68Ga-Trivehexin PET/CT: a promising novel tracer for primary hyperparathyroidism.

INTRODUCTION: This study aims to assess 68Ga-Trivehexin PET/CT for detecting hyperfunctioning parathyroid tissue in comparison to [99mTc]Tc-MIBI scintigraphy-SPECT/CT (MIBI scan) in patients with primary hyperparathyroidism (PHPT). METHODS: The cohort comprised 13 patients diagnosed with PHPT based on biochemical analyses, including serum calcium, phosphorus, and parathyroid hormone (PTH) levels. Each participant underwent cervical ultrasonography, MIBI scan, and 68Ga-Trivehexin PET/CT imaging. Complementary 4D-CT and [18F]fluorocholine PET/CT were conducted in 7 patients. Ten lesions of 7 patients underwent PTH wash-out (WO) procedure. 68Ga-Trivehexin PET/CT findings were compared with other modalities and PTH-WO results. RESULTS: Ten patients had sporadic PHPT, while 3 were diagnosed with MEN-1 syndrome-associated PHPT. One patient did not have any identifiable parathyroid lesion across the imaging modalities. On a patient-based analysis, MIBI scan and 68Ga-Trivehexin PET/CT identified parathyroid lesions in 10 and 11 patients, respectively. However, 68Ga-Trivehexin PET/CT detected 7 additional parathyroid lesions that were negative on the MIBI scan. Consequently, 17 lesions were identified and confirmed as hyperfunctioning parathyroid tissue through imaging, PTH-WO, or a combination of both modalities. In lesion-based evaluation, 68Ga-Trivehexin identified 16 lesions compared to 10 by MIBI scan, resulting in a detection rate of 94.1% and 58.8%, respectively. Notably, in three patients who underwent [18F]fluorocholine PET/CT, no lesions were detected; yet 68Ga-Trivehexin PET/CT successfully identified parathyroid lesions in two of these patients. CONCLUSION: Our study provides the first evidence that 68Ga-Trivehexin PET/CT can effectively identify hyperfunctioning parathyroid tissue with a high detection rate warranting further investigations to comprehensively explore its potential in PHPT management.

Testing for Primary Hyperparathyroidism in 17,491 Patients With Hypercalcemia.

BACKGROUND: Primary hyperparathyroidism (PHPT) is underdiagnosed and associated with many adverse health effects. Historically, many hypercalcemic patients have not received parathyroid hormone (PTH) testing; however, underlying reasons are uncertain. Our goals are to determine the PTH testing rate among hypercalcemic individuals at a large academic health system and to assess for characteristics associated with testing versus not testing for PHPT to inform future strategies for closing testing gaps. METHODS: This retrospective study included adult patients with ≥1 elevated serum calcium result between 2018 and 2022. Based on the presence or absence of a serum PTH result, individuals were classified as "screened" versus "unscreened" for PHPT. Demographic and clinical characteristics of these groups were compared. RESULTS: The sample comprised 17,491 patients: 6567 male (37.5%), 10,924 female (62.5%), mean age 59 y. PTH testing was performed in 6096 (34.9%). Characteristics independently associated with the greatest odds of screening were 5+ elevated calcium results (odds ratio [OR] 5.02, P < 0.0001), chronic kidney disease (OR 3.63, P < 0.0001), maximum calcium >12.0 mg/dL (OR 2.48, P < 0.0001), and osteoporosis (OR 2.42, P < 0.0001). Characteristics associated with lowest odds of screening were age <35 y (OR 0.60, P < 0.0001), death during the study period (OR 0.68, P < 0.0001), age ≥85 y (OR 0.70, P = 0.0007), and depression (OR 0.84; P = 0.0081). CONCLUSIONS: Only 35% of hypercalcemic patients received PTH testing. Although the presence of PHPT-associated morbidity was generally associated with increased rates of screening, hypercalcemic patients with depression were 16% less likely to be tested.

Primary Hyperparathyroidism due to Parathyroid Adenoma in Children and Adolescents.

OBJECTIVE: In contrast to adults, primary hyperparathyroidism (PHPT) in children and adolescents is a rare endocrine disorder. METHODS: A retrospective review of PHPT cases between 2005 and 2022 from a single tertiary university medical center, including clinical signs and symptoms, laboratory findings, radiological evaluation, treatment, and postoperative complications. RESULTS: Ten children (mean age at diagnosis 16.3 ± 1.3 years) were diagnosed with PHPT. All patients were in late pubertal stages without sex predominance and 8 were symptomatic. Mean calcium level was 13.6 ± 2.5 mg/dL, and mean parathyroid hormone levels were 204.8 ± 163.1 pg/mL. Parathyroid adenoma was confirmed by the postsurgical pathology results. CONCLUSIONS: PHPT in children and adolescents is often symptomatic and more severe than adults. The main cause is single parathyroid adenoma. Associated hypercalcemic syndromes were not found. Patients were cured after surgical removal of the adenoma without significant postoperative complications and no recurrence during 10.4 ± 5.9 years follow-up.

Clinical predictors of negative/equivocal SPECT imaging outcomes in primary hyperparathyroidism: Factors calling for 18F-choline-PET.

PURPOSE: For minimally invasive surgery of parathyroid adenomas, exact localization diagnostics are essential. Main imaging modalities used for diagnostics are sonography, SPECT with/without CT (traditional imaging) and 18F-choline-PET. The aim of our study was to identify predictors for inconclusive SPECT imaging and subsequently determine in which cases 18F-choline-PET is needed. METHODS: Retrospective analysis of 138 patients with histologically confirmed primary hyperparathyroidism (pHPT). After sonography, patients underwent SPECT or SPECT/CT imaging, with subsequent 18F-choline-PET in cases of disconcordant results. Logistic regression analysis was used to identify clinical and laboratory factors predictive for negative SPECT results. RESULTS: Sensitivity rates for sonography, SPECT, SPECT/CT, and choline-PET were 47 %, 49 %, 71.7 %, and 97 %, respectively. Logistic regression revealed lower PTH levels (p < 0.001), presence of structural thyroid disease (p = 0.018), and negative sonography (p < 0.001) as predictive of negative/equivocal SPECT outcome. An additional traditional imaging CT scan to a SPECT enhanced detection odds, as did greater adenoma weight. Urolithiasis, osteoporosis, and calcium values as measurement of activity and duration of disease showed no significant association with the detection rate. Furthermore, our study demonstrated that 18F-choline-PET exhibited remarkable sensitivity in detecting adenomas among patients with negative/equivocal SPECT results. CONCLUSION: Our study reveals potential predictive factors for a negative/equivocal SPECT outcome in pHPT. Identifying these factors might allow minimizing futile SPECT examinations and perhaps encourage timely utilization of 18F-choline-PET imaging. Our study reinforces the clinical significance of 18F-choline-PET, especially in complex cases with disconcordant results by conventional parathyroid imaging methods.

Comparing accuracy of machine learning approaches to identifying parathyroid adenomas: Lessons and new directions.

PURPOSE: The purpose of this investigation is to understand the accuracy of machine learning techniques to detect biopsy-proven adenomas from similar appearing lymph nodes and factors that influence accuracy by comparing support vector machine (SVM) and bidirectional Long short-term memory (Bi-LSTM) analyses. This will provide greater insight into how these tools could integrate multidimensional data and aid the detection of parathyroid adenomas consistently and accurately. METHODS: Ninety-nine patients were identified; 93 4D-CTs of patients with pathology-proven parathyroid adenomas were reviewed; 94 parathyroid adenomas and 112 lymph nodes were analyzed. A 2D slice through the lesions in each phase was used to perform sequence classification with ResNet50 as the pre-trained network to construct the Bi-LSTM model, and the mean enhancement curves were used to form an SVM model. The model characteristics and accuracy were calculated for the training and validation data sets. RESULTS: On the training data, the area under the curve (AUC) of the Bi-LSTM was 0.99, while the SVM was 0.95 and statistically significant on the DeLong test. The overall accuracy of the Bi-LSTM on the validation data set was 92 %, while the SVM was 88 %. The accuracy for parathyroid adenomas specifically was 93 % for the Bi-LSTM and 83 % for the SVM model. CONCLUSION: Enhancement characteristics are a distinguishing feature that accurately identifies parathyroid adenomas alone. The Bi-LSTM performs statistically better in identifying parathyroid adenomas than the SVM analysis when using both morphologic and enhancement information to distinguish between parathyroid adenomas and lymph nodes. SUMMARY STATEMENT: The Bi-LSTM more accurately identifies parathyroid adenomas than the SVM analysis, which uses both morphologic and enhancement information to distinguish between parathyroid adenomas and lymph nodes, performs statistically better.

Preoperative Lateralization and Diagnostic Value of Selective Bilateral Internal Jugular Venous Sampling in Primary Hyperparathyroidism: Single-Center Experience.

Background and Objectives: Primary hyperparathyroidism (pHPT) is a common endocrine disorder caused by excessive production of parathyroid hormone (PTH) leading to elevated calcium levels. Diagnosis is primarily based on biochemical evaluation, and surgery is the curative treatment. Imaging techniques like ultrasound and Tc-99m Sestamibi scintigraphy are used for localization, but selective Internal Jugular Venous (SVS) becomes valuable in cases of inconclusive or conflicting results. This study evaluated the diagnostic efficacy of SVS for localizing parathyroid adenomas in cases where non-invasive radiological diagnostic methods yielded inconclusive results or negative findings despite clinical symptoms suggestive of pHPT. Materials and Methods: In this retrospective study, a total of 28 patients diagnosed with pHPT underwent SVS at a tertiary center known for receiving referrals from 2017 to 2022. The diagnoses were confirmed through biochemical analysis. The SVS results in 22 patients were compared with non-invasive imaging methods, including ultrasound, scintigraphy, and computed tomography with/without contrast material. SVS was indicated when at least two non-invasive diagnostic procedures failed to clearly localize the parathyroid glands or provided ambiguous results. Results: SVS demonstrated higher sensitivity for localizing parathyroid adenomas compared to non-invasive imaging methods, accurately lateralizing the adenoma in 68.18% of cases. Among the SVS findings, 31.8% of patients had negative results, with 9.1% not having clinically proven parathyroid adenoma, while 22.7% had false negative SVS findings but were later confirmed to have adenoma during surgery. Ultrasound correctly identified the location in 45.45% of cases, CT in 27.27%, and scintigraphy in 40.9%. Conclusions: SVS is a valuable diagnostic tool for accurately localizing parathyroid adenomas in patients with inconclusive non-invasive imaging results. It aids in targeted surgical interventions, contributing to improved management and treatment outcomes in primary hyperparathyroidism.

Comparison of 4D computed tomography and F-18 fluorocholine PET for localisation of parathyroid lesions in primary hyperparathyroidism: A systematic review and meta-analysis.

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.

Diagnostic utility of 11 C-methionine PET/CT in primary hyperparathyroidism in a UK cohort: A single-centre experience and literature review.

OBJECTIVE: Primary hyperparathyroidism is a common endocrine disorder, with 80% of all cases usually caused by one single hyperfunctioning parathyroid adenoma. Conventional imaging modalities for the diagnostic work-up of primary hyperparathyroidism (PHPT) include ultrasound of the neck, 99mTc-sestamibi scintigraphy, and four-dimensional computed tomography (4D-CT). However, the role of other imaging modalities, such as 11C-methionine PET/CT, in the care pathway for PHPT is currently unclear. Here, we report our experience of the diagnostic utility of 11C-methionine PET/CT in a single-center patient cohort (n = 45). DESIGN: Retrospective single-center cohort study. PATIENTS AND MEASUREMENTS: The data of eligible patients that underwent 11C-methionine PET/CT between 2014 and 2022 at Addenbrooke's Hospital (Cambridge, UK) were collected and analyzed. The clinical utility of imaging modalities was determined by comparing the imaging result with histopathological and biochemical outcomes following surgery. RESULTS: In patients with persistent primary hyperparathyroidism following previous surgery, 11C-methionine PET/CT identified a candidate lesion in 6 of 10 patients (60.0%), and histologically confirmed in 5 (50.0%). 11C-methionine PET/CT also correctly identified a parathyroid adenoma in 9 out of 12 patients (75.0%) that failed to be localized on other imaging modalities. 11C-methionine PET/CT had a sensitivity of 70.0% (95% CI 55.8 - 84.2%) for the detection of parathyroid adenomas. CONCLUSIONS: This study highlights a diagnostic role for 11C-methionine PET/CT in patients that have undergone unsuccessful prior surgery or have equivocal or negative prior imaging results, aiding localization and a targeted surgical approach.

Innate differences in the molecular signature of normal inferior & superior human parathyroid glands: potential implications for parathyroid adenoma.

Primary hyperparathyroidism is a common endocrine disorder. Interestingly, the majority (75%) of parathyroid tumors are localized to the inferior parathyroid glands. To date, the reason for this natural bias has not been investigated. We assessed the global gene expression profile of superior and inferior glands obtained from forensic autopsies. The genes with significant differential expression between superior and inferior parathyroids were further assessed by RT-PCR in 19 pairs. As an iterative approach, additional genes with an established role in parathyroid disorders, i.e., CASR, MAFB, PAX9, TBCE, TBX1, VDR, MEN1, CCND1, and CDC73 were also evaluated by RT-PCR in all 19 pairs of superior and inferior parathyroid glands. Seven homeobox genes, namely HOXA4, HOXA5, HOXBAS3, HOXB4, HOXB6, HOXB9, IRX1, and one encoding for ALDH1A2 showed a lower expression in the inferior parathyroid glands than in the superior. Conversely, SLC6A1 showed a higher expression in the inferior glands. Of the nine genes with significant differential mRNA expression among superior and inferior glands HOXB9, HOXB4 and IRX1 could be detected by western blotting/mass spectrometry. The study is the first to show the differential expression of nine genes HOXA4, HOXA5, HOXBAS3, HOXB4, HOXB6, HOXB9, IRX1, ALDH1A2, and SLC6A1 in inferior versus the superior parathyroid glands. This could have potential implications for the preferential localization of parathyroid tumors to the inferior parathyroid glands as observed in patients with primary hyperparathyroidism.

Brown tumor due to primary hyperparathyroidism in a familial case: a case report.

BACKGROUND: Primary hyperparathyroidism (PHPT) is an uncommon disorder characterised by hypercalcemia with an increased parathyroid hormone level. We reported a PHPT familial case with two subjects, a father and a daughter, and both of them had suffered from the brown tumor. CASE PRESENTATION: The proband, a 43-year-old patient, developed parathyroid adenomas at the age of 15; a histologically confirmed right parathyroid adenoma was removed by parathyroidectomy; and after six months follow-up, the serum calcium level was normalised. At the age of thirty-three, a CT scan of his head and neck revealed a mass in the right maxilla, as well as PHPT (i.e., left inferior parathyroid adenoma). Then, he underwent a biopsy of an exophytic lesion in the right maxilla and was diagnosed by pathology as a brown tumor, with the serum calcium and PTH levels at 2.78 mmol/L and 221 pg/mL, respectively. Subsequently, the patient took a left inferior parathyroid microwave ablation with ultrasound guidance. After three months of follow-up, the serum calcium and PTH levels returned to normal, and the brown tumor was resolved. After three years, it mineralised as revealed in a CT scan. By the time he was 43 years old, during the 28-year follow-up period, the serum calcium and PTH levels were still within the normal range, and there was no discomfort reported. He has consistently taken calcium supplements throughout the 28 years. Since the initial diagnosis, his blood indicators of kidney function have been normal, and ultrasound showed renal calculus in the right kidney and a normal left kidney. The proband's daughter, a 15-year-old girl, experienced left upper extremity pain for ten months. CT scan revealed a mass in the distal left radius, and a giant cell tumor was suspected. A surgical internal fixation was performed, and the pathology showed a brown tumor. Laboratory tests revealed a serum parathyroid hormone (PTH) level of 1554pg/mL, calcium level of 3.14 mmol/L, phosphorus level of 0.72 mmol/L, and alkaline phosphatase level of 1892 U/L. Given the osteitic changes and elevated levels of calcium and PTH, ultrasonography was performed, after which a mass was detected measuring 19 × 9 × 7 mm mixed with solid components and cystic fluid in the right thyroid gland. The results of 99mTc-MIBI scintigraphy confirmed the abnormal accumulation of 99mTc-MIBI in the right thyroid gland but not seen in the bilateral parathyroid glands. The patient underwent thyroidectomy, and the postoperative pathology report indicated an intra-thyroid ectopic parathyroid adenoma. The serum calcium and PTH levels became normal at 4 h after surgery. One to three months after operation, the serum calcium level was low, while the serum PTH level was high. Then, the patient was advised to take calcium supplements. Until the sixth month after the operation, the serum calcium level and serum PTH level returned to normal, and the bone pain was relieved. The patient's blood tests for kidney function remained normal. There was no evidence of bilateral kidney disease (such as nephrolithiasis or nephrocalcinosis) detected by ultrasound scan. There were several similarities in the state of illness between these two subjects. Both the father and the daughter developed parathyroid adenomas at the age of 15, and there was no lesion in other endocrine glands. And genetic testing revealed mutations in the CDC73 genes in both father and daughter. On the other hand, there were also a few differences. The father's first signs of brown tumor were in the right maxilla, while the daughter's appeared in the distal left radius. The father presented pathological changes in the left and right parathyroid glands, whereas the daughter presented with an ectopic parathyroid adenoma in the right thyroid gland. CONCLUSION: We report a familial case in which father and daughter were diagnosed to have brown tumors due to parathyroid adenoma and ectopic parathyroid adenoma, and genetic testing revealed CDC73 gene mutations in both. Therefore, in the diagnostic and differential process of young patients having bone disease, clinicians should not only focus on the clinical manifestations of the skeleton, but also implement a comprehensive analysis of systemic symptoms, considering the possibility that the patient has familial PHPT.

Treating intra-thyroid parathyroid adenoma by radiofrequency is a valuable alternative to hemithyroidectomy.

BACKGROUND: Parathyroid adenoma (PA) is the most common cause of primary hyperparathyroidism (PHPT). One infrequent scenario (0.7%-6%) is represented by intra-thyroid PA (I-PA), an ectopic variant of the parathyroid gland included in the thyroid parenchyma. Radiofrequency (RF) of I-PA seems to be an excellent alternative to hemithyroidectomy for these patients. The present study aimed to report three cases of PHPT and I-PA treated with RF at two institutions. MATERIALS AND METHODS: These two institutions share guidelines for thyroid RF. At both institutions, cases with surgical indication and difficult PA localization are discussed during thyroid multidisciplinary meetings involving all disciplines involved in managing these cases. RF was performed using a Viva RF System generator (STARMED). Ultrasound contrast evaluation was performed using a SonoVue (Bracco). All patients were followed-up by an expert endocrinologist. RESULTS: Three cases had indications for treating I-PA. All patients were proposed to undergo RF rather than hemithyroidectomy, and accepted this option. RF of I-PA was performed with a power of 30-50 W and delivering a total between 0.02 and 0.69 Kcal. The active treatment lasted just more than 1 min. Post-treatment follow-up revealed PTH and calcium normalization. CONCLUSION: This study showed highly encouraging results in favor of treating I-PA with RF.

Correlation between preoperative calcium and parathormone levels with parathyroid gland volume.

Objective. Hyperparathyroidism is a prevalent disease with parathyroid adenomas being the most common cause. Surgical excision remains the standard treatment for parathyroid adenoma. Successful preoperative localization of the parathyroid adenoma could facilitate the decision regarding the extent of surgical exploration. The aim of the current study was to assess the correlation between the preoperative values of parathyroid hormone and ionized calcium with the adenoma weight and volume in patient with primary hyperparathyroidism caused by single-gland adenoma. Patients and Methods. We did this retrospective review for all patients who were diagnosed with primary hyperparathyroidism due to a solitary parathyroid adenoma in our general surgery department over 4 years. SPSS software was used to get the correlation coefficient between the peak preoperative levels of calcium and parathyroid hormone with the parathyroid adenoma weight and volume. Results. Ninety-nine patients were included into the study. The average age at surgery was 62.65±12.00 years. The correlation coefficient between the adenoma volume and weight with the preoperative ionized calcium level was weakly positive (r=0.329, p<0.01) and (r=0.281, p=0.019), respectively, while the correlation with the preoperative parathyroid hormone level was stronger (r=0.708, p<0.01) and (r=0.650, p<0.01), respectively. Conclusions. The strong positive relationship between the preoperative parathyroid hormone and calcium levels with the parathyroid adenoma size and weight can help the surgeon to predict the volume of the involved gland and avoid an unnecessary dissection.

Surgical challenges of giant parathyroid adenomas weighing 10 g or more.

PURPOSE: An average parathyroid adenoma (PA) weighs < 1 g. This study aimed to characterise giant PAs ≥ 10 g (GPAs) to facilitate surgical management of primary hyperparathyroidism (PHPT). METHODS: All patients with a GPA confirmed on histology were recruited from the Monash University Endocrine Surgery Unit database. Clinical and demographic data were collected and compared to a group of non-GPA patients. RESULTS: A total of 14 GPAs were identified between 2007 and 2018 out of 863 patients (1.6%) with a single PA excised for PHPT. The GPA patients were compared to a control group of 849 non-GPA patients in the same period with similar mean age (62 ± 16 vs 63 ± 14, P = 0.66) and gender distribution (64% vs 75% female, P = 0.35). Pre-operative calcium (Ca) and parathyroid hormone (PTH) levels were significantly higher in GPA patients (P < 0.001). A higher percentage of GPA patients (79%) had concordant localisation studies (ultrasound and sestamibi) than control patients (59%), (P = 0.13), but they were significantly less likely to undergo MIP (55% vs 82%, P = 0.02). The median GPA weighed 12.5 g (IQR 10.5-24.3). Median serum Ca normalised by day 1 post-operatively, while PTH remained elevated. Both serum Ca and PTH levels were in the normal range at 3 months. All GPA lesions were benign on histopathology. CONCLUSION: GPAs are rare and display severe clinical and biochemical abnormalities. Despite their large size, concordant pre-operative imaging was not always achieved, and a few patients were suitable for MIP.

Clinical predictors of ectopic parathyroid adenomas: experience with 421 confirmed parathyroid adenoma localizations.

PURPOSE: This study was designed to evaluate whether patients with ectopic parathyroid adenoma (EPA) have clinical predictors by comparing them with other patients operated on for primary hyperparathyroidism (PHPT) with uniglandular parathyroid adenomas in other localizations. METHODS: The data of PHPT patients who underwent parathyroidectomy in our institution were assessed retrospectively. Abnormal gland localization was confirmed by operative and pathology reports as well as normocalcemia that lasted for at least 6 months postoperatively. The relationships of biochemical and clinical findings of patients with confirmed adenoma localizations were analyzed. In order to determine independent factors that can predict EPAs, binary logistic regression was used. RESULTS: Among 421 patients (83.4% female, mean age 49 ± 13.2 years) enrolled in the study, the most common adenoma localization was the lower left parathyroid gland (36.1%; p < 0.001). Parathyroid adenomas were more common in lower localizations compared to upper localizations and were smaller in size (p < 0.001 and p = 0.004, respectively). In univariate analysis, serum intact parathyroid hormone and calcium levels were found to be higher (p = 0.004 and p = 0.002, respectively), moderate/severe hypercalcemia was more common (p = 0.024), phosphorus levels were lower (p = 0.04), and postoperative transient hypocalcemia was more common (p = 0.013) in cases of EPAs than other localizations. There was no significant difference in adenoma size between EPAs and other classical localizations. In multivariate analysis, only a high serum calcium level was an independent predictor of EPAs (OR 2.017, 95% CI 1.142-3.564, p = 0.016). Receiver-operating characteristic curve analysis yielded an optimal cutoff value of 12.25 mg/dL for serum calcium (88% sensitivity, 63% specificity, and area under the curve: 0.861). CONCLUSION: EPAs can cause a more biochemically distinct PHPT picture compared to parathyroid adenomas in classical localizations. A high calcium level at diagnosis may be a clinical predictor for EPAs and may affect the clinical approach and imaging technique choices. Due to the increased risk of transient hypocalcemia in patients with EPAs, caution should be exercised in postoperative follow-up. Furthermore, in the event of negative preoperative imaging, starting the parathyroid exploration from the lower left region may be a good option for the surgeon.

The Diagnostic Value of Contrast Enhanced Ultrasound for Localization of Parathyroid Lesions in Primary Hyperparathyroidism: Comparison With Color Doppler Ultrasound: Comparison With Color Doppler Ultrasound.

OBJECTIVES: Preoperative localization of pathological parathyroid glands with imaging is essential for focused unilateral neck exploration and minimally invasive techniques. Recently published studies suggested that contrast-enhanced ultrasonography (CEUS) had high accuracy in the localization of hyperfunctioning parathyroid glands, with a general increase in the sensitivity as compared to conventional sonography. The purpose of this study was to determine the usefulness of CEUS in the localization of parathyroid lesions relating to surgical and histopathological data, in comparison to color Doppler ultrasound (CDUS), in the same series of patients. METHODS: Records of 142 patients who underwent parathyroidectomy were retrospectively examined comparing imaging and intraoperative/histopathologic findings. RESULTS: The overall sensitivity of CEUS was 77.6% compared with 74.6% for CDUS, although no significative differences were found (P = .516). Conversely, CDUS has shown higher sensitivity than CEUS in the group of patients with associated thyroid pathology but there was no statistical difference (P = .529). The sensitivity for detection of multiple adenomas was the same for both procedures. CONCLUSIONS: We found no significative superior sensitivity of CEUS also in case of concomitant thyroid pathology and multiple glands disease.

Successful localization of abnormal parathyroid tissue with ultrasound-guided methylene blue dye injection before surgery for metastatic or recurrent thyroid cancers and parathyroid adenomas.

OBJECTIVES: A surgery to be performed on a previously operated neck includes difficulties such as increased risk of complications and prolonged operation time. The aim of the present study is to analyze the benefit of pre-anesthetic ultrasound-guided injection of methylene blue into parathyroid adenomas and abnormal lymph nodes to simplify their safe and satisfactory extraction. METHODS: We analyzed the case series records of 14 patients who were operated for reoperative neck surgery due to recurrent thyroid cancer (8 patients) and parathyroid adenoma (6 patients) and in the technique; 0.2 ml of a 1:5 dilution of 1 % methylene blue solution was injected directly onto the target during real-time ultrasound guidance before the operating room. RESULTS: In adenomas, ultrasound-guided methylene blue injection was successfully applied in all cases, an average of 33.1 min before entering the operating room (range = 28-38 min). There were no complications related to dye injection. For patients with recurrent thyroid tumors, preoperative ultrasound-guided methylene blue injection was successfully applied in all patients, on average 27.5 min before entering the operating room (range = 20-35 min). No complications occurred due to dye injection. The blue stained lesion was easily identified during surgery. CONCLUSIONS: We analyzed the feasibility of the injection process, the certainty of defining pathological lymph nodes, and the complications of the procedure. Preoperative administration of methylene blue preserved its intraoperative efficacy and maintained the easy the detection of reoperative or primary pathologies. The present study suggest that methylene blue dye injection is a safe, sufficient, and quietly effective method for identifying recurrent tumors and parathyroid adenomas in scarred reoperative neck surgeries. Our cases had comparatively short operative times and lower complication rates.

Telocytes/CD34+ Stromal Cells in the Normal, Hyperplastic, and Adenomatous Human Parathyroid Glands.

Telocytes/CD34+ stromal cells (TCs/CD34+ SCs) have been studied in numerous organs and tissues, but their presence and characteristics in the parathyroid glands have not been explored. Using immunological and ultrastructural procedures, we assess the location, arrangement, and behavior of TCs/CD34+ SCs in normal human parathyroids, during their development and in their most frequent pathologic conditions. In normal parathyroids, TCs/CD34+ SCs show a small somatic body and long thin processes with a moniliform aspect, form labyrinthine systems, connect other neighboring TCs/CD34+ SCs, vessels, adipocytes, and parenchymal cells directly or by extracellular vesicles, and associate with collagen I. TCs/CD34+ SCs and collagen I are absent around vessels and adipocytes within parenchymal clusters. In developing parathyroids, TCs/CD34+ SC surround small parenchymal nests and adipocytes. In hyperplastic parathyroids, TCs/CD34+ SCs are prominent in some thickened internodular septa and surround small extraglandular parenchymal cell nests. TCs/CD34+ SCs are present in delimiting regions with compressed parathyroids and their capsule in adenomas but absent in most adenomatous tissue. In conclusion, TCs/CD34+ SCs are an important cellular component in the human parathyroid stroma, except around vessels within parenchymal nests. They show typical characteristics, including those of connecting cells, are present in developing parathyroids, and participate in the most frequent parathyroid pathology, including hyperplastic and adenomatous parathyroids.

An extremely rare case of nonfunctioning parathyroid carcinoma occurring in a parathyroid adenoma.

A 53-year-old woman with a 4-month history of fatigue and somnolence was referred to her local doctor because of the worsening of her symptoms. Marked increases in her serum calcium (13.0 mg/dl) and intact-parathyroid hormone (175 pg/ml) were found, she was referred to our hospital. On physical examination, there was a palpable 3 cm mass in her right neck. Ultrasonography showed a 1.9 × 3.6 cm circumscribed hypoechoic lesion in the caudal right lobe of the thyroid gland. There was very mild 99mTc-sestamibi scintigraphic accumulation. Her preoperative diagnosis was primary hyperparathyroidism due to parathyroid carcinoma, and surgery was performed. The tumor weighed 6300 mg and did not invade the surrounding area. The pathology showed a mixture of small cells thought to be parathyroid adenomas and large, pleomorphic nuclei and fissionable carcinomas. Immunostaining showed that the adenoma portion was PTH-positive, chromogranin A-positive, p53-negative, PAX8-positive, PGP 9.5-negative with a Ki 67 labeling index (LI) of 2.2%. Whereas the carcinoma portion was PTH-negative, chromogranin A-negative, p53-positive, PAX8-positive, PGP 9.5-positive with a Ki67 LI of 39.6%, showing a nonfunctioning aspect and highly malignant. Postoperatively, the patient is alive without recurrence 9 years later without hypercalcemia or recurrence. A case of nonfunctioning parathyroid carcinoma in an extremely rare parathyroid adenoma is reported.

[Pheochromocytoma associated with primary hyperparathyroidism and type 1 neurofibromatosis]. / Feokhromotsitoma v sochetanii s pervichnym giperparatireozom i neirofibromatozom tipa 1.

Neurofibromatosis type 1 (NF-1) is a predominantly inherited genetic disease with prevalence of 1 per 2500-3000 newborns and based on clear clinical criteria. In addition to common neurofibromas and gliomas of the visual pathways, these patients have a higher risk of various benign and malignant tumors throughout their lives including tumors of the central nervous system, membranes of peripheral nerves, gastrointestinal stromal tumors and leukemia. Endocrine diseases and neoplasms also occur in patients with NF-1 and can include extrarenal paraganglioma, primary hyperparathyroidism, gastroenteropancreatic neuroendocrine tumors, thyroid tumors and other adrenal neoplasms. We demonstrate multiple neuroendocrine neoplasia (MEN 2A) of neurofibromatosis type 1 combined with pheochromocytoma and primary hyperparathyroidism in a woman with a long history of palpitations, paroxysmal hypertension and osteoporosis. Biochemical analysis revealed severe hypercalcemia with elevated parathyroid hormone indicating primary hyperparathyroidism, as well as high fractionated normetanephrine and metanephrine in the urine as a sign of catecholamine-releasing pheochromocytoma/paraganglioma. Further scintigraphy revealed signs of solitary parathyroid adenoma causing primary hyperparathyroidism and right-sided pheochromocytoma. Clinical diagnosis of MEN-2 syndrome is based on combination of at least two major MEN-2-associated endocrine tumors. Resection of parathyroid adenoma and pheochromocytoma normalized biochemical parameters and blood pressure. Combination of pheochromocytoma with primary hyperparathyroidism and type 1 neurofibromatosis is discussed.

PARATHYROID ADENOMA PRESENTING AS MULTIPLE BROWN TUMORS AND SEVERE ASYMPTOMATIC HYPERCALCEMIA.

Introduction: Primary hyperparathyroidism may have several presentations, varying from an incidental asymptomatic biochemical finding to gastrointestinal, psychiatric, renal and bone manifestations. Brown tumors are rare non-neoplastic lesions because of abnormal bone metabolism. Herein, we describe a patient who presented with lytic bony lesions and severe asymptomatic hypercalcemia due to parathyroid adenoma. Case presentation: A 38-year-old male presented with multiple painful bony lesions over upper and lower limbs. Radiographs of long bones showed multiple lytic lesions with cortical thinning. Investigations revealed hypercalcemia and hyperparathyroidism. A radionuclide scan showed parathyroid adenoma. The patient was treated for hypercalcemia and a parathyroidectomy was performed. Conclusions: In a patient presenting with multiple bony swellings and asymptomatic hypercalcemia, hyperparathyroidism should be suspected. Parathyroid adenoma is a treatable cause of primary hyperparathyroidism.