2024 国际专家共识：继发性和三发性甲状旁腺功能亢进的超声引导热消融治疗

2024 International expert consensus on ultrasound-guided thermal ablation for secondary and tertiary hyperparathyroidism

Ying Weiª, Shu-Rong Wangbª, Jennifer H. Kuoç, Bülent Çekiççd, Lin-Xue Qiane, Hossam Arafa Ghazif, Ying Chegª, Gerardo Amabilehª, Song-Song Wu`, Ajit Yadavî, Gang Dongkª, Ingo Janssenî, Bo-Qiang Fanm, Nobuhiro Fukunarin, Jun-Feng Heº, Le Thanh DungP, Song-Yuan Yuq, Sum Leongr, Jian-Jun Yus, Yi-Hong Chouł, Rafael De Ciccou, Shu-Hang Xu` (ID, YanGu Vd, Kai-Lun ChengwX, Emad Kandilý, Wei-Che LinZaa,ab, Dong Xuac ID, Jonathon Russellad, Man Lu`ae ID, Ralph P. Tufanoª, Lei Liangag, Gregory W. Randolphªh, Jian-Qiao Zhouªi, Giovanni Mauriªj ID, Hong-Hui Suakª, Marika Russellahª, Amr H. Abdelhamidªh, Kaustubh Patelª, Li Zhuoamª, Ya-Jun Zhangan, Yun Niuao, Zhen-Long Zhaoª and Ming-An Yuª ID

aDepartment of Interventional Medicine, China-Japan Friendship Hospital, Beijing, China; bDepartment of Ultrasound, Yantai Hospital of Shandong Wendeng Orthopaedics & Traumatology, Yantai, Shandong, China; bDepartment of Surgery, Columbia University, New York, NY, USA; dDepartment of Interventional Radiology, Antalya Training and Research Hospital, Antalya, Turkey; eDepartment of Ultrasound, Beijing Friendship Hospital, Capital Medical University, Beijing, China; bDepartment of Internal Medicine, Faculty of Medicine, Mansoura University, Mansoura, Egypt; 9Department of Ultrasound, First Affiliated Hospital and Dalian Medical University, Liaoning, China; bDepartment of Advanced Medical and Surgery Sciences, University of Campania Luigi Vanvitelli, Naples, Italy; dDepartment of Ultrasonography, Fuzhou University Affiliated Provincial Hospital, Fuzhou University, Fuzhou, China; dDepartment of Interventional Radiology, Sir Ganga Ram Hospital, New Delhi, India; kDepartment of Ultrasound, First Affiliated Hospital of Zhengzhou University, Zhengzhou, China; dDepartment of Radiology and Nuclear Medicine, MVZ BeRaNuk Medical Center, Berlin, Germany; mDepartment of Ultrasound Medicine, The first affiliated hospital with Nanjing Medical University, Nanjing, China; dDepartment of Surgery, Thyroid Center, Showa University Northern Yokohama Hospital, Patient Safety and Surgical Unit, Showa University, Kanagawa, Japan; dDepartment of Ultrasound, First Affiliated Hospital of Baotou Medical College of Inner Mongolia University of Science and Technology, Baotou, Inner Mongolia, China; pDepartment of Radiology, Viet Duc University Hospital, Hanoi, Vietnam; dDepartment of Medical Ultrasound, Shanghai, Tenth People's Hospital, Shanghai, China; dDepartment of Vascular and Interventional Radiology, Singapore General Hospital, Singapore; dDepartment of Surgery, People's Hospital of Ningxia Hui Autonomous Region, Ningxia, China; dDepartment of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan, China; dDepartment of Head and Neck Surgery, Instituto de Câncer Dr Arnaldo, São Paulo, Brazil; dDepartment of Endocrinology, Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China; mDofthe Medicine, Chung Shan Medical University, Taichung, Taiwan, China; dDepartment of Medical Imaging, Chung Shan Medical University Hospital, Taichung, Taiwan, China; dDepartment of Surgery, Tulane University School of Medicine, New Orleans, LA, USA; dDepartment of Diagnostic Radiology, Kaohsiung Chang Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan, China; dDepartment of Diagnostic Radiology, Kaohsiung Municipal Fong Shan Hospital-Under the management of Chang Gung Medical Foundation, Kaohsiung, Taiwan, China; abThyroid Head and Neck Ablation Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, China; dDepartment of Ultrasound, Zhejiang Cancer Hospital, Hangzhou, China; aDRussell Center for Endocrine Health Columbia, Maryland, USA; aDeDepartment of Ultrasound, Sichuan Cancer Hospital, Chengdu, China; afDivision of Head and Neck Endocrine Surgery, Sarasota Memorial Health Care System, Sarasota, FL, USA; a9Department of Ultrasound, Aerospace Center Hospital, Beijing, China; athOtolaryngology-Head Neck Surgery Thyroid/Parathyroid Endocrine Surgical Division Massachusetts Eye and Ear Infirmary/Harvard Medical School, Boston, MA, USA; a)Department of Ultrasound, Ruijin Hospital, Shanghai, China; aUnit of Diagnostic and Interventional Radiology, IRCCS Ospedale Galeazzi Sant'Ambrogio, Milan, Italy; akDepartment of Interventional Ultrasound, Second Affiliated Hospital of Shantou University Medical College, Shantou, China; aDepartment of Head Neck Oncology, HCG Astha Cancer Centre, Ahmedabad, India; aamDepartment of Nephrology, China-Japan Friendship Hospital, Beijing, China; aDepartment of Anesthesiology, China-Japan Friendship Hospital, Beijing, China; aDepartment of Pathology, China-Japan Friendship Hospital, Beijing, China; atoDepartment of Pathology, China-Japan Friendship Hospital, Beijing, China; aDepartment of Idness, China; a9Department of Diagnostics, China; a9Department of Diagnostics, China; a9Department of Diagnostics, China; a9Department of Di�ness, China; a9Department of Di�ness, China; a9Department of Di�ness, China; a9Department of Di�ness, China; a9Department of Di�ness, China; a9Department of Di�ness, China; a9Department of Di�ness, China; a9Department of Di�ness, China; a9Department of Di�ness, China; a9Department of Di�ness, China; a9Department of Di�ness, China; a9Department of Di�ness, China; a9Department of Di�ness, China; a9Department of Di�ness, China; a9Department of Di�ness, China; a9Department of Di�ness, China; a9Department of Di�ness, China; a9Department of Di ngness, China; a9Department of Di ngness, China; a9Department of Di ngness, China; a9Department of Di ngness, China; a9Department of Di ngness, China; a9Department of Di ngness, China; a9Department of Di ngness, China; a9Department of Di ngness, China; a9Department of Di ngness, China; a9Department of Di ngness, China; a9Department of Di ngness, China; a9Department of Di ngness, China; a9Department of Di ngness, China; a9Department of Di ngness, China; a9Department of Di ngness, China; a9Department of Di ngness, China; a9Department of Di ngness, China; a9Department of Di ngness, China; a9Department of Di ngness, China; a9Department of Di ngness, China; a9Department of Di ngness, China; a9Department of Di ngness, China; a9Department of Di

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ABSTRACT

Treatments for secondary and tertiary hyperparathyroidism (SHPT/THPT) remain significant challenges in patients with end-stage renal disease. Thermal ablation (TA) has emerged as a minimally invasive, safe, and effective alternative to surgical resection (SR). However, technical variations and a lack of standardization have limited its widespread adoption. To address these challenges, an international expert panel developed consensus recommendations using a modified Delphi method, integrated with a systematic literature review. As a result, sixteen recommendations were formulated, addressing diagnosis, preoperative preparation, technical procedures, postoperative management, follow-up strategies, efficacy assessment, and complications associated with TA for SHPT/THPT. These recommendations aim to promote standardized treatment protocols, improve procedural safety, and provide evidence-based guidance for clinical practice and future research in ultrasound-guided TA for SHPT/THPT management.

ARTICLE HISTORY Received 2 April 2025 Revised 3 December 2025 Accepted 13 December 2025

KEYWORDS

Thermal ablation; secondary hyperparathyroidism; tertiary hyperparathyroidism; ultrasound-guided ablation; parathyroid hormone; expert consensus

Introduction

Secondary and tertiary hyperparathyroidism (SHPT/THPT) commonly arise as complications of end-stage renal disease (ESRD) [1,2]. Elevated parathyroid hormone (PTH) levels disrupt calcium and phosphorus metabolism, resulting in abnormalities in bone mineral metabolism and clinical manifestations such as renal osteodystrophy, metastatic calcification, and nervous system damage [3,4]. As the disease progresses, patients face increased risks of cardiovascular and all-cause mortality [5-7].

Currently, SHPT/THPT is primarily managed with pharmacologic therapy, combined with adequate dialysis and dietary control. However, many patients eventually develop drug resistance, leading to autonomous functional SHPT/THPT, also known as refractory SHPT/THPT. Surgical resection (SR) remains the conventional treatment for refractory SHPT/THPT and often provides a radical cure for most patients [3,8–13]. Nevertheless, SR is frequently associated with adverse outcomes, including significant surgical trauma, missed detection of small lesions [14,15], increased complication rates, and, in some cases, permanent hypoparathyroidism requiring long-term calcium and vitamin D supplementation [16–18]. Even for experienced surgeons, achieving the optimal balance between adequate parathyroid resection to prevent recurrent or persistent disease and avoiding permanent hypoparathyroidism remains challenging. Moreover, the risks of surgery and general anesthesia are heightened in many SHPT/THPT patients on long-term dialysis due to complications such as skeletal deformities, short necks, and electrolyte disorders. Consequently, there is an urgent need to refine traditional SR approaches to overcome these limitations.

In recent years, microwave- and radiofrequency-based thermal ablation (TA) techniques have gained increasing clinical recognition for their advantages as minimally invasive treatments for SHPT/THPT. Studies have shown that TA can effectively deactivate target SHPT/THPT lesions, reduce PTH levels, normalize calcium and phosphorus metabolism, and alleviate or even eliminate associated clinical symptoms [19–28]. Several investigations have further demonstrated that, compared with SR, TA provides clear and comparable long-term efficacy in treating SHPT/THPT [19,20,29]. In addition, TA is a viable option for patients ineligible for SR, such as those with thoracic or short-neck deformities, cardiopulmonary insufficiency [14], ectopic SHPT/THPT, or a history of kidney transplantation [30,31].

Although high-quality randomized controlled trials to support standardized practice remain lacking, a growing body of clinical practice and research has confirmed TA as a novel therapeutic approach for patients with SHPT/THPT, characterized by minimal invasiveness, safety, and effectiveness [19,21,23,26]. However, technical variations and a lack of standardization have limited its widespread adoption.

To address this gap, it is necessary to establish expert consensus on TA for SHPT/THPT in order to standardize ultrasound-guided TA protocols and provide interventionalists with detailed technical guidance. Broader adoption of TA for SHPT/THPT would enable more patients to benefit from this minimally invasive management approach.

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 # Materials and methods

# Multidisciplinary expert panel

Under the auspices of the Interventional Medicine Department of the China-Japan Friendship Hospital, internationally renowned experts specializing in TA for hyperparathyroidism (HPT) and thyroid nodules were invited to contribute to the development of this consensus. The author panel was meticulously selected to encompass a broad range of specialties, including surgeons, radiologists, nephrologists, endocrinologists, anesthesiologists, pathologists, and experts in research methodology.

The selection of experts for this consensus adhered to one or more of the following criteria: (1) a substantial publication record of clinical research in the field of TA for HPT or thyroid nodules; (2) extensive clinical experience in TA for HPT or thyroid nodules, with at least 30 HPT ablation procedures performed annually; (3) significant involvement in clinical research on percutaneous TA for tumors, yielding relevant findings; or (4) recognition as an authority in related fields such as nephrology or head and neck surgery.

Based on these rigorous criteria, experts were carefully chosen and convened to establish the International Workshop on Thermal Ablation of Thyroid Tumor and Hyperparathyroidism. The final panel consisted of 42 experts from 17 countries and regions (22 from China and 20 international), representing diverse specialities: 24 interventional radiologists, 10 surgeons, 5 endocrinologists, 1 nephrologist, 1 anesthesiologist, and 1 pathologist. Detailed credentials and institutional affiliations are provided in Supplementary Appendix S1: Qualifications of Experts.

# Modified delphi panel method

The panel developed 16 recommendations based on clinical practice, literature evidence, and expert opinion. This process involved three rounds of anonymous surveys. Initially, the recommendations were evaluated and rated using the modified Delphi method [32] (Figure 1), with the criteria for recommendation levels outlined in Table 1. Consensus was defined as a mean Delphi score ≥ 6.0 on a 9-point scale. After the first round, areas lacking consensus were identified for further discussion. In the second round, revised statements were formulated and reassessed using the same rating system. Statements still lacking consensus after the second round were further refined and discussed during a face-to-face expert meeting.

Following the two rounds of evaluations and revisions, the expert panel convened on 19 October 2023, to deliberate on the proposed recommendations and finalize consensus. All rating rounds were conducted anonymously to minimize bias and prevent dominance by senior participants. This iterative approach ensured the refinement of the recommendations and the effective integration of diverse expert perspectives.

![graph TD\n A1[Expert panel formation 22 Chinese experts 20 international experts] --> A2[Literature search January 1, 2001 – September 1, 2024]\n A2 --> A3[Initial recommendation draft]\n A3 --> A4[Two rounds of Delphi rating Recommendation improvement, especially on areas lacking consensus]\n A4 --> A5[Expert consensus symposium In person or online]\n A5 --> A6[Final consensus recommendations]\n A7[Literature search （total n=363） （PubMed n=90, Medline n=66, EMBASE n=108, Scopus n=99）] --> A8[Literature after duplicates removed （n=106）]\n A8 --> A9[Literature excluded （n=55） - Not in the field of interest （n=36） - Chemical ablation （n=5） - Case reports, review （n=10） - Animal studies （n=4）]\n A8 --> A10[Full-text literature assessed for eligibility （n=51）]\n A10 --> A11[Literatures included in analysis （n=37） Original research （n=33） Meta-analysis （n=4）]\n A10 --> A12[Excluded non-English literatures （n=14）]\n](1/parseimages/figure6cfe9fa57e1f4ad1913c24488bc2f2cd_0_10.png) Figure 1. PRISMA flow diagram and Delphi study flowchart.

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Table 1. Levels of evidence and grades of recommendation.

Grade of recommendation

A. Strong recommendation: Delphi score 8.0-9.0.

B. Moderate recommendation: Delphi score 7.0-7.9

C. Weak recommendation: Delphi score 6.0-6.9

D. Neutral: Delphi score 5.0–5.9

E. Oppose: Delphi score 1.0-4.9

Level of Evidence

High A. Evidence from at least one large randomized, controlled trial of good methodological quality (low potential for bias) or meta-analyses of well-conducted randomized trials without heterogeneity

B. Small randomized trials or large randomized trials with a suspicion of bias (lower methodological quality) or meta-analyses of such trials

C. Prospective comparative studies; retrospective comparative studies with balanced baseline characteristics (using propensity score matching, etc.)

Moderate

D. Case-control studies; retrospective cohort studies

Low E. Studies without a control group, case reports, or expert opinions

Table 2. Literature inclusion and exclusion criteria.

Literature inclusion criteria

(I) Participants: patients diagnosed with secondary or tertiary hyperparathyroidism

(II) Interventions: US-guided thermal ablation (including radiofrequency ablation, microwave ablation, or laser ablation

(III) Outcome measures: post-treatment PTH-related indicators (e.g., absolute values, percentage reduction, or target-achievement rates) and major or minor complications

(IV) Study design: prospective or retrospective clinical studies

Lizerature exclusion criteria

(I) Studies that did not report post-treatment PTH-related outcomes or complications

(II) Sample size < 10 patients

(III) Study design as crossover trial, animal experiment, review, case report, editorials

(IV) Minimal follow-up duration < 6 months

(V) Studies involving non-thermal ablation techniques (e.g., chemical ablation)

(VI) Repeated publications

Evidence acquisition

Systematic literature reviews were conducted across four databases—PubMed, Medline, Embase, and Scopus—for studies published between 1 January 2001, and 1 September 2024, in accordance with PRISMA guidelines [33]. The following keywords were used in combination with Boolean operators to maximize sensitivity: ('secondary hyperparathyroidism' OR 'tertiary hyperparathyroidism') AND ('ablation' OR 'thermal ablation' OR 'microwave ablation' OR 'radiofrequency ablation' OR 'laser ablation').

Studies were included if they met the following criteria: (I) Participants: patients diagnosed with SHPT or THPT; (II) Interventions: ultrasound-guided TA (including radiofrequency ablation, microwave ablation, or laser ablation); (III) Outcomes: post-treatment PTH-related indicators (absolute values, percentage reduction, or target-achievement rates) and major or minor complications; (IV) Study design: prospective or retrospective. Studies were excluded if they did not report PTH-related outcomes, included fewer than 10 patients, adopted a crossover or animal experimental design, were published as reviews, case reports, or editorials, involved chemical ablation, or were duplicate publications. The inclusion and exclusion criteria are summarized in Table 2.

This comprehensive search identified 37 studies (33 original research articles and 4 meta-analyses) on TA involving 1,963 patients with SHPT/THPT (Figure 1). The evidence level of these studies was assessed based on study design, quality, and risk of bias, as detailed in Table 1.

Two reviewers independently screened the titles and abstracts of all retrieved articles, followed by full-text reviews. Disagreements were resolved through discussion or adjudication by a third reviewer. Each included study was assessed and assigned an evidence level (A–E) based on study design, reporting quality, sample size, and risk of bias. These levels informed the formulation and wording of the final consensus recommendations.

Preoperative evaluation

General situation assessment. Evaluation of the patient's mental status should include the level of consciousness, pertinent medical history (including SHPT/THPT), prior surgical interventions, dialysis history, and use of anticoagulant medications.

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Assessment of the patient's physical condition should include cardiopulmonary function, blood pressure monitoring and related treatments, identification of symptoms related to extremity arteriolar occlusion, and recognition of physical conditions that may affect the ablation procedure (e.g., thoracic or short-neck deformity, kyphosis, and a history of neck surgery).

Evaluation of SHPT/THPT-related symptoms should include restless legs, pruritus, insomnia, and osteoporosis.

Assessment of the dialysis regimen and quality should include frequency of dialysis, use of heparin, and observation of blood pressure fluctuations during dialysis.

Special consideration should be given to particular patient populations, such as the elderly, those with severe deformities (e.g., pronounced kyphosis or tracheostomy), and individuals with heart failure or pulmonary hypertension, who may require specialized examinations [34].

Recommendation 1: Multidisciplinary collaboration is recommended for the comprehensive evaluation and management of SHPT/THPT patients scheduled for TA treatment [Strong Recommendation (Delphi score 9.00), low-quality evidence]

Laboratory examination. Routine examinations should include routine blood analysis, assessment of coagulation function (prothrombin time and prothrombin activity), and screening for infectious diseases (HBV, HCV, HIV, and syphilis). The platelet count required for a safe TA procedure should be over 60×10^9/L [35], and the prothrombin time should not exceed the upper limit of normal by 3s or more [36].

Specific SHPT/THPT-related examinations should include evaluation of intact PTH (iPTH), serum calcium and phosphorus, and alkaline phosphatase (ALP) levels.

Patients who are of advanced age, are physically frail, or exhibit signs of cardiopulmonary insufficiency should undergo additional cardiopulmonary function-related evaluations [34].

Recommendation 2: Prior to ablation, it is recommended to conduct comprehensive laboratory tests, including routine examinations and assessments related to SHPT/THPT (e.g., iPTH, blood biochemistry, and bone metabolism indicators) [Strong Recommendation (Delphi score 9.00), moderate-quality evidence].

Diagnosis

Clinical diagnosis. Based on a patient's medical history, presenting symptoms, and biochemical abnormalities, the following criteria should be used for patient selection:

1. ESRD and long-term dialysis;

2. Elevated serum iPTH levels, often accompanied by elevated levels of calcium, phosphorus, or ALP; and

3. At least one of the following symptoms related to SHPT/THPT: renal osteodystrophy (characterized by bone pain, fractures, bone deformities, or brown tumors), neurotoxicity (insomnia, drowsiness, itching, or restless legs), or metastatic calcification (e.g., medial arterial calcification).

Imagining diagnosis. Commonly utilized preoperative imaging modalities include high-frequency ultrasound (US) and technetium⁻$^{99}$m methoxy isobutyl isonitrile ($^{99}$mTc-MIBI) dual-phase planar imaging and single-photon emission computed tomography/computed tomography (MIBI-SPECT/CT) [37,38]. High-frequency US typically exhibits high sensitivity, while MIBI-SPECT/CT offers high specificity in diagnosing SHPT/THPT lesions. Therefore, the combination of high-frequency US and MIBI-SPECT/CT radionuclide imaging is recommended for preoperative diagnostic purposes [39].

SHPT/THPT lesions present distinctive US imaging features useful for diagnosis and differential diagnosis [40]. Contrast-enhanced US (CEUS) also has diagnostic and differential diagnostic value for SHPT/THPT lesions [41–44]. SHPT/THPT lesions typically exhibit hyperenhancement during the arterial phase compared to adjacent thyroid tissues. Conversely, enlarged lymph nodes resulting from chronic inflammatory stimulation generally display hypoenhancement during the arterial phase, despite both SHPT/THPT lesions and enlarged lymph nodes appearing as hypoechoic nodules on routine US.

MIBI-SPECT/CT, a functional imaging modality, has significant value in diagnosing and localizing SHPT/THPT lesions and is often the preferred diagnostic tool owing to its high specificity in detecting orthotopic

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or ectopic SHPT/THPT lesions [45,46]. The characteristic feature of SHPT/THPT lesions typically involves concentrated radioactivity observed in both the early and delayed phases following administration [47,48].

In addition to parathyroid-targeted imaging, conventional evaluations such as chest X-ray and echo- cardiography are recommended to assess cardiopulmonary function. Bone mineral density assessment and laryngoscopy may be selectively employed based on clinical need.

Pathological diagnosis. The clinical diagnosis of SHPT/THPT relies on clinical history, laboratory test results, and imaging findings. A biopsy is commonly performed to differentiate the benign or malignant nature of a lesion. However, histological biopsy can only identify tumors of parathyroid cell origin and offers limited value in differentiating between hyperplastic parathyroid tissue, adenoma, and malignant SHPT/THPT lesions. Moreover, a biopsy carries risks of bleeding and implantation.

Currently, evidence-based practice regarding the necessity and advantages of fine-needle aspiration cytology (FNAC) or biopsy in evaluating SHPT/THPT lesions is lacking. It is crucial to note that patients displaying imaging characteristics suggestive of parathyroid carcinoma, such as substantial or rapid lesion growth, an irregular or discontinuous capsule, border infiltration, and abnormally enlarged peripheral lymph nodes, should refrain from undergoing ablation therapy in the absence of a definitive pathological diagnosis.

Recommendation 3: Imaging examinations before ablation, such as neck US combined with $^{99}$mTc-MIBI scans, are recommended for all SHPT/THPT patients. Additionally, conventional imaging evaluations, including chest X-ray and echocardiography, are advised, whereas bone mineral density examination and laryngoscopy may be selectively employed as needed [Strong Recommendation (Delphi score 8.36), moderate-quality evidence].

Recommendation 4: Preprocedural FNAC or core needle biopsy is not routinely advised. However, FNAC with PTH washout can be considered when discrepancies exist between US findings and nuclear imaging results [Moderate Recommendation (Delphi score 7.91), low-quality evidence].

Indications and contraindications

Indications (patients should meet all of the following criteria).

1. Continuous serum iPTH level persisting above 500 pg/mL (normal range: 12–88 pg/mL) despite adequate dialysis or medical treatment [49] (This threshold is based on regional clinical guidelines and reflects a preference for early intervention in appropriate patients).

2. Presence of refractory hypercalcemia or hyperphosphatemia that remains unresponsive to conservative treatment.

3. Manifestation of clinical symptoms or signs associated with SHPT/THPT, such as progressive ectopic calcification of soft tissues, medial arterial calcification, severe bone pain, osteoporosis, pathological fractures, severe myalgia, pruritus, severe anemia, or erythropoietin resistance.

4. US revealing at least one suspicious SHPT/THPT lesion exhibiting typical signs of benign lesions, with a diameter exceeding 0.6 cm [50] (This threshold was determined by expert consensus, given that smaller lesions present greater challenges for safe and effective targeting under ultrasound guidance).

5. Presence of concentrated radioactivity in both the early and delayed phases on MIBI scans, or negative radionuclide scan findings with typical US imaging characteristics.

6. US evaluation demonstrating a feasible puncture path.

Contraindications (patients meeting any of the following criteria).

1. Inability to cooperate due to abnormal mental status or impaired consciousness.

2. Insufficient discontinuation period for anticoagulant therapy or severe coagulation dysfunction.

3. Inability to maintain a supine position due to severe cardiopulmonary insufficiency.

4. SHPT/THPT lesions exhibiting features of malignancy, including a lesion diameter greater than 3cm, rapid growth, irregular shape, incomplete capsule, border infiltration, and abnormally enlarged peripheral lymph nodes [51,52].

5. Concurrent thyroid cancer or other malignant neoplasm in the neck.

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Recommendation 5: TA is recommended for patients who experience symptomatic SHPT/THPT and/or exhibit resistance to conservative treatments, or who have declined surgery or are deemed ineligible for surgery [Strong Recommendation (Delphi score 8.45), moderate-quality evidence].

Recommendation 6: TA is not advisable for patients with suspected parathyroid carcinoma unless the patient is deemed unsuitable for surgery [Moderate Recommendation (Delphi score 7.82), low-quality evidence].

Procedure

Preoperative education and precautions.

1. A comprehensive overview of the benefits of TA should be provided to improve patient confidence.

2. Patients should be informed of the TA procedure and potential discomfort to help alleviate anxiety.

3. Heparin-free dialysis should be performed the day before ablation in hemodialysis patients.

4. Patients should fast for at least 6h prior to ablation.

5. Informed consent should be obtained before ablation.

Ablation planning. The ablation procedure should be planned in advance. The plan should generally include confirmation of the number of target SHPT/THPT lesions, the puncture point and direction, the hydrodissection strategy, and the extent of local anesthetic infiltration. In addition, for patients with multiple bilateral SHPT/THPT lesions, the order of ablation should be determined, with the largest lesion generally ablated first.

To avoid severe hypocalcemia after ablation in frail ESRD patients, a staged ablation strategy may be applied [22]. In the first session, the larger SHPT/THPT lesions should be ablated, whereas smaller or relatively normal lesions may be left for ablation in the second session. For patients with very large SHPT/THPT lesions, staged ablation should also be considered for safety, with the second session performed 3-6 months later, after significant shrinkage of the ablation zone has occurred.

Recommendation 7: Complete ablation is recommended, and staged ablation should be considered for frail patients or those with large lesions to prevent severe hypocalcemia after TA [Moderate Recommendation (Delphi score 7.55), low-quality evidence].

Patient position and preparation. Patients should be placed in a supine position with a hyperextended neck. Individuals with obesity, cervical spine issues, or a humpback should be comfortably positioned using low pillows and back cushions to facilitate cooperation. Venous access should be established, echocardiographic monitoring performed, and low-flow oxygen administered. Disinfection should extend at least 15 cm outward from the puncture point. Drapes, such as hole towels or square towels should be placed without covering the patient's face to minimize discomfort and anxiety during ablation. A moderate exposure range should be maintained for the operative field.

Mode of anesthesia. It is recommended to use 1% lidocaine for local anesthesia. Intravenous conscious sedation may be administered if local anesthesia proves ineffective or if the patient is excessively anxious or uncooperative.

Recommendation 8: Local anesthesia is recommended, and intravenous conscious sedation may be used if needed [Strong Recommendation (Delphi score 8.82), low-quality evidence].

Hydrodissection. In microwave ablation, normal saline serves as the isolation liquid, whereas sterile distilled water is preferred for radiofrequency ablation. A needle thinner than 18G may be used for the injection of the isolation liquid during ablation.

A minimum separation of 0.5 cm between SHPT/THPT lesions and critical surrounding structures (e.g., the recurrent laryngeal nerve [RLN], trachea, and esophagus) should be maintained, ensuring continuous or intermittent injection to sustain isolation. Lesions should be isolated as 'islands' [76].

Due to the proximity of the upper glands to the RLN, enlarged glands may adhere to or elevate the RLN. Effective hydrodissection is therefore crucial. In a prior study, a hydrodissection technique based on

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the periparathyroid fascial space was developed to isolate SHPT/THPT lesions and minimize the risk of RLN injury [53]. If hydrodissection is difficult and the lesion cannot be separated from the trachea, the possibility of adhesions between the lesion and surrounding structures (e.g., the RLN) should be considered. In such cases, TA should either be canceled or performed with heightened caution to avoid complications.

To prevent interference from RLN anesthesia when evaluating thermal injury to the RLN during the ablation process, the use of lidocaine or any other local anesthetic is not recommended when performing hydrodissection along the RLN course.

Recommendation 9: Continuous or intermittent hydrodissection should be utilized to maintain a minimum isolation distance of 0.5 cm [Strong Recommendation (Delphi score 8.45), low-quality evidence].

Recommendation 10: Hydrodissection with local anesthesia along the RLN course should be avoided [Moderate Recommendation (Delphi score 7.82), low-quality evidence].

Ablation procedure. Following successful hydrodissection and local anesthesia, US-guided puncture of SHPT/THPT lesions is performed using a microwave antenna or a radiofrequency electrode. Multipoint ablation is recommended for lesions smaller than 1.5cm, while a moving-shot strategy is employed for larger lesions.

The moving-shot technique involves initially positioning the electrode tip in the deepest part of the nodule. Ablation begins at this point, and the electrode tip is then slowly and continuously moved until the entire nodule is encompassed by a hyperechoic area [54,55]. Multipoint ablation, in contrast, refers to the use of a fixed ablation applicator with 15-20s of radiation at each point. The antenna tip is then repositioned under US guidance to successive points until the entire lesion is treated [56]. Microwave antennas with a 3.5-mm active tip and a maximum power of 30W are recommended, whereas radiofrequency electrodes with a 7-10mm active tip and a maximum power of 40W are preferred.

The ablation range should encompass hypoechoic SHPT/THPT lesions, the surrounding normal hyper-echoic parathyroid tissue, and parathyroid-nourishing vessels [50]. In patients with bilateral SHPT/THPT nodules, RLN function should be assessed post-ablation on one side by evaluating patient phonation and observing false vocal cord movement with US. If RLN injury is suspected, ablation of contralateral SHPT/THPT lesions should be postponed until recovery of nerve function is confirmed.

The procedure is considered complete once all target lesions have been ablated. CEUS is recommended approximately 2min post-ablation to evaluate the ablation zone [23,41]. Complete ablation is confirmed when the treated SHPT/THPT lesion is fully encompassed by a nonenhanced zone. Any residual enhancement within the zone should prompt immediate additional ablation.

Recommendation 11: Multipoint or moving-shot ablation should be used based on the size of the parathyroid lesion [Strong Recommendation (Delphi score 9.00), low-quality evidence].

Recommendation 12: After ablation of parathyroid lesions on one side, monitoring for voice changes or false vocal cord movement should be performed to assess RLN function. If RLN injury is suspected, ablation of contralateral lesions should be suspended until RLN function recovers to avoid bilateral nerve injury [Strong Recommendation (Delphi score 8.82), moderate-quality evidence].

Recommendation 13: RLN function should be assessed by observing vocal cord movement via US combined with patient phonation or conversation during the procedure [Strong Recommendation (Delphi score 8.82), low-quality evidence].

Recommendation 14: The ablation range should cover hypoechoic parathyroid lesions, hyperechoic normal parathyroid tissue, and parathyroid-nourishing vessels [Strong Recommendation (Delphi score 8.82), low-quality evidence].

Care after TA. Following ablation, neck compression should be applied for at least 30 min to prevent delayed bleeding. Patients should be closely monitored for complications within 24 h. Hemodialysis patients should undergo dialysis without heparin or with half the usual dose of heparin one day after ablation. Serum calcium and phosphorus levels should be monitored within the first week post-ablation to facilitate early detection and management of hypocalcemia [57].

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9

Postablation complication

The major complications of TA for SHPT/THPT in 1,963 patients are summarized in Table 4. The main complications include nerve injury (RLN, superior laryngeal nerve, or cervical sympathetic trunk) and hematoma. The incidence of nerve injury ranges from 4.2% to 9.2% [21,26,58,59]. Side effects primarily include pain, edema, and numbness, which typically do not necessitate further treatment.

The incidence of hypocalcemia and severe hypocalcemia (SH) after MWA ranges from 35.8% to 53.3% and 22.1% to 43.5%, respectively [57,60]. Symptoms may include hypotension, numbness, convulsions, dyspnea, seizures, and, in severe cases, cardiac arrest or sudden death. Hence, vigilant monitoring and prompt management of hypocalcemia are crucial, particularly for patients who undergo ablation of multiple SHPT/THPT nodules or who experience a sharp decline in iPTH post-ablation [60].

Mild to moderate hypocalcemia can be managed with oral calcium supplements and high-calcium dialysate. Severe hypocalcemia (serum calcium <1.875 mmol/L) requires intravenous calcium supplementation, preferably administered via a deep vein [58]. The dosage of calcium supplementation is determined by the serum calcium level, with approximately 100 ml of 10% calcium gluconate typically increasing serum calcium concentration by approximately 1 mmol/L. Hypercalcemic dialysis may be warranted when the serum calcium concentration falls below 1.5 mmol/L.

The literature identifies several risk factors for severe hypocalcemia, including high preoperative serum iPTH, rapid iPTH reduction, multiple SHPT/THPT lesions, low preoperative serum calcium, absence of pruritus, male sex, and younger age. Predictive models incorporating these parameters can effectively forecast severe hypocalcemia, enabling preventive measures such as a staged ablation strategy or timely hypocalcemia monitoring and management post-ablation [60–64].

Recommendation 15: For patients with SHPT who have severe hypocalcemia, intravenous calcium sup- supplementation through a deep vein is recommended [Strong Recommendation (Delphi score 8.27), moderate-quality evidence].

Follow-up. The recommended follow-up times are at 1 and 7 days, as well as 1, 3, 6, 9, and 12 months after ablation, and every 6 months thereafter [65,66]. In cases of hypocalcemia, the frequency of serum calcium monitoring should be increased.

Follow-up assessments should primarily include imaging examinations and blood biochemical tests. Conventional US and CEUS should evaluate ablation zone shrinkage, detect potential local recurrence, and identify new SHPT/THPT lesions—particularly in patients whose serum iPTH continues to rise post-ablation. MIBI scans may aid in the further differential diagnosis of SHPT/THPT lesions. Blood biochemical tests should typically include measurements of serum iPTH, calcium, phosphorus, and ALP levels.

Clinical interventions post-ablation

1. Patients should maintain lifelong adherence to dietary control.

2. Dialysis frequency should be tailored to individual patient needs to ensure high-quality management.

3. Medication regimens should be adjusted based on laboratory test results and clinical symptoms. General management should encompass:

a. Adequate supplementation with active vitamin D and/or calcimimetics;

b. Regulation of serum calcium and phosphorus levels; and

c. Symptomatic treatment if necessary.

Effectiveness evaluation. Extensive evidence from meta-analyses, cohort studies, and case series supports the technical outcomes, safety, and effectiveness of TA for treating SHPT/THPT [7,19-22,26-28,59] (Table 3). Unlike conventional SR, which aims to completely remove SHPT/THPT lesions, TA typically inactivates hyperplastic lesions identified by US without causing extensive adhesion formation. This approach allows for easier repeat procedures for residual lesions. Consequently, the assessment of ablation effectiveness should not mirror that of conventional SR but instead focus on a comprehensive evaluation of target lesion inactivation, blood biochemical changes, improvement in clinical symptoms, and calcium-phosphorus metabolism. It is recommended that assessment outcomes be categorized as

10 Y.WIETAL

|Author|Year/Country|TA method|Patients|Number of SHPT/THPT lesion|Lesion size (mm)|Follow-up time (month)|iPTH at follow-up end (pg/mL)|Rate of goal iPTH at follow-up end (%)|Complication (%)|Study type|Level of Evidence*| |---|---|---|---|---|---|---|---|---|---|---|---| |Yue et al. [27]|2024/China|RFA|165|582|–|51(6–117)|–|78.2|9.9|SCT|Moderate (D)| |Deng et al. [28]|2024/China|RFA|38|136|12.3 (0.8–18.8)|21.5±19.0|261.1(144.6–366.2)|–|–|SCT|Moderate (D)| |Wei et al. [67]|2023/China|MWA|337|731|14(6–26)|–|–|72.7|13.1|SCT|Moderate (D)| |Lin et al. [68]|2023/China|RFA|103|–|–|–|488.2(182.8–1,042.8)|–|26.2|SCT|Moderate (D)| |Zhang et al. [69]|2022/China|RFA|47|3.7±0.6 (per)|20.3±5.5|28.6 (21.3–36.6)|280±307|64.1|12.8|CS|Low (E)| |Qin et al. [41]|2021/China|RFA|32|131|9.88±549.$3mm^{3}$|12|117.6±97.0|71.9|3.1|SCT|Moderate (D)| |Zhao et al. [70]|2021/China|MWA|79|316|–|3|167.7±190.3|86.1|10.1|CS|Low (E)| |Wang et al. [29]|2021/China|MWA|53|2.8±0.9 (per)|16.7±8.1|42.4±15.6|–|68.8|20.8|SCT|Moderate (D)| |Diao et al. [19]|2021/China|MWA|47|2(1–2) (per)|12(8–16)|46±17|–|53.3|–|CS|Low (E)| |Wei et al. [60]|2020/China|MWA|204|387|16±6|6|–|71.6%|–|SCT|Moderate (D)| |Zhuo et al. [14]|2019/China|MWA|35|63|14.9±5.5|15.9±2.2|270(92.0–625.0)|–|0|SCT|Moderate (D)| |Jiang et al. [71]|2019/China|MWA|33|81|15.7±10.6|18.1±2.1|411.0±196.6|81.8|0|CS|Low (E)| |Wei et al. [58]|2019/China|MWA|213|–|–|–|–|–|12.6|SCT|Moderate (D)| |Zhuo et al. [23]|2017/China|MWA|51|96|15.0±6.0|11.1±3.3|400(151.3–629.0)|–|4|SCT|Moderate (D)| |Peng et al. [72]|2017/China|RFA|34|108|–|12|–|–|11.8|SCT|Low (E)| |Zhao et al. [73]|2016/China|MWA|56|138|13.5±6.5|9.3±5.6|442.4±234.6|–|5.4|SCT|Moderate (D)| ||||||||||||| |*Level of evidence refers to Table 1.|||||||||||| |RCT: randomized controlled trail; CS: cohort studies; SCT: self-controlled trail; MWA: microwave ablation; RFA: radiofrequency ablation; TA: thermal ablation.||||||||||||

*Level of evidence refers to Table 1.

RCT: randomized controlled trail; CS: cohort studies; SCT: self-controlled trail; MWA: microwave ablation; RFA: radiofrequency ablation; TA: thermal ablation.

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|Number (incidence rate)|Complication| |---|---| |13 (0.7%)|Permanent hoarseness| |114 (5.8%)|Transient hoarseness| |38 (1.9%)|Choking| |15 (0.8%)|Hematoma| |2 (0.1%)|Horner Syndrome| |16 (0.8%)|Permanent Hypoparathyroidism| |417 (21.2%)|Hypocalcemia| |277 (14.1%)|Severe hypocalcemia| |12 (0.6%)|Fever|

TA: thermal ablation; SHPT: secondary hyperparathroidism; THPT: Tertiary Hyperparathyroidism.

‘effective,’ ‘partially effective,’ or ‘invalid’, defined as follows.

Effective. Target SHPT/THPT lesions exhibit complete inactivation, as confirmed by imaging. Serum iPTH decreases by ≥80% within 3 days post-ablation, while serum calcium and phosphorus levels normalize, accompanied by significant improvement or disappearance of relevant clinical symptoms.

Partially effective. Target SHPT/THPT lesions are inactivated post-TA, with a serum iPTH reduction of ≥50-80% within 3 days post-ablation. Calcium and phosphorus metabolism is improved, with significant improvement or disappearance of relevant clinical symptoms.

Invalid. SHPT/THPT lesions remain active or incompletely inactive, as confirmed by imaging. Serum iPTH decreases by <50%, with no significant improvement in calcium or phosphorus metabolism and no improvement in clinical symptoms.

The persistence or recurrence of SHPT/THPT may be attributed to residual or ectopic lesions, such as those located in the thymus/thyrothymic ligament, retroesophageal region, intrathyroidal region, or mandibular region [74]. TA has been attempted as a treatment option for selected ectopic SHPT/THPT lesions that can be visualized under ultrasound guidance [30]. In one published study, ectopic parathyroid nodules were identified in patients with chronic kidney disease at locations including the suprasternal fossa, lateral to the left carotid artery, within the thyroid gland, and in the submandibular area. Lesion sizes ranged from 1.0 to 3.3 cm, with post-ablation follow-up durations of 2 to 26 months. Most patients demonstrated a reduction in iPTH levels following TA. However, one patient developed Horner's syndrome after ablation of a lesion adjacent to the carotid sheath, highlighting the importance of protecting surrounding neurovascular structures.

While the technical principles of TA for ectopic lesions are generally similar to those for orthotopic lesions, ectopic nodules—particularly those located near critical structures—require precise preprocedural localization and individualized hydrodissection planning to minimize the risk of thermal injury.

Recommendation 16: Considering that TA differs from SR, an independent evaluation method is established and recommended in the present consensus, categorizing the outcome as 'effective', 'partially effective' or 'invalid' [Strong Recommendation (Delphi score 8.64), low-quality evidence].

Conclusion and future directions

Precision medicine represents a pivotal trend in modern healthcare. Compared with traditional SR, TA has demonstrated promising advantages in the treatment of SHPT/THPT, including minimal invasiveness, favorable safety profiles, and reliable efficacy. Accordingly, this international consensus aims to promote the global adoption of TA for SHPT/THPT, ultimately benefiting a broader patient population.

Additionally, recent comparative evidence supports the technical feasibility of both modalities. A meta-analysis reported that MWA and RFA achieved comparable biochemical efficacy and safety, while MWA offered a significantly shorter procedure time and a higher complete ablation rate for lesions ≥15 mm [75]. These findings indicate that both techniques are effective, with MWA providing procedural advantages in selected patients. Emerging evidence also suggests that staged TA may achieve long-term biochemical outcomes comparable to SR while maintaining a more favorable safety profile by reducing the risk of severe hypocalcemia, particularly in frail patients or those with multigland disease or high operative risk [57,76].

12 Y.WEI ET AL.

Nonetheless, most available clinical evidence comes from observational cohort studies, and large-scale prospective randomized controlled trials are still underway. As such, the level and quality of evidence supporting the recommendations remain suboptimal. This underscores important directions for future research, including the need for high-quality, multicenter data to further validate and refine clinical practice. Additionally, a considerable proportion of the included literature and expert contributors originate from China, reflecting the rapid development and widespread clinical application of TA for SHPT/THPT in the Chinese medical community. While the current geographic distribution of research is more concentrated, the technique itself is universally applicable and should not be limited by regional differences. Future studies may further explore potential variations in treatment responses across different racial groups, such as differences in biochemical profiles and bone metabolism after ablation.

In summary, this consensus not only provides technical guidance for the clinical application of TA in SHPT/THPT, but also serves as a foundation for global research collaboration and broader clinical integration.

Conclusion

TA has emerged as a viable treatment option for SHPT/THPT in carefully selected patients, demonstrating promising efficacy with a low incidence of complications. This expert consensus aims to facilitate the clinical adoption and standardization of high-quality TA procedures for the management of SHPT/THPT.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethics approval

Our retrospective study was approved by the institutional review board of our hospital. Written informed consent was obtained from each patient before the ablation procedure. The patients consented to publishing their examination results and radiological images anonymously, and the written informed consent for publication of their data was waived by the ethics committee of China-Japan Friendship Hospital.

Funding

This work was funded by The National Natural Science Foundation of China [62176268], National High Level Hospital Clinical Research Funding [2025-NHLHCRF-JBGS-A-WZ-01], National High-Level Hospital Clinical Research Funding; Elite Medical Professionals Project of China-Japan Friendship Hospital [NO. ZRJY2023-GG19].

ORCID

Shu-Hang Xu http://orcid.org/0000-0002-8619-5376 Dong Xu http://orcid.org/0000-0002-0583-240X Man Lu http://orcid.org/0000-0002-3455-834X Giovanni Mauri http://orcid.org/0000-0003-4726-2692 Ming-An Yu http://orcid.org/0000-0003-0797-4564

Data availability statement

Some or all datasets generated during and/or analyzed during the current study are not publicly available but are available from the corresponding author on reasonable request.

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