溴隐亭联合螺内酯治疗原发性醛固酮增多症患者的疗效：一项产生假设的初步研究。

The therapeutic effect of bromocriptine in combination with spironolactone in patients with primary aldosteronism: a hypothesis generating pilot study.

作者信息

Wu Vin-Cent, Wu Che-Hsiung, Yang Ya-Wen, Huang Kuo-How, Chang Chia-Hui, Yang Shao-Yu, Lin Yen-Hung, Wu Kwan-Dun

机构信息

Division of Nephrology, National Taiwan University Hospital, Taipei, Taiwan.

Division of Nephrology, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei, Taiwan.

出版信息

Oncotarget. 2017 Sep 6;8(44):77609-77621. doi: 10.18632/oncotarget.20670. eCollection 2017 Sep 29.

DOI:10.18632/oncotarget.20670

PMID:29100412

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5652803/

Abstract

BACKGROUND

Dopamine D2-like receptors are attenuated in aldosterone producing adenoma, lead to overproduction of aldosterone in affected patients, and thus reported to serve as a potential treatment target for primary aldosteronism. The D2 dopamine receptor agonist bromocriptine has been used clinically for reducing tumor mass of pituitary adenomas of lactotroph origin. The aim of the present study was to assess the efficacy of adding bromocriptine to spironolactone in the biochemical control of primary aldosteronism.

METHODS

Thirty patients (15 aldosterone producing adenoma) received bromocriptine treatment with dose titration to a daily dose of 7.5mg. Urine aldosterone and potassium excretion ratio of all patients were compared based on the result of metoclopramide test at baseline.

RESULTS

On the basis of response to metoclopramide at baseline, the proportions of patients with lower urine aldosterone and urine potassium level after taking bromocriptine for six months were higher in the high metoclopramide response group. Initial aldosterone-renin ratio and high metoclopramide response at baseline were independent predictors of a decrease in aldosterone secretion after a six-month course of bromocriptine. The effects of bromocriptine added to spironolactone to reduce aldosterone secretion and potassium excretion in primary aldosteronism dissipated at 9 month after the initial treatment.

CONCLUSIONS

In this pilot study, we found that short-term addition of bromocriptine to spironolactone improved the biochemical control of primary aldosteronism. Dopamine agonist is more effective in patients with high baseline aldosterone-renin ratio and those sensitive to metoclopramide stimulation. However, this effect dissipated after 9 months.

CLINICAL TRIAL REGISTRY INFORMATION

ClinicalTrials. Gov number: NCT00451672; https://www.clinicaltrial.gov/ct2/show/NCT00451672?term=NCT00451672&rank =1; trial registry name: The Therapeutic Effect of Bromocriptin in Patients With Primary Aldosteronism.

摘要

背景

多巴胺D2样受体在醛固酮分泌性腺瘤中表达减弱，导致患病患者醛固酮分泌过多，因此据报道其可作为原发性醛固酮增多症的潜在治疗靶点。D2多巴胺受体激动剂溴隐亭已在临床上用于缩小催乳素瘤的肿瘤体积。本研究的目的是评估在螺内酯基础上加用溴隐亭对原发性醛固酮增多症进行生化控制的疗效。

方法

30例患者（15例醛固酮分泌性腺瘤）接受溴隐亭治疗，剂量逐步滴定至每日7.5mg。根据基线时甲氧氯普胺试验结果比较所有患者的尿醛固酮和钾排泄率。

结果

根据基线时对甲氧氯普胺的反应，在高甲氧氯普胺反应组中，服用溴隐亭6个月后尿醛固酮和尿钾水平较低的患者比例更高。基线时的初始醛固酮-肾素比值和高甲氧氯普胺反应是溴隐亭治疗6个月后醛固酮分泌减少的独立预测因素。在原发性醛固酮增多症中，加用溴隐亭至螺内酯中以减少醛固酮分泌和钾排泄的作用在初始治疗9个月后消失。