Don't chase the adenoma: A probabilistic approach to imaging before parathyroidectomy.

BACKGROUND: Preoperative imaging before parathyroidectomy can localize adenomas and reduce unnecessary bilateral neck explorations. We hypothesized that (1) the utility of preoperative imaging varies substantially depending on the preoperative probability of having adenoma(s) and (2) that a selective imaging approach based on this probability could avoid unnecessary patient costs and radiation. METHODS: We analyzed 3,577 patients who underwent parathyroidectomy for primary hyperparathyroidism from 2001 to 2022. The predicted probability of patients having single or double adenoma versus hyperplasia was estimated using logistic regression. We then estimated the relationship between the predicted probability of single/double adenoma and the likelihood that sestamibi or 4-dimensional computed tomography was helpful for operative planning. Current Medicare costs and published data on radiation dosing were used to calculate costs and radiation exposure from non-helpful imaging. RESULTS: The mean age was 62 ± 13 years; 78% were women. Adenomas were associated with higher mean calcium (11.2 ± 0.74 mg/dL) and parathyroid hormone levels (140.6 ± 94 pg/mL) than hyperplasia (9.8 ± 0.52 mg/dL and 81.4 ± 66 pg/mL). The probability that imaging helped with operative planning increased from 12% to 65%, as the predicted probability of adenoma increased from 30% to 90%. For every 10,000 patients, a selective approach to imaging that considered the preoperative probability of having adenomas could save patients up to $3.4 million and >239,000 millisieverts of radiation. CONCLUSION: Rather than imaging all patients with primary hyperparathyroidism, a selective strategy that considers the probability of having adenomas could reduce costs and avoid excess radiation exposure.

Diagnostic Performance of 99mTc-Sestamibi SPECT/CT and 18F-Choline PET/CT in Locating Hyperfunctioning Parathyroid Glands in Patients with Primary Hyperparathyroidism.

OBJECTIVE: This study aimed to assess the diagnostic performance of 99mTc-sestamibi SPECT/CT and 18F-choline PET/CT in detecting hyperfunctioning parathyroid glands in patients undergoing surgery for primary hyperparathyroidism (PHPT). METHODS: A retrospective analysis was conducted on patients who underwent PHPT-related surgery between April 2019 and May 2022. The study focused on patients undergoing either 99mTc-sestamibi SPECT/CT (81 patients) or 18F-choline PET/CT (33 patients) scans before surgery to pinpoint hyperfunctioning parathyroid gland(s). In the majority of patients, 18F-choline PET/CT was performed after negative or inconclusive findings on 99mTc-sestamibi SPECT/CT. Pathohistological reports were utilized as the reference standard for evaluating the accuracy of the imaging findings. RESULTS: The study encompassed 83 patients (70 females, 84.3%) with an average age of 57.2 years (24-80 years). The pathohistological analysis identified a total of 98 glands. In a per-lesion analysis, the detection rate of 99mTc-sestamibi SPECT/CT was 57% (95% CI 45.3-68.1), while the detection rate of 18F-choline PET/CT was 90.3% (95% CI 74.3-98.0). CONCLUSION: The results of our study showed the significant usefulness of 18F-choline PET/CT in patients with negative or inconclusive results of 99mTc-sestamibi SPECT/CT in accurately locating hyperfunctioning parathyroid glands in PHPT patients.

Microwave ablation for recurrent primary hyperparathyroidism in four patients with multiple endocrine neoplasia type 1: a case series report.

Multiple endocrine neoplasia type 1 (MEN1), a rare tumor syndrome, is inherited in an autosomal dominant pattern, mainly manifested as primary hyperparathyroidism (PHPT). Surgery is preferred for patients with MEN1 and PHPT. Thermal ablation has been widely applied for PHPT but rarely for postoperative recurrent PHPT in MEN1 patients. Based on a series of cases, we aimed to investigate the clinical efficacy and safety of ultrasound-guided percutaneous microwave ablation in the treatment of MEN1 patients with postoperative recurrence of PHPT.

Four-Dimensional Computed Tomography for Parathyroid Adenoma Localization: A Pre-Operative Imaging Protocol.

OBJECTIVE: Primary hyperparathyroidism (PHPT) affects approximately 0.86% of the population, with surgical resection as the treatment of choice. A 4D computed tomography (CT) is a highly effective tool in localizing parathyroid adenomas; however, there is currently no defined role for 4D CT when stratified against ultrasonography (USG) and nuclear medicine Technetium Sestamibi SPECT/CT (SES) imaging. STUDY DESIGN: Retrospective Study. SETTING: University Hospital. METHODS: All patients who underwent parathyroidectomy for PHPT between 2014 and 2019 at a single institution were reviewed. Patients who had a 4D CT were included. We compared outcomes of 4D CT as a second line imaging modality to those of USG and SES as first line modalities. An imaging algorithm was proposed based on these findings. RESULTS: There were 84 patients identified who had a 4D CT after unsuccessful first line imaging. A 4D CT localized parathyroid adenoma to the correct quadrant in 64% of cases, and to the correct laterality in 75% of cases. Obese patients had significantly lower rates of adenoma localization with USG (33.4%), compared to non-obese patients (67.5%; P = .006). In determining multigland disease the sensitivity of 4D CT was 86%, while the specificity was 87%. CONCLUSIONS: A 4D CT has impressive rates of accurate localization of parathyroid adenomas; however due to the radiation exposure involved, it should remain a second line imaging modality. PHPT patients should first be evaluated with USG, with 4D CT used if this is unsuccessful and patients are greater than 40 years old, have a high BMI, or are having revision surgery.

Head-to-head comparison of [11C]methionine PET, [11C]choline PET, and 4-dimensional CT as second-line scans for detection of parathyroid adenomas in primary hyperparathyroidism.

PURPOSE: Accurate preoperative localization is imperative to guide surgery in primary hyperparathyroidism (pHPT). It remains unclear which second-line imaging technique is most effective after negative first-line imaging. In this study, we compare the diagnostic effectiveness of [11C]methionine PET/CT, [11C]choline PET/CT, and four dimensional (4D)-CT head-to-head in patients with pHPT, to explore which of these imaging techniques to use as a second-line scan. METHODS: We conducted a powered, prospective, blinded cohort study in patients with biochemically proven pHPT and prior negative or discordant first-line imaging consisting of ultrasonography and 99mTc-sestamibi. All patients underwent [11C]methionine PET/CT, [11C]choline PET/CT, and 4D-CT. At first, all scans were interpreted by a nuclear medicine physician, and a radiologist who were blinded from patient data and all imaging results. Next, a non-blinded scan reading was performed. The scan results were correlated with surgical and histopathological findings. Serum calcium values at least 6 months after surgery were used as gold standard for curation of HPT. RESULTS: A total of 32 patients were included in the study. With blinded evaluation, [11C]choline PET/CT was positive in 28 patients (88%), [11C]methionine PET/CT in 23 (72%), and 4D-CT in 15 patients (47%), respectively. In total, 30 patients have undergone surgery and 32 parathyroid lesions were histologically confirmed as parathyroid adenomas. Based on the blinded evaluation, lesion-based sensitivity of [11C]choline PET/CT, [11C]methionine PET/CT, and 4D-CT was respectively 85%, 67%, and 39%. The sensitivity of [11C]choline PET/CT differed significantly from that of [11C]methionine PET/CT and 4D-CT (p = 0.031 and p < 0.0005, respectively). CONCLUSION: In the setting of pHPT with negative first-line imaging, [11C]choline PET/CT is superior to [11C]methionine PET/CT and 4D-CT in localizing parathyroid adenomas, allowing correct localization in 85% of adenomas. Further studies are needed to determine cost-benefit and efficacy of these scans, including the timing of these scans as first- or second-line imaging techniques.

Sonographic Features of Atypical and Initially Missed Parathyroid Adenomas: Lessons Learned From a Single-Center Cohort.

CONTEXT: Awareness of typical and atypical ultrasonographic (US) features of parathyroid adenomas (PAs) is crucial since US is the most widely used first-line imaging modality. OBJECTIVE: The purpose of this study was to describe the atypical features of PAs on US and other possible factors leading to a false negative examination in a large single-center cohort. MATERIALS AND METHODS: The US records of 457 PAs in 445 patients with biochemically proven primary hyperparathyroidism (PHPT) were evaluated in a prospectively maintained database. Atypical size, composition, shape, echogenicity, location, and vascular pattern on US were noted. For patients who previously had at least one negative US examination in referring centers, the main possible reason was defined accordingly. RESULTS: The study group included 359 female and 86 male patients with PHPT. Typical sonographic features were observed in 231 PAs (51%), whereas 226 (49%) had at least one atypical US feature. The most common atypical features were atypical size (29%), followed by atypical echogenicity (19%), shape (8%), location (7%), and composition (7%), respectively. There were 122 initially missed PAs in all groups. The most frequent main atypical US features leading to false negative examinations were atypical size (22.1%) and atypical location (18.8%). Inexperience was third most common reason (16.3%) for false negative US examinations. CONCLUSIONS: Almost half of PAs have at least one atypical feature on US. Awareness of the high prevalence of atypical US features could increase the accuracy of US examination and potentially decrease demand for more expensive second-line imaging modalities.

Site specific differences in vBMD and geometry in postmenopausal women with primary hyperparathyroidism.

PURPOSE: Primary Hyperparathyroidism (PHPT) is associated with catabolic effects at both trabecular and cortical bone. Mechanical loading is one of the most important natural anabolic stimuli for bone at all ages. The present study was designed to assess the impact of PHPT on vBMD and bone geometry using peripheral quantitative computed tomography (pQCT) at the radius and tibia, sites with similar structural characteristics, but subject to different loading conditions. METHODS: We evaluated the impact of PHPT on bone, by comparing the z-scores of volumetric Bone Mineral Density (vBMD) and indices of bone geometry simultaneously at the tibia and the radius by pQCT, skeletal sites with similar structure, but subject to different loading conditions. Forty-one postmenopausal women with PHPT and 79 controls, comprised the study group. RESULTS: At both trabecular and cortical sites, vBMD and bone geometry indices were significantly lower in patients compared with controls. In patients with PHPT, apart from a lower z-score for total vBMD (p = 0.01) at the radius, there was no other difference between the radius and the tibia at the trabecular sites. On the contrary, at cortical sites, the z-scores of cortical bone mineral content (p = 0.02), cortical vBMD (p = 0.01) and cortical cross-sectional area (p = 0.05) were significantly lower at the radius compared with the tibia, indicating that cortical bone at the weight bearing tibia might be less affected by the catabolic actions of continuous parathyroid hormone (PTH) exposure. PTH levels were positively associated with the difference in z-scores of cort BMD (r = 0.439, p < 0.01) indicating that in more severe cases, as expressed by higher PTH levels, the deleterious effects at the non-weight bearing radius might be accentuated. CONCLUSION: We found that in postmenopausal women with PHPT, both trabecular and cortical bone are adversely affected. However, at the weight bearing tibia as compared with the radius, the deleterious effects, especially on cortical bone, seem to be attenuated. TRIAL REGISTRATION NUMBER: NCT05426512, 21/06/2022, "retrospectively registered".

Using Texture Analysis of Neck Computed Tomography Images to Differentiate Primary Hyperparathyroidism From Normal Controls.

OBJECTIVE: To investigate the utility of texture analysis in detecting osseous changes associated with hyperparathyroidism on neck CT examinations compared with control patients and to explore the best regions in the head and neck to evaluate changes in the trabecular architecture secondary to hyperparathyroidism. METHODS: Patients with hyperparathyroidism who underwent a 4D CT of the neck with contrast were included in this study. Age-matched control patients with no history of hyperparathyroidism who underwent a contrast-enhanced neck CT were also included. Mandibular condyles, bilateral mandibular bodies, the body of the C4 vertebra, the manubrium of the sternum, and bilateral clavicular heads were selected for analysis, and oval-shaped regions of interest were manually placed. These segmented areas were imported into an in-house developed texture analysis program, and 41 texture analysis features were extracted. A mixed linear regression model was used to compare differences in the texture analysis features contoured at each of the osseous structures between patients with hyperparathyroidism and age-matched control patients. RESULTS: A total of 30 patients with hyperparathyroidism and 30 age-matched control patients were included in this study. Statistically significant differences in texture features between patients with hyperparathyroidism and control patients in all 8 investigated osseous regions. The sternum showed the greatest number of texture features with statistically significant differences between these groups. CONCLUSIONS: Some CT texture features demonstrated statistically significant differences between patients with hyperparathyroidism and control patients. The results suggest that texture features may discriminate changes in the osseous architecture of the head and neck in patients with hyperparathyroidism.

Localization of Ectopic Hyperparathyroidism: Ultrasound Versus 99mTc-sestamibi, 4-Dimensional Computed Tomography, and 11C-choline Positron Emission Tomography/Computed Tomography.

OBJECTIVE: To investigate the usefulness of ultrasound (US) for the localization of ectopic hyperparathyroidism and compare it with 99mTc-sestamibi (99mTc-MIBI), 4-dimensional computed tomography (4D-CT), and 11C-choline positron emission tomography/ computed tomography (PET/CT). METHODS: Of the 527 patients with surgically confirmed primary hyperparathyroidism, 79 patients with ectopic hyperparathyroidism were enrolled. The diagnostic performance of US, 99mTc-MIBI, US + MIBI, 4D-CT, and 11C-choline PET/CT was calculated, and the factors affecting the sensitivity of US and 99mTc-MIBI were analyzed. RESULTS: Eighty-three ectopic parathyroid lesions were found in 79 patients. The sensitivity was 75.9%, 81.7%, 95.1%, 83.3%, and 100% for US, 99mTc-MIBI, US + MIBI, 4D-CT, and 11C-choline PET/CT, respectively. The difference in sensitivity among these different modalities did not achieve statistical significance (P > .05). The US sensitivity was significantly higher for ectopic lesions in the neck region than for those in the anterior mediastinum/chest wall (85.9% vs. 42.1%, P < .001). The 99mTc-MIBI and 4D-CT sensitivity was not significantly different between these two groups (84.1% vs. 94.6%, P = .193 and 81.3% vs. 85.7%, P = 1). The 11C-choline PET/CT sensitivity was 100% in both groups. CONCLUSIONS: US is a valuable tool for the localization of ectopic hyperparathyroidism, especially for ectopic lesions in the neck region.

Quantitative CT Evaluation of Bone Mineral Density in the Thoracic Spine on 18F-Fluorocholine PET/CT Imaging in Patients With Primary Hyperparathyroidism.

INTRODUCTION: Measurement of bone mineral density (BMD) with quantitative CT (QCT) carries several advantages over other densitometric techniques, including superior assessment of the spine. As most QCT studies evaluated the lumbar spine, measurements of the thoracic spine are limited. We performed QCT analysis of the thoracic spine in a cohort of patients with primary hyperparathyroidism. MATERIALS AND METHODS: This study was a retrospective QCT analysis of the thoracic spine on 18F-fluorocholine PET/CT scans in patients with primary hyperparathyroidism patients between March 2018 and December 2022. Correlations between QCT-derived BMD or Hounsfield units (HU) and demographic data, laboratory parameters, results from histopathological examination after parathyroidectomy and results of DXA imaging were analyzed, when available. RESULTS: In 189 patients, mean QCT-derived BMD at the thoracic spine was 85.6 mg/cm3. Results from recent DXA were available in 122 patients. Mean thoracic QCT-derived BMD and HU were significantly correlated with DXA-derived BMD in lumbar spine, total hip and femoral neck and with the lowest T-score at DXA imaging. Only weak correlations were found with BMI or 18F-fluorocholine uptake, while no significant correlations were found with adenoma weight, PTH or calcium levels. CONCLUSION: Our study confirms correlation between QCT-derived BMD in the thoracic spine with age and DXA-derived BMD measurements within a population of patients with primary hyperparathyroidism. Establishment of reference BMD values for individual thoracic vertebrae, may allow direct osteoporosis classification on thoracic CT imaging.

Heterogeneous parathyroid near-infrared autofluorescence patterns are associated with single adenomas in primary hyperparathyroidism.

BACKGROUND: Primary adenoma (PA) and multi-gland hyperplasia (MGH) account for 85% and 15% of primary hyperparathyroidism (PHPT) cases, respectively. Near-infrared autofluorescence (NIRAF) enhances intraoperative parathyroid identification. We hypothesized that PA would display a more heterogeneous NIRAF pattern compared to MGH. METHODS: Patients undergoing surgery for sporadic PHPT were categorized based on the presence of PA or MGH. To quantify heterogeneity, we utilized ratios of (1) mean parathyroid gland (PG) NIRAF over background NIRAF (mean ratio), (2) minimum and (3) maximum PG NIRAF over mean PG NIRAF (minimum and maximum ratios). Additionally, a heterogeneity score was quantified using mean ratio (mean PG NIRAF over background NIRAF), and overall NIRAF (mean NIRAF of eight random 15 × 15 pixel areas). A point was assigned to ratios <0.8 or >1.2. Images were quantified by ImageJ software. Mann-Whitney test was performed for all comparisons. RESULTS: Of 78 patients, 63 had a single PA and 15 had MGH, totaling 102 PGs. There was no difference between their mean ratios. PA had a lower minimum ratio compared to that of MGH (0.86 ± 0.01 vs. 0.93 ± 0.01, p = 0.001) and a brighter maximum ratio (1.21 ± 0.02 vs. 1.12 ± 0.01, p = 0.0008). PA also scored higher on their heterogeneity scores compared to MGH (1.27 ± 0.23 vs. 0.33 ± 0.15, p = 0.001). CONCLUSION: Single parathyroid adenomas display a more heterogeneous autofluorescence pattern compared to that of multi-gland hyperplasia. Intraoperative characterization of PGs by real-time NIR imaging patterns may be a beneficial adjunct during parathyroid surgery.

Robotic parathyroidectomy is a feasible technique for primary hyperparathyroidism.

PURPOSE: Focused parathyroidectomy is the gold standard treatment modality for primary hyperparathyroidism, which allows accurate preoperative localization. Robotic parathyroidectomy has emerged as a feasible procedure for focused parathyroidectomy. This study aimed to report the experiences of gasless robotic transaxillary parathyroidectomy for primary hyperparathyroidism in a single center. METHODS: We assessed the data obtained from patients who underwent gasless robotic parathyroidectomy with the transaxillary approach between December 2013 and August 2022 and were diagnosed with primary hyperparathyroidism at our institute. The data included clinical, biochemical, and pathological features and operation time. RESULTS: Of the 12 patients, 11 were women and one was a man. The median age of the patients was 44.5 years (range: 15-65 years). The median preoperative maximum mass diameters on ultrasonography and neck computed tomography were 1.2 ± 0.5 and 1.1 ± 0.6 cm, respectively. The median size of the postoperative maximum mass diameter in gross pathology was 1.3 ± 0.4 cm. The location of the enlarged parathyroid was left superior in five patients, right inferior in four, left inferior in three, and no right superior in one. In the final pathological examination, all cases were parathyroid adenomas. Only one case experienced a postoperative bleeding complication. At six months from surgery, average of an axillary scar length was 5.85 cm, and an average width was 0.21 cm. The mean operative time was 113 ± 48 min. The mean robot docking and console times were 9 ± 5 and 47 ± 52 min, respectively. CONCLUSIONS: Robotic transaxillary parathyroidectomy is a feasible technique in select patients with primary hyperparathyroidism and preoperatively localized disease. The gasless robotic transaxillary approach provides procedural safety as well as superior cosmetic results without a neck scar.

Near-infrared fluorescent imaging for parathyroid identification and/or preservation in surgery for primary hyperparathyroidism.

Introduction: Near infrared autofluorescence (NIRAF) is a novel intraoperative technology that has shown promising results in the localisation of parathyroid glands (PGs) over the last decade. This study aimed to assess the potential utility of NIRAF in first time surgery for primary hyperparathyroidism (PHPT). Methods: An observational study over a period of 3 years in patients who underwent surgery for PHPT was designed. Data on the use of NIRAF and fluorescent patterns in different organs (thyroid and parathyroid) and parathyroid pathology (single versus multi-gland disease) were explored. In addition, cure rates and operating times were compared between the NIRAF and no-NIRAF groups to determine the potential value of NIRAF in this cohort. Results: In 230 patients undergoing first time surgery for PHPT, NIRAF was used in 50 patients. Of these 50 patients, NIRAF was considered to aid parathyroid identification in 9 patients (18%). The overall cure rate at 6 months of follow-up was 96.5% (98% in NIRAF and 96.1% without NIRAF; p=1.0). The median (interquartile range) operating time was longer in the NIRAF arm at 102 minutes (74-120 minutes) compared to the no-NIRAF arm at 75 minutes (75-109 minutes); however, this difference was not statistically significant (p=0.542). Although the median parathyroid to thyroid (P/T) auto-fluorescence (AF) ratio was similar between single gland and multi gland disease (2.5 vs to 2.76; p=1.0), the P/T AF ratio correlated negatively with increasing gland weight (p=0.038). Conclusion: The use of NIRAF resulted in some potential "surgeon-perceived" benefit but did not lead to improvements in cure rates. The negative correlation between fluorescent intensity and gland weight suggests loss of fluorescence with pathology, which needs further investigation. Further studies on larger cohorts of patients, in depth analysis of fluorescence patterns between normal, adenomatous, and hyperplastic glands and evaluation of user experience are needed. Primary hyperparathyroidism, hyperparathyroidism, autofluorescence, near-infrared fluorescence, parathyroid glands, endocrine, surgery.

Ultrasound-guided microwave ablation in the treatment of recurrent primary hyperparathyroidism in a patient with MEN1: a case report.

Background: Multiple endocrine neoplasia type 1 (MEN1) is an inherited endocrine syndrome caused by the mutation in the tumor suppressor gene MEN1. The recurrence rate of primary hyperparathyroidism (PHPT) in patients with MEN1 after parathyroidectomy remains high, and the management of recurrent hyperparathyroidism is still challenging. Case presentation: We reported a 44-year-old woman with MEN1 combined with PHPT who was diagnosed through genetic screening of the patient and her family members. After parathyroidectomy to remove one parathyroid gland, the patient suffered from persistent high levels of serum calcium and parathyroid hormone, which returned to normal at up to 8 months after ultrasound-guided microwave ablation (MWA) for bilateral parathyroid glands, suggesting an acceptable short-term prognosis. Conclusion: Ultrasound-guided MWA for parathyroid nodules may be an effective therapeutic strategy for recurrent PHPT in MEN1 patients.