Division of Endocrinology, Diabetes, and Clinical Nutrition, Inselspital, Bern University Hospital, and Institute of Social and Preventive Medicine, University of Bern, CH-3010 Bern, Switzerland.
J Clin Endocrinol Metab. 2012 Oct;97(10):E1938-42. doi: 10.1210/jc.2012-2432. Epub 2012 Aug 7.
Current treatment guidelines generally suggest using lower and weight-adjusted glucocorticoid replacement doses in patients with insufficiency of the hypothalamic-pituitary-adrenal (HPA) axis. Although data in patients with acromegaly revealed a positive association between glucocorticoid dose and mortality, no comparable results exist in patients with nonfunctioning pituitary adenomas (NFPA).
Our objective was to assess whether higher glucocorticoid replacement doses are associated with increased mortality in patients with NFPA and HPA axis insufficiency.
DESIGN, PARTICIPANTS, AND INTERVENTION: We included 105 patients receiving glucocorticoid replacement after pituitary surgery due to NFPA and concomitant HPA axis insufficiency. Patients were grouped according weight-adapted and absolute hydrocortisone (HC) replacement doses. Mortality was assessed using Kaplan-Meier methodology as well as multivariable Cox regression models.
This was a retrospective analysis conducted at a tertiary referral center.
We evaluated overall mortality based on HC replacement doses.
Average age at inclusion was 58.9±14.8 yr, and mean follow-up was 12.7±9.4 yr. The groups did not differ according to age, follow-up time, pattern of hypopituitarism, and comorbidities. Kaplan-Meier survival probabilities differed significantly when comparing individuals with differing weight-adjusted HC dose (P=0.001) as well as absolute HC dose (5-19, 20-29, and ≥30 mg, P=0.009). Hazard ratios for mortality increased from 1 (0.05-0.24 mg/kg) to 2.62 (0.25-0.34 mg/kg) to 4.56 (≥0.35 mg/kg, P for trend=0.006) and from 1 (5-19 mg) to 2.03 (20-29 mg) to 4 (≥30 mg, P for trend=0.029), respectively.
Higher glucocorticoid replacement doses are associated with increased overall mortality in patients with NFPA and insufficiency of HPA axis. This further substantiates the importance of a balanced and adjusted glucocorticoid replacement therapy in these patients.
目前的治疗指南通常建议对下丘脑-垂体-肾上腺（HPA）轴功能不全的患者使用较低和体重调整的糖皮质激素替代剂量。尽管在肢端肥大症患者中发现糖皮质激素剂量与死亡率之间存在正相关，但在无功能垂体腺瘤（NFPA）患者中尚无可比的结果。
我们的目的是评估 NFPA 和 HPA 轴功能不全患者中较高的糖皮质激素替代剂量是否与死亡率增加相关。
设计、参与者和干预措施：我们纳入了 105 例因 NFPA 而行垂体手术后接受糖皮质激素替代治疗且同时存在 HPA 轴功能不全的患者。根据体重调整和绝对氢化可的松（HC）替代剂量对患者进行分组。使用 Kaplan-Meier 方法和多变量 Cox 回归模型评估死亡率。
这是在一家三级转诊中心进行的回顾性分析。
我们根据 HC 替代剂量评估了总死亡率。
纳入时的平均年龄为 58.9±14.8 岁，平均随访时间为 12.7±9.4 年。两组在年龄、随访时间、垂体功能减退模式和合并症方面无差异。比较不同体重调整 HC 剂量（P=0.001）和绝对 HC 剂量（5-19、20-29 和≥30 mg，P=0.009）的个体时，Kaplan-Meier 生存概率差异有统计学意义。死亡率的风险比从 1（0.05-0.24 mg/kg）增加到 2.62（0.25-0.34 mg/kg）再到 4.56（≥0.35 mg/kg，P 趋势=0.006），从 1（5-19 mg）增加到 2.03（20-29 mg）再到 4（≥30 mg，P 趋势=0.029）。
NFPA 和 HPA 轴功能不全患者较高的糖皮质激素替代剂量与总死亡率增加相关。这进一步证实了在这些患者中进行平衡和调整的糖皮质激素替代治疗的重要性。
