CONTEXT: Parathyroid carcinoma (PC) is a rare endocrine malignancy with no approved systemic therapies for unresectable locally invasive or distant metastatic disease. Understanding the molecular changes in advanced PC can provide better understanding of this disease and potentially help directing targeted therapy.
OBJECTIVE: To evaluate tumor-specific genetic changes using next-generation sequencing (NGS) panels.
DESIGN: All patients with advanced PC were tested for hot-spot panels using NGS panels including a 50-gene panel, a 409-gene panel if the standard 50-gene panel (Ion Torrent, Life Technology) was negative or a FoundationOne panel.
SETTING: The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
PATIENTS OR OTHER PARTICIPANTS: 11 patients with advanced PC were selected to undergo molecular testing.
MAIN OUTCOME MEASURE(S): Genetic profiles of advanced PC.
RESULTS: Among the 11 patients, 4 patients had the 50-gene panel only, 6 had 409-gene panel after a negative 50-gene panel and 1 had FoundationOne. One patient who had 50-gene panel only also had his metastatic site (esophagus) of his tumor tested with FoundationOne. The most common mutations identified were in the PI3 K (PIK3CA, TSC1 and ATM) (4/11 patients) and TP53 (3/11) pathways. Genes not previously reported to be mutated in PC included: SDHA, TERT promoter and DICER1. Actionable mutations were found in 54% (6/11) of the patients.
CONCLUSIONS: Mutational profiling using NGS panels in advanced PC has yielded important potentially targetable genetic alterations. Larger studies are needed to identify commonly mutated genes in advanced PC patients. Development of novel therapies targeting these cellular pathways should be considered.

RATIONALE: Secondary hyperparathyroidism (SHPT) is often complicated with chronic renal failure. Though the total parathyroidectomy (TPTX) with forearm autotransplantation (FAT) has been commonly used to treatment refractory renal SHPT, the recurrence of SHPT is not infrequent, resulting from hyperplastic autograft, remnant parathyroid tissues, and supernumerary parathyroid gland (SPG).
PATIENT CONCERNS: A 67-year-old man undergoing TPTX+FAT 4 years previously for renal SHPT, who received regular hemodialysis with active vitamin D supplements of Rocaltrol treatment postoperatively, was admitted to our hospital with progressively elevated serum intact parathyroid hormone (iPTH) from 176 to 1266 pg/mL for 8 months and bilateral ankle joints pain for 1 month. Tc-sestamibi dual-phase imaging with single positron emission tomography (SPECT)/computed tomography (CT) revealed a nodule in suprasternal fossa, besides a nodule in autografted site, accompanied with intense radioactivity.
DIAGNOSIS: Recurrent SHPT was easily diagnosed based on previous medical history, painful joints, increased serum iPTH level and positive findings of Tc-sestamibi imaging. Routine postoperative pathology showed that the nodules were consistent with an adenomatoid hyperplasic autograft and a supernumerary parathyroid adenoma in suprasternal fossa, respectively.
INTERVENTIONS: Reoperation for removing nodules in suprasternal fossa and autografted site was performed 1 month later. Then regular hemodialysis 3 times a week with Rocaltrol was continued.
OUTCOMES: During 12 months of follow-up, the joints pain improved obviously and the serum iPTH level ranged from 30.1 to 442 pg/mL.
LESSONS: Although rare, recurrent renal SHPT may be caused by a coexistence of both hyperfunctional autograft and SPG after TPTX+FAT. The Tc-sestamibi parathyroid imaging with SPECT/CT is helpful to locate the culprits of recurrent renal SHPT before reoperation. To prevent recurrence of renal SHPT, the present initial surgical procedures should be further optimized in patient on permanent hemodialysis.

Localization of parathyroid adenomas for treatment of primary hyperparathyroidism can be challenging. This retrospective study compared single-photon emission computed tomography/computed tomography (SPECT/CT), 4D-CT, and US studies in detection of adenomas prior to surgery. A retrospective chart review was performed on all consecutive patients with parathyroid adenoma presenting to an urban tertiary care medical center. A total of 58 patients (45 female, 13 male) underwent surgery for parathyroid adenoma. Patients aged 28 to 80 years (mean: 58.8) with parathyroid hormone levels ranging from 42 to 424 pg/mL (mean: 168). All patients underwent preoperative SPECT/CT with 20 mCi technetium-99m MIBI (

Parathyroid carcinoma (PC) is an uncommon cause of primary hyperparathyroidism (pHPT). The tumor is mostly functioning with following high serum calcium and parathyroid hormone (PTH) levels. Consideration of PC in differential diagnosis of pHPT is important because the mortality and the prognosis depend on early recognition and surgical approach. A case of PC in 51-year old female patient with persistent pHPT is reported. A patient, referred with anterior cervical hematoma, dysphagia, underwent neck ultrasound, barium X-ray swallow test and neck computed tomography. On the posterior surface of left thyroid lobe, close to the esophagus the heterogenic lesion with irregular margins was found. The preoperative calcemia was slightly elevated. The patient underwent cervical exploration with parathyroidectomy. Histological exam showed parathyroid lesion with immunohistochemical confirmation of PC. After 2 months follow-up there are no signs of a residual-recurrent disease. Although laboratory tests revealed pHPT preoperatively, no clinical effects of elevated calcium and PTH concentration levels were presented. As histological features are not specific for the differential diagnosis between the parathyroid adenoma and PC, the immunohistochemistry remains the only useful tool for the definite diagnosis.

PURPOSE: Preoperative localization of a parathyroid adenoma is usually obtained by the combination of ultrasound and scintigraphy with technetium-99m methoxyisobutylisonitrile. We evaluated the role of F18-fluorocholine in neck positron emission tomography/magnetic resonance imaging as a novel tool for localizing parathyroid adenomas.
METHODS: Patients with primary hyperparathyroidism were recruited from February 2016 to August 2017 and F18-fluorocholine positron emission tomography/magnetic resonance imaging was performed to localize the parathyroid adenoma prior to surgery. We compared sensitivity and accuracy of this modality with ultrasound and technetium-99m methoxyisobutylisonitrile scintigraphy using the verified location of the diseased parathyroid as found in surgery.
RESULTS: Nineteen patients were included in our study (15 women and 4 men, mean age 60.5 ± 9.8 years). Positron emission tomography/magnetic resonance imaging precisely localized the pathologic parathyroid gland in 16/19 cases (84.2%) and predicted the diseased side in 19/19 cases (100%). Ultrasound and technetium 99 m methoxyisobutylisonitrile sestamibi scintigraphy predicted the location of the parathyroid adenoma in 16/19 (84.2%) and 14/19 (74%), respectively. In 3/19 patients, positron emission tomography/magnetic resonance imaging localized the parathyroid adenoma where as other modalities failed. Positron emission tomography/magnetic resonance imaging was more accurate when compared to each modality separately (p < 0.001, p = 0.017), however, when comparing the three modalities all together no differences were found (p = 0.506).
CONCLUSIONS: Localizing parathyroid adenomas with F18-fluorocholine positron emission tomography/magnetic resonance imaging may be a promising secondary imaging modality.

PURPOSE: To describe CT features of parathyroid carcinomas (PCs) by comparison with benign parathyroid lesions (BPs).
METHODS: This retrospective study comprised 82 patients with 76 BPs (62 adenomas and 14 hyperplastic lesions) and 6 PCs. CT features (size, short-to-long axis ratio, shape, peritumoral infiltration, homogeneity, calcification, attenuation values on unenhanced CT, and contrast enhancement during arterial and venous phases) were compared between PCs and BPs. The diagnostic performance of CT features for diagnosing PCs was calculated for these individual parameters.
RESULTS: Short-to-long axis ratio was significantly larger in PCs (0.7 ± 0.1) than in BPs (0.5 ± 0.1, p = 0.004). Irregular shape (33%), the presence of peritumoral infiltration (50%), and calcification (33%) were significantly more common in PCs than BPs. The contrast enhancement value was significantly lower in PCs than BPs during arterial (p = 0.004) and venous phases (p = 0.044). The 100% sensitivity criterion for the short-to-long axis ratio (≥ 0.53), enhancement during arterial phase (≤ 56.6HU), and venous phase (≤ 59.5HU) yielded accuracies (62.1%, 71.9%, and 75.4%, respectively). Irregular shape, peritumoral infiltration, and calcification showed high specificity (98.7%) and accuracy (93.9%, 95.1%, and 93.9%, respectively).
CONCLUSIONS: CT features of high short-to-long axis ratio, irregular shape, the presence of peritumoral infiltration and calcification, and low contrast enhancement may aid in distinguishing PCs from BPs.

BACKGROUND Primary hyperparathyroidism is an endocrine disease characterized by excessive secretion of parathyroid hormone and hypercalcemia. Although scintigraphy is commonly used for pre-operative localization, it does not always localize the parathyroid lesion. In such patients, ultrasonography can visualize the suspected lesion and needle washout sample for parathyroid hormone titer can be used to confirm parathyroid tissue. The aim of this study was to investigate the accuracy of the parathyroid hormone needle aspiration washout method in detecting the localization of parathyroid adenoma. MATERIAL AND METHODS Patients with primary hyperparathyroidism who underwent surgery between 2010 and 2017 at the Dicle University Medical Faculty Hospital were retrospectively evaluated using medical records. Patients undergoing parathyroid hormone needle aspiration washout were performed in the suspected lesion were included in the study. Accompanied by ultrasonography, the suspected area was penetrated with needle, and negative aspiration was performed. Pre-operative scintigraphic data of patients were evaluated. Patients with positive scintigraphy, negative scintigraphy or patients who did not undergo scintigraphy were included in our study. Demographic data were presented as continuous data means ± standard deviation. Categorical variables were presented as frequency and percentage. RESULTS Forty-nine patients (female/male, 40/9) who underwent parathyroid hormone needle aspiration washout were included in the study. Parathyroid hormone washout result was positive in 47 patients (47/49) and negative in 2 patients (2/49), sensitivity/positive predictive value (PPV) 95.91%. Twenty-six patients who had negative/suspicious scintigraphic results were diagnosed using the parathyroid hormone needle aspiration washout method (24/26, 92.3% accuracy). Parathyroid hormone needle aspiration washout without scintigraphy was performed in 13 patients (13/13, 100% accuracy). CONCLUSIONS Parathyroid adenoma localization can be easily done using parathyroid hormone needle aspiration washout in centers experienced in adenoma localization in primary hyperparathyroidism cases in which scintigraphic results are negative or scintigraphy cannot be performed. We believe that primary parathyroid hormone needle aspiration washout can be a new localization method for adenoma localization.

PURPOSE: The aim of this study was to assess the feasibility of four-dimensional magnetic resonance imaging (4D MRI) at 3 T for the localization of parathyroid adenomas.
MATERIALS AND METHODS: Preoperative 4D MRI scans, encompassing dynamic contrast-enhanced (DCE) sequences and non-contrast enhanced (non-CE) sequences, including a T2-weighted multipoint Dixon (T2-mDixon) sequence, with in-phase, out-phase, and water-only images, were evaluated retrospectively in 41 patients with surgically proven parathyroid lesions. Two readers who were blinded to the surgical findings independently reviewed the images in two sessions (non-CE sequences alone and non-CE + DCE sequences). The MRI localization of the suspected adenoma in each session and the consensus interpretation of the MRI images, were compared with the surgical results and interobserver agreement was assessed.
RESULTS: By interpreting the non-CE sequences alone, reader 1 correctly localized 34 parathyroid lesions (sensitivity 81.0%, positive predictive value (PPV) 87.2%), and reader 2 correctly localized 34 parathyroid lesions (sensitivity 81.0%, PPV 91.9%). With the addition of DCE sequences, reader 1 correctly identified 35 parathyroid lesions (sensitivity 83.3%, PPV 87.5%), while reader 2 correctly identified 36 parathyroid lesions (sensitivity 85.7%, PPV 92.3%). Overall, MRI detected 38 parathyroid lesions (sensitivity 90.5%, PPV 95.0%). Interobserver agreement was slightly superior in non-CE + DCE sequences compared to non-CE sequences alone (ĸ = 0.796 vs. ĸ = 0.738).
CONCLUSION: 4D MRI with DCE sequencing is a reliable method for the localization of parathyroid adenomas.

Ectopic parathyroid are most frequently found in the anterior mediastinum, in association with the thymus or the thyroid gland. Ectopic parathyroid glands are a major cause of persistent and recurrent Hyperparathyroidism. We report a case of 65-year-old female was referred from Surgical Endocrine department to the department of Cardiac Surgery on 20 September, 2017 in Bangabandhu Sheikh Mujib Medical University with parathyroid crisis due to an ectopic mediastinal parathyroid adenoma with her serum calcium and PTH markedly increased in short time. Computed tomography of the chest and lower neck showed an ovoid soft tissue density area measuring about 25×20×15mm in the anterior mediastinum. Technetium-99m-sestamibi (MIBI) scintigraphy scan showed positive and detected localized parathyroid adenoma/hyperplasia in superior mediastinum. Ectopic parathyroid adenoma resection was performed via median sternotomy approach. But after 4 hours patient developed the color change of the left arm due to acute left upper limb ischemia of unknown cause for which the patient was rushed to operation theatre suspecting it to be embolic occlusion and managed by both surgical and medical therapy.

RATIONALE: Cystic parathyroid adenomas are rare and seldom arise in ectopically located glands which may be found within the carotid sheath, mediastinum, thymus, or thyroid grand. They cannot be detected consistently by any imaging methods. Unusual symptoms may bring about certain pitfalls and difficulties for the diagnosis of primary hyperparathyroidism (PHPT) caused by cystic parathyroid adenomas. Until now, there are no specific guidelines on the management of cystic ectopic intrathyroidal parathyroid adenoma (ETPA).
PATIENT CONCERNS: An 82-year-old male musician presented abrupt thyroid enlargement, hoarseness, and trachea compression when he was playing the clarinet. Thyroid and renal function tests were normal. Serum-free calcium and parathyroid hormone (PTH) were in high concentration. Thyroid ultrasonography (US) detected a giant and cystic nodule within right thyroid lobe, which is the very image of cystic nodular goiter. Parathyroid US was negative. The cystic nodule had a decreasing radioactive uptake of Technetium-99m-methoxyisobutylisonitrile (Tc-MIBI). At patient's request, the invasive fine-needle aspiration (FNA) was not conducted.
DIAGNOSES: The patient was initially diagnosed as cystic nodular goiter and inconclusive PHPT.
INTERVENTIONS: Enucleation of solitary cystic intrathyroidal nodule was conducted.
OUTCOMES: The cystic nodule strongly resembled a nodular goiter grossly, but it was proved cystic ETPA by histopathology. Postoperative follow-ups found that serum-free calcium and PTH decreased sharply into normal range, and hoarseness and trachea displacement were obviously improved.
LESSONS: The diagnosis of cystic ETPA is easily overlooked for its rarity. Diagnostic pitfalls, including atypical symptoms, inconclusive imaging manifestation, and unidentified gross specimen, are highlighted. They make the diagnosis of PHPT caused by cystic ETPA challenging. Patients would rather choose surgical excision directly than invasive FNA. Acute hemorrhage of the preexisting ETPA may account for the cystic degeneration.

RATIONALE: Spontaneous anterior cervical or mediastinal hemorrhage is a rare presentation of parathyroid adenoma.
PATIENT CONCERNS: A 69-year-old woman presented with neck hematoma and dysphagia and was found to have a soft tissue mass adjacent to her thyroid gland as seen on MRI and neck ultrasound.
DIAGNOSIS: Laboratory testing demonstrated elevated calcium and parathyroid hormone supporting diagnosis of parathyroid adenoma.
INTERVENTIONS: She underwent right inferior parathyroidectomy and en bloc right hemithyroidectomy due to significant fibrosis.
OUTCOMES: Pathology confirmed hypercellular parathyroid and normal thyroid tissue. Postoperatively, patient's calcium and parathyroid hormone levels had normalized.
LESSONS: In conclusion, imaging may not always be specific in identifying the source of neck hematoma and so laboratory studies should be done to rule out parathyroid adenoma as the underlying etiology.

RATIONALE: Primary hyperparathyroidism, usually as a result of a hyperfunctioning parathyroid gland, represents more than 90% cases of patients evaluated for hypercalcemia. Combined techniques of preoperative scintigraphy and SPECT/CT serve as a successful minimally-invasive parathyroidectomy. This recent imaging method provides four-dimensional functional images with advanced contrast resolution which greatly facilitates preoperative localization of parathyroid adenomas.
PATIENT CONCERNS: We presented the case of a male Caucasian patient, aged 67 years, who was investigated for hypercalcemia. Increased levels of parathormone, cervical ultrasonography without pathological changes, and negative planar parathyroid scintigraphy have led to the performance of a parathyroid scintigraphy combined with SPECT/CT.
DIAGNOSES: The diagnosis of right inferior parathyroid adenoma was confirmed by the 99mTc-MIBI-SPECT/CT that revealed on early phase increased radiotracer uptake in the area of projection of the lower third of the right thyroid lobe. The SPECT/CT scan localized this area behind the lower pole of the right thyroid lobe, in the right side of the trachea, with CT correspondent of hypodense lesion, with a maximum diameter of 20 mm.
INTERVENTIONS: During hospitalization, the decision to undergo surgical intervention was taken. The patient underwent surgical intervention, and minimally-invasive right inferior parathyroidectomy was performed.
OUTCOMES: The histopathological examination confirmed the diagnosis and the patient's recovery was complete, with the normalization of parathormone, calcium levels, and metabolic parameters.
LESSONS: Modern combined techniques of scintigraphy and SPECT/CT proved to be of excellent clinical utility in the preoperative diagnosis of primary hyperparathyroidism, localizing a parathyroid tumor undetected by planar scintigraphy alone.

Parathyroid carcinoma (PC) is a rare endocrine malignancy, accounting for <1% of all cases of sporadic primary hyperparathyroidism (PHPT) and up to 15% in the hereditary hyperparathyroidism-jaw tumor syndrome. Genomic alterations identified in PC are mostly represented by CDC73 gene mutations, codifying for a loss-of-function protein termed parafibromin. Whole exome sequencing identified mutations in other genes, such as mTOR, KMT2D, CDKN2C, THRAP3, PIK3CA, and EZH2 genes, CCND1 gene amplification. The diagnosis of PC is quite difficult due to the lack of reliable clinical diagnostic criteria, and in the majority of cases is made postoperatively at histological examination. The clinical manifestations of PC are primarily due to the excessive secretion of PTH by the tumor rather than spread to local or distant organs. En bloc resection of the parathyroid tumor represents the initial mainstay treatment of patients with PC. Multiple surgical procedures may be required, although surgical morbidity should be taken into account. A 5- and 10-year survival between 77-100 and 49-91%, respectively, has been reported. When the tumor is no more resectable, medical treatment of hypercalcemia has a pivotal role in the management of these patients.

BACKGROUND Primary hyperparathyroidism is most common in women during the menopause and its occurrence in pregnant women is rare. However, because neonatal mortality is associated with maternal hyperparathyroidism, early diagnosis is essential. This report describes the case of a late diagnosis of primary hyperparathyroidism in a 28-year-old pregnant woman and describes the effects on the mother and neonate. CASE REPORT During her second pregnancy, a 28-year-old woman presented with symptoms of general weakness, bone and joint pain, multiple fractures with bone deformity, muscle weakness, and gait disturbance. Due to the high risk of perinatal pathology, a cesarean section was performed. Several weeks later, she underwent thoracoscopic removal of an ectopic parathyroid gland located at the aortic arch. Hypocalcemia in the newborn infant required treatment with calcium and magnesium supplements. CONCLUSIONS This case demonstrates that primary hyperparathyroidism during pregnancy requires timely diagnosis and treatment to reduce potential maternal and fetal complications. Screening for primary hyperparathyroidism should be undertaken in pregnant women with any symptoms associated with hypercalcemia. Treatment should be individualized and includes conservative management, parathyroidectomy in the second trimester, or parathyroidectomy performed in the early postpartum period.

Paediatric hypercalcaemia is a rare condition which can be easily overlooked or misdiagnosed. We report two paediatric patients who presented to the Department of Paediatrics, Pardubice Hospital, Pardubice, Czech Republic, in 2009 and 2010, respectively. Each patient was diagnosed with hypercalcaemia due to a different cause. The first case involved a seven-month-old infant who presented with failure to thrive, vomiting and psychomotor retardation. Fluorescent

Parathyroid carcinoma (PC) is a rare malignancy, presenting sporadically or as part of a genetic syndrome. Diagnosis of PC includes the histopathological diagnosis based on capsular, perineural, or vascular invasion or metastasis. High suspicion for malignancy includes hypercalcaemia greater than 14 mg/dL, extremely high serum parathyroid hormone (PTH) levels, as well as large masses. Given the rarity of PC, it is challenging to design clinical trials for newer therapy. Currently, complete initial surgical excision of the tumour in high-risk patients offers the best chance of cure and prolonged disease-free survival in PC. In the absence of definite data, non-surgical therapies such as radiation and chemotherapy are not routinely recommended. For early detection of recurrence; long-term clinical follow-up with interval measurements of serum calcium and PTH is recommended. Localising studies of PC are helpful. Early screening for CDC73 mutation and multidisciplinary treatment by an endocrine/ENT/surgical oncology team is recommended.

OBJECTIVE: To investigate the accuracy of dual-tracer scintigraphy for locating parathyroid adenomas in patients with primary hyperparathyroidism (PHPT).
METHODS: We reviewed 268 patients with PHPT. All patients underwent technetium-99m pertechnetate (
RESULTS: The positive and negative predictive values of
CONCLUSIONS: These finding suggest that

Parathyroid carcinoma (PC) is a rare disease with an indolent behavior due to the low malignant potential. The etiology is unknown. Somatic mutations of CDC73 gene, the same gene involved in the hyperparathyroidism-jaw tumor syndrome, can be identified in up to 70% of patients with PC and in one-third of cases the mutations are germline. Therefore, in patients who carry germline CDC73 gene mutations, its finding permits to identify the carriers among relatives and sometimes to early detect a parathyroid lesion in such subjects. The diagnosis of PC is commonly made after surgery, however there are some clinical/biochemical features that should raise the suspicion of PC, namely markedly elevated serum calcium and PTH levels, a large parathyroid lesion with suspected ultrasonographic features of malignancy, the damages of kidney and bones. The best chance of cure is the complete surgical resection with the en-bloc excision at the first operation, however several recurrences are often observed during the follow-up. Since PC is an indolent tumor with long-lasting survival and the death is due to complications of untreatable hypercalcemia, multiple surgical interventions with debulking of tumoral tissues along with medical treatment for reducing hypercalcemia are often needed. Patients with PC should be followed up along their lifetime.

We report a case of 53-year-old woman with the parathyroid adenoma (PA) located in the aortopulmonary window with an aberrant right subclavian artery. Her preoperative calcium level was 11.3 mg/dL (reference range = 8.8-10.6 mg/dL). The parathyroid hormone level was significantly elevated at 127.4 pg/mL (reference range = 12-88 pg/mL) as measured on immunoradiometric assay. Dual-phase technetium-99m-labeled sestamibi parathyroid scintigraphy and fluorine-18 F-fluorocholine positron emission tomography/computed tomography revealed a mediastinal tumor measuring 3 × 5 × 6 mm located anterolateral to the aortopulmonary window. Minimally invasive removal of PA was performed through 3.5-cm reverse J-shaped partial upper sternotomy to the third intercostal space. Postoperative recovery was uneventful, and serum calcium and parathyroid hormone levels normalized within 24 hours of surgery. Our case represents the rare occurrence of a mediastinal PA associated with aberrant right subclavian artery treated with targeted minimally invasive approach using different imaging modalities including technetium-99m-sestamibi scintigraphy and fluorine-18 F-fluorocholine positron emission tomography/computed tomography, and intraoperative use of gamma probe for precise localization PA.

Parathyroid tumors represent an elusive endocrine neoplasia, which lead to primary hyperparathyroidism, pHPT, a common endocrine calcium disorder characterized by hypercalcemia and normal-high parathormone secretion. Parathyroid tumours are benign adenomas or multiple glands hyperplasia in the vast majority (>99% of cases), while malignant neoplasms are rare (less than 1%). Despite pHPT is a common disorder, our knowledge about the genetic predisposition and molecular pathophysiology is limited to the familial syndromic forms of parathyroid tumour, that, however, represent not more than the 10% of all the cases; instead, the pathophysiology of sporadic forms remains an open field, although data about epigenetic mechanisms or private genes have been supposed. Here we present an overview of more recent acquisitions about the genetic causes along with their molecular mechanisms of benign, but also, malignant parathyroid tumours either in sporadic and familial presentation.

OBJECTIVE: The purposes of this study were to describe trends in parathyroid imaging utilization and to compare the sensitivities of sonography, scintigraphy, and 4-dimensional computed tomography (4DCT) in different imaging algorithms.
METHODS: A retrospective review of consecutive patients who underwent parathyroid surgery from 2009 to 2014 was performed. Utilization and accuracy were compared for sonography, scintigraphy, and 4DCT.
RESULTS: The study population was composed of 604 patients with 850 adenomas or hyperplastic glands. Sonography was the most common imaging modality, performed in 91.2% (551/604) of patients. The utilization of 4DCT increased in the study period from 1.5% (2/133) in 2009-2010 to 75.8% (72/95) in 2013-2014 (P < 0.01). The overall sensitivities of sonography, scintigraphy, and 4DCT, regardless of order of imaging or imaging algorithm, were 58.6% (456/778), 49.1% (317/645), and 82.3% (121/147), respectively (P < 0.01).
CONCLUSIONS: Four-dimensional CT has the highest sensitivity for localization of parathyroid adenomas regardless of order of imaging or imaging algorithm.

BACKGROUND AND OBJECTIVES: The accurate identification of hyper functioning parathyroid gland is needed for definitive surgical treatment in primary hyperparathyroidism. Ultrasonography and 99mTechnetium sestamibi scintigraphy are the two most used methods with varying sensitivities. This study aimed to assess the value of parathyroid hormone (PTH) assay in preoperative ultrasound guided fine needle aspiration (FNA)-PTH washout fluid to verify the correct localisation of lesions with negative or inconclusive scintigraphy results.
METHODS: We evaluated data of 28 lesions in 21 patients who underwent US-guided parathyroid fine-needle aspiration (FNA) with PTH washout, retrospectively. The PTH washout results and the reports of parathyroid surgery and imaging studies were reviewed.
RESULTS: Of operated 28 lesions 23 had positive and 5 had negative washout results. The median FNA-PTH washout was 2315.5 pg/ ml (min-max: 12.3-6978 pg/ ml). The calculated sensitivity of FNA-PTH washout was 85.7% and the specifity was 28.6%. The positive and negative predictive values were 78.3% and 40.0%, respectively.
CONCLUSIONS: FNA-PTH can be used to establish the nature of the lesion, discriminate parathyroid gland from thyroid lesions or cervical lymph nodes, improving the surgical outcomes. It can be used to localise parathyroid lesions preoperatively when negative or discordant ultrasound and scintigraphy findings are obtained.

In addition to nuclear cardiac and breast imaging, Tc-sestamibi scintigraphy is often used to localize parathyroid adenomas. F- fluorodeoxyglucose (FDG) PET is heavily utilized in oncology, although its use in identifying parathyroid adenomas is limited. We describe a case of a 57-year-old woman who underwent parathyroid scintigraphy and F-FDG PET/CT in the same week due to hyperparathyroidism and an enlarging breast mass, respectively. A right paratracheal mediastinal mass that otherwise would be suspicious for nodal metastases by CT alone was correctly identified to be an ectopic parathyroid adenoma using a combination of the nuclear medicine studies performed.

BACKGROUND Solitary parathyroid adenomas are the leading cause of primary hyperparathyroidism in 0% to 85% of cases. Diagnosis of parathyroid adenoma is based on typical clinical presentation of hypercalcemia, biochemical profile, and modern imaging studies. The purpose of this article is to present the diagnostic and therapeutic approach used for a 73-year-old female patient with a giant parathyroid adenoma measuring 5×2.5×2.5 cm and weighing 30 grams. CASE REPORT A 73-year-old female was referred to the outpatient clinic of our Surgical Department with the diagnosis of primary hyperparathyroidism. The patient suffered from typical symptoms of hypercalcemia such as weakness, bone disease, and recurrent nephrolithiasis; she had a painless cervical mass for 5 months. Primary hyperparathyroidism was confirmed based on the patient's biochemical profile, which showed increased levels of serum calcium and parathyroid hormone. SestaMIBI scintigraphy with 99mTechnetium and cervical ultrasonography revealed a large nodule at the inferior pole of the right lobe of the thyroid gland. Intraoperatively, a giant parathyroid adenoma was found and excised. Additionally, levels of intact parathyroid hormone (IOiPTH) were determined intraoperatively and a 95% reduction was found, 20 minutes after the removal of the adenoma. CONCLUSIONS This is an extremely rare case of a giant solitary parathyroid adenoma. Diagnosis of a giant hyperfunctioning solitary parathyroid adenomas was based on clinical presentation, biochemical profile, and imaging studies. Selective treatment was based on surgical excision combined with IOiPTH levels measurement.

BACKGROUND: Accurate localization of parathyroid adenomas is of critical importance in surgical planning for minimally invasive parathyroidectomy. SPECT/CT is considered the investigation of choice but has limitations regarding localization of superior versus inferior adenomas. We proposed a novel method for localization using SPECT/CT by determining the anterior-posterior relationship of the adenoma to a horizontal line in the coronal plane through the tracheoesophageal groove. Our objective was to determine the accuracy, validity, and inter-rater reliability of this method.
METHOD: This was a retrospective review of patients who underwent parathyroidectomy for a single adenoma between 2010-2017. SPECT/CT images were reviewed by two staff Otolaryngologists, a Radiologist, an Otolaryngology fellow and Otolaryngology resident. Results were compared using intra-operative report as the gold standard. Overall accuracy in determining superior/inferior and right/left adenomas was calculated, as well as Cohen's Kappa to determine agreement with operative report and inter-rater reliability. The performance was compared to that of the original radiology report.
RESULTS: One hundred thirty patients met criteria and were included. Our method correctly identified the location of the adenoma in terms of both side and superior/inferior position in 80.4% [76 - 84%] of patients, which considerably outperformed the original radiology report at 48.5% [4-78%] accuracy. The agreement level between our method and operative report was high (Kappa=0.717 [0.691-0.743]), as was the inter-rater reliability (Kappa=0.706 [0.674-0.738]).
CONCLUSION: We report a novel method for localization of parathyroid adenomas using SPECT/CT which outperforms standard radiology reporting. This tool can be used by surgeons and radiologists to better inform and plan for minimally invasive parathyroidectomy.

Parathyroid carcinoma (PC) is a rare endocrine malignancy. Surgical resection is curative for local lesions, while effective therapies are lacking for recurrent or metastatic PCs. To study whether targeted therapies could be applied in recurrent or metastatic PCs, potential therapeutic targets were identified with next-generation sequencing (NGS). DNA was extracted from formalin-fixed, paraffin-embedded (FFPE) sections from 19 recurrent or metastatic PC samples. A panel of 560 genes was sequenced with NGS to identify genomic alterations at an average sequencing depth of 581×. In total, 190 genomic alterations were identified. Nine PC samples (47%) harbored at least one potentially actionable genomic alteration including in the after genes: ROS1 (5/19; 26%), PTEN (3/19; 16%), TSC1 (2/19; 11%), PIK3CA (1/19; 5%), AKT1 (1/19; 5%), MTOR (1/19; 5%), ERBB2 (1/19; 5%), NTRK1 (1/19; 5%), IDH1 (1/19; 5%) and FGFR3 (1/19; 5%). CDC73 mutations were detected in 9/19 (47%) PC samples. Additional recurrent genomic alterations were identified in MSH2 (15/19; 79%), AR (9/19; 47%), BCR (8/19; 42%), SLC45A3 (6/19; 32%), MAGI1 (5/19; 26%), ZNF521 (4/19; 21%), KMT2C (4/19; 21%) and NOTCH4 (4/19; 21%). Our study identified a relatively high frequency of potentially actionable genomic alterations in PC patients in a Chinese population for the first time. A series of recurrent mutant genes was detected as well. Our study contributes to both the selection of novel targeted therapies for PC and further molecular understanding of this refractory malignancy.

Hyperparathyroidism, commonly observed in asymptomatic middle-aged women, with mild hypercalcemia, is usually caused by a benign adenoma. Some cases present with more severe manifestation and greater hypercalcemia. Within this spectrum, several familial/genetic associations have been discovered. While the majority are caused by benign disease, adenomas, or hyperplasia, a small proportion (< 1%) are associated with malignant tumors and present with more severe symptoms. Although usually sporadic, recent reports document various gene mutations that strongly predispose to the development of parathyroid carcinoma. An increasing number of cases of hyperparathyroidism, benign or malignant, require and benefit from genetic analysis. We describe a 25-year-old male with hyperparathyroidism presenting with a pathological fracture, brown tumors, hypercalcemia, and markedly elevated parathyroid hormone levels. There was no family history of hyperparathyroidism or jaw tumors. Surgical removal revealed a single large tumor confirmed to be malignant. Immunohistochemical analysis revealed the absence of parafibromin and decreased APC (adenomatosis polyposis coli) expression. Genetic analysis revealed a rare germline nonsense mutation (R76X) in the parafibromin gene, HRPT2/CDC73. Parathyroid carcinoma should be suspected as a cause of hyperparathyroidism when clinical manifestations are severe, particularly in young individuals, < 59 years. Immunohistochemistry may lead to suspicion for a germline mutation as a significant contributor despite absence of a family history. The discovery of a germline mutation in parathyroid carcinoma alters the clinical management of the index case and that of family members. Long-term follow-up studies of such patients are necessary to develop evidence-based clinical guidelines.

AIM: Aim of this study was to firstly describe reproducible, objective perfusion parameters of contrast-enhanced ultrasound (CEUS) kinetics of parathyroid gland adenoma (PA) using perfusion analysis software (VueBox®, Bracco, Italy). Thereby the efficiency of quantitative CEUS for characterization of PA should be evaluated comparing US to postoperative histopathological findings after PA resection.
MATERIAL AND METHODS: 42 patients with symptoms/lab work suggestive of pHPT presented a parathyroid gland lesion in B-mode US, which was consequently analyzed by dynamic CEUS. CEUS was performed by one experienced examiner after i.v.-injection of max. 2.4 ml sulphurhexaflouride microbubbles saving digital DICOM cine loops (up to 25 s) and images. PA were evaluated during arterial, venous and late phase (up to 3 min.) for perfusion characterization. A retrospective, blinded VueBox® perfusion analysis of arterial phase of 28/42 PA was performed by a second, independent examiner placing 3 ROIs manually in the PA (center, rim of PA, surrounding thyroid gland tissue) to objectify findings. US findings were correlated to postoperative histology after PA resection.
RESULTS: Out of 42 patients with PA findings in CEUS, perfusion analysis could be performed in 28/42 cases only as some CEUS cine loops had too much moving. In three cases the second examiner could not detect PA retrospectively, in 25 cases PA were characterized correctly resulting in a sensitivity rate of 89.3 %. VueBox® perfusion analysis confirmed that PA present a persisting hypervascularization of the rim with higher TTP (mean 7.93 s centrally, 8.36 s rim-sided), mTT (mean 56.6 s centrally, 64.5 s rim-sided) and lower PE (mean 10542.93 rm2 centrally, 8909.21 rm2 rim-sided) peripherally followed by a central wash-out during later phases. RT was comparable in all defined regions.
CONCLUSION: VueBox® analysis of parathyroid gland CEUS examinations seemed to be a valuable tool for quantification of a PA's perfusion and can help to detect and localize hyperfunctional parathyroid glands prior to surgery.