氢化可的松治疗垂体功能减退症患者时会调节皮质类固醇代谢，从而增加组织糖皮质激素暴露。
The modulation of corticosteroid metabolism by hydrocortisone therapy in patients with hypopituitarism increases tissue glucocorticoid exposure.
机构信息
Centre for EndocrinologyDiabetes and Metabolism, University of Birmingham, Birmingham, UKDepartment of Endocrinology and DiabetesAdelaide and Meath Hospitals, Incorporating the National Children's Hospital and Trinity College, Tallaght Hospital, Dublin 24, IrelandDepartment of EndocrinologyDiabetes and Metabolism, Beaumont Hospital and RCSI Medical School, Dublin, IrelandDepartment of EndocrinologyLeeds Teaching Hospitals NHS Trust, St James's University Hospital, Leeds, UKDepartment of Nuclear MedicineQueen Elizabeth Hospital, Birmingham, UKDepartment of Medicine and EndocrinologyUniversity of Leeds, Leeds, UK Centre for EndocrinologyDiabetes and Metabolism, University of Birmingham, Birmingham, UKDepartment of Endocrinology and DiabetesAdelaide and Meath Hospitals, Incorporating the National Children's Hospital and Trinity College, Tallaght Hospital, Dublin 24, IrelandDepartment of EndocrinologyDiabetes and Metabolism, Beaumont Hospital and RCSI Medical School, Dublin, IrelandDepartment of EndocrinologyLeeds Teaching Hospitals NHS Trust, St James's University Hospital, Leeds, UKDepartment of Nuclear MedicineQueen Elizabeth Hospital, Birmingham, UKDepartment of Medicine and EndocrinologyUniversity of Leeds, Leeds, UK
Centre for EndocrinologyDiabetes and Metabolism, University of Birmingham, Birmingham, UKDepartment of Endocrinology and DiabetesAdelaide and Meath Hospitals, Incorporating the National Children's Hospital and Trinity College, Tallaght Hospital, Dublin 24, IrelandDepartment of EndocrinologyDiabetes and Metabolism, Beaumont Hospital and RCSI Medical School, Dublin, IrelandDepartment of EndocrinologyLeeds Teaching Hospitals NHS Trust, St James's University Hospital, Leeds, UKDepartment of Nuclear MedicineQueen Elizabeth Hospital, Birmingham, UKDepartment of Medicine and EndocrinologyUniversity of Leeds, Leeds, UK Centre for EndocrinologyDiabetes and Metabolism, University of Birmingham, Birmingham, UKDepartment of Endocrinology and DiabetesAdelaide and Meath Hospitals, Incorporating the National Children's Hospital and Trinity College, Tallaght Hospital, Dublin 24, IrelandDepartment of EndocrinologyDiabetes and Metabolism, Beaumont Hospital and RCSI Medical School, Dublin, IrelandDepartment of EndocrinologyLeeds Teaching Hospitals NHS Trust, St James's University Hospital, Leeds, UKDepartment of Nuclear MedicineQueen Elizabeth Hospital, Birmingham, UKDepartment of Medicine and EndocrinologyUniversity of Leeds, Leeds, UK.
出版信息
Eur J Endocrinol. 2015 Nov;173(5):583-93. doi: 10.1530/EJE-15-0490. Epub 2015 Aug 11.
CONTEXT
Patients with hypopituitarism have increased morbidity and mortality. There is ongoing debate about the optimum glucocorticoid (GC) replacement therapy.
OBJECTIVE
To assess the effect of GC replacement in hypopituitarism on corticosteroid metabolism and its impact on body composition.
DESIGN AND PATIENTS
We assessed the urinary corticosteroid metabolite profile (using gas chromatography/mass spectrometry) and body composition (clinical parameters and full body DXA) of 53 patients (19 female, median age 46 years) with hypopituitarism (33 ACTH-deficient/20 ACTH-replete) (study A). The corticosteroid metabolite profile of ten patients with ACTH deficiency was then assessed prospectively in a cross over study using three hydrocortisone (HC) dosing regimens (20/10 mg, 10/10 mg and 10/5 mg) (study B) each for 6 weeks. 11 beta-hydroxysteroid dehydrogenase 1 (11β-HSD1) activity was assessed by urinary THF+5α-THF/THE.
SETTING
Endocrine Centres within University Teaching Hospitals in the UK and Ireland.
MAIN OUTCOME MEASURES
Urinary corticosteroid metabolite profile and body composition assessment.
RESULTS
In study A, when patients were divided into three groups - patients not receiving HC and patients receiving HC≤20 mg/day or HC>20 mg/day - patients in the group receiving the highest daily dose of HC had significantly higher waist-to-hip ratio (WHR) than the ACTH replete group. They also had significantly elevated THF+5α-THF/THE (P=0.0002) and total cortisol metabolites (P=0.015). In study B, patients on the highest HC dose had significantly elevated total cortisol metabolites and all patients on HC had elevated THF+5α-THF/THE ratios when compared to controls.
CONCLUSIONS
In ACTH-deficient patients daily HC doses of >20 mg/day have increased WHR, THF+5α-THF/THE ratios and total cortisol metabolites. GC metabolism and induction of 11β-HSD1 may play a pivitol role in the development of the metabolically adverse hypopituitary phenotype.
背景
患有垂体功能减退症的患者发病率和死亡率较高。关于最佳糖皮质激素（GC）替代疗法仍存在争议。
目的
评估垂体功能减退症患者 GC 替代治疗对皮质类固醇代谢的影响及其对身体成分的影响。
设计和患者
我们评估了 53 例垂体功能减退症患者（19 名女性，中位年龄 46 岁）的尿皮质类固醇代谢产物谱（使用气相色谱/质谱法）和身体成分（临床参数和全身 DXA）（研究 A）。然后，在一项交叉研究中，使用三种氢化可的松（HC）剂量方案（20/10mg、10/10mg 和 10/5mg），前瞻性评估了 10 例 ACTH 缺乏症患者的皮质类固醇代谢产物谱（研究 B），每个方案持续 6 周。通过尿 THF+5α-THF/THE 评估 11β-羟类固醇脱氢酶 1（11β-HSD1）活性。
地点
英国和爱尔兰大学教学医院的内分泌中心。
主要观察指标
尿皮质类固醇代谢产物谱和身体成分评估。
结果
在研究 A 中，当患者分为三组 - 未接受 HC 治疗的患者和接受 HC≤20mg/天或 HC>20mg/天的患者 - 接受最高日剂量 HC 的组的患者与 ACTH 补充组相比，腰臀比（WHR）显著更高。他们的 THF+5α-THF/THE 也显著升高（P=0.0002），总皮质醇代谢产物升高（P=0.015）。在研究 B 中，与对照组相比，接受最高 HC 剂量的患者总皮质醇代谢产物显著升高，所有接受 HC 治疗的患者 THF+5α-THF/THE 比值升高。
结论
在 ACTH 缺乏的患者中，每日 HC 剂量>20mg/天会增加 WHR、THF+5α-THF/THE 比值和总皮质醇代谢产物。GC 代谢和 11β-HSD1 的诱导可能在代谢不良的垂体功能减退表型的发展中起关键作用。
Zotero 插件