【作者】 吴锡；

【导师】 陈涛；

【作者基本信息】 四川大学 ， 内科（内分泌）， 2022， 硕士

【摘要】 目的:1.评估真实世界中降压药对原发性醛固酮增多症(PA)筛查试验的影响,醛固酮/肾素浓度(ARR)在降压药洗脱期前及洗脱期后诊断PA的一致性;探讨进行PA筛查的高血压患者常用的降压方案及相应的ARR切点。2.通过检测血浆中的甘草次酸(GA)以评估无明确甘草制剂摄入史的高血压患者进行PA筛查时的甘草沾染率及甘草制剂在真实世界中对PA筛查试验的影响。方法:本研究分为两部分。第一部分:纳入2010年1月～2020年12月在四川大学华西医院内分泌代谢科住院进行PA筛查的高血压患者488例,收集患者洗脱期前后的降压药、舒张压、收缩压、血电解质、血浆肾素活性(PRA)、血浆醛固酮(PAC)、ARR,卡托普利试验前及试验后的醛固酮(ALD)、盐水负荷试验前及试验后的ALD。2020年10月后收集肾素浓度(DRC)、PAC,并计算ARR。第二部分:纳入2019年10月～2020年10月在四川大学华西医院内分泌代谢科肾上腺组住院进行PA筛查的高血压患者209例,收集患者的临床资料,以丙酸睾酮为内标物,采用高效液相色谱法检测患者血浆中的GA。结果:1.降压药洗脱期前,PA患者的PRA低于原发性高血压患者,PAC、ARR均高于原发性高血压患者。服用1-3种降压药的患者采用洗脱期前的ARR与洗脱后的ARR筛查PA的诊断结果具有显著的差异性。服用4种及以上降压药的患者洗脱期前ARR与洗脱期后的ARR筛查PA的诊断结果没有显著性差异。纳入的488例患者中,CCB和(或)ACEI/ARB为最常用的降压方案,未进行降压药洗脱可采用ARR≥23.6ng/dl:ng/ml·h作为洗脱期前ARR筛查PA的切点,其敏感性88.5%,特异性68.9%。2.纳入的209例患者中有4例患者的血浆中检测出GA,甘草沾染率为1.91%,其95%的可信区间为(0.0,3.8%)。4例患者中,ARR阳性2例,盐水输注试验及卡托普利试验结果提示1例为PA,另1例为原发性高血压。结论:1.高血压患者进行PA筛查时,服用4种及以上降压药的患者可直接进行PA的筛查。服用1-3种降压药的患者,如使用CCB和(或)ACEI/ARB,可选择ARR≥23.6ng/dl:ng/ml·h作为诊断的切点。如患者不能依照指南进行降压药的洗脱时,可选用CCB和(或)ACEI/ARB作为洗脱期的降压方案。2.甘草沾染可能导致PA筛查的假阳性,但进行PA筛查的高血压患者无意识摄入甘草类制剂是小概率事件,临床上可根据病史的询问以排除甘草制剂对筛查试验的影响。更多还原

【Abstract】 Objective:1.To evaluate the effect of antihypertensive agents on primary aldosteronism(PA)screening test in the real world clinical practice,and the consistency of aldosterone and renin activity ratio(ARR)in diagnosing PA before and after the washout phase of antihypertensive agents;to explore the antihypertensive regimen and the corresponding ARR cut-off point of hypertension patients undergoing PA screening.2.To evaluate the effect of glycyrrhetinic acid(GA)on PA screening test in the real world clinical practice by measuring plasma GA in hypertensive patients without a clear history of liquorice agents use.Methods:This study includes two parts.Part 1.A total of 488 patients with hypertension who were hospitalized in the Department of Endocrinology and Metabolism,West China Hospital of Sichuan University from January 2010 to December 2020 and underwent PA screening were enrolled.The antihypertensive drugs,diastolic blood pressure,systolic blood pressure,blood electrolyte,plasma renin activity(PRA),plasma aldosterone concentration(PAC),ARR,aldosterone(ALD)before and after captopril challenge test,and ALD before and after saline infusion test were collected.were collected before and after the washout period.Renin concentration(DRC)and PAC were collected after October 2020,and ARR was calculated.Part2.A total of 209 patients with hypertension admitted to the Adrenal group,Department of Endocrinology and Metabolism,West China Hospital of Sichuan University from October 2019 to October 2020 for PA screening and diagnosis were enrolled.With testosterone propionate as internal standard,GA in plasma was detected by high-performance liquid chromatography.Results:1.Before the washout period,PRA of PA patients was lower than that of essential hypertension patients,while PAC and ARR were higher than that of essential hypertension patients.There was a significant difference in diagnostic results for PA screening between pre-eluting ARR and post-eluting ARR among patients taking 1-3antihypertensive agents;however,there was no significant difference among patients taking 4 or more antihypertensive agents.Among the 488 patients included,CCB and/or ACEI/ARB were the most used antihypertensive regimen.ARR≥23.6ng/dl:ng/ml·h could be used as the cut-off point of ARR screening PA before elution,with sensitivity of 88.6.0%and specificity of 68.9%.2.GA was detected in the plasma of 4 patients in 4 of the 209 enrolled patients,with a licorice contamination rate of 1.91%with a 95%confidence interval(0.0,3.8%).Among the four patients,two patients were positive for the ratio of aldosterone to renin activity(ARR);the saline infusion test and captopril test suggested that one patient had PA,and the other had essential hypertension.Conclusion:1.When PA screening is performed in patients with hypertension,ARR with the can be directly screened for patients taking 4 or more antihypertensive drugs,As to patients taking 1-3 antihypertensive drugs,such as CCB and/or ACEI/ARB,ARR≥23.6ng/dl:ng/ml·h can be selected as the cut-off value.CCB and/or ACEI/ARB can also be used as antihypertensive regimens during the elution period if patients cannot follow the guidelines for antihypertensive drug elution.2.Licorice contamination may lead to false-positive in PA screening,but it is a small probability event for hypertension patients undergoing PA screening.The influence of licorice preparations on ARR screening can be ruled out by review medical history.更多还原