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Acta Endocrinologica (Bucharest) logoLink to Acta Endocrinologica (Bucharest)
. 2022 Jul-Sep;18(3):316–323. doi: 10.4183/aeb.2022.316

DIAGNOSTIC PERFORMANCES OF 18F-FLUOROCHOLINE POSITRON EMISSION TOMOGRAPHY-COMPUTED TOMOGRAPHY AND REPEATED ULTRASONOGRAPHY IN DETECTING UNDEFINED LESIONS IN PATIENTS WITH AN INDICATION FOR PRIMARY HYPERPARATHYROIDISM SURGERY

R Yildiz 1,*, H Şan 2, E Alagöz 3
PMCID: PMC9867814  PMID: 36699176

Abstract

Context

18F-fluorocholine (FCH) has been used as a positron emission tomography (PET) tracer in the localization of hyper-functioning parathyroid glands (HPGs).

Objective

We performed this methodological study to evaluate the diagnostic performance of 18F-FCH PET/computerized tomography (CT) and repeated ultrasonography (USG) in detecting unidentified lesions in patients with primary hyperparathyroidism (PHPT).

Design

In this retrospective methodological study, we studied the diagnostic performance of 18F-FCH PET/CT and a repeated USG in detecting unidentified parathyroid lesions.

Subjects and Methods

Twenty-eight patients who were diagnosed with PHPT, had an indication for surgery following the current guidelines and had no identified lesion on 99mTc-MIBI SPECT/CT, USG, or other imaging methods than 18F-FCH PET/CT, included in the study.

Results

While lesions were detected in 26 patients via 18F-FCH PET/CT among 28 patients [92.9% (95% CI: 76.6%-99.1%)], the lesion detection rate was 95.7% (95% CI: 78.1%-99.9%) in 23 patients who underwent a repeated USG. The sensitivity and the accuracy of both 18F-FCH PET/CT and repeated USG were 95.2% (95% CI: 76.2%-99.9%) and 95.0 (95% CI: 75.1%-99.9%), respectively.

Conclusions

This study supports that the combination of 18F-FCH PET/CT and repeated USG has promising potential for being an imaging technique for early detection and localization of HPGs.

Keywords: 18F-Fluorocholine Positron Emission Tomography/Computerized Tomography, Hyperfunctioning Parathyroid Gland, Primary Hyperparathyroidism, Radioguided Occult Lesion Localization-Minimally Invasive Parathyroidectomy

INTRODUCTION

Primary hyperparathyroidism (PHPT) is one of the common endocrine diseases with a prevalence of 1/1000 to 7/1000 in adults (1). PHPT is more common in people over the age of 50 years, and approximately the three-quarters of the cases are females (2, 3). The diagnosis of PHPT is made by a high level of total serum calcium and elevated parathormone (PTH) levels. While solitary parathyroid adenomas (70-80% of the cases) are the predominant underlying pathology in patients with PHPT, multiglandular disease or hyperplasia is reported in 10-20% of patients. Parathyroid carcinomas, on the other hand, are less common in PHPT patients (<1% of cases) (4, 5).

The diagnosis of PHPT is generally made incidentally because symptoms are mild and non-specific in most cases. However, an increase in plasma PTH can cause bone loss and increase the risk of kidney stones (6). The standard curative treatment of the hyperfunctioning parathyroid gland (HPG) is parathyroidectomy, and the normalization of serum calcium and PTH levels is the main indicator of therapeutic success (7).

Nowadays, minimally invasive parathyroidectomy (MIP) guided by preoperative diagnostic imaging techniques has become the preferred surgical approach for HPG in clinical practice instead of bilateral neck exploration (4, 8). It was reported that MIP has similar efficiency to bilateral neck exploration with several additional advantages including shorter operation duration, faster recovery, and fewer complications (9, 10).

Ultrasonography (USG), computed tomography (CT), magnetic resonance imaging (MRI), and hybrid technology of single-photon emission computed tomography (SPECT) and CT (SPECT/CT) are commonly used imaging techniques for the detection and localization of HPG (9, 11). The lower performance of USG in detecting ectopic parathyroid adenomas limits its further utilization. Therefore, 99mTc-Sestamibi scintigraphy is considered to be an initial imaging procedure to determine pathologic glands in patients with PHPT (11). However, its low spatial resolution and unsatisfactory lesion/background ratio are the major limitations that decrease the sensitivity and the accuracy. In addition, high radiation emission and requiring more acquisition time than newer modalities such as PET are its other disadvantages (12, 13). Although 99mTc-MIBI SPECT/CT and USG are used as basic preoperative imaging modalities in PHPT patients and are considered the preferred imaging techniques for the detection and localization of pathologic parathyroid glands, they have variable sensitivity and accuracy in patients with PHPT (11, 14, 15).

Positron emission tomography/computed tomography (PET/CT) is used for detecting lesions that are undetermined by conventional methods (9). 18F-fluorocholine (FCH) is a marker of cellular proliferation and has been used as a PET tracer in the detection and localization of parathyroid adenomas. In several studies, 18F-FCH PET/CT demonstrated superior sensitivity and accuracy over the conventional imaging techniques in patients with PHPT (16, 17).

Despite these diagnostic studies, to the best of our knowledge, there is no study evaluating the diagnostic performances of 18F-FCH PET/CT and repeated USG in detecting the lesion in PHPT patients. We performed this methodological study to compare the diagnostic performances of 18F-FCH PET/CT and repeated USG in detecting undefined lesions in patients with an indication for PHPT surgery. The secondary aim of the study was to evaluate the efficiency and safety of radio-guided occult lesion localization (ROLL)-MIP performed in patients with lesions detected by these imaging methods.

MATERIALS AND METHODS

Study design and setting

In this retrospective methodological study, we studied the diagnostic performance of 18F-FCH PET/CT and repeated USG in detecting parathyroid lesions in the patients who were admitted to our clinic with hyperparathyroidism symptoms between 2017 and 2020 and had no identified lesion on 99mTc-MIBI SPECT/CT and USG. We conducted this study following Good Clinical Practice standards, and in accordance with the Standards for the Reporting of Diagnostic Accuracy Studies (STARD) statement (18), after obtaining the approval of the Gulhane Non-invasive Investigation Ethics Committee. This study was performed in a general surgery department, which has a specialized endocrine surgery clinic providing surgical and medical care approximately to 1500 patients annually, at a tertiary care research hospital with advanced diagnostic imaging technology.

Patients

We did not calculate a minimum required sample size for the study, because we intended to evaluate all patients who were admitted to our clinic with hyperparathyroidism symptoms for eligibility. The inclusion criteria of the study were: (1) having a diagnosis of PHPT, (2) having an indication for surgery determined by the hospital endocrine council following the current guidelines, (3) having no identified lesion on 99mTc-MIBI SPECT/CT and USG, (4) having no identified lesion on other imaging methods than 18F-FCH PET/CT, if performed. The two exclusion criteria were: (1) not approving for 18F-FCH PET/CT or surgical procedures, and (2) failing to reach imaging scans or patient records.

The American Association of Endocrine Surgeons Guidelines were used for the diagnosis of PHPT, and the management of the patients included in the study (19). 99mTc-MIBI SPECT/CT and USG are used as basic preoperative localization modalities in PHPT patients in our clinic. In some cases, patients may also apply hospital with the results of other imaging modalities they have done in different medical centers. Therefore, the patients whose parathyroid pathologies could not be localized despite all imaging efforts were included in the study.

The demographics and baseline clinical and laboratory features of all patients were recorded. The clinical and surgical outcomes of the patients who underwent surgery were also recorded. All clinical and laboratory data were obtained from hospital patient records.

99mTc-MIBI SPECT/CT protocol and image interpretation

After an intravenous administration of 740 MBq 99mTc-MIBI, 20th- and 120th-minute static images of cervical and thoracic regions were acquired via a dual-head SPECT/CT camera (Discovery NM/CT 670, GE Healthcare, USA) in a matrix size of 256×256. SPECT/CT was conducted 120 minutes after obtaining static images. SPECT data were obtained over 360°, yielding 60 projections with 15 s/projection in a matrix size of 128×128 with a zoom size of 1.0. CT features were; a tube current of 20 mAs, a peak kilovoltage of 140 kVp, and a slice thickness of 2.5 mm.

18F-FCH PET/CT protocol and image interpretation

Neck and thorax PET/CT images were obtained by a hybrid PET/CT device (Discovery 710, GE Healthcare, USA) 45 to 60 minutes after the intravenous administration of 100 MBq 18F-FCH in the supine position. PET scans were obtained for 2 minutes per bed position, and they were reconstructed with non-contrast CT scans which were acquired using a protocol of 140 kVp, 70 mA, a 0.5 s/rotation tube rotation time, a pitch of 6, and a 5 mm slice thickness. Patients were allowed to have normal breathing throughout the procedure. PET/CT scans were evaluated in transaxial, coronal, and sagittal planes (Advance Workstation Volumeshare 4.5, GE Medical Systems, USA). PET/CT positivity was defined as a higher focal uptake in the cervico-mediastinal region and/or a nodular lesion. Two nuclear medicine specialists who were blinded to all patient data examined the images retrospectively.

Ultrasound examination

A preoperative parathyroid ultrasound was performed (LOGIQ E9, GE Healthcare, USA) using a linear probe with a frequency ranging between 7 and 11 MHz. First, patients were placed in a supine position, then the anterior and lateral cervical area, superior mediastinum, and supraclavicular fossae were examined at least on two orthogonal slices. Ultrasound examinations were performed independently by two radiologists.

Surgery

The reference standard of this methodological study was the “surgically true localization of the HPG”. All patients were assessed using The American Society of Anesthesiologists (ASA) score for pre-anesthesia consultation before surgery. All surgeries were performed by two endocrine surgeons who had at least 15 years of experience in thyroid and parathyroid surgery. Before the operation, the surgeons had all imaging results to provide the best guide for the surgery.

ROLL-MIP

The lesions that were detected by both 18F-FCH PET/CT and subsequent repeated USG were marked with 0.5 mCi of TC99m macro-aggregated albumin (MAA) injection on a neck map in the nuclear medicine clinic on the morning of the operation day. Then, the measurements for radioactive activity were made with a gamma probe to localize the lesion in the operating theatre. The skin and subcutaneous tissue were incised with an approximately 3 cm Kocher’s necklace incision, and the anterior thyroid muscles were separated. Then the lesion was excised after confirming by the gamma probe. Finally, the thyroid lodge was scanned with the gamma probe for residual activity, and the operation was completed when it was ensured that there was no additional activity.

During the operations, the number and the precise localization of all HPGs were recorded by operating surgeons. The surgical success was defined as the normalization of blood PTH and Ca levels on the postoperative first day. Post-operative complications were monitored, and patients were consulted with the endocrine clinic before discharging. They were also evaluated on the 7th day after discharge by the surgeons. The pathological specimens of the patients were evaluated by pathologists with more than 10 years of experience.

Statistical analysis

Statistical analyses were performed with SPSS version 23 (IBM Corp. in Armonk, NY) and Medcalc version 16 (MedCalc Software bvba, Ostend, Belgium). Descriptive statistics were presented as frequency (n) and percentage (%) for qualitative data, and median with interquartile range (IQR) for non-normally distributed numeric data. Sensitivity, specificity, and accuracy with 95% confidence intervals (CIs) were used to evaluate the diagnostic performance of imaging modalities. Pearson’s Chi-square Test or Fisher’s Exact Test was used for the comparison of qualitative variables. Mann-Whitney U test was used for the comparison of numeric variables. p<0.05 was approved as the statistical significance level.

RESULTS

During the study period, a total of 147 patients were diagnosed with hyperparathyroidism in our clinic. Of these patients, 119 were excluded according to the inclusion and exclusion criteria (2 were diagnosed with secondary or tertiary hyperparathyroidism, and lesions were located by any imaging techniques other than 18F-FCH PET/CT in 117 patients). After the exclusion of those, 28 patients were considered eligible to be included in the study. In all eligible patients, 18F-FCH PET/CT was performed, and lesions were detected in 26 patients [detection rate: 92.9% (95% CI: 76.6%-99.1%)], but not in 2 patients. Of these two 18F-FCH PET/CT negative patients, one lost to follow-up and the other underwent exploratory surgery. Of the 18F-FCH PET/CT positive patients, three patients lost to follow-up, and a repeated USG was performed in the remaining 23 patients. While a lesion was detected in 22 patients among those who underwent a repeated USG [Detection rate: 95.7% (95% CI: 78.1%-99.9%)], no lesion was detected in one patient, and therefore an exploratory surgery was performed in this patient. Of the 22 18F-FCH PET/CT and repeated USG positive cases, three patients lost to follow-up, and 19 underwent the ROLL-MIP surgery (Fig. 1).

Figure 1.

Figure 1

Flow diagram of the study.

The demographics and clinical features of the patients were presented in Table 1. Among the 28 patients included in the study, 22 (78.6%) were female and the median age of the study population was 55.0 years. While one-quarter of those had at least one comorbid disease, the most common comorbid diseases are hypertension, diabetes mellitus, and hypercholesterolemia, respectively (data not shown). Before admission to our clinic, two patients had a history of parathyroid surgery, one patient had a history of thyroid surgery, and one patient had a concurrent left thyroid lobectomy and parathyroid adenoma surgery. The median SUVmax on 18F-FCH PET/CT was 4.85 with an IQR of 3.78 and 6.25. While lesions were located in the left and right lower poles in almost two-thirds of the patients, a lesion located in the right tracheoesophageal groove and another behind the sternum were detected. The median preoperative serum PTH level was 139.3 pg/mL, and the median preoperative corrected serum Ca level was 11.0 mg/dL (Table 1).

Table 1.

Demographics and clinical features of the patients

Variables (n=28)
Age (years), Median (IQR) 55.0 (46.8-60.5)
Female, n (%) 22 (78.6)
Comorbid disease, n (%) 7 (25.0)
Previous surgery, n (%)
PS 2 (7.2)
TS 1 (3.6)
PS, TS 1 (3.6)
SUVmax on 18F-FCH PET/CT, Median (IQR) 4.85 (3.78-6.25)
Localization of lesion on 18F-FCH PET/CT, n (%)
Left lower 11 (39.3)
Right lower 7 (25.0)
Left middle 2 (7.1)
Right middle 2 (7.1)
Left upper 1 (3.6)
Right upper 1 (3.6)
Right tracheoesophageal groove 1 (3.6)
Behind the sternum 1 (3.6)
Preoperative serum PTH (pg/ml), Median (IQR) 139.3 (108.3-183.0)
Preoperative serum Ca (mg/dl), Median (IQR) 11.0 (10.2-11.4)
Preoperative serum vitamin D (ng/ml), Median (IQR) 22.6 (19.2-28.8)
Preoperative BMD (Z-score), Median (IQR) -2.1 (-2.7--1.7)

Note: IQR: Interquartile range, PS: Parathyroid surgery, TS: Thyroid surgery, SUVmax: Maximum standardized uptake value, 18F-FCH PET/CT: 18F-fluorocholine positron emission tomography-computed tomography, PTH: Parathyroid hormone, BMD: Bone mineral density. BMD was measured at the lumbar spine (L1–L4) and femoral neck.

Table 2 shows the cross-tabulation of 18F-FCH PET/CT and repeated USG results with surgical histopathology. First, it is seen that there was no false-positive result in both evaluation approaches, but false negatives were observed in one patient each. Therefore, specificity could not be calculated for both methods. However, the sensitivity and the accuracy of 18F-FCH PET/CT and repeated USG were 95.2% (95% CI: 76.2%-99.9%) and 95.0 (95% CI: 75.1%-99.9%), respectively. Both the sensitivity and accuracy of 18F-FCH PET/CT and repeated USG were statistically similar (p=0.482 and p=0.482, respectively).

Table 2.

Cross tabulation of 18F-FCH PET/CT and repeated USG results with surgical histopathology

Diagnostic test Surgical histopathology Sensitivity (95% CI) Specificity (95% CI) Accuracy (95% CI)
Positive Negative
18F-FCH PET/CT Positive 20 0 95.2 (76.2-99.9) na 95.2 (76.2-99.9)
Negative 1 0
Repeated USG Positive 19 0 95.0 (75.1-99.9) na 95.0 (75.1-99.9)
Negative 1 0
p 0.482 0.482

Note: CI: Confidence interval, 18F-FCH PET/CT: 18F-fluorocholine positron emission tomography-computed tomography, USG: Ultrasonography, na: Not applicable.

The clinical features and outcomes of the patients who underwent surgery were shown in Table 3. In comparisons other than the length of surgery (LOS), outcomes are statistically similar between the surgical techniques. All but one of the 21 patients who underwent ROLL-MIP or exploratory surgery had an ASA score of 1 or 2. While the median LOS for ROLL-MIP was 35 minutes, the exploratory surgery took 70 minutes in one patient and 110 minutes in the other. There is a statistically significant difference in LOS between the surgical approaches (p=0.01).

Table 3.

Clinical features and outcomes of the patients who underwent surgery

Variables ROLL-MIP (n=19) Exploration Surgery (n=2) p
ASA score, n (%) 0.567
1 5 (26.3) 1 (50.0)
2 13 (68.4) 1 (50.0)
3 1 (5.3) 0 (0.0)
LOS (minute), Median (IQR) 35.0 (30.0-45.0) 110.0 (70.0-na) 0.010
Lesion volume (mm3), Median (IQR) 251.2 (78.5-690.8) 543.0 (497.0-na) 0.343
Histopathologic diagnosis, n (%) 0.567
Adenoma 13 (68.4) 1 (50.0)
Hyperplasia 3 (15.8) 1 (50.0)
Concurrent adenoma and hyperplasia 3 (15.8) 0 (0.0)
Surgical success, n (%) 19 (100.0) 2 (100.0) na
Complication, n (%) 3 (15.8) 1 (50.0) 0.352

Note: ROLL-MIP: Radio-guided occult lesion localization-minimally invasive parathyroidectomy, ASA: American Society of Anesthesiology, LOS: Length of surgery, na: Not applicable.

Four of the 19 patients who underwent ROLL-MIP surgery had also thyroid surgery concurrently, and the LOS ranged from 45 to 60 minutes in these patients. In the remaining 15 patients, the maximum LOS was 40 minutes. However, partial sternotomy was performed for the resection of mediastinal parathyroid glands in one patient who underwent exploratory surgery with a LOS of 110 minutes (data not shown).

The median excised tissue volume was 251.1 mm3 and 543.0 mm3 in ROLL-MIP and the exploratory surgery, respectively. The histopathological diagnosis was adenoma in the majority of ROLL-MIP patients, on the other hand, hyperplasia was found in one of the exploratory surgery patients and adenoma in the other. While the surgical success was 100% for both surgical procedures, hypocalcemia developed in three patients in the ROLL-MIP group and one patient in the exploratory surgery group (Table 3). Postoperative hypocalcemia, which was classified as Clavien-Dindo grade 2, was resolved with oral calcium replacement in all patients (data not shown).

DISCUSSION

In the recently published literature, an increasing trend has been reported that MIP is the preferred surgical approach for the treatment of PHPT. Firstly, MIP can be performed under local or general anesthesia. It has a shorter operative time, better cosmetic results, and similar success to bilateral exploration with a lower risk of recurrent or persistent hyperparathyroidism and a lower risk of postoperative hypocalcemia (9, 19, 20). However, it is mentioned that the accurate detection and localization of the HPG are mandatory for the success of the MIP procedure (21). In the present study, none of the patients had any identified lesion on conventional imaging modalities, 99mTc-MIBI SPECT/CT and USG. The sensitivity and the accuracy of 18F-FCH PET/CT and repeated USG for detection of hyperfunctioning parathyroid tissue were found as 95.2% (95% CI: 76.2%-99.9%) and 95.0 (95% CI: 75.1%-99.9%), respectively. All patients treated surgically achieved a 100% cure rate and the complication rate was very low.

Surgical removal of HPG constitutes the definitive treatment for patients with PHPT. Currently, MIP has a shorter operative time, a reduced operative trauma, and a lower complication risk with similar treatment success to bilateral neck exploration (1). In our study, the median LOS for ROLL-MIP was 35 minutes, the exploratory surgery took 70 minutes in one patient and 110 minutes in the other. While the surgical success was 100% for both surgical procedures, hypocalcemia developed as a complication in three patients (15%) in the ROLL-MIP group and one patient (50%) in the exploratory surgery group. The hypocalcemia was resolved with oral calcium replacement in all patients. Our results are compatible with the literature. It is reported that repeated surgical intervention in patients with PHPT increases the probability of complications and treatment failure (7). Recurrent laryngeal nerve (RLN) palsy and hypoparathyroidism are the major surgery-related complications, and repeated surgery increases the risk of permanent RLN palsy and permanent hypoparathyroidism (7, 22). Therefore, in case of poor localization or discordant results with first-line imaging modalities, additional diagnostic modalities having higher sensitivity and accuracy should be performed to increase the success of primary surgery (4).

Currently, hybrid imaging techniques, such as parathyroid scintigraphy supplemented by USG or CT, are the most commonly used imaging methods for the detection and localization of parathyroid adenomas (16). 99mTc-MIBI SPECT/CT tends to be considered an accurate imaging method (23, 24). However, the declared sensitivity of these hybrid scintigraphic modalities ranges between 58% and 86% with lower performance in small lesions and multiple HPGs (23). Additional investigations were performed when conventional scintigraphic techniques could not detect the lesion, or they were discordant with the sonographic evaluation of the neck. PET/CT is a promising imaging method for these patients and there is a growing body of evidence about 18F-FCH which is a promising PET tracer for the detection and localization of HPGs (11). Mathey et al. reported that 18F-FCH PET/CT showed a better diagnostic performance than 11C-MET PET/CT for the detection and localization of HPGs (per-patient–based sensitivity for 18F-FCH and 11C-MET were 96% and 60% respectively) (25).

Beheshti et al. reported that 18F-FCH PET/CT showed better sensitivity (93.7% versus 60.8%), and superiority in detecting and localizing small adenomas in PHPT patients when compared to 99mTc tetrofosmin SPECT/CT (9). Similarly, Michaud et al. found that HPGs can be localized by FCH-PET/CT with a detection rate of 92% and a sensitivity of 89% (26). Bossert et al. showed that 18F-FCH PET/CT has a superior capacity for the detection and localization of pathologic parathyroid glands than 99mTctetrofosmin SPECT/CT and USG (12). The possible reasons why 18F-FCH PET/CT shows better performance and sensitivity might be its advanced technical characteristics, including high spatial resolution (9, 17).

Although conventional hybrid scintigraphic techniques, including 99mTc tetrofosmin SPECT/CT, had significantly lower diagnostic performance than 18F-FCH PET/CT, 18F-FCH PET/CT was applied as a second-line diagnostic imaging method in most studies. This algorithm increases radiation exposure and costs in patients with PHPT (23). Currently, PHPT is diagnosed with incidental measurements of serum calcium levels because many patients are in the subclinical or asymptomatic stage of the disease (12). Presumably, these subclinical or asymptomatic patients have small adenoma and a low level of serum PTH. A decrease in diagnostic capacity of 99mTc tetrofosmin SPECT/CT was reported in patients with low PTH levels and small size adenoma in two recent studies (12, 15). The authors of these studies emphasized that 18F-FCH PET/CT can be considered a first-line imaging modality in patients with normocalcemic or hypercalcemic hyperparathyroidism, even when the size of the lesion is small. Our results further support that 18F-FCH PET/CT can be preferred as the initial diagnostic modality in patients with a low level of PTH and/or small-size adenoma. This approach can reduce unnecessary radiation exposure and costs because the major technical advantages of PET/CT are low dose radiation exposure for both patients and staff, its simple preparation, and short acquisition time (27).

In our study, one false-negative result was observed. False-negative results have been attributed to the small size or pathological characteristics of adenomas including low functional conditions of adenoma-like cells or the low number of oxyphilic cells (9). Chen et al. reported that the sensitivity of 18F-FCH PET/CT positively correlated with the size of the lesion, and they are 90% and 95% for parathyroid lesions ≥175 mg and ≥200 mg, respectively (14).

It was stated that 18F-FCH PET/CT, as a diagnostic approach, was superior to conventional scintigraphic imaging techniques in patients with PHPT (23, 28). However, its place in diagnostic algorithms remains uncertain in the literature (23). Although 18F-FCH PET/CT might be a cost-effective imaging technology for PHPT, prospective cost-effectivity studies should be conducted taking into account the benefit of avoiding multiple imaging tests and repeat surgery when 18F-FCH PET/CT was performed as an initial diagnostic imaging method (17).

LIMITATIONS

This study has several limitations. First, because of studying in a single center with a relatively small sample size the external validity of our study is limited. Therefore, the findings of our study may not be generalized to all other patient populations. Since we studied with a restricted population that consisted of the patients prediagnosed biochemically, there was no false-positive patient among the pre-diagnosed patients. Therefore, we could not calculate the specificity of the imaging modalities. When interpreting the findings of this study, all these limitations should be kept in the mind.

The results of this study show that parathyroid lesions that cannot be detected by conventional imaging methods can be detected with 18F-FCH PET/CT and a secondary USG examination, thus allowing minimally invasive surgical treatment.

In conclusion, 18F-FCH PET/CT might have a promising potential for being an imaging technique for early detection and localization of hyperfunctioning parathyroid lesions. Cost-effectiveness analysis, on the other hand, should be performed to consider 18F-FCH PET/CT to be an initial imaging technique in patients with PHPT.

Conflict of interest

The authors declare that they have no conflict of interest.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

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