Essentials for parathyroid imaging and intervention: what radiologists need to know

Hye Jeong Choi; Ji-hoon Kim

doi:10.14366/usg.25102

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Choi and Kim: Essentials for parathyroid imaging and intervention: what radiologists need to know

Review Article

Ultrasonography 2025;44(5):324-345.

Published online: 28 August 2025

DOI: https://doi.org/10.14366/usg.25102

Essentials for parathyroid imaging and intervention: what radiologists need to know

Hye Jeong Choi¹

, Ji-hoon Kim²

¹Department of Radiology, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea

²Department of Radiology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea

Correspondence to: Ji-hoon Kim, MD, PhD, Department of Radiology, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea Tel. +82-2-2072-3617 Fax. +82-2-747-7418 E-mail: jihnkim@gmail.com, jihnkim@snu.ac.kr

Received 30 May 2025 Revised 17 July 2025 Accepted 22 July 2025

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The parathyroid glands play a key role in maintaining calcium–phosphate homeostasis by secreting parathyroid hormone (PTH). Hyperparathyroidism, characterized by the inappropriate overproduction of PTH, is classified as primary, secondary, or tertiary according to its pathophysiology. Although diagnosis is principally biochemical, imaging is essential for accurately localizing hyperfunctioning glands. Precise localization allows for focused minimally invasive surgery, reduces the risk of persistent or recurrent disease, and avoids unnecessary bilateral neck exploration. Current techniques include high-resolution ultrasonography, ^99mTc-sestamibi scintigraphy with single-photon emission computed tomography/computed tomography (CT), four-dimensional CT, magnetic resonance imaging, and positron emission tomography/CT with tracers such as ¹⁸F-fluorocholine. Parathyroidectomy remains the mainstay of treatment; however, recent advances in thermal ablation have expanded treatment options for patients unsuitable for surgery.

Keywords: Parathyroid glands, Hyperparathyroidism, Ultrasonography, Parathyroidectomy, Radiofrequency ablation

Key point

While ultrasonography (US) is fundamental, a multimodal approach—including ^99mTc-sestamibi scintigraphy with single-photon emission computed tomography/computed tomography (CT), four-dimensional CT, and ¹⁸F-fluorocholine positron emission tomography/CT—is necessary, as each modality plays a complementary and sometimes indispensable role in various clinical settings of parathyroid imaging and intervention. While parathyroidectomy remains the standard treatment for most cases of hyperparathyroidism, US-guided ablation is effective for selected patients who are not suitable candidates for surgery.

Introduction

Hyperparathyroidism is an endocrine disorder characterized by the dysregulated function of one or more parathyroid glands, resulting in excessive, uncontrolled secretion of parathyroid hormone (PTH) [1]. Based on its underlying pathophysiology, it is classified into three types: primary hyperparathyroidism (PHPT), secondary hyperparathyroidism (SHPT), and tertiary hyperparathyroidism (THPT) [1]. Recent data indicate a rising incidence of parathyroid disorders [1]. PHPT is now frequently detected through routine laboratory screening, even in asymptomatic individuals or those presenting with nonspecific neurocognitive symptoms, including impaired memory, difficulty concentrating, mood disturbances, and fatigue [2]. Furthermore, the increasing use of high-resolution neck ultrasonography (US) for evaluating thyroid and nonthyroid cervical lesions has contributed to a higher detection rate for incidental parathyroid lesions [3-5]. The primary role of imaging in hyperparathyroidism is the precise localization of hyperfunctioning glands [2]. Several imaging modalities are used for this purpose, including US, parathyroid scintigraphy with single-photon emission computed tomography (SPECT)/computed tomography (CT), four-dimensional (4D) CT, positron emission tomography (PET)/CT, and magnetic resonance imaging (MRI) [2,6,7]. Fine-needle aspiration (FNA) with PTH assay of needle washout fluid plays a confirmatory role in cases of suspected parathyroid lesions [5]. Parathyroidectomy remains the standard treatment for PHPT, refractory SHPT, and THPT, while US-guided minimally invasive therapies have been proposed as alternatives for patients unsuitable for surgery [8,9]. This review discusses key aspects of parathyroid imaging and emerging minimally invasive treatment strategies, highlighting their clinical significance in localization and management.

Embryology, Anatomy, and Ectopic Parathyroid Glands

Normal parathyroid glands typically measure 2-7 mm in length and weigh 35-55 mg [1]. Most individuals have four parathyroid glands—two superior and two inferior [10]. Specifically, approximately 81.4% of people have four glands, while 13.2% have three or fewer, and 5.4% have five or more [11]. Parathyroid glands originate from the endoderm of the third and fourth pharyngeal pouches [1,12]. The inferior parathyroid glands and thymus arise from the third pouch, whereas the superior glands derive from the fourth pouch [1,12]. Due to their embryological descent, the inferior parathyroid glands are more likely to be ectopic and may be found along the thymic migration pathway, such as within the thymus, thyroid gland, or anterosuperior mediastinum (Table 1) [1,12]. The superior parathyroid glands, which migrate with the thyroid, are usually located posterior to the middle and upper poles of the thyroid [12]. Ectopic superior glands are less common than inferior ones, with a reported superior-to-inferior ratio of 1:1.6, and are generally found in posterior locations such as the tracheoesophageal groove, retroesophageal region, and posterosuperior mediastinum (Table 1) [13].

Pathophysiology, Epidemiology, and Management of Hyperparathyroidism

PHPT, SHPT, and THPT exhibit distinct pathophysiological mechanisms (Table 2) [14]. PHPT results from autonomous PTH secretion by parathyroid tissue [1]. SHPT arises as a compensatory response to chronic hypocalcemia—often secondary to chronic kidney disease (CKD), vitamin D deficiency, or malabsorption—leading to parathyroid hyperplasia [14]. THPT represents a progression from SHPT in which parathyroid hyperplasia becomes autonomous, causing persistent hypercalcemia despite resolution of the initial stimulus [14]. PHPT is the third most common endocrine disorder, with a prevalence of 0.1%-0.7% in the general population, although this varies based on race, age, and sex [15]. Its incidence ranges from 34 to 120 per 100,000 person-years in women and from 13 to 36 per 100,000 in men, predominantly affecting individuals aged 55 to 65 years [15]. Improved access to routine biochemical screening has led to earlier detection of asymptomatic cases [14-16]. In South Korea, the annual incidence of PHPT increased sixfold from 0.23 per 100,000 in 2005 to 1.75 per 100,000 in 2020 [17]. The global burden of SHPT is also rising due to the increasing prevalence of CKD, which is estimated at 13.4% [18,19]. A meta-analysis reported that SHPT affects approximately 49.5% of patients with CKD, although prevalence rates vary regionally [19]. The prevalence of THPT also differs across studies; one prospective cohort found an incidence of 21.5% among kidney transplant recipients 1-year post-transplant [20].

PHPT is primarily caused by parathyroid adenomas (75%-85%) followed by multiglandular disease (15%-20%), with parathyroid carcinoma accounting for less than 1% of cases [14]. Risk factors include aging, prior radiation exposure, lithium therapy, vitamin D deficiency, and genetic syndromes such as multiple endocrine neoplasia and hyperparathyroidism-jaw tumor syndrome [14]. The 2022 World Health Organization classification incorporates recent advances in the understanding of parathyroid pathology [21]. "Parathyroid hyperplasia" is now primarily used to describe secondary hyperplasia related to CKD, whereas "multiglandular parathyroid adenoma" more accurately describes PHPT-related multiglandular disease [21]. The previous term "atypical parathyroid adenoma" has been replaced by "atypical parathyroid tumor" to reflect uncertain malignant potential [21]. Parathyroid carcinoma is diagnosed based on specific criteria, including vascular or lymphatic invasion or metastasis [21]. Mutations in the cell division cycle 73 gene leading to parafibromin loss represent key molecular markers for parathyroid carcinoma and are critical for diagnosis, prognosis, and genetic counseling [21].

Management strategies are tailored to the specific type of hyperparathyroidism [22]. Parathyroidectomy is the definitive treatment for PHPT, effectively normalizing PTH levels and reducing the risk of complications such as bone disease (Table 2) [23]. Current guidelines recommend surgery for asymptomatic PHPT based on factors including age, serum calcium levels, bone density, and renal function (Table 3) [24]. In patients who are not surgical candidates, pharmacologic management may be considered [23]. SHPT is primarily managed medically, using phosphate binders, vitamin D analogs, and calcimimetics to regulate calcium–phosphate balance and suppress PTH levels [25,26]. Parathyroidectomy is reserved for severe or refractory cases [25,26]. In THPT, surgery is considered when medical therapy fails to control hypercalcemia and PTH levels [27-29]. Emerging ablation techniques have gained attention as nonsurgical options for patients with inoperable hyperparathyroidism or who are unwilling to undergo surgery [9].

Localization for Hyperparathyroidism

US, ^99mTc-sestamibi scintigraphy with SPECT/CT, and 4D CT are the primary imaging modalities currently employed in clinical practice to localize parathyroid lesions, each offering complementary strengths (Table 4) [30]. When these primary techniques are limited—such as in cases of ectopic, recurrent, or persistent disease, low-functioning lesions, or concerns about radiation exposure or contrast use—MRI and ¹⁸F-fluorocholine PET/CT serve as valuable alternatives [2].

Ultrasonography

US represents a fundamental imaging tool for evaluating the parathyroid glands due to its wide availability, cost-effectiveness, and absence of radiation exposure [32]. It also facilitates US-guided diagnostic and therapeutic procedures [32]. Imaging is typically performed using a high-frequency linear transducer (10-15 MHz), covering the area from the carotid bifurcation to the thoracic inlet, including the tracheoesophageal groove and paraesophageal region [33]. Historically, detecting normal parathyroid glands on US has been challenging due to their subtle features. However, recent studies have identified characteristic sonographic findings that aid detection (Video clip 1 ). Normal parathyroid glands are identified in approximately 91% of cases as small, ovoid, hyperechoic structures lacking intraglandular vascular flow (Fig. 1) [32,34-37]. Their hyperechogenicity results from diffusely distributed stromal fat and a heterogeneous internal architecture, in contrast to parathyroid adenomas, which are typically hypoechoic due to their homogeneous proliferation of chief cells [38,39]. Parathyroid adenomas usually appear oval but may become bean-shaped or lobulated as they enlarge, typically aligning with the long axis of the neck (Fig. 2) [40]. They are generally hypoechoic relative to the thyroid gland and may have a well-circumscribed hyperechoic peripheral rim, likely representing an interface echo between the lesion and surrounding tissue (Fig. 3A) [2,41]. Atypical sonographic features—including heterogeneous echotexture, cystic changes, and calcifications—occur in approximately 10% of patients [42]. These features may reflect the histological complexity of the lesion, including acinar dilatation, fibrosis, hemorrhage, cystic degeneration, and fat deposition [42]. Color Doppler US can reveal a feeding polar artery, typically originating from the inferior thyroid artery, and a peripheral vascular arc ("polar vessel sign"; Figs. 2B, 3B). These features distinguish parathyroid lesions from lymph nodes, which exhibit hilar vascularity and an echogenic hilum (Fig. 4) [41,43]. Rarely, parathyroid tumors may cause spontaneous neck hematoma due to rupture of feeding vessels—a potentially life-threatening event (Fig. 5). Multiglandular disease often manifests as multiple enlarged, lobulated glands, which may appear symmetric or asymmetric [44]. In the evaluation of PHPT, US demonstrates sensitivity rates ranging from 72% to 92% in single-gland disease [45,46]. However, sensitivity declines significantly in multiglandular disease, often falling below 35% [45]. Parathyroid carcinoma is a rare but aggressive endocrine malignancy that poses diagnostic challenges due to its overlap with benign adenomas [47]. Clinical indicators such as markedly elevated PTH levels, severe hypercalcemia, significant end-organ damage, local invasion, and lymphadenopathy may suggest malignancy, but these signs are not definitive. Diagnosis usually requires postoperative histopathological confirmation [48]. Suspicious US features include lesion length >3 cm, depth-to-width ratio >1, irregular margins, calcifications, infiltration into adjacent tissues, and cervical lymphadenopathy (Fig. 6) [44,49-51]. FNA cytology with PTH assay of the aspirate can help confirm the parathyroid origin of a suspicious lesion, but its use should be highly selective [23]. Based on current guidelines, parathyroid FNA is not recommended as a routine diagnostic procedure due to the risk of fibrosis or adhesions that may complicate surgery [23]. Instead, it should be considered in specific scenarios, such as when morphological imaging (including ultrasound or CT), functional imaging (such as 99m-Tcsestamibi scintigraphy), and biochemical findings are discordant, or in technically challenging cases such as intrathyroidal lesions or reoperative neck procedures [23]. FNA cytology alone has limited diagnostic utility for differentiating parathyroid from thyroid lesions, with sensitivity ranging from 29% to 41.7% [3,52,53]. In one study, cytology alone correctly identified parathyroid cells in only 31% of cases; however, the addition of PTH assay significantly increased the sensitivity to 84% [54]. Despite this advantage, FNA is associated with risks such as hematoma, fibrosis, tumor seeding, and capsular disruption, which can obscure the distinction between benign and malignant lesions [54,55]. Consequently, FNA is not recommended in cases of suspected parathyroid carcinoma [23]. When definitive localization is needed for treatment planning in hyperparathyroidism and imaging results are equivocal, FNA with PTH assay can be an invaluable adjunct for clinical decision-making [56].

^99mTc-sestamibi Scintigraphy with SPECT/CT

Radionuclide imaging enables the detection of hyperfunctioning parathyroid tissue in both typical and ectopic locations [6]. The most widely used tracer, ^99mTc-sestamibi, is a lipophilic, cationic agent that preferentially accumulates in hyperactive parathyroid tissue due to its high mitochondrial content, especially in oxyphil cells [2,6]. Following intravenous administration of 400-900 MBq of ^99mTc-sestamibi, imaging is performed in two phases: early (10-30 minutes post-injection) and delayed (90-180 minutes post-injection) [6]. Parathyroid adenomas typically retain radiotracer uptake in delayed-phase images, whereas thyroid tissue exhibits washout, enabling effective dual-phase imaging localization (Figs. 2, 3) [6,57]. Integration of SPECT with CT has improved lesion localization compared with planar imaging, offering higher sensitivity and better anatomical detail [58]. In cases where US findings are ambiguous—such as cystic changes, heterogeneous echotexture, or calcifications—^99mTc-sestamibi scintigraphy can be valuable for localization (Fig. 7). Combining US with ^99mTc-sestamibi SPECT/CT significantly improves sensitivity (95%) compared with either modality alone (64% for US and 90% for SPECT/CT) [59]. False-positives may arise from thyroid pathologies (such as multinodular goiter, thyroiditis, or carcinoma), lymph nodes, malignancies, brown adipose tissue, or brown tumors [2]. False-negatives may result from small gland size, multiglandular disease, ectopic location, or rapid radiotracer washout [2].

Four-Dimensional Computed Tomography

Multiphase parathyroid CT, also known as 4D CT, has become a preferred method for preoperative parathyroid imaging and as a problem-solving technique in complex or repeat surgical cases [2,60,61]. The term "4D CT" refers to three-dimensional CT with the addition of a temporal dimension, representing dynamic changes in contrast perfusion over time [61]. The appropriate number of contrast phases in 4D CT remains a topic of ongoing debate among radiologists, with protocols varying across institutions [62]. Approximately half of institutions employ a three-phase protocol—pre-contrast, arterial (25-40 seconds), and delayed (60-80 seconds)—to balance radiation exposure and diagnostic accuracy [62-64]. The enhancement patterns reflect the highly vascular nature of parathyroid lesions, enabling differentiation from radiologically similar thyroid nodules or lymph nodes [65,66]. Unlike the thyroid gland, hyperfunctioning parathyroid tissue lacks iodine; accordingly, it typically exhibits lower attenuation than thyroid tissue on pre-contrast images (Figs. 8, 9) [65,66]. Due to its abundant arterial blood supply, parathyroid tissue demonstrates rapid contrast enhancement during the arterial phase, followed by rapid washout in delayed imaging (Figs. 8, 9) [65,66]. Studies have identified three or four distinct enhancement patterns in parathyroid lesions; the most common pattern for parathyroid adenoma (approximately 60% of cases, Fig. 8D) involves low attenuation in the precontrast phase. Although parathyroid lesions generally show lower absolute attenuation than the thyroid gland in the arterial phase, they typically exhibit a steeper enhancement slope and more rapid washout on dynamic contrast-enhanced imaging [66,67]. A major concern with the use of 4D CT as a first-line imaging modality, even for younger patients, is its increased radiation exposure—particularly the higher thyroid dose compared with parathyroid scintigraphy and other imaging methods (Table 4) [68–70]. Mahajan et al. [70] reported effective doses of 10.4 mSv for four-phase 4D CT versus 7.8 mSv for ^99mTc-sestamibi SPECT. Hoang et al. [69] reported even higher doses: 28 mSv for three-phase 4D CT and 12 mSv for SPECT/CT. Nevertheless, both modalities were found to contribute negligibly to lifetime cancer risk [70]. Contraindications for 4D CT include contrast hypersensitivity and the use of radioiodine therapy for thyroid malignancies [2]. Notably, 4D CT has demonstrated superior sensitivity (70.6%) in localizing hyperfunctioning glands compared with combined US and SPECT (51.9%) [71].

Positron Emission Tomography

PET has emerged as a promising imaging modality for localizing hyperfunctioning parathyroid glands, demonstrating high sensitivity (Fig. 10) [72,73]. Various PET tracers, including ¹⁸F-fluorocholine and ¹¹C-choline, have been explored, although standardized acquisition protocols are still lacking [6]. Choline PET targets increased membrane metabolism through upregulated choline transporter activity and choline kinase expression [74]. ¹⁸F-fluorocholine is preferred over ¹¹C-choline due to its longer half-life, enabling transport from cyclotron-equipped centers, and its lower positron energy, which reduces image noise and improves spatial resolution [6]. The utility of ¹⁸F-fluorocholine PET in parathyroid imaging was initially observed incidentally in patients undergoing evaluation for prostate cancer [75]. A recent meta-analysis encompassing 119 studies demonstrated that choline PET/CT displayed the highest surface under the cumulative ranking curve for the localization of PHPT [76]. With ongoing advancements in PET technology, hybrid PET/4D CT techniques have demonstrated improved localization sensitivity (¹⁸F-fluorocholine PET/CT, 80%; 4D CT alone, 74%; PET/4D CT, 100%) [77]. Additionally, ¹⁸F-fluorocholine PET/MRI has exhibited superior accuracy in inconclusive cases following conventional parathyroid scintigraphy and US [78,79]. However, choline PET/CT has limitations due to nonspecific uptake, as inflammatory, infectious, or malignant conditions—as well as benign thyroid nodules and lymph nodes—may also exhibit choline avidity [2,80]. Furthermore, physiologic thyroid uptake can obscure normally positioned glands, leading to false-negatives [6]. Despite these drawbacks, choline PET/CT remains valuable for problem-solving when standard imaging is negative or inconclusive, although its cost-effectiveness warrants further investigation [6].

Magnetic Resonance Imaging

While MRI is not typically employed as a first-line tool for parathyroid localization, it serves as a problem-solving modality in recurrent or persistent disease when conventional imaging fails [72]. Parathyroid adenomas typically appear isointense to hypointense on T1-weighted images and hyperintense on T2-weighted images, without diffusion restriction [40,81]. Lesions larger than 1.5 cm may exhibit a marbled T2 appearance due to internal fibrosis, hemorrhage, or cholesterol clefts [82]. Although imaging cannot reliably distinguish carcinoma from adenoma, carcinomas tend to be larger, more heterogeneous, and invasive (Fig. 11) [81]. Similar to 4D CT, 4D dynamic contrast-enhanced MRI can reveal rapid enhancement patterns helpful in lesion localization [83].

Parathyroid Incidentaloma

Parathyroid incidentalomas are lesions identified incidentally during imaging or surgery for unrelated reasons [3,4]. The frequent use of high-resolution neck US for evaluating thyroid abnormalities has resulted in an increased detection rate of incidental parathyroid lesions [3,4]. The reported prevalence of parathyroid incidentalomas detected on thyroid US ranges from 0.45% to 0.6% [3,4]. Among detected cases, 37.5% were functional adenomas [84]. On US, a well-defined, oval, homogeneously hypoechoic lesion with a feeding vessel outside the thyroid capsule may suggest an enlarged parathyroid gland [3,84]. Differential diagnosis should also consider exophytic thyroid nodules, lymph nodes, fat, or other soft tissue masses [5]. If imaging suggests a parathyroid origin, biochemical evaluation (serum calcium and PTH) is recommended [85]. Preoperative imaging evaluation is essential for accurately localizing parathyroid lesions and minimizing the risk of reoperation [86]. If a suspected parathyroid neoplasm is incidentally detected during thyroid FNA, immediate aspiration should be deferred. Instead, further evaluation using biochemical tests and/or functional imaging, such as ^99mTc-sestamibi scintigraphy, is recommended to guide appropriate clinical management [86]. Cytologic diagnosis of parathyroid incidentalomas is often challenging due to overlapping cytologic features with thyroid and lymphoid tissues, resulting in relatively low sensitivity (31.6%-41.7%) when relying solely on FNA cytology [3,5]. To improve diagnostic accuracy, ultrasound-guided FNA combined with PTH assay of the aspirated fluid can significantly increase sensitivity, up to 92.9% [3]. A comprehensive clinical assessment—including serum PTH and calcium levels, renal function, and bone mineral density—is crucial for determining the necessity and optimal timing of intervention [85].

Nonsurgical Treatment of Parathyroid Lesions

Parathyroidectomy remains the definitive treatment for PHPT, refractory SHPT, and THPT; however, minimally invasive techniques yield comparable outcomes with fewer postoperative complications, which is especially beneficial for patients who are poor surgical candidates or decline surgery [8,87-89]. These approaches include percutaneous ethanol injection therapy and thermal ablation techniques such as radiofrequency ablation (RFA) and microwave ablation (MWA) [8]. US-guided simple aspiration is the preferred diagnostic and initial treatment method for nonfunctioning parathyroid cysts, with clear fluid and elevated PTH confirming the diagnosis (Fig. 12) [32,90]. Although approximately one-third of cases resolve with aspiration alone, recurrence often necessitates adjunctive ethanol ablation [32]. Both RFA and MWA induce lesion necrosis via thermal energy, differing in heat delivery and clinical utility [91]. MWA is faster and preferred for larger lesions [92], while RFA is safer near critical structures—such as the recurrent laryngeal nerve, trachea, or esophagus—due to its precise control (Fig. 13) [93]. A multicenter study involving 104 patients with PHPT (114 nodules) reported similar cure rates for MWA (88.3%) and RFA (88.9%) at 12 months [94]. In SHPT, RFA achieved biochemical control in 78.2% of 165 patients (582 glands) over 51 months [95]. For THPT, RFA yielded an 86.4% success rate at 1 year, defined as PTH <585 pg/mL [89]. A meta-analysis of 13 studies involving 444 patients reported major complications (including permanent voice change, severe hypocalcemia, or permanent hypoparathyroidism) in 7.5% and minor complications (such as transient voice changes, hematoma, or infection) in 20.0% [96].

Conclusion

Current multimodal imaging approaches are essential for the precise localization of hyperfunctioning parathyroid glands, a crucial step for ensuring the success of minimally invasive treatments and preventing recurrence. US, ^99mTc-sestamibi scintigraphy with SPECT/CT, and 4D CT are the primary imaging modalities currently used in clinical practice, each offering complementary strengths for localizing parathyroid lesions. ¹⁸F-fluorocholine PET/CT demonstrates excellent localization performance and may become more widely adopted with the development of novel tracers. Although parathyroidectomy remains the mainstay of treatment for hyperparathyroidism, US-guided ablation offers a viable alternative for patients unsuitable for surgery, showing favorable biochemical outcomes and acceptable complication rates.

Notes

Author Contributions

Conceptualization: Kim JH, Choi HJ. Data acquisition: Kim JH, Choi HJ. Data analysis or interpretation: Kim JH, Choi HJ. Drafting of the manuscript: Kim JH, Choi HJ. Critical revision of the manuscript: Kim JH, Choi HJ. Approval of the final version of the manuscript: all authors.

Conflict of Interest

No potential conflict of interest relevant to this article was reported.

Acknowledgments

We thank Dr. Sung-Hye You (Korea University Anam Hospital) for providing the image used in Fig. 11.

Supplementary Material

Video clip 1.

Preoperative thyroid evaluation in a 65-year-old woman with papillary thyroid carcinoma. During ultrasonography examination, an abrupt, well-defined, oval-shaped hyperechoic lesion measuring approximately 7 mm was observed at the inferior aspect of the left thyroid lobe (white arrow). This finding represents a normal inferior parathyroid gland, which commonly appears at this location and should not be mistaken for a metastatic lymph node in this clinical context (https://doi.org/10.14366/usg.25102.v1).

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Fig. 1.

Sonographic features of a normal inferior parathyroid gland in a 71-year-old woman undergoing thyroid nodule surveillance.

A. Longitudinal grayscale ultrasonography (US) demonstrates a well-defined, oval, hyperechoic lesion (arrow). B. Color Doppler US depicts the lesion encircled by the inferior thyroid artery (arrowhead), without significant internal vascularity.

Fig. 2.

Typical imaging presentation of a superior parathyroid adenoma.

A 57-year-old woman presented with asymptomatic hypercalcemia (11.3 mg/dL) and osteopenia (T-score, -1.9) identified during routine screening. Laboratory testing revealed elevated parathyroid hormone levels (234 pg/mL). A. Grayscale ultrasonography (US) shows a 2.4-cm elongated, hypoechoic lesion posterior to the right thyroid lobe. B. Color Doppler US reveals the polar vessel sign (white arrowheads). C, D. Early and delayed ^99mTc-sestamibi scintigraphy images demonstrate persistent radiotracer uptake in the right thyroid bed (black arrowhead), consistent with parathyroid adenoma. E. Axial fused single-photon emission computed tomography/computed tomography confirms focal hypermetabolism posterior to the right thyroid lobe (arrow).

Fig. 3.

Parathyroid adenoma with an incidentally detected brown tumor.

A 32-year-old man with nephrolithiasis was found to have hypercalcemia (13.2 mg/dL) and a markedly elevated parathyroid hormone level (684 pg/mL). A. Grayscale ultrasonography (US) reveals a large, well-demarcated, hypoechoic mass posterosuperior to the right thyroid lobe with a hyperechoic rim (arrows). B. Color Doppler US shows the polar vessel sign, associated with the right inferior thyroid artery (arrowheads). C, D. ^99mTc-sestamibi scintigraphy at 10 minutes and 2 hours 30 minutes confirms persistent uptake in the right thyroid bed (arrowhead), consistent with superior parathyroid adenoma. E. Axial fused single-photon emission computed tomography/computed tomography incidentally shows an expansile, osteolytic, hypermetabolic lesion in the left scapula (arrow), suggestive of a brown tumor. The black arrowhead indicates an area of asymmetric hypermetabolism in the right thyroid bed, corresponding to the location of the parathyroid adenoma.

Fig. 4.

Differentiation between parathyroid adenoma and a mimicking lesion.

Case 1: A 58-year-old woman presented with hyperparathyroidism (parathyroid hormone [PTH], 372.9 pg/mL). A. Ultrasonography (US) reveals a well-defined, oval, hypoechoic lesion in the right thyroid bed, with a thin hyperechoic peripheral rim. B. Color Doppler imaging shows prominent peripheral vascularity supplied by the inferior thyroid artery. Surgical excision confirmed parathyroid adenoma, and PTH levels normalized postoperatively. Case 2: A 35-year-old woman presented with thyroiditis. C. US demonstrates an oval, hypoechoic lesion in the right thyroid bed, with a central hyperechoic hilum. D. Microvascular flow imaging reveals central hilar vascularity. These findings are consistent with a benign lymph node. No hypercalcemia or elevated PTH was observed.

Fig. 5.

Spontaneous hemorrhage in a parathyroid adenoma.

A 64-year-old man without a history of trauma presented with acute neck swelling and hoarseness. A. Physical examination reveals extensive subcutaneous neck ecchymosis. B. Laryngoscopy shows diffuse submucosal ecchymosis involving the pharyngolaryngeal region. C, D. Pre- and post-contrast computed tomography (CT) identifies a heterogeneous hematoma in the left thyroid bed without active bleeding (arrow). E. Follow-up CT performed 1 month later shows a suspected parathyroid lesion in the left superior thyroid bed (arrow). F. Gross specimen confirms a hemorrhagic superior parathyroid adenoma with cystic degeneration (white arrowheads) and a solid tumor component (black arrowheads).

Fig. 6.

Misdiagnosis of parathyroid carcinoma as a thyroid nodule on fine-needle aspiration (FNA).

A 63-year-old woman was initially diagnosed with a benign thyroid nodule on FNA. Subsequent abdominal computed tomography (CT) for abdominal pain revealed renal stones. Further workup showed hypercalcemia (12.9 mg/dL) and a markedly elevated parathyroid hormone level (1,155 pg/mL). A. Ultrasonography (US) reveals a 5-cm heterogeneous hypoechoic nodule with calcifications and irregular margins (arrow). B. Color Doppler US shows increased internal and peripheral vascularity (arrow). C, D. ^99mTc-sestamibi scintigraphy demonstrates persistent uptake in the upper left thyroid region (arrow). E, F. Pre- and post-contrast CT reveal an isoattenuating lesion with internal calcifications (arrowhead) inferior to the left thyroid lobe (arrow). Histopathology confirmed parathyroid carcinoma with focal soft tissue invasion.

Fig. 7.

Parathyroid adenoma with atypical features detected by single-photon emission computed tomography/computed tomography (SPECT/CT).

A 52-year-old woman undergoing preoperative evaluation for papillary thyroid carcinoma was found to have a rim-calcified lesion. Laboratory tests showed hypercalcemia (11.6 mg/dL) and elevated parathyroid hormone (96.1 pg/mL). A. Contrast-enhanced CT reveals a rim-calcified mass in the left level VI neck region (arrow). B. Delayed ^99mTc-sestamibi imaging shows focal radiotracer uptake (arrow), suggesting parathyroid adenoma. C. SPECT/CT localizes the lesion to the left inferior parathyroid gland (arrow). D. Histology (H&E, ×12) shows an encapsulated parathyroid adenoma with oncocytic features and dystrophic calcification (arrowheads). Immunohistochemistry demonstrated positivity for GATA-3, negativity for S-100 and calcitonin, and a Ki-67 index of <1%, confirming oncocytic parathyroid adenoma.

Fig. 8.

Four-dimensional computed tomography (4D CT) findings in parathyroid adenoma.

A 69-year-old woman with elevated parathyroid hormone (184 pg/mL) and hypercalcemia (10.4 mg/dL) underwent 4D CT. A. Pre-contrast CT shows an isoattenuating lesion in the inferoposterior aspect of the right thyroid lobe (arrow), in contrast to the hyperattenuating thyroid gland (asterisk). The left cervical level IV lymph node (arrowhead) shows similar isoattenuation to the parathyroid lesion. B. Axial arterial-phase (30 seconds) CT reveals avid enhancement of the right inferior parathyroid lesion (arrow), whereas the cervical lymph node demonstrates less enhancement (arrowhead). The thyroid parenchyma shows a relatively stable enhancement pattern (asterisk). C. Axial delayed-phase (60 seconds) CT shows rapid washout in the parathyroid lesion (arrow) and relatively delayed enhancement in the lymph node (arrowhead). The thyroid parenchyma displays a relatively stable washout pattern (asterisk). D. The graph illustrates attenuation levels over time for the thyroid parenchyma, parathyroid adenoma, and cervical lymph node before contrast, at 30 seconds, and at 60 seconds. Histopathology confirmed parathyroid adenoma.

Fig. 9.

Intrathyroidal parathyroid adenoma in a patient with refractory osteoporosis.

A 51-year-old woman presented with osteoporosis and hypercalcemia (11.0 mg/dL). A. Grayscale ultrasonography reveals a 0.9-cm hypoechoic nodule within the left thyroid parenchyma (arrowhead). B. Axial fused single-photon emission computed tomography/computed tomography shows ^99mTc-sestamibi uptake in the left thyroid lobe (arrow). C-E. Four-dimensional computed tomography images demonstrate an isoattenuating lesion that exhibits enhancement in the arterial phase and rapid washout in the delayed phase (arrow). Fine-needle aspiration with washout parathyroid hormone measurement (707 pg/mL) confirmed a functioning intrathyroidal parathyroid adenoma. The patient opted for radiofrequency ablation, resulting in normalization of calcium levels and lesion resolution.

Fig. 10.

Localization of a parathyroid adenoma using ¹⁸F-fluorocholine positron emission tomography (PET)/computed tomography (CT) and four-dimensional (4D) CT.

A 69-year-old woman with a history of left thyroidectomy for papillary thyroid carcinoma presented with hypercalcemia (12.1 mg/dL) and high-normal parathyroid hormone (64 pg/mL). A. ¹⁸F-fluorocholine PET shows focal uptake in the right neck (arrow). B. Axial PET/CT localizes the lesion to the right tracheoesophageal groove (arrow). C-E. 4D CT demonstrates a low-attenuation lesion with arterial enhancement and delayed washout (arrow), adjacent to the inferior thyroid artery (arrowhead). Parathyroidectomy confirmed the diagnosis.

Fig. 11.

Magnetic resonance imaging (MRI) of parathyroid carcinoma.

A 70-year-old man with elevated parathyroid hormone (182.3 pg/mL) was referred for evaluation of a neck mass detected by ultrasonography (US). A. Grayscale US reveals a lobulated hypoechoic lesion in the posterosuperior left thyroid region, containing an internal anechoic area. B. Color Doppler US demonstrates marked vascularity. C. Coronal T2-weighted fat-suppressed MRI shows a nodule (arrow) with heterogeneous signal intensities in the posterosuperior aspect of the left thyroid lobe, demonstrating a characteristic "marbled" appearance. D. Axial contrast-enhanced T1-weighted fat-suppressed MRI reveals heterogeneous enhancement (arrow) with a central nonenhancing area. Histopathological analysis confirmed parathyroid carcinoma with capsular and lymphovascular invasion.

Fig. 12.

Nonfunctioning parathyroid cyst. A 62-year-old woman was referred for evaluation of a cystic lesion incidentally detected on neck ultrasonography (US).

A. US shows a well-circumscribed, anechoic lesion posterior to the right thyroid lobe. B. Axial post-contrast computed tomography shows the cystic lesion (arrow) posterior to the thyroid gland, without enhancing solid components. Fine-needle aspiration yielded approximately 5 mL of clear fluid with an intracystic parathyroid hormone (PTH) level of 75.4 pg/mL; serum PTH was within the normal range (25.2 pg/mL). The lesion was diagnosed as a nonfunctioning parathyroid cyst and treated with simple aspiration.

Fig. 13.

Radiofrequency ablation (RFA) for primary hyperparathyroidism in an 80-year-old woman with elevated parathyroid hormone (PTH) (129.1 pg/mL).

A-C. Pre-ablation evaluation findings show a hyperfunctioning parathyroid gland in multiple imaging modalities. A. Axial fused singlephoton emission computed tomography/computed tomography (SPECT/CT) shows a ^99mTc-sestamibi-avid lesion in the posterior aspect of the left thyroid lobe (arrow), consistent with a hyperfunctioning parathyroid gland. B. Axial contrast-enhanced CT reveals a well-circumscribed, enhancing lesion posterior to the left thyroid lobe (arrow). C. Longitudinal ultrasonography (US) demonstrates a hypoechoic, ovoid lesion adjacent to the thyroid gland (arrow). D-F. Post-ablation follow-up images demonstrate progressive reduction in lesion size and successful treatment response. D. Immediate post-RFA US shows increased echogenicity, internal heterogeneity, and transient volume enlargement of the ablated lesion (arrow). E. Three-month follow-up US demonstrates marked size reduction (arrow). F. Six-month follow-up US shows further shrinkage with no residual or recurrent lesion. At 12 months, the serum PTH level had normalized.

Table 1.

Distribution of superior and inferior ectopic parathyroid glands

Origin	Location	Frequency (%)
Superior	Tracheoesophageal groove	43
	Retroesophageal	22
	Posterosuperior mediastinum	14
	Carotid sheath	7
	Intrathyroidal (superior pole)	7
	Paraesophageal	7
Inferior	Intrathymic	30
	Anterosuperior mediastinum	22
	Intrathyroidal (inferior pole)	22
	Thyrothymic ligament	17
	Submandibular	9

Data were sourced from Phitayakorn and McHenry [13].

Table 2.

Comparison of primary, secondary, and tertiary hyperparathyroidism

Category	Primary hyperparathyroidism	Secondary hyperparathyroidism	Tertiary hyperparathyroidism
Definition	Autonomous PTH secretion due to parathyroid pathology	Compensatory PTH increase from chronic hypocalcemia	Autonomous PTH secretion after prolonged SHPT
Key etiologies	Adenoma (75%-85%)	CKD (stages 3-5)	Prolonged SHPT → gland autonomy
	Multiglandular disease (15%-20%)	Vitamin D deficiency
	Carcinoma (<1%)	Calcium malabsorption
Biochemical profile	↑↑ PTH	↑↑ PTH	↑↑ PTH
	↑↑ Ca²⁺ (≥10.5 mg/dL)	↓ Ca²⁺ (<8.5 mg/dL)	↑↑ Ca²⁺
	↓ PO₄^3-	↑ PO₄^3-	Variable PO₄^3- (often normal/high)
Clinical setting	Sporadic cases or MEN syndrome	CKD stages 3-5, dialysis	Post–renal transplantation
Symptoms	Kidney stones, osteoporosis, fatigue, depression, bone pain	Bone pain, muscle weakness, osteomalacia	Similar to secondary hyperparathyroidism but with more severe symptoms
First-line treatment	Parathyroidectomy (definitive)	Medical treatments	Parathyroidectomy (subtotal or total parathyroidectomy with/without autotransplantation)
		Phosphate binders
		Vitamin D supplementation
		Calcium supplementation
Second-line treatment	Medical treatments	Parathyroidectomy (in cases of persistent PTH elevation)	Medical treatment
Strategy for inoperable cases	Ablation treatment (RFA or MWA)
Treatment target	Normalize calcium and PTH	Control PTH (2-9 times upper normal limit)	Normalize calcium and adjust PTH based on post-transplant renal function and clinical status

PTH, parathyroid hormone; SHPT, secondary hyperparathyroidism; CKD, chronic kidney disease; MEN, multiple endocrine neoplasia; RFA, radiofrequency ablation; MWA, microwave ablation.

Table 3.

Indications for parathyroidectomy in primary hyperparathyroidism

Category	Specific criteria
Symptomatic patients	Symptoms of hypercalcemia (e.g., kidney stones, osteoporosis, fractures, neuropsychiatric symptoms)
Asymptomatic patients	Any of the following
1. Calcium level	Serum calcium ≥1.0 mg/dL (0.25 mmol/L) above the upper limit of normal
2. Bone density	T-score ≤-2.5 (lumbar spine, total hip, femoral neck, or distal one-third radius)
3. History of fractures	Documented fragility fractures or evidence of vertebral compression fractures on imaging
4. Renal function	GFR <60 mL/min
5. Nephrolithiasis/nephrocalcinosis	Confirmed by ultrasound, CT, or clinical history
6. 24-Hour urinary calcium	Urinary calcium excretion >400 mg/day
7. Age	Patient under 50 years of age

GFR, glomerular filtration rate; CT, computed tomography.

Table 4.

Comparison of localization modalities in primary hyperparathyroidism

Modality	Cost-effective	Disadvantage
US	No radiation	Operator-dependent
	Easily accessible	Patient-dependent (e.g., obesity)
	Advantage	Limited scan coverage
	Simultaneous thyroid and neck evaluation and FNA
	US-guided treatment
^99mTc-sestamibi Scintigraphy with SPECT/CT	Easy interpretation	Radiation ☢☢☢
	Effective for identifying ectopic glands	Long scan time
		Limited thyroid evaluation
4D CT	Excellent anatomical detail	Radiation ☢☢☢☢
	Fast scanning	Exposes thyroid to radiation
	Effective for ectopic and multiglandular disease	Iodinated contrast use
		Susceptible to artifacts
MRI	No radiation	Limited sensitivity
	Can detect ectopic glands	Motion artifact
		Lower spatial resolution for small adenomas
		Challenges with implanted devices
PET/CT	High resolution over SPECT	Radiation ☢☢☢
	Effective for small nodules and ectopic/multiglandular disease	High cost
		Limited availability
		Risk of nonspecific tracer uptake

Adapted from Naik M et al. Radiographics 2022;42(3):841-860, Table 2 with permission of the Radiological Society of North America (RSNA) [2].

US, ultrasonography; FNA, fine-needle aspiration; 99mTc-sestamibi; technetium ^99m-sestamibi; SPECT, single-photon emission computed tomography; CT, computed tomography; ☢☢☢, relative radiation level designations (1-10 mSv); 4D, four-dimensional; ☢☢☢☢, relative radiation level designations (10–30 mSv); MRI, magnetic resonance imaging; PET, positron emission tomography [2,31].

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Essentials for parathyroid imaging and intervention: what radiologists need to know

Abstract

Key point

Introduction

Embryology, Anatomy, and Ectopic Parathyroid Glands

Pathophysiology, Epidemiology, and Management of Hyperparathyroidism

Localization for Hyperparathyroidism

Ultrasonography

99mTc-sestamibi Scintigraphy with SPECT/CT

Four-Dimensional Computed Tomography

Positron Emission Tomography

Magnetic Resonance Imaging

Parathyroid Incidentaloma

Nonsurgical Treatment of Parathyroid Lesions

Conclusion

Notes

Supplementary Material

Video clip 1.

References

Fig. 1.

Sonographic features of a normal inferior parathyroid gland in a 71-year-old woman undergoing thyroid nodule surveillance.

Fig. 2.

Typical imaging presentation of a superior parathyroid adenoma.

Fig. 3.

Parathyroid adenoma with an incidentally detected brown tumor.

Fig. 4.

Differentiation between parathyroid adenoma and a mimicking lesion.

Fig. 5.

Spontaneous hemorrhage in a parathyroid adenoma.

Fig. 6.

Misdiagnosis of parathyroid carcinoma as a thyroid nodule on fine-needle aspiration (FNA).

Fig. 7.

Parathyroid adenoma with atypical features detected by single-photon emission computed tomography/computed tomography (SPECT/CT).

Fig. 8.

Four-dimensional computed tomography (4D CT) findings in parathyroid adenoma.

Fig. 9.

Intrathyroidal parathyroid adenoma in a patient with refractory osteoporosis.

Fig. 10.

Localization of a parathyroid adenoma using 18F-fluorocholine positron emission tomography (PET)/computed tomography (CT) and four-dimensional (4D) CT.

Fig. 11.

Magnetic resonance imaging (MRI) of parathyroid carcinoma.

Fig. 12.

Nonfunctioning parathyroid cyst. A 62-year-old woman was referred for evaluation of a cystic lesion incidentally detected on neck ultrasonography (US).

Fig. 13.

Radiofrequency ablation (RFA) for primary hyperparathyroidism in an 80-year-old woman with elevated parathyroid hormone (PTH) (129.1 pg/mL).

Table 1.

Table 2.

Table 3.

Table 4.

^99mTc-sestamibi Scintigraphy with SPECT/CT

Localization of a parathyroid adenoma using ¹⁸F-fluorocholine positron emission tomography (PET)/computed tomography (CT) and four-dimensional (4D) CT.