Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Eur J Endocrinol. 2022 Sep 14;187(4):519-530. doi: 10.1530/EJE-22-0286. Print 2022 Oct 1.
Concurrent autonomous cortisol secretion (ACS) in patients with primary aldosteronism (PA) is being reported more frequently. Several somatic mutations including PRKACA, GNAS, and CTNNB1 were identified in cortisol-producing adenomas (CPAs). The presence of these mutations in unilateral PA (uPA) patients concurrent with ACS (uPA/ACS) is not well known. This study aimed to investigate the prevalence of these mutations and their clinical vs pathological characteristics in uPA/ACS.
This is a retrospective cohort study.
Totally 98 uPA patients from the Taiwan Primary Aldosteronism Investigation registry having overnight 1-mg dexamethasone suppression test (DST) and adrenalectomy from 2016 to 2018 were enrolled. Their adrenal tumors were tested for PRKACA, GNAS, and CTNNB1 mutations.
11 patients had CPA-related mutations (7 PRKACA and 4 GNAS). The patients carrying these mutations had higher post-DST cortisol (5.6 vs 2.6 μg/dL, P = 0.003) and larger adenoma (2.2 ± 0.3 vs 1.9 ± 0.7 cm, P = 0.025). Adenomas with these mutations had a higher prevalence of non-classical uPA (72.7% vs 26.3%, P = 0.014). Numerically, slightly more complete clinical success of uPA patients with these mutations was noticed after adrenalectomy, although it was statistically non-significant. Post-DST cortisol levels, adenoma size >1.9 cm, and the interaction of adenoma size >1.9 cm with potassium level were found to be associated with the presence of these mutations.
Our study showed that CPA-related mutations were detected in 36.7% of uPA/ACS adenomas. The presence of these mutations was associated with higher post-DST cortisol levels, larger adenoma sizes, and a high percentage of non-classical uPA. However, these mutations did not significantly affect the clinical and biochemical outcomes after adrenalectomy of uPA/ACS patients but they showed a better trend.
原发性醛固酮增多症（PA）患者并发自主皮质醇分泌（ACS）的情况越来越多。在产生皮质醇的腺瘤（CPAs）中，已经发现了 PRKACA、GNAS 和 CTNNB1 等几种体细胞突变。这些突变在并发 ACS（uPA/ACS）的单侧 PA（uPA）患者中的存在情况尚不清楚。本研究旨在探讨这些突变在 uPA/ACS 中的发生率及其临床与病理特征。
这是一项回顾性队列研究。
2016 年至 2018 年，从台湾原发性醛固酮增多症调查登记处招募了 98 例接受过夜 1mg 地塞米松抑制试验（DST）和肾上腺切除术的 uPA 患者。对他们的肾上腺肿瘤进行了 PRKACA、GNAS 和 CTNNB1 突变检测。
11 例患者存在与 CPA 相关的突变（7 例 PRKACA 和 4 例 GNAS）。携带这些突变的患者 DST 后皮质醇水平更高（5.6 对 2.6μg/dL，P=0.003），腺瘤更大（2.2±0.3 对 1.9±0.7cm，P=0.025）。具有这些突变的腺瘤中非经典型 uPA 的患病率更高（72.7%对 26.3%，P=0.014）。虽然统计学上无显著意义，但术后肾上腺切除术的 uPA 患者的完全临床缓解率略有增加。DST 后皮质醇水平、腺瘤大小>1.9cm 以及腺瘤大小>1.9cm 与血钾水平的相互作用与这些突变的存在相关。
我们的研究表明，在 uPA/ACS 腺瘤中，检测到与 CPA 相关的突变占 36.7%。这些突变的存在与 DST 后皮质醇水平升高、腺瘤体积增大以及非经典型 uPA 比例升高有关。然而，这些突变并未显著影响 uPA/ACS 患者术后的临床和生化结局，但它们显示出了更好的趋势。
