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大剂量(15万国际单位)胆钙化醇治疗下活动性肢端肥大症中维生素D代谢的特征

Characterization of vitamin D metabolism in active acromegaly in the setting of bolus (150,000 IU) cholecalciferol treatment.

作者信息

Povaliaeva Alexandra A, Bogdanov Viktor P, Zhukov Artem Yu, Pigarova Ekaterina A, Dzeranova Larisa K, Rozhinskaya Liudmila Ya, Mel'nichenko Galina A, Mokrysheva Natalia G

机构信息

Endocrinology Research Centre, 11, Dmitriya Ul'yanova street, Moscow, 117036, Russia.

出版信息

Endocrine. 2022 May;76(2):407-418. doi: 10.1007/s12020-022-02994-0. Epub 2022 Feb 9.

Abstract

PURPOSE

To reveal distinctive features of vitamin D metabolism in patients with active acromegaly compared to healthy individuals, particularly in the setting of cholecalciferol treatment.

METHODS

The study group included 34 adults with active acromegaly, and the control group included 30 apparently healthy adults with similar age, sex, and BMI. All participants received a single dose (150,000 IU) of cholecalciferol aqueous solution orally. Laboratory assessments including serum vitamin D metabolites (25(OH)D, 25(OH)D, 1,25(OH)D, 3-epi-25(OH)D and 24,25(OH)D), free 25(OH)D, vitamin D-binding protein (DBP) and parathyroid hormone (PTH) as well as serum and urine biochemical parameters were performed before the intake and on Days 1, 3, and 7 after the administration. All data were analyzed with nonparametric statistics.

RESULTS

Patients with acromegaly had tendency to lower baseline 25(OH)D levels (p = 0.05) and lower 25(OH)D levels (p < 0.05) during the follow-up. They were also characterized by PTH suppression (lower baseline PTH levels and lower prevalence of secondary hyperparathyroidism), altered production of main vitamin D metabolites (higher 1,25(OH)D and lower 24,25(OH)D levels with corresponding lower 25(ОН)D/1,25(ОН)D and higher 25(ОН)D/24,25(ОН)D ratios) as well as concordant biochemical features (higher levels of serum phosphorus and albumin-adjusted calcium levels) throughout the study (p < 0.05). The acromegaly group showed an increase in DBP levels after cholecalciferol intake as opposed to the control group (p < 0.05) and had lower increase in free 25(OH)D levels (p < 0.05). Δ25(OH)D was similar between the groups (p > 0.05), showed a negative correlation with the disease activity markers-both IGF-1 levels (r = -0.44, p < 0.05) and fasting GH levels (r = -0.56, p < 0.05)-and lacked correlation with BMI in the acromegaly group (p > 0.05).

CONCLUSION

Patients with active acromegaly have dysregulated vitamin D metabolism characterized by higher 1,25(ОН)D, lower 24,25(ОН)D and altered DBP production. The response to vitamin D supplementation in acromegaly patients might be influenced by hormonal excess. Obtained results require reproducibility check and further study to develop specific clinical recommendations.

TRIAL REGISTRATION

NCT04844164 (release date: April 9, 2021; retrospectively registered).

摘要

目的

揭示与健康个体相比,活动期肢端肥大症患者维生素D代谢的独特特征,尤其是在胆钙化醇治疗的情况下。

方法

研究组包括34名活动期肢端肥大症成年患者,对照组包括30名年龄、性别和体重指数(BMI)相似的明显健康的成年人。所有参与者口服单剂量(150,000 IU)胆钙化醇水溶液。在摄入前以及给药后的第1、3和7天进行实验室评估,包括血清维生素D代谢物(25(OH)D、25(OH)D、1,25(OH)D、3-表-25(OH)D和24,25(OH)D)、游离25(OH)D、维生素D结合蛋白(DBP)和甲状旁腺激素(PTH)以及血清和尿液生化参数。所有数据采用非参数统计分析。

结果

肢端肥大症患者在随访期间基线25(OH)D水平有降低趋势(p = 0.05),25(OH)D水平降低(p < 0.05)。其特征还包括PTH抑制(较低的基线PTH水平和较低的继发性甲状旁腺功能亢进患病率)、主要维生素D代谢物产生改变(较高的1,25(OH)D和较低的24,25(OH)D水平,相应的25(ОН)D/1,25(ОН)D较低,25(ОН)D/24,25(ОН)D较高)以及整个研究过程中一致的生化特征(较高的血清磷水平和白蛋白校正钙水平)(p < 0.05)。与对照组相比,肢端肥大症组在摄入胆钙化醇后DBP水平升高(p < 0.05),游离25(OH)D水平升高较低(p < 0.05)。两组间Δ25(OH)D相似(p > 0.05),与疾病活动标志物——胰岛素样生长因子-1(IGF-1)水平(r = -0.44,p < 0.05)和空腹生长激素(GH)水平(r = -0.56,p < 0.05)均呈负相关,在肢端肥大症组中与BMI无相关性(p > 0.05)。

结论

活动期肢端肥大症患者维生素D代谢失调,特征为1,25(ОН)D升高、24,25(ОН)D降低以及DBP产生改变。肢端肥大症患者对维生素D补充的反应可能受激素过多影响。所得结果需要进行重复性检查和进一步研究以制定具体的临床建议。

试验注册

NCT04844164(发布日期:2021年4月9日;回顾性注册)

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