 2.9). The commonest cause of death was cardiovascular diseases (SMR, 3.3; 95% CI, 2.6 to 4.3). Excess mortality was also found associated with infections and suicide. For patients in remission, the SMR was 1.9 (95% CI, 1.5 to 2.3); bilateral adrenalectomy and glucocorticoid replacement therapy were independently associated with increased mortality, whereas GH replacement was associated with improved outcome.
Findings from this large nationwide study indicate that patients with CD have excess mortality. The findings illustrate the importance of achieving remission and continued active surveillance, along with adequate hormone replacement and evaluation of cardiovascular risk and mental health.
库欣病（CD）缓解患者的死亡率是否增加仍存在争议。
研究未选择的全国性 CD 患者队列的总体和疾病特异性死亡率及预测因素。
设计、患者和方法：对 1987 年至 2013 年间在瑞典国家患者登记处诊断为 CD 的患者进行回顾性研究。系统地审查病历以验证诊断。计算标准化死亡率（SMR）和 95%置信区间（CI），并使用 Cox 回归模型识别死亡率的预测因素。
共确定了 502 例 CD 患者（n = 387 名女性；77%），其中 419 例（83%）被确认为缓解期。诊断时的平均年龄为 43（SD，16）岁，中位随访时间为 13（四分位间距，6 至 23）年。观察到的死亡人数为 133 人，预期为 54 人，总 SMR 为 2.5（95%CI，2.1 至 2.9）。最常见的死亡原因是心血管疾病（SMR，3.3；95%CI，2.6 至 4.3）。还发现死亡率过高与感染和自杀有关。对于缓解期患者，SMR 为 1.9（95%CI，1.5 至 2.3）；双侧肾上腺切除术和糖皮质激素替代治疗与死亡率增加独立相关，而 GH 替代治疗与改善结局相关。
这项大型全国性研究的结果表明，CD 患者的死亡率过高。这些发现表明，实现缓解和持续积极监测，以及充分的激素替代以及评估心血管风险和心理健康至关重要。
