尿中表雄酮/雄酮比值作为血清睾酮/双氢睾酮比值的替代指标用于诊断印度尼西亚2型5α-还原酶缺乏症患者及携带者的准确性。

Accuracy of Urinary Etiocholanolone/Androsterone Ratio as Alternative to Serum Testosterone/Dihydrotestosterone Ratio for Diagnosis of 5 Alpha-reductase Type 2 Deficiency Patients and Carriers in Indonesia.

作者信息

Marzuki Nanis Sacharina, Idris Firman Pratama, Kartapradja Hannie, Renata Shirley, Harahap Alida, Batubara Jose Rizal Latief

机构信息

Eijkman Institute for Molecular Biology, Jakarta, Indonesia.

Faculty of Medicine, University of Indonesia, Jakarta, Indonesia.

出版信息

Int J Endocrinol Metab. 2021 Apr 18;19(2):e109510. doi: 10.5812/ijem.109510. eCollection 2021 Apr.

DOI:10.5812/ijem.109510

PMID:34149847

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8198621/

Abstract

BACKGROUND

The 5 Alpha-reductase type 2 deficiency (5ARD2) is an inherited condition, which clinically presents as variable degrees of under virilization in affected 46,XY individuals. In the diagnostic pathway of 5ARD2, the testosterone/dihydrotestosterone (T/DHT) ratio is broadly employed before molecular analysis of the SRD5A2 gene. However, due to cost-benefit considerations, the DHT test in our country is routinely lacking in clinical settings; therefore, we considered applying the urinary etiocholanolone/androsterone (Et/An) ratio as an alternative test.

OBJECTIVES

We aimed to determine the diagnostic value of the urinary Et/An ratio versus the T/DHT ratio in diagnosing 5ARD2 patients and carriers.

METHODS

Sixty-six suspected 5ARD2 46,XY disorders of sex development (DSD) individuals and 95 family members were recruited in the study. Their clinical manifestations, T/DHT and urinary Et/An ratios, and genes were analyzed. Using molecular analysis of the SRD5A2 gene as the gold standard, we compared the accuracy of both ratios in diagnosing 5ARD2 patients and carriers with receiver operating characteristic (ROC) curve analysis.

RESULTS

Thirty-seven patients were confirmed molecularly to have 5ARD2, and the rest (n = 29) were assessed as normal controls, while in the carrier group, 53 were molecularly confirmed as carriers and 42 as controls. The AUCs (areas under the curve) of the T/DHT and urinary Et/An ratios were 57.7% (95% CI 43.0 - 72.4%, P > 0.05) and 79.7% (95% CI 69.0 - 90.4%, P < 0.001), respectively, in diagnosing 5ARD2 patients and 54.1% (95% CI 42.4 - 65.8%, P > 0.05) and 75.1% (95% CI 65.1 - 85.1%, P < 0.001), respectively, in diagnosing carriers. The cutoff value of the urinary Et/An ratio was set at ≥ 0.95 for detecting 5ARD2 patients and ≥ 0.99 for detecting carriers.

CONCLUSIONS

The testosterone/DHT ratio was inaccurate in diagnosing 5ARD2 patients. When molecular analysis for the gene is lacking, the urinary Et/An ratio may be a useful test to diagnose 5ARD2 patients and carriers.

摘要

背景

2型5α-还原酶缺乏症（5ARD2）是一种遗传性疾病，临床上表现为46,XY个体不同程度的男性化不足。在5ARD2的诊断流程中，在对SRD5A2基因进行分子分析之前，广泛采用睾酮/双氢睾酮（T/DHT）比值。然而，出于成本效益的考虑，我国临床常规缺乏双氢睾酮检测；因此，我们考虑应用尿中表雄酮/雄酮（Et/An）比值作为替代检测方法。

目的

我们旨在确定尿Et/An比值与T/DHT比值在诊断5ARD2患者及携带者中的诊断价值。

方法

本研究招募了66例疑似5ARD2的46,XY性发育障碍（DSD）个体和95名家庭成员。分析他们的临床表现、T/DHT和尿Et/An比值以及基因。以SRD5A2基因的分子分析作为金标准，我们通过受试者工作特征（ROC）曲线分析比较了两种比值在诊断5ARD2患者及携带者中的准确性。

结果

37例患者经分子检测确诊为5ARD2，其余（n = 29）被评估为正常对照，而在携带者组中，53例经分子检测确诊为携带者，42例为对照。T/DHT比值和尿Et/An比值在诊断5ARD2患者时的曲线下面积（AUC）分别为57.7%（95%可信区间43.0 - 72.4%，P > 0.05）和79.7%（95%可信区间69.0 - 90.4%，P < 0.001），在诊断携带者时分别为54.1%（95%可信区间42.4 - 65.8%，P > 0.05）和75.1%（95%可信区间65.1 - 85.1%，P < 0.001）。尿Et/An比值的截断值设定为检测5ARD2患者时≥0.95，检测携带者时≥0.99。