以半定量分析之NP-59腎上腺造影預測原發性皮質醛酮症病患之KCNJ5突變

Predicting KCNJ5 Mutation in Primary Aldosteronism Patients by Semiquantification Analysis of NP-59 Adrenal Scintigraphy

路景竹(Ching-Chu Lu)

指導教授 ： 林菀俞

國立臺灣大學/公共衛生學院/流行病學與預防醫學研究所/博士(2021年)

https://doi.org/10.6342/NTU202101401

摘要

背景︰KCNJ5體細胞突變為原發性皮質醛酮症重要的致病機轉，且與疾病嚴重程度相關。然而KCNJ5突變狀態僅能經由腎上切除術後的組織所獲得。NP-59腎上腺造影為分子影像，以非侵入性的方式評估原發性皮質醛酮症的功能狀態以及疾病程度。本研究探討NP-59腎上腺造影與KCNJ5突變狀態的關聯，並期藉由NP-59腎上腺造影預測原發性皮質醛酮症的KCNJ5突變狀態。
方法：62位具有NP-59腎上腺造影且在一年內接受腎上腺切除術並有KCNJ5突變狀態的原發性皮質醛酮症病患被納入研究。從NP-59腎上腺造影中得到的兩個半定量指標，患側腎上腺與肝臟對比值(ALR)以及患側腎上腺對對側腎上腺對比值(CON)，用以比較在有無KCNJ5突變的差異性。NP-59腎上腺造影預測原發性皮質醛酮症的KCNJ5突變狀態的能力以Youden’s index所得到的最佳切點分析之。
結果：在62位原發性皮質醛酮症病患中，20位具有KCNJ5突變，42位無KCNJ5突變。有KCNJ5突變者的ALR顯著高於無KCNJ5突變者(p值為0.0031)，而CON則呈現邊緣性的偏高(p值0.0833)。在ALR切點為2.10與CON切點為1.95下，NP-59腎上腺造影預測KCNJ5突變的能力最佳，其敏感度與特異度分別為85%、57%與45%、 93%。在具有突變的病患中，16位G151R點突變的病患其ALR明顯低於另外4位L168R點突變的病患(p值為0.0471)。
結論：原發性皮質醛酮症中的KCNJ5突變導致較高的NP-59攝取，在腎上腺造影中包含經背景值校正後的患側腎上腺攝取以及患側與對側腎上腺攝取比值皆呈現偏高。具有KCNJ5突變的病人中，具有G151R點突變者其 ALR明顯低於具有L168R點突變者。藉由以上發現可推論NP-59腎上腺掃描可以非侵入性的方式評估原發性皮質醛酮症病患的KCNJ5突變狀態。

關鍵字

原發性皮質醛酮症 ； NP-59腎上腺掃描 ； 單光子電腦斷層掃描 ； 半定量 ； KCNJ5

並列摘要

Purpose: Somatic KCNJ5 mutation accounts for the pathophysiology of primary aldosteronism (PA) and is associated with disease severity. However, mutation status can only be identified by surgical specimen from adrenalectomy. NP-59 adrenal scintigraphy is a noninvasive molecular imaging assessing disease activity. The study aimed to evaluate the correlation between NP-59 adrenal scintigraphy and somatic KCNJ5 mutation, and possible predictive value of somatic KCNJ5 mutation by NP-59 adrenal scintigraphy among PA patients underwent adrenalectomy.
Methods: Sixty-two PA patients received adrenalectomy within 1 year after NP-59 adrenal scintigraphy with available KCNJ5 mutation status were included. The differences of adrenal to liver ratio (ALR) and lesion to contralateral ratio of bilateral adrenal glands (CON) derived from NP-59 adrenal scintigraphy among patients with and without KCNJ5 mutation were evaluated. Cutoff values from Youden’s index were used for the predictive ability of NP-59 adrenal scintigraphy in KCNJ5 mutation.
Results: Twenty patients had KCNJ5 mutation and 42 patients were wild type. ALR was significantly higher in patients with KCNJ5 mutation than those without KCNJ5 mutation (p=0.0031), while CON showed borderline higher in patients with KCNJ5 mutation (p=0.0833). With ALR and CON cutoff of 2.10 and 1.95, NP-59 adrenal scintigraphy showed the best predictive value of KCNJ5 mutation and the sensitivity and specificity were 85%, 57% and 45%, 93%, respectively. Sixteen patients had G151R point mutation (KCNJ5- G151R) and 4 had L168R point mutation (KCNJ5-L168R), which former one had significantly lower ALR (p=0.0471).
Conclusion: Somatic KCNJ5 mutation of PA patients lead to significantly higher NP-59 uptake, in terms of background-corrected adrenal uptake of lesion side (ALR) and lesion to non-lesion side adrenal ratio (CON). APAs with KCNJ5-G151R point mutation showed significantly lower ALR than those with KCNJ5-L168R point mutation. The findings suggested that NP-59 adrenal scintigraphy may predict KCNJ5 mutation in noninvasive way.

並列關鍵字

primary aldosteronism ； NP-59 adrenal scintigraphy ； SPECT ； semiquantification ； KCNJ5

參考文獻

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