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Efficacy and Safety of Microwave and Radiofrequency Ablation in the Treatment of Hyperparathyroidism in Older Participants: A Multicenter Prospective Study
微波和射频消融治疗老年甲状旁腺功能亢进症的有效性和安全性：一项多中心前瞻性研究

Research types: multicenter prospective observational study
研究类型：多中心前瞻性观察性研究

Manuscript Type: original article
文稿类型：原创文章

Summary Statement: In older participants with hyperparathyroidism, microwave and radiofrequency ablation were safe and effective minimally invasive alternatives to surgery, and preoperative parathyroid hormone levels were found to be an independent predictor of treatment outcomes
摘要声明：在患有甲状旁腺功能亢进症的老年参与者中，微波和射频消融是安全有效的微创手术替代方案，术前甲状旁腺激素水平被发现是治疗结果的独立预测因素.

Key Results:
主要结果：

1. In this prospective study of 153 older participants with hyperparathyroidism who received microwave ablation (MWA) or radiofrequency ablation (RFA), 80.3% (61/76) of participants with primary hyperparathyroidism (PHPT) were cured, with similar rates observed between MWA (77.8% [42/54]) and RFA (86.4% [19/22], P=.59).
1. 在这项对 153 名接受微波消融（MWA）或射频消融（RFA）治疗的甲状旁腺功能亢进症老年参与者进行的前瞻性研究中，76 名原发性甲状旁腺功能亢进症（PHPT）参与者中有 80.3%（61/76）被治愈，微波消融（77.8% [42/54]）和射频消融（86.4% [19/22]，P=.59）的治愈率相似

2. In participants with secondary hyperparathyroidism (SHPT), the parathyroid hormone (PTH) achievement rate was 89.6% (69/77), with similar rates observed between MWA (92.3% [36/39]) and RFA (86.8% [33/38], P=.48)
2. 在继发性甲状旁腺功能亢进症（SHPT）患者中，甲状旁腺激素（PTH）达标率为 89.6%（69/77），MWA（92.3% [36/39]）和 RFA（86.8% [33/38]，P=0.48）的达标率相似.

3. Preoperative PTH levels were the only independent predictor of treatment outcomes, as determined by univariable (PHPT: odds ratio=1.01, P=.007; SHPT: odds ratio=1.00, P=.01) and multivariable analyses (PHPT: odds ratio=1.01, P=.02; SHPT: odds ratio=1.00, P=.02)
3. 术前 PTH 水平是治疗结果的唯一独立预测因素，单变量分析（PHPT：优势比=1.01，P=0.007；SHPT：优势比=1.00，P=0.01）和多变量分析（PHPT：优势比=1.01，P=0.02；SHPT：优势比=1.00，P=0.02）均支持这一结论.

Abbreviations:
缩写：

ALP: alkaline phosphatase
ALP：碱性磷酸酶

MWA: microwave ablation
MWA：微波消融

PHPT: primary hyperparathyroidism
PHPT：原发性甲状旁腺功能亢进症

PTH: parathyroid hormone
PTH: 甲状旁腺激素

RFA: radiofrequency ablation
RFA: 射频消融术

SHPT: secondary hyperparathyroidism
SHPT: 继发性甲状旁腺功能亢进

Abstract
摘要

Background: Hyperparathyroidism significantly impacts older patients' quality of life and increases mortality risk. While parathyroidectomy remains the standard treatment, thermal ablation techniques have gained increasing attention due to their minimal invasiveness and repeatability.
背景：甲状旁腺功能亢进症显著影响老年患者的生活质量，并增加死亡风险。虽然甲状旁腺切除术仍然是标准治疗方法，但由于其微创性和可重复性，热消融技术正受到越来越多的关注。

Purpose: To evaluate and compare the efficacy and safety of microwave ablation (MWA) and radiofrequency ablation (RFA) in the treatment of older participants with primary hyperparathyroidism (PHPT) and secondary hyperparathyroidism (SHPT)
目的：评估和比较微波消融（MWA）和射频消融（RFA）在治疗原发性甲状旁腺功能亢进症（PHPT）和继发性甲状旁腺功能亢进症（SHPT）的老年患者中的有效性和安全性.

Materials and Methods: This prospective, multicenter study included older participants (≥55 years of age) with PHPT or SHPT who underwent either MWA or RFA therapy between September 2017 and March 2022. Treatment outcomes were assessed through cure rates, parathyroid hormone (PTH) achievement rates (defined as the proportion of participants who maintain target PTH levels for at least 6 months during follow-up), or biochemical parameters. Early and late complications were evaluated during the 24-month follow-up period. A generalized linear mixed model was used to evaluate changes in PTH, calcium, phosphate, and alkaline phosphatase (ALP) levels. Inverse probability weighting was employed to minimize selection bias. Univariable and multivariable analyses were performed to pinpoint risk factors linked to treatment outcomes. Odds ratios with 95% CIs were calculated.
材料与方法：这项前瞻性、多中心研究纳入了 2017 年 9 月至 2022 年 3 月期间接受 MWA 或 RFA 治疗的 PHPT 或 SHPT 老年患者（年龄≥55 岁）。通过治愈率、甲状旁腺激素（PTH）达标率（定义为随访期间至少 6 个月维持目标 PTH 水平的患者比例）或生化指标评估治疗效果。在 24 个月的随访期间评估早期和晚期并发症。采用广义线性混合模型评估 PTH、钙、磷和碱性磷酸酶（ALP）水平的变化。采用逆概率加权法以减少选择偏倚。进行单变量和多变量分析以确定与治疗结果相关的风险因素。计算了 95%置信区间（CI）的比值比。

Results: This study includes 153 participants (mean: 63.3±6.9 years[SD], 98 female) with hyperparathyroidism. The overall cure rate for participants with PHPT was 80.3% (61/76), with similar rates observed between MWA (77.8% [42/54]) and RFA (86.4% [19/22], P= .59), while the PTH achievement rate for SHPT was 89.6% (69/77), with similar rates observed between MWA (92.3% [36/39]) and RFA (86.8% [33/38], P=.48). Both techniques resulted in decreases in serum PTH, calcium, and ALP levels from baseline through follow-up to 24 months. Preoperative PTH levels were the only independent predictor of treatment outcomes, as determined by univariable (PHPT: odds ratio=1.01, P=.007; SHPT: odds ratio=1.00, P=.01) and multivariable analyses (PHPT: odds ratio=1.01, P=.02; SHPT: odds ratio=1.00, P=.02). Complications were predominantly transient, with transient hypocalcemia being the most common (PHPT: 13.2% [10/76], SHPT: 50.6% [39/77]). No evidence of a difference was observed in complication rates between MWA and RFA groups (PHPT: 14.8% [8/54] in MWA vs 27.3% [6/22] in RFA, P = .21; SHPT: 92.3% [36/39] in MWA vs 86.8% [33/38] in RFA, P = .48)
结果：本研究包括 153 名参与者（平均年龄：63.3±6.9 岁[标准差]，98 名女性），患有甲状旁腺功能亢进症。PHPT 参与者的总体治愈率为 803%（61/76），MWA（77.8% [42/54]）和 RFA（86.4% [19/22]，P=0.59）的治愈率相似，而 SHPT 的 PTH 达标率为 89.6%（69/77），MWA（92.3% [36/39]）和 RFA（86.8% [33/38]，P=0.48）的达标率相似。两种技术均导致血清 PTH、钙和 ALP 水平从基线到 24 个月随访期间下降。术前 PTH 水平是治疗结果的唯一独立预测因素，单变量分析（PHPT：优势比=1.01，P=0.007；SHPT：优势比=1.00，P=0.01）和多变量分析（PHPT：优势比=1.01，P=0.02；SHPT：优势比=1.00，P=0.02）均支持这一结论。并发症主要为暂时性，其中暂时性低钙血症最为常见（PHPT：132% [10/76]，SHPT：50.6% [39/77] ）。MWA 组和 RFA 组在并发症发生率上未观察到差异（PHPT：MWA 组 14.8% [8/54] vs RFA 组 27.3% [6/22]，P=0.21；SHPT：MWA 组 92.3% [36/39] vs RFA 组 86.8% [33/38]，P=0.48）。.

Conclusion: In older participants with hyperparathyroidism, MWA and RFA were safe and effective minimally invasive alternatives to surgery, and preoperative PTH levels were found to be an independent predictor of treatment outcomes
结论：对于患有甲状旁腺功能亢进症的老年患者，MWA 和 RFA 是安全有效的微创手术替代方案，并且术前 PTH 水平被发现是治疗结果的独立预测因素.

Chinese Clinical Trial Registry: ChiCTR-ONC-17012760
中国临床试验注册：ChiCTR-ONC-17012760

Introduction
引言

Primary hyperparathyroidism (PHPT) and secondary hyperparathyroidism (SHPT) represent prevalent endocrine disorders. PHPT predominantly arises from parathyroid adenomas [1], whereas SHPT develops due to parathyroid chief cell hyperplasia resulting from calcium and phosphorus metabolic imbalances secondary to renal dysfunction [2]. Both conditions are characterized by elevated parathyroid hormone (PTH) secretion. Persistent elevation of PTH levels exacerbates mineral bone metabolism disorders, heightens the risk of osteoporosis and fractures, and may precipitate severe cardiovascular complications [1,3-5]. These complications significantly diminish patients' quality of life and increase mortality risk, with particularly profound implications for elderly individuals.
原发性甲状旁腺功能亢进症（PHPT）和继发性甲状旁腺功能亢进症（SHPT）是常见的内分泌疾病。PHPT 主要是由甲状旁腺腺瘤引起的[1]，而 SHPT 是由于肾功能导致的钙和磷代谢失衡引起的甲状旁腺主细胞增生而发展[2]。这两种疾病的特点是甲状旁腺激素（PTH）分泌增加。PTH 水平的持续升高会加剧矿物质骨代谢紊乱，增加骨质疏松和骨折的风险，并可能引发严重的心血管并发症[1,3-5]。这些并发症会显著降低患者的生活质量，增加死亡风险，对老年人尤其影响深远。

Parathyroidectomy improves long-term improvements in quality of life for hyperparathyroidism, with systematic reviews showing sustained Short Form (36) Health Survey score or Parathyroidectomy Assessment of Symptoms enhancements in over 87% of cases at a minimum of 1-year postoperative follow-up [6]. It improves distal radius bone geometry in PHPT [7], reduced hip fracture risk in dialysis patients without prior osteoporotic fractures [8], lowers calcific uremic arteriolopathy wound deterioration risk[9] and ameliorates anemic[10]. However, the overall complication rate of parathyroidectomy ranges from 3.8% to 15.1% [11-14], including hemorrhage (0.0-5.7%), infection (0.8-4.9%), permanent hypoparathyroidism (9.2-10%), and permanent recurrent laryngeal nerve injury (2.1%), transient hypocalcemia (15-59%) , and permanent hypocalcemia (0-27%). Moreover, accumulating evidence highlights the unique risks of parathyroidectomy in older patients [15]. A study of 7313 patients revealed that elders experienced significantly higher rates of respiratory complications (0.9% versus 0.3%, P< .01) and extended hospital stays compared to younger cohorts [16]. Against this backdrop, MWA and RFA technologies have demonstrated promising applications as minimally invasive therapeutic modalities. While cure rates between thermal ablation and parathyroidectomy for primary hyperparathyroidism are comparable [17], thermal ablation achieves similar efficacy (microwave ablation [MWA]: 77.8%; radiofrequency ablation [RFA]: 86.4%) with fewer major complications (6.9% versus 3.4%, P=.50) and faster recovery. So, thermal ablation may represent a suitable treatment approach for older patients. However, existing studies on thermal ablation for hyperparathyroidism have largely focused on general adult populations, with limited representation of older patients.
甲状旁腺切除术可改善甲状旁腺功能亢进症患者的长期生活质量，系统评价显示，术后至少 1 年的随访中，超过 87%的病例持续保持短期健康调查量表（36）评分或甲状旁腺切除术症状评估的改善[6]。它可改善甲状旁腺功能亢进症患者的桡骨远端骨几何形态[7]，降低无既往骨质疏松性骨折的透析患者的髋部骨折风险[8]，降低钙化性尿毒症性动脉病伤口恶化风险[9]，并改善贫血[10]。然而，甲状旁腺切除术的总并发症发生率在 3.8%至 15.1%之间[11-14]，包括出血（0.0-5.7%）、感染（0.8-4.9%）、永久性甲状旁腺功能减退（9.2-10%）、永久性喉返神经损伤（2.1%）、暂时性低钙血症（15-59%）和永久性低钙血症（0-27%）。此外，越来越多的证据突出了老年患者接受甲状旁腺切除术的独特风险[15]。一项涉及 7313 名患者的研究显示，与年轻群体相比，老年人经历呼吸并发症的比率显著更高（0.9% versus 0.3%，P< .01）且住院时间更长[16]。 在此背景下，MWA 和 RFA 技术已展现出作为微创治疗方式的良好应用前景。虽然对于原发性甲状旁腺功能亢进症，热消融术与甲状旁腺切除术的治愈率相当[17]，但热消融术在达到相似疗效（微波消融术[MWA]: 77.8%；射频消融术[RFA]: 86.4%）的同时，并发症更少（6.9%对比 3.4%，P=.50），且恢复更快。热消融术可能适合老年患者。然而，目前关于甲状旁腺功能亢进症热消融术的研究大多集中于普通成人群体，老年患者的代表性有限。

MWA employs high-frequency electromagnetic waves to generate heat, thereby directly destroying pathological tissue; conversely, RFA utilizes electrodes to produce high-frequency currents that heat and eliminate diseased tissue. Both techniques feature minimal trauma, quick recovery, few complications, and can be performed under local anesthesia [18-21]
MWA 利用高频电磁波产生热量，从而直接破坏病变组织；相反，RFA 通过电极产生高频电流，加热并消除病变组织。这两种技术均具有创伤小、恢复快、并发症少的特点，且可在局部麻醉下进行[18-21].

We hypothesized that MWA and RFA would provide safe and effective treatment in older participants with PHPT and SHPT. Accordingly, this study aims to evaluate and compare the efficacy and safety of MWA and RFA techniques in the treatment of older participants with PHPT and SHPT
我们假设 MWA 和 RFA 能为患有 PHPT 和 SHPT 的老年患者提供安全有效的治疗。因此本研究旨在评估并比较 MWA 和 RFA 技术在治疗患有 PHPT 和 SHPT 的老年患者中的疗效与安全性.

Material and Methods
材料与方法

Study Design
研究设计

The protocol was registered at chictr.org.cn (ChiCTR-ONC-17012760) and approved by the Medical Ethics Committee of PLA General Hospital (S2017-058-03). All participants provided informed consent. This study collected data from participants aged ≥55 years with PHPT or SHPT treated at five hospitals between September 2017 and March 2022. The 55-year threshold was chosen because participants with chronic kidney disease–mineral and bone disorder or PHPT exhibit accelerated aging features, including earlier vascular calcification, indicating a physiological mismatch in aging [1,3-5]
该方案已在中国临床试验注册中心注册（ChiCTR-ONC-17012760），并获得解放军总医院医学伦理委员会批准（S2017-058-03）。所有参与者均签署了知情同意书。本研究收集了 2017 年 9 月至 2022 年 3 月间在五家医院接受治疗的年龄≥55 岁的 PHPT 或 SHPT 患者数据。选择 55 岁作为阈值是因为慢性肾脏病-矿物质与骨病或 PHPT 患者表现出加速衰老特征，包括更早的血管钙化，表明其衰老存在生理性不匹配[1,3-5].

Diagnosis of PHPT and SHPT were established followed guidelines [22,23]. PHPT inclusion criteria (Figure 1): (1) symptomatic PHPT with renal, skeletal, neurological, gastrointestinal, and psychiatric symptoms; or asymptomatic PHPT meeting at least one of the following treatment conditions recommended by the American Association of Endocrine Surgeons (AAES) guidelines [22]: serum calcium > 0.25 mmol/L above normal; dual-energy X-ray absorptiometry revealing T-scores of <-2.5 at the lumbar spine, total hip, femoral neck, or distal radius; vertebral fractures; creatinine clearance <60 mL/min; 24-hour urinary calcium >400 mg/day with stone risk, or nephrolithiasis/renal calcifications; (2) ultrasound revealing at least one hypoechoic parathyroid nodule >5 mm; (3) participants unsuitable for surgery or who refuse surgery and active monitoring with suitable percutaneous access; (4) adequate coagulation status; (5) aged ≥55 years
PHPT 和 SHPT 的诊断遵循指南[22,23]。PHPT 纳入标准（图 1）：(1)有症状的 PHPT 伴肾脏、骨骼、神经、胃肠道和精神症状；或无症状 PHPT 符合美国内分泌外科医师协会（AAES）指南[22]推荐的至少以下一种治疗条件：血清钙高于正常值 0.25 mmol/L；双能 X 射线吸收测定法显示腰椎、总髋部、股骨颈或远端桡骨 T 值≤-2.5；椎体骨折；肌酐清除率<60 mL/min；24 小时尿钙>400 mg/天伴结石风险，或肾结石/肾钙化；(2)超声显示至少一个直径>5 mm 的低回声甲状旁腺结节；(3)不适合手术或拒绝手术且无合适经皮通路进行积极监测的参与者；(4)凝血功能良好；(5)年龄≥55 岁.

PHPT exclusion criteria: (1) secondary/tertiary hyperparathyroidism; (2) no ultrasound-visible lesion; (3) severe coagulopathy; (4) significant cardiopulmonary insufficiency; (5)Follow-up <6 months; (6)age <55 years
PHPT 排除标准：(1)继发性/三发性甲状旁腺功能亢进；(2)无超声可见病变；(3)严重凝血功能障碍；(4)显著心肺功能不全；(5)随访<6 个月；(6)年龄<55 岁.

SHPT inclusion criteria: (1) SHPT participants unable to tolerate pharmacological treatment; (2) PTH >800 pg/mL, or persistent hypercalcemia/hyperphosphatemia below this threshold; (3) ultrasound revealing at least one hypoechoic parathyroid nodule >5 mm; (4) severe symptoms such affecting quality of life; (5) participants unsuitable for surgery or who refuse surgery and active monitoring with suitable percutaneous access; (6) adequate coagulation status; (7) aged ≥55 years.
SHPT 纳入标准：(1)无法耐受药物治疗的原发性甲状旁腺功能亢进症（SHPT）患者；(2)甲状旁腺激素（PTH）>800 pg/mL，或持续性高钙血症/高磷血症低于此阈值；(3)超声检查显示至少有一个直径>5 mm 的低回声甲状旁腺结节；(4)严重症状影响生活质量；(5)不适合手术或拒绝手术且无合适经皮通路进行积极监测的患者；(6)凝血功能良好；(7)年龄≥55 岁。

SHPT exclusion criteria: (1) primary/tertiary hyperparathyroidism; (2) no ultrasound-visible lesion; (3) prior neck surgery; (4) coagulopathy; (5) severe cardiopulmonary insufficiency; (6) Follow-up <6 months; (7)age <55 years. To facilitate reading and comparison, the inclusion and exclusion criteria in tabular form have been presented in Supplementary Table 1
SHPT 排除标准：(1)原发性/继发性甲状旁腺功能亢进；(2)无超声可见病变；(3)既往颈部手术；(4)凝血功能障碍；(5)严重心肺功能不全；(6)随访时间<6 个月；(7)年龄<55 岁。为便于阅读和比较，纳入和排除标准以表格形式呈现于补充表 1.

Basic participant information, including age, gender, underlying conditions, dialysis history, clinical symptoms, and treatment methods, were collected. Laboratory assessments included pre-ablation serum levels of PTH, calcium, phosphorus, alkaline phosphatase (ALP), creatinine, and nitrogen. Clinical data encompassed the number, size, volume, and location of parathyroid nodules.
收集了基本参与者信息，包括年龄、性别、基础疾病、透析史、临床症状和治疗方式。实验室评估包括消融前血清甲状旁腺激素（PTH）、钙、磷、碱性磷酸酶（ALP）、肌酐和氮水平。临床数据涵盖甲状旁腺结节的数量、大小、体积和位置。

Ablation Procedure
消融手术

Each center focused on MWA or RFA according to its technical expertise and available equipment.
每个中心根据其技术专长和可用设备，专注于微波消融（MWA）或射频消融（RFA）。

The five chief physicians, from five distinct centers, performed MWA and RFA procedures. They had individually completed a cumulative total of 1200 MWA/RFA thyroid/parathyroid cases and possessed 10-12 years of experience in interventional ultrasound. All operators were certified through the standardized training system of their respective centers.
来自五个不同中心的五位首席医师执行了 MWA 和 RFA 手术。他们分别完成了 1200 例甲状腺/甲状旁腺 MWA/RFA 病例，并在介入超声领域拥有 10-12 年的经验。所有操作医师均通过各自中心的标准化培训系统获得认证。

MWA employs generators from Kangyou Medical (China) or ECO Microwave Systems (China), equipped with cooling electrodes. RFA utilizes the Cooltip radiofrequency ablation system (USA) or generators from Covidien (USA), also featuring cooling electrodes. All procedures were conducted under ultrasound guidance[24] with local anesthesia (lidocaine). Hydrodissection (saline or 5% dextrose) was employed to protect surrounding tissues (Figure 2)
MWA 采用来自中国康莱德医疗的发电机或中国 ECO 微波系统公司的发电机，配备冷却电极。RFA 使用美国 Cooltip 射频消融系统或美国科迪恩公司的发电机，同样配备冷却电极。所有手术均在超声引导[24]下进行，使用局部麻醉（利多卡因）。采用水分离技术（生理盐水或 5%葡萄糖）以保护周围组织（图 2）。.

The ablation method was complete conformal ablation, which means that the hyperplastic, solitary parathyroid gland would be completely ablated without extending the ablation margin beyond the lesion boundaries For SHPT participants, all ultrasonographically visible parathyroid nodules were ablated in one session to maximize PTH reduction. Ultrasound microbubbles formation signifies ablation completion
消融方法是完全适形消融，这意味着增生性、单个的甲状旁腺将被完全消融，消融边缘不会超出病灶边界。对于 SHPT 参与者，所有超声可见的甲状旁腺结节均在一次手术中消融，以最大程度降低 PTH 水平。超声微泡的形成标志着消融完成。.

Ablation success was defined as complete nodule coverage[25], confirmed by contrast-enhanced ultrasound (CEUS) 5–10 minutes post-procedure[26]. Comprehensive procedural parameters, including device specifications, preoperative imaging protocols, ablation techniques for both PHPT and SHPT, and intraoperative assessment methods, are provided in Supplementary Table 2
消融成功定义为完全结节覆盖[25]，并通过术后 5–10 分钟增强超声（CEUS）确认[26]。补充表 2 提供了全面的操作参数，包括设备规格、术前影像协议、甲状旁腺功能亢进（PHPT）和 SHPT 的消融技术，以及术中评估方法.

Follow-up and Outcomes
随访与结果

Follow-up occurred at 2 hours, 1 day, 3 days, 7 days, 1 month, 3 months, and 6 months post-procedure, with evaluations every 6 months thereafter. Assessments focused on serum PTH, calcium, phosphorus, and ALP dynamics. Following Interventional Radiology Society standards[25], safety comparisons between the RFA and MWA groups was conducted, documenting all complications, and adverse events.
术后 2 小时、1 天、3 天、7 天、1 个月、3 个月和 6 个月进行随访，之后每 6 个月评估一次。评估内容包括血清 PTH、钙、磷和 ALP 的干预后动态变化，遵循介入放射学协会标准[25]，进行了 RFA 组和 MWA 组的比较，记录了所有并发症和不良事件。

For PHPT, the primary outcome was cure rate, defined as the proportion of participants who maintain normal serum levels of PTH (15-65 pg/mL) and calcium (2.09-2.54 mmol/L) for at least 6 months during follow-up after receiving treatment . For SHPT, the primary outcome was PTH achievement rates, defined as the proportion of participants who maintain PTH <585 pg/mL for at least 6 months during follow-up according to The Kidney Disease: Improving Global Outcomes (KDIGO) 2024 chronic kidney disease–mineral and bone disorder guidelines [23]
对于 PHPT，主要结局是治愈率，定义为在治疗后随访期间至少 6 个月维持 PTH（15-65 pg/mL）和钙（2.09-2.54 mmol/L）正常血清水平的参与者比例。对于 SHPT，主要结局是 PTH 达标率，定义为根据《肾脏病：改善全球结局》（KDIGO）2024 慢性肾脏病-矿物质与骨异常指南[23]，在随访期间至少 6 个月维持 PTH <585 pg/mL 的参与者比例。.

The secondary outcome included longitudinal changes in serum levels of PTH, calcium, phosphorus, ALP over time and the incidence of complications. Hypocalcemia is defined as serum calcium level <2.09 mmol/L, categorized as transient (≤6 months) and persistent (>6 months) forms[27]. Complications were classified as early (≤30 days post-ablation) or late (>30 days) [25]. Early complications included procedure-related events (e.g., fever, hematoma, transient hypocalcemia, etc.), while late complications encompassed metabolic derangements (e.g., persistent hypocalcemia, etc.).
次要结局包括 PTH、钙、磷、ALP 血清水平的纵向变化以及并发症的发生率。低钙血症定义为血清钙水平 <2.09 mmol/L，分为暂时性（≤6 个月）和持续性（>6 个月）两种形式[27]。并发症分为早期（消融术后≤30 天）或晚期（>30 天）[25]。早期并发症包括与手术相关的并发症（如发热、血肿、暂时性低钙血症等），而晚期并发症包括代谢紊乱（如持续性低钙血症等）。

Statistical Analysis
统计分析

This study utilized SPSS 27.0 and R 4.0.2 for data analysis (performed by Zhang LX). Continuous variables were represented as mean ± standard deviation or median(IQR), categorical variables as frequencies and percentages, and baseline intergroup balance was assessed using standardized differences. Categorical variables were compared using chi-square test or Fisher's exact test. All tests were two-sided, with a p-value of less than 0.05 considered statistically significant.
本研究采用 SPSS 27.0 和 R 4.0.2 进行数据分析（由张 LX 执行）。连续变量以均值±标准差或中位数（四分位数间距）表示，分类变量以频率和百分比表示，并使用标准化差异评估基线组间均衡性。分类变量比较采用卡方检验或 Fisher 精确检验。所有检验均为双侧检验，p 值小于 0.05 视为具有统计学意义。

To mitigate selection bias between MWA and RFA groups, inverse probability weighting based on propensity scores was applied.The propensity models included preoperative biochemical parameters relevant to PHPT and SHPT. Logistic regression models were used for univariable and multivariable analyses of prognostic factors. Longitudinal changes in PTH, calcium, phosphorus, and ALP were assessed using generalized linear mixed models with fixed effects (ablation type, time, interaction) and random effects (participants, centers), with pairwise Wald tests used to assess intergroup differences at each follow-up time point. Interaction terms were included to explore whether associations between key parameters and outcomes differed between PHPT and SHPT participants
为减轻 MWA 组和 RFA 组之间的选择偏倚，采用了基于倾向评分的逆概率加权方法。倾向模型包含了与 PHPT 和 SHPT 相关的术前生化参数。采用逻辑回归模型进行预后因素的单变量和多变量分析。使用具有固定效应（消融类型、时间、交互作用）和随机效应（参与者、中心）的广义线性混合模型评估 PTH、钙、磷和 ALP 的纵向变化，并使用配对 Wald 检验在每个随访时间点评估组间差异。纳入交互项以探索关键参数与结果之间的关联是否在 PHPT 和 SHPT 参与者之间存在差异。.

Results
结果

Participant Characteristics.
参与者特征。

This study included a total of 153 participants aged 55 years and older with hyperparathyroidism(mean age: 63.3±6.9 years [SD], age range: 55 to 86 years, 98 female), comprising 76 participants with PHPT and 77 participants with SHPT (Table 1). For PHPT, 135 participants were initially assessed, with 12 exclusions (1 due to tertiary hyperparathyroidism and 11 lost to follow-up), subsequently excluded 47 participants aged <55 years，resulting in a final analysis study sample of 76 participants≥55 years , where 73 participants had a single adenoma and 3 had double adenomas (Figure 1). For SHPT, 255 participants were initially assessed, and 73 participants were excluded (28 due to tertiary hyperparathyroidism, 17 with a history of cervical surgery, 3 with PTH levels below 800 pg/mL and no uncontrolled hypercalcemia or hyperphosphatemia, and 25 lost to follow-up), subsequently excluded 105 participants aged <55 years. Ultimately, 77 participants≥55 years were included in the final analysis. Of these 77 participants, 7, 17, 21, and 32 had one, two, three, and four adenomas, respectively. The demographics and clinical characteristics of the study population are summarized in Table 1. Baseline characteristics before and after inverse probability weighting are presented in Supplementary Table 3
这项研究共包括 153 名 55 岁及以上的甲状旁腺功能亢进症患者（平均年龄：63.3±6.9 岁 [标准差]，年龄范围：55 至 86 岁，98 名女性），其中包括 76 名原发性甲状旁腺功能亢进症患者（PHPT）和 77 名继发性甲状旁腺功能亢进症患者（SHPT）（表 1）。对于 PHPT，最初评估了 135 名患者，排除 12 名患者（1 名因三发性甲状旁腺功能亢进症被排除，11 名因失访被排除），随后排除 47 名年龄<55 岁的患者，最终分析研究样本为 76 名年龄≥55 岁的患者，其中 73 名患者有一个腺瘤，3 名患者有两个腺瘤（图 1）。对于 SHPT，最初评估了 255 名患者，排除 73 名患者（28 名因三发性甲状旁腺功能亢进症被排除，17 名有颈椎手术史，3 名 PTH 水平低于 800 pg/mL 且无未控制的血钙或血磷升高，25 名因失访被排除），随后排除 105 名年龄<55 岁的患者，最终分析研究样本为 77 名年龄≥55 岁的患者。在这 77 名患者中，有 1 个、2 个、3 个和 4 个腺瘤的患者分别有 7、17、21 和 32 名。 研究人群的人口统计学和临床特征总结于表 1。反概率加权前后的基线特征列于补充表 3.

Primary outcome: Cure Rate in PHPT and PTH Achievement in SHPT
主要结果：PHPT 治愈率和 SHPT PTH 达标率

Both MWA and RFA successfully ablated the target nodules in all participants with PHPT and SHPT, with no evidence of a difference in outcomes (P=.59 for PHPT and P= .48 for SHPT). Among participants with PHPT, the cure rate was 80.3% (61/76), with similar rates between MWA (77.8% [42/54]) and RFA 86.4% ([19/22], P=.59). For participants with SHPT, the overall PTH achievement rate attained was 89.6% (69/77). Both the MWA and RFA groups exhibited similar PTH achievement rates in participants with SHPT (92.3% [36/39] for MWA, 86.8% [33/38] for RFA, P=.48)
对于 PHPT 和 SHPT 患者，MWA 和 RFA 均成功消融了目标结节，且结果无显著差异（PHPT P=.59，SHPT P=48）。在 PHPT 患者中，治愈率为 80.3%（61/76），MWA（77.8% [42/54]）和 RFA（86.4% [19/22]，P=.59）的治愈率相似。在 SHPT 患者中，总体 PTH 达标率为 89.6%（69/77）。MWA 和 RFA 组在 SHPT 患者中的 PTH 达标率相似（MWA 为 92.3% [36/39]，RFA 为 86.8% [33/38]，P=.48）.

Secondary outcome: Longitudinal Changes in Serum PTH, Calcium, Phosphorus, and ALP
次要结果：血清 PTH、钙、磷及 ALP 的纵向变化.

Both PHPT and SHPT groups demonstrated changes in serum PTH, calcium, phosphorus, and ALP levels throughout the 24-month follow-up period (Figure 3). In participants with PHPT, serum PTH, calcium, and ALP levels decreased from baseline to 24 months (MWA: 191.66 to 60.14 pg/mL, P<.001; 2.68 to 2.49 mmol/L, P<.001; 98.67 to 63.80 IU/L, P<.001, respectively) (RFA: 195.84 to 45.57 pg/mL, P<.001; 2.71 to 2.37 mmol/L, P<.001; 126.71 to 73.89 IU/L, P=.01, respectively), while phosphorus levels increased following both MWA and RFA procedures (MWA: 0.90 to 1.17 mmol/L, P<.001; RFA: 0.85 to 1.21 mmol/L, P<.001) (Figures 3A-D). In PHPT participants, serum PTH levels decreased from pre-ablation baselines (MWA: 191.66 ± 11.89 pg/mL [SD]; RFA: 195.84 ± 16.93 pg/mL[SD]) to nadir values (MWA: 31.43 ± 11.98[SD] pg/mL, P<.001; RFA: 25.40 ± 17.36[SD] pg/mL, P<.001). Despite a slight rebound in PTH values on day 7 post-procedure (MWA: 85.77 ± 13.34[SD] pg/mL; RFA: 34.87 ± 17.62[SD] pg/mL), mean values remained within normal ranges throughout the follow-up. No differences were observed between MWA and RFA groups in the changes of all biochemical parameters for PHPT participants throughout the 24-month follow-up (PTH: P=.48; calcium: P=.21; phosphorus: P=.21; ALP: P=.36).
PHPT 组和 SHPT 组在整个 24 个月的随访期间均显示出血清 PTH、钙、磷和 ALP 水平的变化（图 3）。在 PHPT 患者中，血清 PTH、钙和 ALP 水平从基线到 24 个月下降（MWA：191.66 至 60.14 pg/mL，P<.001；2.68 至 2.49 mmol/L，P<.001；98.67 至 63.80 IU/L，P<.001，分别）（RFA：195.84 至 45.57 pg/mL，P<.001；2.71 至 2.37 mmol/L，P<.001；126.71 至 73.89 IU/L，P=.01，分别），而磷水平在 MWA 和 RFA 手术后均升高（MWA：0.90 至 1.17 mmol/L，P<.001；RFA：0.85 至 1.21 mmol/L，P<.001）（图 3A-D）。在 PHPT 患者中，血清 PTH 水平从消融前基线（MWA：191.66 ± 11.89 pg/mL [SD]；RFA：195.84 ± 16.93 pg/mL[SD]）下降至最低值（MWA：31.43 ± 11.98[SD] pg/mL，P<.001；RFA：25.40 ± 17.36[SD] pg/mL，P<.001）。尽管在术后第 7 天 PTH 值略有反弹（MWA：85.77 ± 13.34[SD] pg/mL；RFA：34.87 ± 17.62[SD] pg/mL），但平均值在整个随访期间均保持在正常范围内。 在整个 24 个月的随访期间，对于 PHPT 参与者，MWA 组和 RFA 组在所有生化参数的变化方面没有观察到差异（PTH：P=.48；钙：P=.21；磷：P=.21；ALP：P=.36）。

Similarly, participants with SHPT exhibited a decrease in serum PTH levels from baseline (MWA: 1605.46 ± 138.93 pg/mL; RFA: 1377.37 ± 143.66 pg/mL) to relatively stable levels (1 month, MWA: 128.68 ± 60.92[SD] pg/mL, P<.001; RFA: 225.46 ± 61.79[SD] pg/mL, P<.001) after both procedures (Figures 3E-H). Calcium and phosphorus levels also decreased during follow-up from baseline to 1 months (MWA: 2.54 to 2.13 mmol/L, P<.001; 2.41 to 1.98 mmol/L, P<.001, respectively). Differences in calcium levels between MWA and RFA groups were observed at 2 hours, and 6 months (2 hours: 2.37 versus 2.18 mmol/L, P=.03; 6 months: 2.30 versus 1.96 mmol/L, P=.001, respectively). In contrast, ALP levels showed an initial increase (at 2 hours, MWA: 243.08 to 337.30 IU/L, P=.09; at 7 days, RFA: 244.05 to 270.00 IU/L , P=.55) followed by a gradual decline (MWA: 97.74 IU/L, P<.001; RFA: 98.05 IU/L at 24 months, P<.001) (Figure 3H). To provide a clearer depiction of trends over time, the follow-up analyses are also presented as differences from baseline (Figure 4). Specifically, the changes in serum PTH, calcium, phosphorus, and ALP levels are calculated as the difference between each follow-up time point and the baseline measurement for both PHPT and SHPT participants
同样地，患有 SHPT 的参与者在基线后血清 PTH 水平有所下降（MWA：1605.46 ± 138.93 pg/mL；RFA：1377.37 ± 143.66 pg/mL），在两种手术后的水平相对稳定（1 个月 MWA：128.68 ± 60.92[SD] pg/mL，P<.001；RFA：225.46 ± 61.79[SD] pg/mL，P<.001）（图 3E-H）。钙和磷水平在随访期间从基线到 1 个月也下降（MWA：2.54 至 2.13 mmol/L，P<.001；241 至 1.98 mmol/L，P<.001，分别）。MWA 组和 RFA 组之间的钙水平差异在 2 小时和 6 个月时出现（2 小时：2.37 与 2.18 mmol/L，P=.03；6 个月：2.30 与 1.96 mmol/L，P=.001，分别）。相比之下，ALP 水平最初上升（在 2 小时，MWA：243.08 至 337.30 IU/L，P=0.9；在 7 天 RFA：24405 至 27000 IU/L，P=0.55），随后逐渐下降（MWA：97.74 IU/L，P<.001；RFA：98.05 IU/L 在 24 个月，P<.001）（图 3H）。为了更清晰地展示随时间变化的趋势，随访分析也以与基线的差异形式呈现（图 4）。 具体来说，对于 PHPT 和 SHPT 参与者，血清 PTH、钙、磷和 ALP 水平的改变被计算为每个随访时间点与基线测量值的差值.

Risk Factors Associated with Treatment Outcomes
与治疗结果相关的风险因素

Both univariable and multivariable analyses were performed to pinpoint risk factors linked to treatment outcomes in participants with PHPT and SHPT (Table 2). In PHPT participants, univariable analysis showed that preoperative PTH levels were associated with a lower probability of cure (odds ratio=1.01, 95% CI: 1.00-1.01, P=.007), and this association persisted in multivariable analysis (odds ratio=1.01, 95% CI: 1.00-1.01, P=.02). For participants with SHPT, preoperative PTH was also the only predictor of failure (univariable odds ratio=1.00, 95% CI: 1.00-1.00, P=.01; multivariable odds ratio=1.00, CI: 1.00-1.00, P=.02). The optimal PTH cut-off values for predicting treatment failure were 263.3 pg/mL for PHPT and 1749.65 pg/mL for SHPT, with area under the receiver operating characteristic curve (AUC) values of 0.76 (95% CI: 0.59, 0.92) and 0.79 (95% CI: 0.54, 0.95), respectively (Supplementary Figure 4). In addition, to investigate whether the associations between various parameters and treatment outcomes differ between participants with PHPT versus SHPT, interaction terms were introduced between Disease Type and key parameters (calcium, phosphorus, parathyroid size volume, number of parathyroid, ablation method, and maximum diameter) in the model. The interaction analysis revealed that none of the interaction terms reached statistical significance, and there is no evidence of a difference in these parameters and treatment outcomes between participants with PHPT versus SHPT (P values: calcium =.92, phosphorus=.17, volume =.80, diameter=.57, ablation method .80, number of parathyroid=.22).
对 PHPT 和 SHPT 参与者进行了单变量和多变量分析，以确定与治疗结果相关的风险因素（表 2）。 在 PHPT 参与者中，单变量分析显示术前 PTH 水平与治愈概率较低相关（优势比=1.01，95%置信区间：1.00-1.01，P=.007），这种关联在多变量分析中仍然存在（优势比=1.01，95%置信区间：1.00-1.01，P=.02）。对于 SHPT 参与者，术前 PTH 也是失败的唯一预测因子（单变量优势比=1.00，95%置信区间：1.00-1.00，P=.01；多变量优势比=1.00，置信区间：1.00-1.00，P=.02）。预测治疗失败的 PTH 最佳截断值分别为 PHPT 的 263.3 pg/mL 和 SHPT 的 1749.65 pg/mL，其受试者工作特征曲线下面积（AUC）值分别为 0.76（95%置信区间：0.59，0.92）和 0.79（95%置信区间：0.54，0.95）（补充图 4）。此外，为了研究不同参数与治疗结果之间的关联在 PHPT 与 SHPT 参与者之间是否存在差异，在模型中引入了疾病类型与关键参数（钙、磷、甲状旁腺体积大小、甲状旁腺数量、消融方法和最大直径）之间的交互项。 交互分析显示，没有任何交互项达到统计学显著性，且在 PHPT 与 SHPT 参与者之间，这些参数和治疗结果无差异（P 值：钙=0.92，磷=0.17，体积=0.80，直径=0.57，消融方法=0.80，甲状旁腺数量=0.22）。

Complications
并发症

Most complications were temporary and resolved within one month without specific treatment, and there was no evidence of a difference in the incidence of complications between participants who received MWA versus RFA within both the PHPT and SHPT subgroups (PHPT: 14.8% [8/54] in MWA vs 27.3% [6/22] in RFA, P=.21; SHPT: 92.3% [36/39] in MWA vs 86.8% [33/38] in RFA, P=.48). In participants with PHPT, early complications included transient hypocalcemia in 13.2% (10/76) of participants (11.1% [6/54] in MWA and 18.2% [4/22] in RFA, P=.46) resolving within 3-30 days. Late complications comprised temporary hoarseness in 2.6% (2/76) of participants (1.9% [1/54] in MWA, 4.5% [1/22] in RFA, P=.50) with a recovery range of 30-180 days, and persistent hypocalcemia in 2.6% (2/76) of participants (1.9% [1/54] in MWA, 4.5% [1/22] in RFA, P=.50), with no cases of persistent hypoparathyroidism observed.
大多数并发症是暂时的，在一个月内无需特定治疗即可自行解决，且在 PHPT 和 SHPT 亚组中，接受 MWA 治疗的患者与接受 RFA 治疗的患者之间并发症发生率无显著差异（PHPT：MWA 组为 14.8% [8/54]，RFA 组为 27.3% [6/22]，P=.21；SHPT：MWA 组为 92.3% [36/39]，RFA 组为 86.8% [33/38]，P=.48）。在 PHPT 患者中，早期并发症包括 132%的参与者（10/76）出现暂时性低钙血症（MWA 组为 111% [6/54]，RFA 组为 18.2% [4/22]，P=.46），在 3-30 天内自行恢复。晚期并发症包括 2.6%的参与者（2/76）出现暂时性声音嘶哑（MWA 组为 1.9% [1/54]，RFA 组为 4.5% [1/22]，P=50），恢复时间为 30-180 天，以及 2.6%的参与者（2/76）出现持续性低钙血症（MWA 组为 1.9% [1/54]，RFA 组为 4.5% [1/22]，P=.50），未观察到持续性甲状旁腺功能减退的病例。

For participants with SHPT, early complications were dominated by transient hypocalcemia in 50.6% (39/77) of participants (59% [23/39] in MWA, 42.1% [16/38] in RFA, P=.21) resolving within 3-30 days, and coughing was reported in 5.2% (4/77) of participants ([3/39] in MWA, [1/38] in RFA, P=.62), resolving within 1-7 days. Late complications included transient hoarseness in 10.4% (8/77) of participants (12.8% [5/39] in MWA, 7.9% [3/38] in RFA, P=.71) with a recovery range of 30-180 days, persistent hypocalcemia in 20.8% (16/77) of participants (12.8% [5/39] in MWA, 28.9% [11/38] in RFA group, P=.14), and persistent hypoparathyroidism in 2.6% (2/77) of participants (0% [0/39] in MWA and 5.3% [2/38] in RFA, P=.24). Participants with persistent complications received appropriate medical management and regular follow-up.
对于患有高磷血症性骨病（SHPT）的参与者，早期并发症主要表现为暂时性低钙血症，占 506%（39/77 名参与者）（其中 MWA 组占 59%[23/39]，RFA 组占 421%[16/38]，P=.21），在 3-30 天内缓解；5.2%（4/77）的参与者出现咳嗽（MWA 组占 3/39，RFA 组占 1/38，P=.62），在 1-7 天内缓解。晚期并发症包括暂时性声音嘶哑，占 10.4%（8/77）（MWA 组占 12.8%[5/39]，RFA 组占 7.9%[3/38]，P=.71），恢复时间为 30-180 天；持续性低钙血症占 20.8%（16/77）（MWA 组占 12.8%[5/39]，RFA 组占 289%[11/38]，P=.14）；持续性甲状旁腺功能减退占 2.6%（2/77）（MWA 组占 0%[0/39]，RFA 组占 5.3%[2/38]，P=24）。出现持续性并发症的参与者接受了适当的药物治疗和定期随访。

Discussion
讨论

In this multicentre and prospective study, we evaluated the safety and efficacy of microwave ablation (MWA) and radiofrequency ablation (RFA) in older participants (≥ 55 years) with primary hyperparathyroidism (PHPT) and secondary hyperparathyroidism (SHPT). Our findings demonstrated an overall cure rate of 80.3% in participants with PHPT and a parathyroid hormone (PTH) achievement rate of 89.6% in participants with SHPT, with no significant differences between MWA and RFA (P=.59 and P=.48, respectively). Furthermore, both techniques demonstrated improvements from baseline in serum PTH (P < .001), calcium (P < .001), alkaline phosphatase (ALP) (P < .001) and phosphorus (P < .001) levels throughout the follow-up period. PTH level before ablation was identified as the independent predictor of treatment outcomes in both PHPT (odds ratio=1.01, CI: 1.00-1.01, P=.02) and SHPT participants (odds ratio=1.00, CI: 1.00-1.00, P= .02). Complication rates were minimal and transient
在这项多中心前瞻性研究中，我们评估了微波消融（MWA）和射频消融（RFA）在 55 岁及以上原发性甲状旁腺功能亢进（PHPT）和继发性甲状旁腺功能亢进（SHPT）患者中的安全性和有效性。我们的研究结果显示，PHPT 患者的总体治愈率为 80.3%，SHPT 患者的甲状旁腺激素（PTH）达标率为 89.6%，MWA 和 RFA 之间无显著差异（P=.59 和 P=.48，分别）。此外，两种技术均显示在整个随访期间，血清 PTH（P < .001）、钙（P < .001）、碱性磷酸酶（ALP）（P < .001）和磷（P < .001）水平均较基线有所改善。消融前 PTH 水平被确定为 PHPT（优势比=1.01，置信区间：1.00-1.01，P=.02）和 SHPT 患者（优势比=1.00，置信区间：1.00-1.00，P= .02）治疗结果的独立预测因子。并发症发生率低且短暂。.

Thermal ablation has long been proposed as a minimally invasive alternative for patients who are poor candidates for parathyroidectomy, yet evidence in older cohorts has remained fragmentary. Earlier single- or multi-center series of mixed-age patients have shown that MWA and RFA are feasible and generally safe treatment options[18-21,28]. Importantly, no studies have identified age as an independent predictor of ablation failure in hyperparathyroidism, supporting our conclusion that advanced age does not diminish ablation efficacy. When contrasted with parathyroidectomy for hyperparathyroidism management [11-14,16,17], the minimal complication rates following ablative procedures further substantiate the favorable safety profile of these minimally invasive modalities among older patients.
热消融长期以来被提议作为甲状旁腺切除术不适合患者的微创替代方案，但针对老年人群组的证据仍然零散。早期的单中心或多中心混合年龄患者系列研究表明，微波消融（MWA）和射频消融（RFA）是可行且通常安全的治疗选择[18-2128]。重要的是，没有研究将年龄确定为甲状旁腺功能亢进消融失败的独立预测因素，这支持了我们的结论，即高龄不会降低消融疗效。与用于甲状旁腺功能亢进管理的甲状旁腺切除术[11-141617]相比，消融术后的并发症发生率极低，进一步证实了这些微创方法在老年患者中的良好安全性。

Importantly, our analysis identified preoperative PTH level as the sole independent predictor of treatment outcomes in both PHPT and SHPT participants. This association may be explained by factors linked to elevated PTH, which often indicate larger nodule volume and a higher likelihood of multiglandular involvement [29,30]. In PHPT, elevated PTH is strongly associated with increased adenoma size and multigland disease prevalence[1,30]. For SHPT, higher PTH often correlates with hyperplastic gland proliferation and nodule growth due to chronic kidney disease-mineral and bone disorder stimulation[2-4]. These conditions may be more challenging to completely ablate. Moreover, although PHPT and SHPT differ pathophysiologically, interaction analysis indicates that the associations between key prognostic indicators and treatment outcomes do not differ significantly between the two groups.
重要的是，我们的分析确定了术前 PTH 水平是 PHPT 和 SHPT 参与者治疗结果的唯一独立预测因素。这种关联可能由与 PTH 升高相关的因素解释，这些因素通常表明结节体积较大，且多腺体受累的可能性更高[29,30]。在 PHPT 中，PTH 升高与腺瘤体积增大和多腺体疾病患病率显著相关[130]。对于 SHPT，较高的 PTH 通常与慢性肾脏病-矿物质和骨病刺激引起的增生性腺体增殖和结节生长相关[2-4]。这些情况可能更难完全消融。此外，尽管 PHPT 和 SHPT 在病理生理学上有所不同，交互分析表明，关键预后指标与治疗结果之间的关联在两组之间没有显著差异。

Although parathyroidectomy remains the gold standard for PHPT/SHPT with 90-95% cure rates[31,32], a meta-analysis of 29 studies showed that elderly patients face excess postoperative cardiovascular events, delirium, phlebitis, and other morbidities [33]. While our cure/PTH achievement rates were modestly lower, all enrolled participants were aged ≥55 years, and procedures performed solely under local anesthesia resulted in low complication rates. This contrasts with the higher complication rates of parathyroidectomy in older adults, underscoring MWA and RFA as a highly attractive option for frail or surgically contraindicated patients. This discrepancy in efficacy is understandable: 1) our cohort consisted exclusively of older participants, including those with significant comorbidities and frequent multi-glandular involvement (particularly in SHPT); 2) ablation lacks the direct visual confirmation attainable in open surgery. Furthermore, vapor clouds generated during ablation may obscure imaging and potentially compromise treatment completeness.
尽管甲状旁腺切除术仍然是 PHPT/SHPT 的金标准，治愈率可达 90-95%[3132]，但一项对 29 项研究的荟萃分析显示，老年患者在术后面临心血管事件、谵妄、静脉炎和其他并发症的风险增加[33]。尽管我们的治愈/PTH 达标率略有下降，但所有入组参与者的年龄均≥55 岁，且仅采用局部麻醉进行的手术并发症率较低。这与老年人甲状旁腺切除术的高并发症率形成对比，突显了 MWA 和 RFA 对于虚弱或手术禁忌患者的高度吸引力。这种疗效差异是可以理解的：1）我们的队列仅由老年参与者组成，包括患有严重合并症和频繁多腺体受累（尤其是在 SHPT 中）的患者；2）消融术缺乏开放手术中可直接获得的直接视觉确认。此外，消融过程中产生的蒸汽云可能会模糊影像，并可能影响治疗的完整性。

Several limitations of our study should be noted. First, the limited sample size may have affected the precision of our findings. Second, although we employed inverse probability weighting to minimize selection bias, the non-randomized study design remains a limitation. Third, the allocation of participants to undergo either MWA or RFA was determined by center-specific factors rather than individual participant characteristics, which may not fully reflect real-world clinical decision-making processes. Fourth, the exclusion of tertiary hyperparathyroidism(THPT) limits the generalizability of our findings to this distinct clinical entity. Additionally, all procedures were performed by highly experienced interventional physicians, potentially limiting the generalizability of our results to centers with less experienced operators. Future studies should address these limitations through larger-scale randomized controlled trials that incorporate more comprehensive assessment parameters and consider individual patient characteristics in treatment selection.
我们的研究存在一些局限性。首先，样本量有限可能影响了我们研究结果的精确性。其次，尽管我们采用了逆概率加权方法以尽量减少选择偏倚，但非随机研究设计仍然是一个局限性。第三，参与者被分配接受微波消融（MWA）或射频消融（RFA）是由中心特定因素而非个体参与者特征决定的，这可能无法完全反映现实世界中的临床决策过程。第四，排除继发性甲状旁腺功能亢进症（THPT）限制了我们的研究结果对这一独特临床实体的普适性。此外，所有手术均由经验丰富的介入医生进行，这可能限制了研究结果对操作经验较少的医疗中心的普适性。未来的研究应通过更大规模的随机对照试验，结合更全面的评估参数，并在治疗选择中考虑个体患者特征来解决这些局限性。

In elderly participants with hyperparathyroidism, microwave and radiofrequency ablation (MWA, RFA) were safe and effective minimally invasive alternatives to surgery, and preoperative parathyroid hormone (PTH) levels were found to be an independent predictor of treatment outcomes. Future work should focus on randomized comparisons with parathyroidectomy and development of predictive models that integrate PTH, imaging parameters to personalize ablation strategies.
在甲状旁腺功能亢进症的老年患者中，微波和射频消融（MWA、RFA）是手术的安全有效的微创替代方案，术前甲状旁腺激素（PTH）水平被发现是治疗结果的独立预测因素。未来的研究应着重于与甲状旁腺切除术的随机比较，以及开发整合 PTH、影像参数以个性化消融策略的预测模型。

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Tables
表格

Table 1. Baseline characteristics of participants with PHPT or SHPT before and after IPTW.
表 1. PHPT 或 SHPT 患者在接受 IPTW 前后的基线特征。

Note.— Values are given as mean ± standard deviation or median (interquartile range), and categorical variables as n (%). This table describes baseline characteristics of the total cohort and subgroups stratified by hyperparathyroidism type. PHPT: primary hyperparathyroidism; SHPT: secondary hyperparathyroidism; MWA: microwave ablation; RFA: radiofrequency ablation; PTH: parathyroid hormone; ALP: alkaline phosphatase
注。—— 数值以均值±标准差或中位数（四分位间距）表示，分类变量以 n（%）表示。该表描述了总队列和按甲状旁腺功能亢进类型分层亚组的基线特征。PHPT：原发性甲状旁腺功能亢进；SHPT：继发性甲状旁腺功能亢进；MWA：微波消融；RFA：射频消融；PTH：甲状旁腺激素；ALP：碱性磷酸酶.

Table 2. Univariable and multivariable analysis of prognostic factors for outcomes after thermal ablation.
表 2. 热消融术后预后因素的单变量和多变量分析

Note.— Data in parentheses are 95% confidence intervals. Regression coefficients represent the log odds. For continuous variables, coefficients indicate the change in log odds per unit increase. Variables included in both univariable and multivariable logistic regression models were selected based on clinical relevance. Preoperative PTH was identified as an independent predictor of outcomes after thermal ablation in both PHPT and SHPT groups, values rounded to 2 decimal places; exact ORs were 1.005 (PHPT) and 1.001 (SHPT). PHPT: primary hyperparathyroidism; SHPT: secondary hyperparathyroidism; PTH: parathyroid hormone
注意。—— 括号中的数据是 95%置信区间。回归系数表示对数优势比。对于连续变量，系数表示每增加一个单位对数优势比的变化。单变量和多变量逻辑回归模型中均包含的变量是根据临床相关性选择的。术前甲状旁腺激素被确定为 PHPT 组和 SHPT 组热消融术后结果独立预测因子；数值四舍五入至小数点后两位；确切的优势比分别为 1.005（PHPT）和 1.001（SHPT）；PHPT：原发性甲状旁腺功能亢进；SHPT：继发性甲状旁腺功能亢进；PTH：甲状旁腺激素

Table 3. Comparison of complications in participants with PHPT versus SHPT
表 3. PHPT 患者与 SHPT 患者并发症比较

Note.— P values were calculated using the chi-square test for categorical variables; Fisher exact test was used when expected counts were <5. Persistent hypoparathyroidism is defined as a prolonged reduction in parathyroid function lasting for more than 6 months. There was no evidence of significant differences in complication rates between MWA and RFA groups in both PHPT and SHPT participants, and most complications resolved within 30 days. MWA: microwave ablation; RFA: radiofrequency ablation. PHPT: primary hyperparathyroidism, SHPT: secondary hyperparathyroidism, No.: number, d: days; NA: not applicable
注。—— 级别变量采用卡方检验计算 P 值；当期望计数<5 时使用 Fisher 精确检验。持续性甲状旁腺功能减退定义为甲状旁腺功能持续降低超过 6 个月。在 PHPT 和 SHPT 参与者中，MWA 组和 RFA 组的并发症发生率无显著差异，且大多数并发症在 30 天内得到解决。MWA：微波消融；RFA：射频消融。PHPT：原发性甲状旁腺功能亢进，SHPT：继发性甲状旁腺功能亢进，No.：例数，d：天；NA：不适用.

Figure Legends
图注

Figure 1. Study Flowchart of Selection of Elderly Participants with Hyperparathyroidism for Microwave and Radiofrequency Ablation.
图 1. 适用于微波和射频消融的甲状旁腺功能亢进症老年受试者选择研究流程图。

PHPT: primary hyperparathyroidism; SHPT: secondary hyperparathyroidism; PTH: parathyroid hormone
PHPT：原发性甲状旁腺功能亢进症；SHPT：继发性甲状旁腺功能亢进症；PTH：甲状旁腺激素

Figure 2. Ultrasound-Guided Microwave Ablation for Primary Hyperparathyroidism: A Case Illustration
图 2. 超声引导下微波消融治疗原发性甲状旁腺功能亢进症：病例说明

This figure shows a case of a 56-year-old woman with primary hyperparathyroidism treated using ultrasound-guided microwave ablation. (A) Pre-ablation ultrasound reveals a hypoechoic parathyroid nodule (white arrow) measuring 4.84 cm × 1.86 cm × 2.53cm. The left black and white B-mode image shows the nodule, while the orange right image is a contrast-enhanced scan demonstrating homogeneous enhancement. The white coordinate axes indicate the measured maximum diameters. (B) Under ultrasound guidance, percutaneous injection of saline solution (white arrow) creates an isolation zone to protect surrounding tissues. (C) The ablation needle (white arrow) is precisely positioned within the nodule for microwave ablation. (D) Post-ablation ultrasound displays a hyperechoic lesion area (white arrow) on the left black-and-white B-mode image, while the right orange contrast-enhanced ultrasound shows no residual enhancement, indicating complete ablation (4.51 cm × 1.85 cm × 2.04 cm). The yellow and green coordinate axes indicate the maximum diameters of the ablation zone.
这张图展示了一位 56 岁原发性甲状旁腺功能亢进症女性使用超声引导微波消融治疗的情况(A)消融前超声显示一个低回声的甲状旁腺结节（白色箭头），大小为 4.84 厘米×1.86 厘米×2.53 厘米。左侧黑白 B 模式图像显示结节，而右侧橙色图像是增强扫描，显示均匀增强。白色坐标轴指示测量的最大直径。(B)在超声引导下，经皮注射生理盐水（白色箭头）形成隔离区以保护周围组织。(C)消融针（白色箭头）精确地位于结节内进行微波消融。(D)消融后超声显示左侧黑白 B 模式图像上出现高回声病变区域（白色箭头），而右侧橙色增强超声显示无残余增强，表明完全消融（4.51 厘米×1.85 厘米×2.04 厘米）。黄色和绿色坐标轴指示消融区的最大直径。

Figure 3. Longitudinal Changes in PTH, Calcium, Phosphate, and ALP Levels Following Ablation Therapy
图 3.消融治疗后 PTH、钙、磷和 ALP 水平的纵向变化

Panels (A) to (D) show plots demonstrating changes in PTH, calcium, phosphate, and ALP levels in participants with PHPT following ablation therapy with either MWA or RFA. Panels (E) to (H) show plots demonstrating changes in the same parameters for participants with SHPT. "Baseline" refers to pre-ablation serum levels. Error bars indicate standard error. A generalized linear mixed model was utilized for repeated measures analysis to assess longitudinal changes and interaction effects. Pairwise Wald tests were used to compare MWA and RFA at each time point. Both MWA and RFA groups showed significant reductions in serum PTH, calcium, and ALP levels, while phosphorus levels exhibited an initial increase followed by stabilization. No sustained differences in biochemical parameters were observed between MWA and RFA across the full follow-up period.
图(A)至(D)展示了在甲状旁腺功能亢进症受试者接受微波或射频消融治疗后，PTH、钙、磷和 ALP 水平变化的曲线图。图(E)至(H)展示了甲状旁腺功能减退症受试者相同参数变化的曲线图。"基线"指消融治疗前的血清水平。误差线表示标准误差。采用广义线性混合模型进行重复测量分析，以评估纵向变化和交互作用。使用配对 Wald 检验比较每个时间点的微波和射频消融效果。微波和射频消融组均显示血清 PTH、钙和 ALP 水平显著降低，而磷水平初始升高后趋于稳定。在整个随访期间，微波和射频消融在生化参数方面未观察到持续差异。

MWA: Microwave Ablation; RFA: Radiofrequency Ablation; PTH: Parathyroid Hormone; ALP: Alkaline Phosphatase; PHPT: primary hyperparathyroidism; SHPT: secondary hyperparathyroidism, D: days, M: months
MWA：微波消融；RFA：射频消融；PTH：甲状旁腺激素；ALP：碱性磷酸酶；PHPT：原发性甲状旁腺功能亢进；SHPT：继发性甲状旁腺功能亢进，D：天，M：月

Figure 4. Changes in PTH, Calcium, Phosphate, and ALP Levels from Baseline Over Time Following Ablation Therapy
图 4. 消融治疗后 PTH、钙、磷和 ALP 水平从基线随时间的变化.

The figure illustrates the change in PTH, calcium, phosphorus, and ALP levels (shown in Figure 3) from baseline to various time points following ablation therapy. Panels (A)–(D) illustrate the decline in levels in participants with PHPT, while panels (E)–(H) display the corresponding changes in participants with SHPT. "Baseline" represents pre-ablation serum levels measured before ablation therapy. These plots demonstrate substantial and sustained reductions in PTH, calcium, and ALP levels, with mild fluctuations over time, reflecting the overall biochemical improvement after ablation. In contrast, phosphorus levels initially increased before stabilizing.
该图展示了消融治疗后从基线到不同时间点 PTH、钙、磷和 ALP 水平的变化（如图 3 所示）。面板(A)–(D)展示了 PHPT 患者水平的下降，而面板(E)–(H)显示了 SHPT 患者相应的变化。"基线"代表消融治疗前测量的血清水平。这些图表显示了 PTH、钙和 ALP 水平显著且持续的降低，随时间有轻微波动，反映了消融后的整体生化改善。相比之下，磷水平最初上升后趋于稳定。

PHPT: primary hyperparathyroidism; SHPT: secondary hyperparathyroidism; PTH: parathyroid hormone; ALP: Alkaline Phosphatase, D: days, M: months
PHPT：原发性甲状旁腺功能亢进；SHPT：继发性甲状旁腺功能亢进；PTH：甲状旁腺激素；ALP：碱性磷酸酶，D：天，M：月

Figure 5. Interaction Analysis of Disease Type (PHPT versus SHPT) with Prognostic Parameters in Predicting Treatment Outcomes.
图 5. 疾病类型（PHPT 与 SHPT）与预后参数在预测治疗结果中的交互分析。

This forest plot illustrates the interaction effects between disease type (PHPT versus SHPT) and various prognostic parameters on treatment outcomes, which refer to achieving cure (PHPT) or PTH achievement (SHPT), as defined by maintaining normal serum calcium and PTH levels (PHPT) or PTH <585 pg/mL for at least 6 months (SHPT). Each dark blue dot represents the estimated odds ratio (OR) for the association between the parameter and treatment outcomes, with horizontal lines indicating the 95% confidence intervals (CIs). The vertical dashed line at OR = 1 indicates no effect. P values were calculated using Wald tests from logistic regression models. All cutoff values represent the thresholds used for categorization. The ORs for the interaction terms between disease type and these parameters were not statistically significant, suggesting there was no evidence of a difference between participants with PHPT versus SHPT in terms of their relationships with the treatment outcomes.
这张森林图展示了疾病类型（原发性甲状旁腺功能亢进症 PHPT 与继发性甲状旁腺功能亢进症 SHPT）和各种预后参数对治疗结果（指治愈 PHPT 或达到 PTH 目标 SHPT）的交互作用，其中治愈 PHPT 定义为维持正常的血清钙和 PTH 水平，而达到 PTH 目标 SHPT 定义为至少 6 个月 PTH < 585 pg/mL。每个深蓝色圆点代表参数与治疗结果之间关联的估计优势比（OR），水平线表示 95%置信区间（CI）。在 OR = 1 处的垂直虚线表示无效应。P 值通过逻辑回归模型的 Wald 检验计算得出。所有截断值代表分类所使用的阈值。疾病类型与这些参数之间的交互项的优势比（OR）没有统计学显著性，表明在 PHPT 与 SHPT 患者之间，他们与治疗结果的关系没有差异。

MWA: Microwave Ablation; RFA: Radiofrequency Ablation; PHPT: primary hyperparathyroidism; SHPT: secondary hyperparathyroidism
MWA：微波消融；RFA：射频消融；PHPT：原发性甲状旁腺功能亢进症；SHPT：继发性甲状旁腺功能亢进症