This study aimed to determine the ultrasound (US) features of normal parathyroid glands (PTGs) and to evaluate whether normal PTGs can be differentiated from metastatic lymph nodes (LNs) in thyroid cancer.
This retrospective study included 10 normal PTGs and 95 metastatic LNs from thyroid cancer showing suspicious US features. The echogenicity, echotexture, echogenic foci (calcifications), cystic change, abnormal vascularity, size, shape, and location were retrospectively assessed and compared between normal PTGs and metastatic LNs.
The echogenicity of normal PTGs was significantly different from that of metastatic LNs (P<0.001). Normal PTGs exhibited marked hyperechogenicity (100%), homogeneous echotexture (80%), focal intraglandular hypoechogenicity (20%), ovoid shape (90%), and focal cystic change in one case (10%). The echogenicity of metastatic LNs was markedly hyperechoic (0%), moderately hyperechoic (15.8%), mildly hyperechoic (53.7%), and hypoechoic (28.4%). The size and long axis/short axis ratios of normal PTGs were significantly smaller and larger than those of metastatic LNs (P<0.01 and P=0.022, respectively).
Marked hyperechogenicity was found only in normal PTGs, and small, ovoid, markedly hyperechoic structures in the paramedian central neck characterized normal PTGs. Normal PTGs may be differentiated from metastatic LNs in thyroid cancer.
A small, ovoid, homogeneous, markedly hyperechoic structure located in the paramedian central neck characterizes a normal parathyroid gland. All normal parathyroid glands consistently showed marked hyperechogenicity, whereas no metastatic lymph node showed marked hyperechogenicity. Normal parathyroid glands may be differentiated from metastatic lymph nodes in thyroid cancer.
Ultrasonography (US) is an essential primary tool for the evaluation of nodular thyroid disease and parathyroid lesions. Many have believed that normal parathyroid glands (PTGs) are typically invisible and difficult to reliably identify on US [
This study was performed in accordance with the Declaration of Helsinki. This human study was approved by the GangNeung Asan Hospital Institutional Review Board (2021-08-010). Due to the retrospective nature of this study, the need for informed consent was waived.
Between March 2017 and August 2021, 118 consecutive patients with thyroid nodules underwent biopsy for 141 suspicious cervical lesions showing suspicious US features of metastatic LNs on preoperative FNA or core needle biopsy (CNB) for thyroid nodules. Twenty-one consecutive patients underwent biopsy for 32 suspicious metastatic lesions during postoperative surveillance of thyroid cancer. Therefore, during the study period, 139 consecutive patients underwent FNA for 173 suspicious metastatic lesions presenting suspicious US features of cervical metastatic LNs in thyroid cancer. A lesion was classified as suspicious for metastasis if any suspicious US feature of metastatic LNs (hyperechogenicity, calcification, cystic change, and abnormal vascularity) was identified [
A normal PTG was defined as a parathyroid lesion without a typical US feature of parathyroid cyst or neoplasm [
During the same study period, 398 consecutive patients underwent preoperative thyroid US examinations and thyroid surgery for malignant thyroid tumors. The group of patients with metastatic LNs (group 2) only included patients with metastatic LNs that exhibited US features suspicious for metastatic LNs on preoperative thyroid US. Group 2 was used to compare the US features between normal PTGs and metastatic LNs. After a review of the electronic medical records and US reports of all patients, 351 patients without metastatic LNs showing suspicious US features on preoperative US were excluded. The exclusion criteria were as follows: (1) no metastatic LNs (n=245) in the postoperative pathology report, (2) microscopic metastatic LNs (n=66), and (3) macroscopic metastatic LNs without suspicious US features on preoperative US (n=40). Based on a retrospective level-by-level radiologic-pathologic correlation of metastatic LNs, 47 patients (37 women and 10 men; mean age, 58.8 years) with 95 metastatic LNs showing suspicious US features were finally included in the group of patients with metastatic LNs (group 2) (
US-guided FNA was performed in one to two suspicious metastatic LNs in most patients, while CNB was selectively performed for suspicious metastatic LNs (large LNs, suspected high-grade thyroid cancer or medullary carcinoma, and suspected metastatic LNs from non-thyroid organs). Freehand technique US-guided FNA was performed using a 21- or 23-gauge needle and a 5-mL disposable syringe. The combined method of a capillary and aspiration technique was employed. SurePath (BD, Franklin Lakes, NJ, USA) liquid-based cytology was used to establish a cytopathologic diagnosis via FNA. US-guided CNB procedures were performed using a disposable 1.1-cm excursion, 18-gauge, single- or double-action spring-activated needle (Stericut [TSK, Tokyo, Japan] or Ace-cut [Create Medic, Yokohama, Japan]). The CNB needle notch was positioned within the target lesions. Strict vessel mapping along the approach route was performed using color Doppler US during the procedure to avoid vessel injury. FNA-washout thyroglobulin was routinely measured for patients with lateral neck lesions and selectively for those with central neck lesions. FNA-washout PTH measurements were selectively obtained for central neck lesions to rule out parathyroid lesions. The parathyroid lesions were suspected when the lesions showed typical US features of parathyroid cyst or parathyroid adenoma [
All US examinations and biopsy procedures for the thyroid nodules and cervical LNs were performed using a 5-12 MHz linear-array transducer (EPIQ7, Philips Healthcare, Bothell, WA, USA) by two radiologists with 22 and 4 years of experience, respectively, in performing thyroid US imaging and interventions. The US images of all suspicious US features found in suspicious metastatic lesions were routinely obtained during the US examinations. The US features of normal PTGs and metastatic LNs were retrospectively assessed by an experienced radiologist (D.G.N.) blinded to the patients’ clinical histories and final diagnoses. The reviewer assessed the echogenicity, echotexture, echogenic foci (calcifications), cystic change, abnormal vascularity, size, shape, and location of the lesions. The echogenicity was categorized as marked hyperechogenicity (hyperechoic relative to the normal thyroid gland), moderate hyperechogenicity (isoechoic relative to that of the normal thyroid gland), mild hyperechogenicity (hyperechoic relative to the neck muscles and hypoechoic relative to the normal thyroid gland), and hypoechogenicity (isoechoic or hypoechoic relative to the neck muscles). In patients with diffuse thyroid disease and decreased parenchymal echogenicity, the homogenous hyperechoic echogenicity of the presumed normal thyroid gland was used as the reference structure. The echotexture of PTGs and metastatic LNs was categorized as homogeneous or heterogeneous. The homogeneous echotexture was defined as uniform echogenicity with one category of echogenicity. In contrast, heterogeneous echotexture was defined as mixed echogenicity with more than one category of echogenicity. If the lesion had a mixed pattern, echogenicity was determined using the predominant echogenicity. Echogenic foci (calcifications) were classified as punctate echogenic foci (microcalcification) (punctate [≤1 mm] hyperechoic foci with or without posterior acoustic artifacts) or large echogenic foci (large [>1 mm] hyperechoic foci with or without posterior acoustic artifact), including macrocalcification and rim calcification [
Categorical variables are reported as frequencies and percentages for each category. Continuous variables are presented as the median (interquartile range) or the mean±standard deviation, according to whether they had a parametric or nonparametric distribution, respectively. The Pearson chi-square test was used to compare the US findings between normal PTGs and metastatic LNs. The Mann–Whitney U Test was used to compare the long and short diameters for size and L/S ratios between normal PTGs and metastatic LNs. The statistical analysis was performed using SPSS version 24.0 for Windows (IBM Corp., Armonk, NY, USA). A significant difference was defined as one with a P-value <0.05.
The demographic data are summarized in
The clinical characteristics of the 10 identified normal PTGs are summarized in
The US features of normal PTGs and metastatic LNs are summarized in
Homogeneous echotexture was found in eight of 10 normal PTGs (80%), while heterogeneous echotexture in two of 10 normal PTGs (20%). The two normal PTGs with heterogeneous echotexture showed a focal, linear, relatively hypoechoic lesion in the center of the PTG and a focal, round hypoechoic lesion with suspicion of anechoic cystic change (
Focal cystic change was found in one case (10%), and echogenic foci (calcification) or abnormal vascularity on color Doppler images was not found in any of the normal PTGs. Meanwhile, echogenic foci (calcifications) were found in 60 (63.2%) and abnormal vascularity in 29 (30.5%) of 95 metastatic LNs (P<0.001 and P=0.011, respectively) (
The distribution of normal PTGs and metastatic LNs in the central neck are summarized in
In this study, all normal PTGs exhibited marked hyperechogenicity, whereas no metastatic LNs showed marked hyperechogenicity. Metastatic LNs showed variable echogenicity, including hypoechogenicity and mild or moderate hyperechogenicity. Cystic change was mostly found in metastatic LNs, whereas echogenic foci (calcifications) and abnormal vascularity were exclusively found in metastatic LNs.
The present study suggests that the US pattern of a small, ovoid, homogeneous, markedly hyperechoic structure located in the paramedian central neck is a distinctive feature of normal PTGs. Normal PTGs may uncommonly show focal hypoechogenicity within the gland. In two cases of normal PTGs with focal intraglandular hypoechogenicity, the residual hyperechoic area consistently showed the same homogeneous marked hyperechogenicity as the other typical normal PTGs. A recent study [
The origin of hyperechogenicity of normal PTGs may be caused by abundant stromal fat content diffusely distributed in the PTG, accounting for 35%-50% of the gland, and the stromal fat content increases with aging [
Until recently, normal PTGs were hardly detected on US [2–4]. The reason may be mainly because the US features of normal PTGs are not well recognized and small differences in echogenicity make it difficult to distinguish normal PTGs from thyroid or perithyroid adipose tissue. This may also possibly be due to the limited resolution capability of applied US equipment.
Normal PTGs may mimic metastatic LNs with suspicious US features in thyroid cancer patients. Metastatic LNs from thyroid cancer are frequently found in the central neck, and their location overlaps with that of normal PTGs. Nodal focal or diffuse hyperechogenicity is a characteristic US feature of metastatic LNs in thyroid cancer [
These results provide a basis for the potential clinical application of the preoperative localization of normal PTGs in patients undergoing thyroid surgery. An accurate preoperative localization of normal PTGs via US may help prevent possible injury of normal PTGs during thyroid surgery and might reduce postoperative hypoparathyroidism [
This study has several limitations. First, it included only a small number of normal PTGs because this retrospective study analyzed only incidentally detected normal PTGs during the study period when the US features of normal PTGs were not fully recognized. It would be very difficult to collect percutaneous US images of a large number of normal PTGs identified by a histopathological or biochemical method for research purposes. Second, selection bias inevitably existed in the group of patients with normal PTGs. Therefore, the evaluation of the frequency and distribution of normal PTGs identified in the present study was limited. Third, only one experienced radiologist retrospectively assessed the US features of normal PTGs and metastatic LNs, and the interobserver reliability was not evaluated. Fourth, this study did not compare US features of normal PTGs and metastatic LNs showing indeterminate or benign US features. However, normal PTGs will be clearly distinguished from metastatic LNs showing indeterminate or probably benign US feature, as these metastatic LNs have hypoechogenicity similar to the anterior neck muscles.
In conclusion, the US feature of a small ovoid structure with homogeneous marked hyperechogenicity is the distinctive typical feature of normal PTGs. All normal PTGs consistently showed marked hyperechogenicity, whereas no metastatic LNs showed marked hyperechogenicity. Moreover, metastatic LNs showed variable echogenicity and frequently other suspicious US features. Thus, normal PTGs may be differentiated from metastatic LNs in thyroid cancer.
Conceptualization: Na DG. Data acquisition: Kim SJ, Na DG. Data analysis or interpretation: Na DG, Noh BJ. Drafting of the manuscript: Kim SJ, Na DG. Critical revision of the manuscript: Kim SJ, Na DG, Noh BJ. Approval of the final version of the manuscript: all authors.
No potential conflict of interest relevant to this article was reported.
This research was supported by the Medical Research Promotion Program through the Gangneung Asan Hospital funded by the Asan Foundation (2022II0011).
LN, lymph node; PTH, parathyroid hormone.
A, B. Transverse and longitudinal images show an ovoid, homogeneous, markedly hyperechoic parathyroid gland brighter than the thyroid gland at the inferior posterior margin of the left thyroid gland (arrows).
A, B. Transverse and longitudinal images show an ovoid, homogeneous, markedly hyperechoic parathyroid gland in the left infrathyroid central neck (arrows).
The transverse image shows ovoid, moderately hyperechoic lymph nodes (arrows) showing similar echogenicity to that of the thyroid gland in the right inferior posterior perithyroidal central neck (level VI). The lymph node does not show echogenic foci or a cystic change. The metastatic lymph nodes were diagnosed by surgery.
A. A longitudinal image shows an ovoid, markedly hyperechoic parathyroid gland with central linear mild hypoechogenicity (arrow) in the left infrathyroid central neck in a 44-year-old female patient. B, C. Transverse and longitudinal images show a round, markedly hyperechoic parathyroid gland with a small, round, anechoic cystic lesion with posterior acoustic enhancement (arrows) at the inferior pole of the left thyroid gland in a 49-year-old male patient. The intraglandular cystic lesion was identified as a parathyroid cyst showing clear fluid on fine needle aspiration.
A. A transverse image shows a lymph node (arrows) that is slightly hyperechoic compared to the neck muscle at the pretracheal midline central neck (level VI) in a 63-year-old female patient. The lymph node shows an ovoid shape on the longitudinal image (long axis/short axis ratio, 1.8) (not shown). It does not show echogenic foci or a cystic change. The metastatic lymph node was diagnosed by fine needle aspiration and surgery. B. A transverse image shows an ovoid, mildly hyperechoic lymph node in the left infrathyroid paramedian central neck (level VI) in a 42-year-old female patient. The lymph node shows echogenic foci (arrows). The shape was ovoid on the longitudinal image (long axis/short axis ratio, 2) (not shown). The metastatic lymph node was diagnosed by surgery.
Demographic data of participants with normal PTGs and those with metastatic LNs
Parameter | Normal PTG | Metastatic LN | P-value |
---|---|---|---|
No. of patients | 10 | 47 | N/A |
No. of women, n (%) | 7 (70.0) | 37 (78.7) | 0.551 |
Age (year), mean±SD | 49.1±11.0 | 58.8±14.4 | 0.049 |
No. of lesions | 10 | 95 | N/A |
Size | |||
Long diameter (cm) | 0.009 | ||
Median (IQR) | 0.7 (0.6-0.9) | 1.2 (0.7-1.6) | |
Range | 0.5-1.6 | 0.4-6.0 | |
Short diameter (cm) | <0.001 | ||
Median (IQR) | 0.3 (0.7-1.6) | 0.6 (0.4-0.9) | |
Range | 0.2-0.5 | 0.3-3.5 | |
L/S ratio | 0.022 | ||
Median (IQR) | 3.1 (1.8-3.4) | 1.8 (1.5-2.3) | |
Range | 1.3-4.1 | 1.0-8.0 | |
Histology type of malignant thyroid tumors, n (%) | N/A | 47 | N/A |
Papillary carcinoma | - | 44 (93.6) | |
Follicular thyroid carcinoma | - | 1 (2.1) | |
Medullary carcinoma | - | 1 (2.1) | |
Anaplastic carcinoma | - | 1 (2.1) |
PTG, parathyroid gland; LN, lymph node; N/A, not applicable; SD, standard deviation; IQR, interquartile range; L/S, long axis/short axis.
Summary data of 10 patients with identified normal PTHs
Case No. | Age (year) | Sex | Biopsy result of the thyroid nodule | Ultrasound feature |
Location | FNAwashout PTH (pg/mL) | FNA-washout thyroglobulin (ng/mL) | Serum PTH (pg/mL) (reference: 11-62 pg/mL) | Serum calcium (mg/dL) (reference: 8.6-10.4 mg/dL) | ||
---|---|---|---|---|---|---|---|---|---|---|---|
Echogenicity | Echotexture | Shape | |||||||||
1 | 65 | M | Indeterminate |
Marked hyperechogenicity | Homogeneous | Ovoid | Left inferior posterior | >1,500 | N/A | 30.1 | 9.9 |
2 | 38 | F | Indeterminate |
Marked hyperechogenicity | Homogeneous | Ovoid | Left inferior posterior | >1,500 | N/A | 42.4 | 9.5 |
3 | 38 | F | Benign |
Marked hyperechogenicity | Homogeneous | Ovoid | Left inferior pole | >1,500 | N/A | 30.9 | 9.4 |
4 | 63 | F | Follicular neoplasm |
Marked hyperechogenicity | Homogeneous | Ovoid | Left inferior lateral | >1,500 | N/A | 26.7 | 9.5 |
5 | 41 | F | Benign |
Marked hyperechogenicity | Homogeneous | Ovoid | Left infrathyroid | >1,800 | 0.17 | 38.9 | 9.5 |
6 | 64 | F | PTC |
Marked hyperechogenicity | Homogeneous | Ovoid | Left infrathyroid | >1,500 | <0.2 | 59.3 | 9.2 |
7 | 44 | F | PTC |
Marked hyperechogenicity | Heterogeneous |
Ovoid | Left infrathyroid | >1,500 | <0.2 | 32.2 | 9.3 |
8 | 49 | M | PTC |
Marked hyperechogenicity | Heterogeneous |
Round | Left inferior pole | >1,500 | 0.26 | 23.9 | 7.9 |
9 | 40 | M | Benign |
Marked hyperechogenicity | Homogeneous | Round | Left inferior posterior | 1,350 | N/A | 44.7 | 9.6 |
10 | 49 | F | Benign |
Marked hyperechogenicity | Homogeneous | Ovoid | Left infrathyroid | >1,500 | <0.2 | 28.5 | 9.7 |
PTH, parathyroid hormone; FNA, fine-needle aspiration; M, male; N/A, not applicable; F, female; PTC, papillary thyroid carcinoma.
Diagnosis by core needle biopsy.
Diagnosis by fine needle aspiration.
Focal linear hypoechogenicity.
Focal nodular hypoechogenicity (cystic change).
Comparison of ultrasound features between normal PTGs and metastatic LNs
Ultrasound feature | Normal PTG (n=10) | Metastatic LN (n=95) | P-value |
---|---|---|---|
Echogenicity | |||
Marked hyperechogenicity | 10 (100) | 0 | <0.001 |
Moderate hyperechogenicity | 0 | 15 (15.8) | |
Mild hyperechogenicity | 0 | 51 (53.7) | |
Hypoechogenicity | 0 | 27 (28.4) | |
N/A |
0 | 2 (2.1) | |
Echotexture | |||
Homogeneous | 8 (80.0) | 40 (42.1) | 0.072 |
Heterogeneous | 2 (20.0) | 42 (55.8) | |
N/A |
0 | 2 (2.1) | |
Echogenic foci (calcifications) | |||
Punctate | 0 | 47 (49.5) | <0.001 |
Large | 0 | 27 (28.4) | |
None | 10 (100) | 35 (36.8) | |
Cystic change | |||
Present | 1 (10.0) | 21 (22.1) | 0.371 |
None | 9 (90.0) | 74 (77.9) | |
Abnormal vascularity | |||
Present | 0 | 29 (30.5) | 0.011 |
None | 10 (100) | 41 (43.2) | |
N/A |
0 | 25 (26.3) | |
Shape | |||
Round (L/S ratio ≤1.5) | 2 (20.0) | 22 (23.2) | 0.821 |
Ovoid (L/S ratio >1.5) | 8 (80.0) | 73 (76.8) |
Values are number of lesions (%).
PTG, parathyroid gland; LN, lymph node; N/A, not applicable; L/S, long axis/short axis.
Entirely calcified lymph nodes in which echogenicity cannot be assessed.
Lymph nodes in which color Doppler images were not available.
Distribution of normal PTGs and metastatic LNs in the central neck
Location | Normal PTG (n=10) | Metastatic LN (n=31) |
---|---|---|
Midline | ||
Prelaryngeal | 0 | 1 (3.2) |
Pretracheal | 0 | 10 (32.3) |
Paramedian | ||
Superior thyroid pole | 0 | 0 |
Superior perithyroid | 0 | 0 |
Inferior perithyroid | 4 (40.0) | 7 (22.6) |
Anterior | 0 | 0 |
Posterior | 3 (30.0) | 7 (22.6) |
Medial | 0 | 0 |
Lateral | 1 (10.0) | 0 |
Inferior thyroid pole | 2 (20.0) | 2 (6.5) |
Infrathyroid | 4 (40.0) | 11 (35.5) |
Values are number of lesions (%).
PTG, parathyroid gland; LN, lymph node.