Diagnostic accuracy of radionuclide imaging for parathyroid lesions in patients with primary hyperparathyroidism and nodular and autoimmune thyroid disorders: a cross-sectional study

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BACKGROUND

Primary hyperparathyroidism (PHPT) is an endocrine disorder that occurs when one or more parathyroid glands become overactive, resulting in the excessive secretion of parathyroid hormone (PTH) and hypercalcemia. The global prevalence of PHPT is approximately 1% [1]. In Russia, the annual incidence rate is two cases per million population [2]. A delayed diagnosis of PHPT can result in disability and a considerable decrease in quality of life [3]. The most common complications include osteoporosis, fractures, nephrolithiasis, nephrocalcinosis, and gastric ulcers [4].

Radionuclide imaging techniques using ^99mTc-methoxyisobutylisonitrile (^99mTc-MIBI) are used to visualize the parathyroid glands, including planar scintigraphy and single-photon emission computed tomography (SPECT), which can be combined with computed tomography (SPECT/CT). Additional imaging modalities include ultrasound (US), contrast-enhanced CT, and, less frequently, magnetic resonance imaging (MRI) and positron emission tomography/computed tomography (PET/CT) with ¹⁸F-fluorocholine or ¹¹C-methionine. However, none of the above modalities can locate parathyroid gland lesions with 100% accuracy [9].

Publications report that 60%–93% of patients with PHPT have thyroid diseases [10–12], including single-nodule and multinodular goiter (19%–67% of all cases), and autoimmune diseases (4%–57%) [12–14]. A systematic review of 28 studies on localization techniques in patients with PHPT and concomitant thyroid disease showed that a combination of ultrasound and ^99mTc-MIBI scintigraphy demonstrated the highest overall sensitivity (86%) compared with other modalities and their combinations [15]. However, this review only included a few studies (one and two, respectively) that evaluated SPECT/CT and contrast-enhanced CT. Further research demonstrated that contrast-enhanced CT, ultrasound, and SPECT showed 10%, 19%, and 12% decreases in diagnostic performance, respectively, in patients with PHPT and concomitant thyroid disease compared with those without. Additionally, the combination of ultrasound and contrast-enhanced CT provided more information than the combination of ultrasound and SPECT [16]. Notably, this study and the others included in the aforementioned systematic review focused on thyroid disease as a whole, without stratification by specific disorders.

The sensitivity of radionuclide imaging in patients with PHPT and concomitant thyroid disease was substantially lower compared with other localization techniques [17, 18]. Autoimmune thyroid disease is reported to be associated with suboptimal planar scintigraphy performance. SPECT/CT provides better visualization of altered parathyroid glands in patients with these diseases [18]. In patients with PHPT and thyroid nodules, sensitivity of scintigraphy with ^99mTc-MIBI was 5%–24% lower [19], whereas SPECT/CT was shown to detect parathyroid lesions equally effectively in patients with and without thyroid nodules [20]. However, as far as we know, there are no data on the diagnostic accuracy of localization techniques for autoimmune diseases or thyroid nodules in patients with parathyroid lesions. It is essential to determine the most effective combination of imaging modalities for optimizing the diagnostic workflow for patients with parathyroid lesions.

AIM

To evaluate effects of nodular and autoimmune thyroid disease on the diagnostic accuracy of radionuclide imaging for parathyroid lesions in patients with PHPT and compare it with the accuracy of other imaging modalities.

METHODS

Study Design

This was a retrospective, non-comparative, cross-sectional, single-center study based on medical records.

Study Setting

The study included data from patients who underwent outpatient examinations in the Consultation and Diagnostic Center, as well as at the ultrasound and radionuclide imaging departments, and then received treatment in the Surgery Department of the Dedov National Medical Research Center for Endocrinology in Moscow from January 2017 to December 2022.

Eligibility Criteria

Inclusion criteria:

• Laboratory-confirmed PHPT, i.e. hypercalcemia and/or hypercalciuria combined with persistently elevated PTH levels;
• Parathyroid lesion verified by histological examination;
• Typical location of parathyroid lesions (at the posterior surface or lower pole of the thyroid lobe); and
• Ultrasound, planar scintigraphy, and SPECT/CT scans obtained sequentially for preoperative localization prior to selective minimally invasive parathyroidectomy.

Exclusion criteria:

• History of thyroidectomy; and
• History of parathyroidectomy (persistence/recurrence).

Study Groups

The study used three convenience samples of a fixed size (n = 50 each): patients without thyroid disease (group 1), patients with concomitant autoimmune thyroid disease (group 2), and patients with thyroid nodules (group 3). The absence of thyroid disease was reported if the following criteria were met:

• Euthyroid state;
• Lack of information about the history of thyroid disease; and
• Absence of structural changes in ultrasound findings.

An autoimmune thyroid disease was reported if at least one of the following criteria was met:

• Diagnosed autoimmune thyroiditis, toxic diffuse goiter (Graves’ disease); and
• Elevated blood levels of antithyroid antibodies (anti-thyroid peroxidase, anti-thyroglobulin, and anti-thyroid-stimulating hormone antibodies).

Thyroid nodules were identified based on ultrasound findings.

The data on the inclusion criteria were retrieved from the medical records.

Localization of Parathyroid Lesions

The time between ultrasound, planar scintigraphy, and SPECT/CT scans did not exceed 6 months, and the total time from the initial scan to surgery was no more than 12 months. If the findings were negative or questionable, a contrast-enhanced CT scan and biopsy were performed to measure PTH levels in the needle washout. Experienced radiologists and radiographers processed and interpreted all radionuclide imaging and contrast-enhanced CT data. For some patients, ultrasound data were obtained from medical records issued by third-party healthcare providers.

The study personnel were aware of the previous diagnostic test results of the patients and had access to their clinical and laboratory data.

Ultrasound Imaging

Ultrasound was performed using Voluson® E8 Expert (GE Healthcare, USA); Aplio® 500 (Toshiba [Canon Medical Systems], Japan); and LOGIQ® E9 (GE Healthcare, USA) with high-frequency linear sensors (7–12 MHz). In addition to assessing the presence/absence of parathyroid lesions, we evaluated their vascularity using a semi-quantitative scale:

• 0: no vessels;
• 1: single vessels;
• 2: moderate vascularity; and
• 3: significant vascularity.

A score of ≥2 was defined as increased vascularity. When ultrasound data suggested the need for a differential diagnosis between parathyroid and other lesions (e.g., thyroid nodules or lymph nodes), a needle biopsy was performed to determine PTH levels in the needle washout.

Radionuclide Imaging

Prior to the procedure, patients received an intravenous injection of 700 MBq of technetium (^99mTc) sestamibi. The first stage involved dual-phase planar scintigraphy using GE Discovery® NM/CT 670 and GE Discovery® NM630 (GE Healthcare, USA). Two 10-minute static images of the neck and superior mediastinum were acquired at 15 and 90 minutes after the injection of the radiopharmaceutical. The hardware requirements and technical settings were as follows:

• Low Energy High Resolution (LEHR) collimators;
• Matrix: 256 × 256;
• Zoom: 2.0; and
• Energy window with E_peak = 141 ± 14 keV, δ_Epeak = 10%.

The second stage involved a SPECT/CT scan of the neck and upper mediastinum right after the delayed planar image with GE Discovery® NM/CT 670 (GE Healthcare, USA). SPECT settings were as follows:

• Matrix: 256 × 256;
• Zoom: 2.0; and
• Step-and-shoot acquisition (60 projections, 30 s per exposure, 6° step).

CT settings were as follows:

• Tube voltage: 120–140 kV;
• Current (modulated): 80–400 mA/s;
• Slice thickness: 3.75 mm with a 1.25-mm reconstruction interval; and
• Couch increment: 1 mm.

A Xeleris® workstation (GE Healthcare, USA) was used to process radionuclide imaging scans.

Contrast-enhanced computed tomography

The scans were performed using two systems: a GE Discovery® NM/CT 670 hybrid SPECT/CT system (GE Healthcare, USA) and an Optima® multidetector CT scanner (GE Healthcare, USA). The SPECT/CT intravenous contrast protocol consisted of three phases: non-contrast, arterial, and venous. A bolus of contrast agent (60 mL of iopromide, 370 mg I/mL) was administered through a catheter in the cubital vein at a rate of 3.5–4.0 mL/s via a single-syringe autoinjector. The standard protocol for the Optima® CT scanner (General Electric, USA) consists of four phases: non-contrast, arterial, venous, and delayed. For this protocol, a dual-syringe autoinjector was used to administer 50 mL of iomeprol (400 mg I/mL) at a rate of 4 mL/s, followed by a 40 mL bolus of 0.9% sodium chloride. The arterial and venous phases were acquired with 5- and 20-second delays, respectively, after reaching the aortic trigger threshold (Bolus Tracking). The delayed phase was acquired three minutes after contrast injection.

Evaluation of Localization Accuracy

We evaluated the diagnostic accuracy of localization techniques and their combinations (ultrasound and SPECT/CT, ultrasound and contrast-enhanced CT, ultrasound and planar scintigraphy, and SPECT/CT and contrast-enhanced CT) using two parameters: sensitivity and positive predictive value (PPV). These parameters were assessed in relation to two diagnostic outcomes: the presence of parathyroid lesions (tumors) and their localization. The location of the excised parathyroid lesion was deemed consistent with the imaging data if the surgical report correlated with the diagnostic findings.

Sensitivity (Se) was defined as the percentage of true positives:

$\text{S}e=\frac{TP}{TP+FN}\times 100\text{\%}$, (1)

where: TP is the number of true positives; FN is the number of false negatives.

The PPV was calculated using the following formula:

$\text{PPV}=\frac{TP}{TP+FP}\times 100\text{\%}$, (2)

where: TP is the number of true positives; FP is the number of false positives.

A true positive result was defined as a case in which an imaging modality (or combination of modalities) accurately identified and/or located a parathyroid lesion that was confirmed by intraoperative findings.

A false positive result was defined as a case in which an imaging modality (or combination of modalities) identified and/or located a parathyroid lesion that was not confirmed by intraoperative findings.

A false negative result was defined as a case in which an imaging modality (or combination of modalities) did not identify and/or locate a parathyroid lesion that was confirmed by intraoperative findings.

Ethics Approval

The study was approved by the local Ethics Committee of the Dedov National Medical Research Center for Endocrinology (Minutes No. 1 dated January 25, 2017). All patients provided written informed consent prior to study enrollment.

Statistical Analysis

The required sample size was not predetermined.

Data analysis was performed using STATISTICA® 13.3.0 (TIBCO Software Inc., USA) and the R 4.2.2 programming language. The quantitative data are presented as Me [Q1; Q3], where Me is the median, Q1 is the first quartile, and Q3 is the third quartile. The Clopper–Pearson exact method was used to calculate 95% confidence intervals (CIs) for frequencies. The Mann–Whitney U test was used to compare two independent samples based on quantitative characteristics. The Kruskal–Wallis test was used to compare more than two independent samples simultaneously. The Pearson chi-squared test was used to compare two independent samples based on their qualitative characteristics. Yates continuity correction was used when the expected number of observations in a cell of the table was < 5). The JavaStat online calculator was used to calculate sensitivity and PPV values.¹

The cutoff thyroid volume was determined using ROC analysis and the Youden index calculation with SPSS® software (v.23.0, IBM, USA).

Differences and associations were considered significant at p <  0.05.

RESULTS

Study Sample Formation

During the study period, 1150 patients were diagnosed with PHPT, as confirmed by laboratory tests. Of those patients, 760 had preoperative parathyroid imaging data obtained via ultrasound, radionuclide imaging, or contrast-enhanced CT. Three study groups were formed:

• Group 1: patients with no thyroid disease (n = 50);
• Group 2: patients with autoimmune thyroid disease, namely, toxic diffuse goiter (n = 4) and chronic autoimmune thyroiditis (n = 46); and
• Group 3: patients with nodular goiter, including with single nodule (n = 6) and multiple nodules (n = 44) (see Fig. 1).

 

Fig. 1. Study sample formation. SPECT/CT, single-photon emission computed tomography/computed tomography.

 

Characteristics of Study Groups

The groups were comparable in sex, age, and laboratory markers of hyperparathyroidism (see Table 1). However, they differed in the morphology of thyroid gland and parathyroid lesions (tumors).

 

Table 1. Comparison of study groups
Parameters	Group 1, n = 50	Group 2, n = 50	Group 3, n = 50	p
Age, years	58 [47; 65]	60.5 [55; 67]	60 [55; 65]	0.314
Female sex, n (%)	47 (94)	49 (98)	50 (100)	0.324
PTH, pg/mL	132 [99; 174]	150 [110; 199]	158 [125; 210]5	0.054
Total calcium, mmol/L	2.74 [2.67; 2.87]1	2.73 [2.66; 2.91]3	2.74 [2.63; 2.86]	0.85
Ionized calcium, mmol/L	1.37 [1.31; 1.43]2	1.39 [1.28; 1.49]4	1.38 [1.32; 1.44]6	0.972
Thyroid volume, cm3	11.1 [8.5; 13.4]	14.0 [10.7; 20.5]3	15.2 [10.5; 24.6]	< 0.001
Volume of the parathyroid tumor, cm3	0.36 [0.25; 0.79	0.38 [0.18; 0.69]	0.86 [0.47; 1.5]	< 0.001
Thyroid attenuation, HU	98 [90; 110]	62 [58; 70]	81.5 [75; 90]	< 0.001
Increased thyroid vascularity, n (%)7	0 (0)	37 (90)	3 (8)	< 0.001
Note. Quantitative characteristics are presented as Me [Q1; Q3], where Me is the median, Q1 is the first quartile, and Q3 is the third quartile. 1 n = 48; 2 n = 42; 3 n = 47; 4 n = 46; 5 n = 49; 6 n = 45; 7 n = 40 (an ultrasound-based semi-quantitative scale; scores of 2 and 3 indicate moderate and significant vascularity, respectively). PTH, parathyroid hormone; HU, Hounsfield units.

 

Primary Results

Specialists from the National Medical Research Center for Endocrinology performed and interpreted ultrasounds for 46 patients. Data for 4 patients were obtained from reports issued by other healthcare providers.

In group 1, all localization techniques demonstrated high diagnostic accuracy (sensitivity and PPV > 82% and > 91%, respectively) (see Tables 2, 3). Although the sensitivity of contrast-enhanced CT was 100% in group 1, a comprehensive analysis of its performance was not possible because of the small sample size (n = 11). In group 2, contrast-enhanced CT was the most informative modality (n = 25), whereas radionuclide imaging techniques (planar scintigraphy and SPECT/CT) had substantially lower sensitivity with relatively high PPVs (> 75%). In group 3, the highest sensitivity rates were obtained for SPECT/CT. This group had high PPVs (> 90%) for SPECT/CT, ultrasound, and contrast-enhanced CT (n = 20). Planar scintigraphy had the lowest diagnostic accuracy rates.

 

Table 2. Sensitivity of localization techniques in detecting parathyroid lesions
Methods	Sensitivity, % (95% confidence interval)
	Group 1, n = 50	Group 2, n = 50	Group 3, n = 50
Planar scintigraphy	82 (82–82)	36 (36–42)	68 (68–75)
Single-photon emission computed tomography/computed tomography	98 (98–100)	54 (54–60)	85 (85–90)
Ultrasound Imaging	88 (88–90)	62 (62–66)	75 (75–79)
Contrast-enhanced computed tomography	100 (100–100)	79 (79–83)	74 (74–79)

 

Table 3. Positive predictive value of localization techniques in detecting parathyroid lesions
Methods	Sensitivity, % (95% confidence interval)
	Group 1, n = 50	Group 2, n = 50	Group 3, n = 50
Planar scintigraphy	100 (100–100)	76 (76–89)	73 (73–81)
Single-photon emission computed tomography/computed tomography	96 (96–98)	86 (86–94)	91 (91–96)
Ultrasound Imaging	98 (98–100)	91 (91–97)	92 (92–97)
Contrast-enhanced computed tomography	91 (91–91)	95 (95–100)	93 (93–100)

 

The highest sensitivity rates were reported for the following combinations: ultrasound and SPECT/CT in group 1, ultrasound and contrast-enhanced CT in group 2, and ultrasound and SPECT/CT in group 3 (see Table 4).

 

Table 4. Compared sensitivity of localization technique combinations in detecting parathyroid lesions
Methods	Sensitivity, % (95% confidence interval)
	Group 1, n = 50	Group 2, n = 50	Group 3, n = 50
Ultrasound + Planar scintigraphy	92 (92–92)	68 (68–68)	82 (82–82)
Ultrasound + Single-photon emission computed tomography/computed tomography	96 (96–96)	74 (74–74)	88 (88–88)
Ultrasound + Contrast-enhanced computed tomography	100 (100–100)	85 (85–85)	80 (80–80)
Single-photon emission computed tomography/computed tomography + Contrast-enhanced computed tomography	90 (90–90)	76 (76–76)	80 (80–80)

 

Note that 25 patients in group 2 were examined using all three localization techniques. However, the results obtained demonstrated high discordance (see Fig. 2). These modalities correctly located parathyroid lesions in only 2 of 25 cases. However, in 3 cases, these modalities failed to correctly identify the lesions. The highest and lowest numbers of positive results were obtained for combinations of ultrasound with either contrast-enhanced CT (n = 7) or SPECT/CT (n = 2).

 

Fig. 2. Concordance of localization findings from ultrasound, single-photon emission computed tomography/computed tomography, and contrast-enhanced computed tomography in group 2. SPECT/CT, single-photon emission computed tomography/computed tomography.

 

Diagnostic Predictors of Single-Photon Emission Computed Tomography/Computed Tomography Findings

Univariate analysis identified thyroid volume, attenuation, and ultrasound-assessed vascularity as factors associated with the diagnostic performance of SPECT/CT for parathyroid lesions (see Table 5). The ROC-analysis showed that for thyroid volume, the AUC was 0.765 (95% CI: 0.623–0.908), with the optimal cutoff of 13.2 cm³ defined using the Youden index. The probability of positive SPECT/CT localization was substantially lower in patients with autoimmune thyroid disease and thyroid volume of ≥13.2 cm³ than in patients with smaller volumes (see Table 6).

 

Table 5. Factors associated with the detection of parathyroid lesions using single-photon emission computed tomography/computed tomography
Parameters	Lesion detected, n = 111	No lesion detected, n = 39	p
No thyroid disease, n (%)	47 (42)	3 (8)	< 0.001
Autoimmune thyroid disease, n (%)	25 (23)	25 (64)	< 0.001
Thyroid nodules, n (%)	39 (35)	11 (28)	< 0.001
Age, years	61 [53; 66]	58 [52; 64]	0.341
Female sex, n (%)	109 (98)	37 (95)	0.277
Thyroid volume, cm3	11.7 [9.8; 15.3]1	16.6 [13.5; 24.1]	< 0.001
Thyroid attenuation, HU	86 [76; 100]	64 [54; 75]	< 0.001
PTH, pg/mL	148 [111; 200]	142.5 [110; 177]3	0.732
Total calcium, mmol/L	2.745 [2.65; 2.87]1	2.71 [2.67; 2.88]4	0.506
Ionized calcium, mmol/L	1.37 [1.30; 1.45]	1.39 [1.32; 1.45]5	0.485
Increased thyroid vascularity, n (%)7	21 (21)2	19 (68)6	0.001
Note. Quantitative characteristics are presented as Me [Q1; Q3], where Me is the median, Q1 is the first quartile, and Q3 is the third quartile. 1 n = 108; 2 n = 102; 3 n = 38; 4 n = 37; 5 n = 35; 6 n = 28; 7 an ultrasound-based semi-quantitative scale (scores of 2 and 3 indicate moderate and significant vascularity, respectively). PTH, parathyroid hormone; HU, Hounsfield units.

 

Table 6. Detection of parathyroid lesions using single-photon emission computed tomography/computed tomography in patients with autoimmune thyroid disease, by thyroid volume
Thyroid volume	No lesion detected, n = 25	Lesion detected, n = 22	Total, n = 47
≥13.2 cm3, n	21	6	27
< 13.2 cm3, n	4	16	20
Note. The diagnostic accuracy levels at a cutoff thyroid volume of 13.2 cm3: Sensitivity, 84% (95% CI: 69%–94%); Specificity, 73% (95% CI: 56%–84%); Positive predictive value, 78% (95% CI: 64%–87%); Negative predictive value, 80% (95% CI: 61%–92%). Three patients with positive localization results were excluded due to a lack of information on thyroid volume. CI, confidence interval.

 

DISCUSSION

Summary of Primary Results

For patients with PHPT, SPECT/CT and its combination with ultrasound provided the best results for visualizing parathyroid lesions, regardless of the presence of thyroid nodules. For patients with autoimmune thyroid disease, contrast-enhanced CT and its combination with ultrasound demonstrated the highest diagnostic accuracy. Accuracy of radionuclide imaging in detecting parathyroid lesions in patients with autoimmune thyroid disease is defined by thyroid volume, attenuation, and vascularity.

Discussion of Study Results

Combined ^99mTc-MIBI scintigraphy and neck ultrasound is the most common preoperative imaging protocol for parathyroid lesion detection in patients with PHPT, with a sensitivity rate of 81%–95% [21]. Our study confirmed the high diagnostic performance of this combination for patients without thyroid disease. The sensitivity was 92% for planar scintigraphy and ultrasound and 96% for SPECT/CT and ultrasound. However, we found that the accuracy of all imaging modalities was lower in patients with thyroid disease than in those without. Radionuclide imaging demonstrated the lowest sensitivity in patients with PHPT and concomitant autoimmune thyroid disease, with rates 46% lower for planar scintigraphy and 44% lower for SPECT/CT than in patients without thyroid disease.

Autoimmune thyroid disease is reported to be present in 4%–57% of patients with PHPT [12–14], but their impact on radionuclide imaging results is not well understood. The European Association of Nuclear Medicine (EANM), for example, considers inflammatory thyroiditis to be one of the primary causes of false-positive results in ^99mTc-MIBI imaging. Radionuclide imaging is also proposed to be superior to ultrasound for identifying normally located hyperfunctioning parathyroid glands in patients with thyroiditis [21]. Our study classifies up to 85% of false results from planar scintigraphy and SPECT/CT in patients with PHPT and concomitant autoimmune thyroid disease as false negatives. This finding aligns with prior studies that revealed 66.7% of false-negative scintigraphy and SPECT with ^99mTc-MIBI results were attributed to autoimmune thyroid disease (Hashimoto thyroiditis and Graves’ disease), with no false-positives reported [17].

The lower diagnostic accuracy of radionuclide imaging of parathyroid lesions in patients with concomitant autoimmune thyroid disease can be primarily attributed to the increased uptake and persistent tissue retention of ^99mTc-MIBI [22–24]. Our unpublished data suggest that, in autoimmune thyroid disease, the tissue accumulation of ^99mTc-MIBI often exceeds the levels in parathyroid lesions, substantially complicating visualization, especially with planar scintigraphy. However, patients with atrophic chronic autoimmune thyroiditis caused by long-term hypothyroidism and severe fibrous changes were reported to demonstrate low uptake of ^99mTc-MIBI and a notable decrease in thyroid volume [22]. Our unpublished data show that thyroid accumulation of the radiopharmaceutical does not affect the interpretation of scintigraphic images in these cases.

SPECT/CT demonstrates higher diagnostic accuracy for parathyroid lesions than planar scintigraphy when ^99mTc-MIBI is retained in thyroid tissue during delayed scanning in patients with autoimmune thyroid disease [18]. The addition of the anatomical CT component to SPECT/CT improves diagnostic accuracy compared with SPECT alone. However, patients with hypertrophic autoimmune thyroiditis or Graves’ disease may develop thyroid changes that lead to increased thyroid volume and lumpy contours, decreased parenchyma attenuation to 50–70 HU, and increased numbers and sizes of reactive lymph nodes in the paratracheal area. In some cases, these changes can obscure a juxtathyroidal parathyroid lesion on non-contrast CT images [25, 26]. The cutoff thyroid volume identified in our study (13.2 cm³) suggests that SPECT/CT is less likely to detect parathyroid lesions in patients with PHPT or autoimmune thyroid disease if their thyroid volumes are larger. Contrast-enhanced CT scans show a less marked decline in accuracy in these cases. As a result, the combination of ultrasound and contrast-enhanced CT is 11% more accurate than ultrasound and SPECT/CT in detecting parathyroid lesions in patients with PHPT and autoimmune thyroid disease.

In patients with PHPT and thyroid nodules, SPECT/CT demonstrated the highest accuracy in detecting parathyroid lesions. In most cases, nodules did not interfere with the detection of parathyroid adenomas. In our study, parathyroid lesions and thyroid nodules were found to be in close proximity in 18% of cases, manifesting as a single focus of radiopharmaceutical accumulation on planar and SPECT images. The CT component of SPECT/CT was essential for detecting parathyroid lesions in these patients.

Based on our findings regarding the diagnostic accuracy of localization techniques and the factors affecting the SPECT/CT results in patients with autoimmune thyroid disease, we have developed an imaging algorithm to localize parathyroid lesions in patients with PHPT and concomitant thyroid disease (see Fig. 3). This algorithm does not use fine-needle aspiration biopsy with needle washout as an alternative or independent method for localizing parathyroid lesions based on PTH levels. However, it can distinguish parathyroid tissue from thyroid tissue and lymph nodes.

 

Fig. 3. Algorithm for parathyroid lesion localization in patients with primary hyperparathyroidism and concomitant thyroid disease. PHPT, primary hyperparathyroidism; DTG, diffuse toxic goiter; CAIT, chronic autoimmune thyroiditis; TPO, thyroid peroxidase; TG, thyroglobulin; US, ultrasound; SPECT, single-photon emission computed tomography; SPECT/CT, single-photon emission computed tomography/computed tomography; CT, computed tomography; PET/CT, positron emission tomography/computed tomography; MRI, magnetic resonance imaging; FNAB, fine-needle aspiration biopsy; PTH, parathyroid hormone.

 

Study Limitations

The study used a non-representative convenience sample, partly because the data were obtained from a tertiary medical center. The low percentage of men in the sample was related to the higher prevalence of hyperparathyroidism with thyroid disease in women [27]. Additionally, patients with atypical parathyroid lesion localization were excluded from the study. Therefore, the calculated diagnostic accuracy levels of localization imaging techniques can only be applied to cases with a typical parathyroid adenoma location (on the posterior surface or lower pole of a thyroid lobe), which accounts for 80%–85% of cases of this condition [28].

Not all patients included in the study underwent contrast-enhanced CT scans because ultrasound, scintigraphy, and SPECT/CT scans are the primary diagnostic imaging techniques for parathyroid adenomas [29]. A separate X-ray–based imaging procedure (CT scan) in addition to these modalities would have resulted in an unjustified increase in radiation exposure for the patients. This factor may have affected the accuracy of the calculations used to determine the diagnostic performance of contrast-enhanced CT. Additionally, in some cases, the interval between the imaging procedure and parathyroidectomy was up to 12 months. However, we believe this factor could not affect the discrepancy rate for the presence or localization of parathyroid lesions.

Finally, we should consider the retrospective nature of our study.

CONCLUSION

In patients with PHPT, a concomitant thyroid disease was associated with lower diagnostic accuracy of all preoperative localization imaging techniques for parathyroid lesion detection. Radionuclide imaging (planar scintigraphy and SPECT/CT) demonstrated the lowest diagnostic accuracy in patients with PHPT and concomitant autoimmune thyroid disease. In these cases, a combination of contrast-enhanced CT and ultrasound is preferable. SPECT/CT can be used as a first-line localization tool for parathyroid lesions in patients with thyroid nodules. The results of radionuclide imaging for parathyroid lesions in patients with PHPT depend on thyroid volume, attenuation, and vascularity.

ADDITIONAL INFORMATION

Author contributions: M.V. Degtyarev: conceptualization, methodology, investigation, writing—original draft, visualization; P.O. Rumyantsev: conceptualization, formal analysis, writing—original draft; K.Yu. Slashchuk: formal analysis, writing—original draft; S.S. Serzhenko: formal analysis; A.P. Pershina-Miliutina: formal analysis. All the authors approved the version of the manuscript to be published and agreed to be accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Ethics approval: The study was approved by the local Ethics Committee of the National Medical Research Center for Endocrinology (Minutes No. 1 dated January 25, 2017). All patients provided written informed consent to undergo the examination.

Funding sources: No funding.

Disclosure of interests: The authors have no relationships, activities, or interests for the last three years related to for-profit or not-for-profit third parties whose interests may be affected by the content of the article.

Statement of originality: No previously obtained or published material (text, images, or data) was used in this study or article.

Data availability statement: The editorial policy regarding data sharing does not apply to this work.

Generative AI: No generative artificial intelligence technologies were used to prepare this article.

Provenance and peer-review: This article was submitted unsolicited and reviewed following the standard procedure. The peer review process involved one external reviewer, a member of the Editorial Board, and the in-house science editor.

 

¹ JavaStat — 2-way Contingency Table Analysis [Internet]. In: StatPages.info, 2009–2024. Available at: https://statpages.info/ctab2x2.html Accessed on November 13, 2024.

About the authors

Mikhail V. Degtyarev

Endocrinology Research Centre

Email: germed@mail.ru
ORCID iD: 0000-0001-5652-2607
SPIN-code: 7725-7831

MD

Russian Federation, Moscow

Pavel O. Rumyantsev

Clinics group “My Medical Center”

Email: pavelrum@gmail.com
ORCID iD: 0000-0002-7721-634X
SPIN-code: 7085-7976

MD, Dr. Sci. (Medicine)

Russian Federation, Saint Peterburg

Sergei S. Serzhenko

Endocrinology Research Centre

Author for correspondence.
Email: vv1ld@yandex.ru
ORCID iD: 0000-0003-2326-1396
SPIN-code: 4713-8986

MD

Russian Federation, Moscow

Konstantin Yu. Slashchuk

Endocrinology Research Centre

Email: slashuk911@gmail.com
ORCID iD: 0000-0002-3220-2438
SPIN-code: 3079-8033

MD, Cand. Sci. (Medicine)

Russian Federation, Moscow

Anastasiia P. Pershina-Miliutina

Endocrinology Research Centre

Email: oa11111998@gmail.com
ORCID iD: 0000-0002-9462-8522
SPIN-code: 6392-5111

MD

Russian Federation, Moscow

References

Supplementary files