Comparison of 4D Computed Tomography and F-18 Fluorocholine PET for Localisation of Parathyroid Lesions in Primary Hyperparathyroidism

A Systematic Review and Meta-Analysis

Dhrumil Deveshkumar Patel; Samiksha Bhattacharjee; Avaneesh Kumar Pandey; Chirag Rajkumar Kopp; Abhiram G. Ashwathanarayana; Himani Vinayak Patel; Rohit Barnabas; Sanjay Kumar Bhadada; Manjunath Havalappa Dodamani

Disclosures

Clin Endocrinol. 2023;99(3):262-271.

Abstract and Introduction

Abstract

Minimally invasive parathyroidectomy (MIP) is the standard of care for primary hyperparathyroidism (PHPT). Four dimensional computed tomography(4DCT) and F-18 Fluorocholine positron emission tomography/computed tomography (FCH PET/CT) localize adenomas accurately to perform MIP. We aimed to conduct a systematic review and metanalysis to evaluate the diagnostic performance of 4DCT and FCH PET/CT scan for quadrant wise localisation in PHPT patients and to do head-to-head comparison between these two modalities.

Design, Patients and Measurement: After searching through PubMed and EMBASE databases, 46 studies (using histology as a gold standard) of 4DCT and FCH PET/CT were included.

Results: Total number of patients included were 1651 and 952 for 4DCT scan (studies n = 26) and FCH PET/CT scan (studies n = 24) respectively. In per patient analysis, FCH PET/CT and 4DCT had pooled sensitivities of 92% (88–94) and 85% (73–92) respectively and in per lesion analysis, 90% (86–93) and 79% (71–84), respectively. In the subgroup with negative conventional imaging/persistent PHPT, FCH PET/CT had comparable sensitivity to 4DCT (84% [74–90] vs. 72% [46–88]). As per patient wise analysis, FCH PET/CT had better detection rates than 4DCT ([92.4 vs. 76.85], odds ratio –3.89 [1.6–9.36] p = .0024) in the subpopulation where both FCH PET/CT and 4DCT were reported.

Conclusion: Both 4DCT and FCH PET/CT scan performed well in newly diagnosed patients, patients with persistent disease and in those with inconclusive conventional imaging results. FCH PET/CT scan had a higher pooled sensitivity than 4DCT in detecting patients with PHPT in head to head comparison.

Introduction

Primary hyperparathyroidism (PHPT) is a common endocrine disorder due to autonomous hyperfunctioning parathyroid gland(s). It commonly occurs due to benign overgrowth of parathyroid tissue, in some cases due to hyperplasia, and very rarely due to parathyroid carcinoma.^[1] It is biochemically characterized by hypercalcemia, hypophosphatemia, hypercalciuria accompanied by elevated parathyroid hormone levels.^[2] If untreated, it leads to significant morbidity, including osteolytic lesions with pathological fracture, osteomalacia, nephrocalcinosis, renal calculi and chronic kidney disease.^[3,4]

Abnormal parathyroid resection is curative treatment option for PHPT.^[5] Minimally invasive parathyroidectomy (MIP) is the current standard of care for treating PHPT with equal cure rates compared to conventional bilateral neck exploration. The potential advantages of MIP include—procedure under local anaesthesia with a smaller incision, lower incidence and severity of hypocalcemia, decreased hospital stay with less medical cost, fewer complications, and favourable operative field in patients who require reoperation for recurrent disease.^[6] Hence, it is crucial to have a modality with better sensitivity to localize abnormal parathyroid glands accurately. Neck ultrasonography (USG) and 99mTc-sestamibi imaging (either alone or combined with either single-photon emission computerized tomography [SPECT]) have an optimal detection ability in the majority of patients and are still the first-line imaging techniques in patients with PHPT. However, the performance of these modalities could be affected in patients with mild elevation of PTH and calcium, small adenomas, multiglandular disease, and concomitant thyroid abnormality. Several studies have shown promising results for both Four dimensional computed tomography (4DCT)^[7] and F-18 Fluorocholine positron emission tomography/computed tomography (FCH PET/CT) scans,^[8] but a systematic comparison of studies of these two techniques is still lacking.

The majority of all previous meta-analyses and systematic reviews of FCH PET/CT scan in PHPT have analysed per patient data. None of these studies clearly describe the performance of FCH PET/CT scan in previously operated patients with persistent disease, patients with inconclusive conventional imaging, and ectopic lesions. Hence, we conducted this meta-analysis to address the gaps in the literature. The primary objective of the present study was to compare the quadrant wise localising accuracy of FCH PET/CT scan and 4DCT at per patient and per lesion level in PHPT. Secondary objectives of the study were to compare these two modalities in homogenous populations of PHPT patients, to determine the sensitivity in patients with negative/inconclusive conventional scans/persistent disease requiring resurgery, newly diagnosed cases of PHPT, and those with ectopic lesions.

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Table 1. Characteristics of studies for four dimensional computed tomography (4DCT) included in the meta-analysis
Author	Year	Retrospective/prospective	Negative conventional scans	Multiglandular disease	Ectopic adenomas	Amount of contrast	Precontrast scans	Postcontrast phases
Acar N	2020	Retrospective	Yes	Yes	Yes	0.1 ml/kg	One	Three
Amadou C	2019	Retrospective	No	No	Yes	NA	One	Two
Bahl M	2019	Retrospective	No	Yes	No	NA	One	Two
Beland M	2011	Retrospective	Yes	Yes	yes	100 ml	One	Three
Cunha-Bezerra P	2018	Retrospective	No	No	No	2 ml/kg	One	Three
Ginsburg M	2015	Retrospective	Yes	No	No	120 ml	One	Three
Goroshi M	2017	Retrospective	No	Yes	No	60 ml	One	Three
Hinson A	2015	Retrospective	Yes	Yes	yes	75 ml	One	Three
Hunter G	2012	Retrospective	No	No	No	120 ml	One	Three
Kedarisetty S	2019	Retrospective	Yes	No	Yes	75 ml	One	Two
Kelly H	2014	Retrospective	No	No	No	100 ml	One	Two
Krakauer M	2016	Prospective	No	Yes	Yes	100 ml	One	Two
Lubitz C	2010	Retrospective	Yes	No	No	100 ml	One	Three
Lundstroem A	2016	Retrospective	Yes	Yes	No	100 ml	One	Three
Murugan	2021	Prospective	No	No	Yes	1–1.5 ml/kg	One	two
Naqvi S	2020	Retrospective	No	Yes	Yes	NA	One	Two
Piccardo A	2018	Prospective	Yes	No	No	80–100 ml	One	two
Pretet V	2020	Retrospective	No	No	Yes	75 ml	One	Two
Rameau A	2016	Retrospective	Yes	No	Yes	100–120 ml	One	Two
Suh Y	2014	Retrospective	No	No	No	90 ml	One	Three
Taywade S	2017	Retrospective	No	Yes	Yes	75 ml	One	two
Vu T	2019	Retrospective	No	No	No	120 ml	One	Three
Yeh R	2019	Retrospective	No	Yes	No	75 ml	One	Three
Zeina A	2017	Retrospective	Yes	No	Yes	120 ml	One	Two

Table 2. Characteristics of studies F-18 Fluorocholine positron emission tomography/computed tomography (FCH PET/CT) included in the meta-analysis
Author	Year	Retrospective/Prospective	Negative conventional scans^a	Multiglandular disease	Ectopic adenomas	Injected dose	Uptake time
Amadou C	2019	Retrospective	Yes	No	Yes	231 MBq	60 min
Ballester	2020	Prospective	Yes	Yes	No	362 MBq	60 min
Broos W	2019	Retrospective	No	Yes	No	150 MBq	60 min
Bossert I	2018	Prospective	No	No	No	3–3.5 MBq/kg	60 min
Christakis I	2019	Prospective	Yes	No	Yes	300 MBq	60 min
Cuderman A	2019	Prospective	No	Yes	No	100 MBq	60 min
Fischli S	2018	Retrospective	Yes	Yes	Yes	160 MBq	45 min
Gauthe M	2020	Retrospective	No	Yes	No	3 MBq/kg	20 min
Grimaldi S	2018	Prospective	Yes	Yes	No	100 MBq	30 min
Hocevar M	2017	Retrospective	No	Yes	No	100 MBq	60 min
Huber G	2018	Retrospective	Yes	NA	Yes	150 MBq	12–16 min
Khafif A	2019	Prospective	No	No	Yes	93.75 MBq	16 min
Kluijfhout W	2015	Retrospective	No	Yes	No	2 MBq/kg	30 min
Kluijfhout W	2017	Prospective	No	Yes	Yes	3 MBq/kg	40 min.
Lezaic L	2014	Prospective	No	Yes	No	100 MBq	60 min
López-Mora D	2020	Prospective	No	Yes	No	0.1 MBq/kg	60 min
Michaud L	2014	Prospective	No	Yes	Yes	3 MBq/kg	10 min
Morland D	2020	Retrospective	Yes	Yes	Yes	2.5 MBq/kg	60 min
Orevi M	2014	Prospective	No	Yes	Yes	370 MBq	NA
Piccardo A	2018	Prospective	Yes	No	Yes	100 MBq	10 min
Prabhua M	2018	Prospective	No	Yes	No	185–296 MBq	60 min
Pretet V	2020	Retrospective	Yes	Yes	No	2 MBq/kg	60 min
Singh P	2019	Retrospective	No	No	Yes	150–185 MBq	60 min
Taywade S	2017	Prospective	No	Yes	Yes	185 MBq	60 min
Thanseer N	2017	Prospective	No	Yes	Yes	150–185 MBq	10 and 60 min
Zajíčková K	2018	Retrospective	Yes	Yes	No	180 MBq	30 min

^aInclude-Cervical ultrasonography and sestamibi imaging.

Table 3. Summary for results of meta-analysis
Parameter	4DCT		FCH PET/CT
Parameter	Pooled value (95% CI)	I ²	Pooled value (95% CI)	I ²
Overall
Patient wise pooled sensitivity	0.85 (0.73–0.92)	79%	0.91 (0.87–0.94)	46%
Lesion wise pooled sensitivity	0.79 (0.71–0.85)	78%	0.90 (0.86–0.93)	47%
Lesion wise pooled PPV	0.91 (0.86–0.95)	81%	0.92 (0.88–0.95)	38%
Ectopic lesions
Patient wise pooled sensitivity	0.91 (0.84–0.95)	0%	0.87 (0.78–0.93)	0%
Lesion wise pooled sensitivity	0.89 (0.83–0.93)	0%	0.89 (0.84–0.93)	0%
Lesion wise pooled PPV	0.87 (0.83–0.91)	0%	0.85 (0.79–0.90)	0%
Reoperative patients/negative conventional scans
Patient wise pooled sensitivity	0.70 (0.23–0.95)	73%	0.89 (0.77–0.95)	46%
Lesion wise pooled sensitivity	0.72 (0.46–0.88)	73%	0.84 (0.74–0.90)	14%
Lesion wise pooled PPV	0.92 (0.75–0.98)	76%	0.91 (0.79–0.96)	48%
Newly diagnosed patients
Patient wise pooled sensitivity	0.89 (0.78–0.95)	74%	0.93 (0.91–0.95)	0%
Lesion wise pooled sensitivity	0.81 (0.75–0.86)	74%	0.91 (0.87–0.94)	46%
Lesion wise pooled PPV	0.91 (0.86–0.95)	80%	0.92 (0.88–0.95)	29%

Abbreviations: CI, confidence interval, FCH PET/CT, F-18 Fluorocholine positron emission tomography/computed tomography; PPV, Positive predictive value; 4DCT, Four dimensional computed tomography.

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Comparison of 4D Computed Tomography and F-18 Fluorocholine PET for Localisation of Parathyroid Lesions in Primary Hyperparathyroidism

A Systematic Review and Meta-Analysis

Abstract and Introduction

Abstract

Introduction

Tables

Tables

Tables

References

Authors and Disclosures

Authors and Disclosures

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