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Mitochondrial DNA (mtDNA) variations have been implicated in various cancer types. Several attempts have been made in benign parathyroid adenoma (PA); however, mtDNA variants and copy number alterations have not been investigated in parathyroid carcinoma (PC). The present study aimed to explore the variations in the mitochondrial genome in parathyroid neoplasms. In this study, ultradeep targeted sequencing of mtDNA was performed in 12 cases with PC and 25 cases with PA. Germline and somatic variants in the mitochondrial genome were analysed according to clinical features. The mtDNA copy number relative to nuclear DNA was measured. A total of 821 germline variants and 23 somatic mutations were identified. All 160 germline nonsynonymous variants in the coding sequence (CDS) were predicted to be likely benign, and germline variants frequently occurred (26.3%) in the displacement loop region. Tumour somatic mutation in a CDS with heteroplasmic factor (HF) >0.8 showed a higher mtDNA copy number (p = 0.039). Using Spearman’s rank test, tumour mtDNA copy number revealed a positive correlation with serum levels of intact parathyroid hormone and calcium. Our results demonstrate that null recurrent mtDNA mutational hotspots were PC specific. An increased mtDNA copy number in parathyroid neoplasms was associated with somatic CDS mutations with a high HF and major clinical features. Larger cohort investigations should be performed in future analyses.

Background Hyperparathyroidism is caused by parathyroid adenoma, hyperplasia or carcinoma. Parathyroid adenomas are the most common cause of parathyroid disease (85-88%) while atypical parathyroid adenomas and carcinomas are the least frequently seen parathyroid neoplasms which cause diagnostic difficulty. This series aims to identifiy lesions of parathyroidectomy specimens in our center and draw attention to borderline cases in between parathyroid adenoma and carcinoma. Methods 638 parathyroidectomy materials diagnosed in our center between the years 2005 and 2016 were examined retrospectively and all were included in the study. Results In all the 638 parathyroidectomy cases evaluated, 427 were diagnosed with adenoma, 117 with hyperplasia, 54 with normal parathyroid tissue, 32 with parathyroid neoplasm with uncertain malignant potential, 7 with parathyroid carcinoma and 1 with normal thyroid tissue. Conclusions Parathyroid neoplasm with uncertain malignant potential defines cases with suspicious histopathological features of carcinoma but doesn't meet the criteria for parathyroid carcinoma. In our series, these cases are identified as atypical parathyroid adenoma. We present clinical and morphological features of our parathyroidectomy cases in an 11-year period and aim to raise concern about borderline cases in between adenoma and carcinoma. We think that such tumors, similar to the thyroid neoplasm classification, should be defined as parathyroid neoplasms with uncertain malignant potential and should be followed closely.

Discriminating thyroid and parathyroid lesions may sometimes pose a diagnostic difficulty. Medullary thyroid carcinomas (MTCs) display various cytologic and architectural features that resemble other thyroid and even rarely some parathyroid neoplasms. Moreover, some MTCs may have negative serum calcitonin, rendering them difficult to diagnose. Hence, to reach an appropriate diagnosis in problematic cases of these three categories – thyroid lesions, MTC and parathyroid lesions – the use of several immunohistochemical panels has been suggested and applied. However, conventional markers are not always conclusive in problematic cases. Thus, in the current study we aim to evaluate the diagnostic utility of using GATA3 and INSM1 (insulinoma-associated protein 1) as novel nuclear markers to be applied as an adjunct in case of histopathologic suspicion. A retrospective study was carried out on samples of lesions from three groups: group 1: thyroid lesions (27), group 2: medullary thyroid carcinoma (25); 1/25 had negative serum levels of calcitonin, and group 3: parathyroid lesions (36). Biopsies were received at the Pathology Laboratory of Ain Shams University Hospitals. INSM1 showed 98% diagnostic accuracy in diagnosing MTC and differentiating it from other thyroid lesions. The case of MTC with negative serum calcitonin showed positive INSM1 staining. GATA3 showed 96.8% diagnostic accuracy in diagnosing parathyroid lesions and differentiating them from thyroid lesions. Using immunohistochemical staining by GATA3 and INSM1, in the appropriate histopathological setting, significantly aids in the differentiation between thyroid lesions, parathyroid lesions and MTCs. INSM1 could serve as a potential diagnostic marker in the rare cases of non-secretory MTC and in metastatic work up.

Introduction Ectopic calcification is associated with secondary hyperparathyroidism (HPT) in patients with end-stage renal failure (ESRD). Metastatic pulmonary calcification (MPC) is another rare type of ectopic calcification, and there are a few reports on MPC in dialysis patients. Case presentation We report the case of a 52-year-old woman admitted with general fatigue and appetite loss, who was on peritoneal dialysis (PD) for 7 years. Although she was initially suspected of having secondary HPT due to ESRD, we finally diagnosed ectopic HPT that was caused by a cystic mass behind her thyroid gland overlapping with secondary HPT. We carefully observed her under conservative therapy because she refused surgery. On admission, she was diagnosed as having MPC because she had ground-glass-like opacification in her lung fields on high-resolution computed tomography scan, which was caused by a parathyroid tumor complicated by secondary HPT associated with ESRD. After she began intravenous injection of etelcalcetide hydrochloride, serum calcium, and intact parathyroid hormone (iPTH), values were adjusted, and the opacification disappeared. Conclusion In a patient on PD, this is the first case of MPC that developed due to acute hypercalcemia, hyperphosphatemia, and dehydration and in which the ectopic pulmonary calcification clearly decreased with optimization of iPTH.

Parathyroid carcinoma is a rare malignant disease that presents as a sporadic or familial primary hyperparathyroidism (PHP). The latter is associated with some genetic syndromes. It occurs with equal frequency in both sexes, unlike PHP caused by parathyroid adenoma that is more common in women. It should be suspected in cases of severe hypercalcemia, with high parathyroid hormone levels and a palpable cervical mass. Given the difficulty in distinguishing between parathyroid carcinoma and adenoma prior to the surgery, the diagnosis is often made after parathyroidectomy. The only curative treatment is complete surgical resection with oncologic block resection of the primary tumor to ensure free margins. Adjuvant therapies with chemotherapy or radiation therapy do not modify overall or disease-free survival. Recurrences are common and re-operation of resectable recurrent disease is recommended. The palliative treatment of symptomatic hypercalcemia is crucial in persistent or recurrent disease after surgery since morbidity and mortality are more associated with hypercalcemia than with tumor burden.

Primary hyperparathyroidism in children and adolescents is rare and often symptomatic at presentation. A 15-year-old boy presented with bilateral genu valgum for two years. Biochemical results were consistent with primary hyperparathyroidism. Calcium levels normalized two months after removal of a left inferior parathyroid adenoma.

A previously well 49-year-old patient presented to our hospital with symptomatic hypercalcaemia complaining of polyuria and polydipsia, as well as abdominal and lower back pain (serum/ionized calcium at 3.66 milli mole/l and 1.90 milli moles/l). At admission, he had a normocytic anemia (Hb, 99 g/L) and acute kidney injury (creatinine at 161 μM). His parathyroid hormone (PTH) levels were at 67.6 pico moles/l. A plain X-ray of the lumbar spine showed the presence of a lytic lesion in the L4 vertebrae. CT and MRI confirmed this to be a destructive lesion. A subsequent pan CT scan showed a 2.8 cm complex nodule in the left lobe of the thyroid posteriorly. Excisional biopsy of the resected mass was associated with an infiltrative cellular parathyroid neoplasm with solid and nested architectural growth pattern admixed with hemorrhage and focal calcifications. The tumor showed lymphovascular and perineural invasion. At the time of workup and despite the absence of a positive SPEP/UPEP, a bone marrow biopsy was requested to rule out multiple myeloma. His normocellular bone marrow biopsy showed marked paratrabecular fibrosis and extensive bony remodelling but no metastatic invasion. The diagnosis of a metastatic parathyroid carcinoma was made. He is subsequently considered for palliative radiotherapy to the primary tumor bed and the lumbar spine. In addition, a role for immunotherapy with ipilimumab and nivolumab in context of clinical trials is envisioned and he is being considered for enrollment.

Tertiary hyperparathyroidism is defined as a state of excessive secretion of parathyroid hormone after long-standing secondary hyperparathyroidism, which typically occurs in patients with chronic kidney disease. Tertiary hyperparathyroidism is typically characterized by marked parathyroid hyperplasia or parathyroid adenomas. Here we present a case of multiple parathyroid adenomas in a 23-year-old woman with tertiary hyperparathyroidism due to chronic kidney disease and describe the ultrasonography and computed tomography findings. To our knowledge, this is the first case of four parathyroid adenomas showing variable radiological features in a patient with tertiary hyperparathyroidism. Keywords: Parathyroid neoplasm, Chronic kidney failure, Hyperparathyroidism, Ultrasonography, Computed tomography

Spontaneous bleeding is a rare but serious complication of parathyroid adenomas and few cases were reported in the literature. Clinical manifestations and treatment may vary but sometimes an immediate surgery is required. In other cases a conservative approach can be preferred based on clinical stability and patients’ conditions. The purpose of this work is to describe our case and to carry out a review of the current literature on this topic. We reported a case of a parathyroid adenoma hemorrhage in an elderly patient describing its management. Moreover, a literature review of 57 cases was carried out, with the aim of collecting data about the most involved parathyroid gland and identifying the most correct management based on clinical manifestations and chosen treatments. The patients had an age between 29 and 81 years (mean 56.9 ± 16.4 years). Forty-four patients were females (77.2%), whereas 12 were males (21.8%). Based on clinical severity, age, comorbidities and calcemic status, three possible scenarios were identified, each with a recommended management. In parathyroid adenoma hemorrhages a careful clinical assessment is crucial to identify emergency conditions requiring immediate intubation, tracheostomy or neck exploration. Elderlies and comorbid patients have a higher risk of perioperative complications and indication for surgery should be evaluated case by case: whenever feasible, a conservative approach should be preferred in these subjects, especially in those with a stable course and without hypercalcemia-related symptoms.

OBJECTIVE: This study aimed to evaluate the efficacy and safety of ultrasound (US)-guided minimally invasive treatment in patients with parathyroid lesions. MATERIALS AND METHODS: This study included 27 patients who had undergone US-guided radiofrequency ablation (RFA) or ethanol ablation (EA) for parathyroid lesions between January 2010 and 2018. RFA was performed in 19 patients with primary hyperparathyroidism (PHPT, n = 11) or secondary hyperparathyroidism (SHPT, n = 8), and EA was performed in eight patients with symptomatic nonfunctioning parathyroid cysts (SNPCs). Nodule size, volume, serum parathyroid hormone (PTH) and calcium levels were recorded before and after treatment. Complications were evaluated during and after treatment. RESULTS: In patients with PHPT, significant reductions in size and volume were noted after RFA at 6- and 12-month follow-up (all, p < 0.05). Seven nodules nearly completely disappeared (residual volume < 0.1 mL); serum PTH and calcium levels were reduced to normal ranges (7/11, 63.6%). Four patients experienced partial reductions of serum PTH and calcium levels (4/11, 36.4%). In patients with SHPT, three experienced therapeutic response of serum PTH (3/8, 37.5%), while five showed persistent hyperparathyroidism (5/8, 62.5%) within 6 months after RFA. In patients with SNPCs, EA resulted in significant reductions in cyst size and volume (all, p < 0.05) at the last follow-up. A total of four complications (two transient hypocalcemia [RFA], one permanent [RFA], and one transient [EA] hoarseness) were observed. CONCLUSION: Minimally invasive treatments, such as RFA and EA, may serve as therapeutic alternatives for patients with PHPT or SNPCs; they may have limited usefulness in patients with SHPT.

Undescended parathyroid adenoma is a rare cause of primary hyperparathyroidism that happens < 1% of cases. If not suspected, it can lead to a negative bilateral parathyroid exploration and extensive iatrogenic trauma. We propose that with proper imaging the correct diagnosis can be established to simplify surgical management. We describe two cases of patients who underwent a targeted neck exploration due to an undescended parathyroid adenoma diagnosed with an appropriate preoperative imaging protocol. With an appropriate imaging protocol for primary hyperparathyroidism and parathyroid hormone aspirates, an undescended parathyroid adenoma can be primarily diagnosed to guide a focused parathyroidectomy.

We sought to develop an immunohistochemical (IHC) tool to support the diagnosis of parathyroid carcinoma (PC) and help differentiate it from atypical parathyroid neoplasms (atypical) and benign adenomas. Distinguishing PC from benign parathyroid neoplasms can be challenging. Many cases of PC are histopathologically borderline for definitive malignancy. Recently, individual IHC biomarkers have been evaluated to aid in discrimination between parathyroid neoplasms. PC, atypical parathyroid neoplasms, and parathyroid adenomas treated at our institution from 1997 to 2014 were studied retrospectively. IHC analysis was performed to evaluate parafibromin, retinoblastoma (RB), protein gene product 9.5 (PGP9.5), Ki67, galectin-3, and E-cadherin expression. Receiver operating characteristic (ROC) analysis and multivariable logistic regression model for combinations of biomarkers were evaluated to classify patients as PC or atypical/adenoma. A diagnostic nomogram using 5 biomarkers was created for PC. Sixty-three patients were evaluated. The percent staining of parafibromin (p < 0.0001), RB (p = 0.04), Ki67 (p = 0.02), PGP9.5 (p = 0.04), and Galectin-3 (p = 0.01) differed significantly in the three diagnostic groups. ROC analysis demonstrated that parafibromin had the best performance in discriminating PC from atypical/adenoma; area under the curve (AUC) was 81% (cutoff, 92.5%; sensitivity rate, 64%; specificity rate, 87%). We created a diagnostic nomogram using a combination of biomarkers; AUC was 84.9% (95% confidence interval, 73.4-96.4%). The optimism-adjusted AUC for this model was 80.5% (mean absolute error, 0.043). A diagnostic nomogram utilizing an immunoexpression, a combination of immunohistochemical biomarkers, can be used to help differentiate PC from other parathyroid neoplasms, thus potentially improving diagnostic classification.

Eight cases of parathyroid carcinoma were identified (8 females; median age 45 years, range 28-72). Half of whom were diagnosed preoperatively. Hypercalcemic symptoms were seen in 87.5% of the patients and the main complication was nephrolithiasis. At presentation, the median calcium was 3.675 mmol/L, median phosphate of 0.68 mmol/L, median intact parathyroid hormone (iPTH) was 211 pmol/L. Five patients had regional nodes metastasis and 1 had distant metastasis to the lungs. Parathyroid gland invasion to adjacent structures was seen in 62.5% of cases while another 62.5% showed capsular or vascular infiltration on histology with median tumour size of 3.2 cm. Recurrent hypercalcemia occurred in 50% of the patients with median time of recurrence of 21 months. In this case series, we found that patients with severe hypercalcemia and high iPTH also exhibited a high index suspicion of PC.

Background Parathyroid adenoma (PTA) is known as an adenomatous hyperparathyroidism syndrome. At earlier times, the major symptoms of this disease included high blood calcium and low phosphorus. PTA is a benign neuroendocrine neoplasm. We have reviewed the literature and found that it is rare for patients with hyperparathyroidism to have benign tumors with multiple organs at the same time. This report describes a patient with a PTA and four nonfunctional adenomas. Case summary We report a case of primary hyperparathyroidism in a 39-year-old woman with multiple organ tumors. The patient was admitted to hospital because of hypercalcemia. Laboratory, imaging, and histological examinations confirmed a left parathyroid neoplasm. Right thyroid adenoma was discovered during hospitalization. She had a medical history of uterine fibroids, right benign mammary gland tumor, and meningioma. The patient recovered after surgical and conservative treatments. Conclusion Primary hyperparathyroidism with multiple organ tumors is uncommon, and further studies should be conducted to determine if there is genetic heterogeneity.

Introduction Parathyroid carcinoma represents a rare cause of primary hyperparathyroidism. Distinguishing carcinoma from the benign tumors underlying primary hyperparathyroidism remains challenging. The diagnostic criteria for parathyroid carcinoma are local and/or metastatic spreading. Atypical parathyroid adenomas share other histological features with carcinomas but lack invasive growth. Somatostatin receptors are commonly expressed in different neuroendocrine tumors, but whether this also holds for parathyroid tumors remains unknown. Aim Our aim is to examine the immunohistochemical expression of somatostatin receptor 1–5 in parathyroid typical adenomas, atypical adenomas and carcinomas. Methods We used a tissue microarray construct from a nationwide cohort of parathyroid carcinomas (n = 32), age- and gender-matched typical parathyroid adenomas (n = 72) and atypical parathyroid adenomas (n = 27) for immunohistochemistry of somatostatin receptor subtypes 1–5. We separately assessed cytoplasmic, membrane and nuclear expression and also investigated the associations with histological, biochemical and clinical characteristics. Results All parathyroid tumor subgroups expressed somatostatin receptors, although membrane expression appeared negligible. Except for somatostatin receptor 1, expression patterns differed between the three tumor types. Adenomas exhibited the weakest and carcinomas the strongest expression of somatostatin receptor 2, 3, 4 and 5. We observed the largest difference for cytoplasmic somatostatin receptor 5 expression. Conclusions Parathyroid adenomas, atypical adenomas and carcinomas all express somatostatin receptor subtypes 1–5. Somatostatin receptor 5 may serve as a potential tumor marker for malignancy. Studies exploring the role of somatostatin receptor imaging and receptor-specific therapies in patients with parathyroid carcinomas are needed.

Background: Primary hyperparathyroidism (PHPT) is a disease characterized by autonomous production of parathyroid hormone (PTH) from one or more parathyroid glands. Over the past 50 years asymptomatic form of the disease have become more prevalent in developed countries. Aims: To evaluate the clinical forms of PHPT presented in recent years and to specify the clinical and laboratory features in patients with symptomatic and asymptomatic forms of the disease. Materials and methods: We reviewed medical records of 449 patients admitted to three Medical Centers (Saint-Petersburg, Russia) between 2011–2018. Anamnesis, anthropometric data, laboratory (PTH, serum total calcium and ionized calcium, phosphorus, alkaline phosphatase, 24-h calciuria level, 25(OH)D) and instrumental (ultrasonography, scintigraphy, CT/MRI scan, DXA) tests were analyzed. Results: Patients’ average age was 59 years, with 93.1% women, and an F:M ratio of 13.5:1. Symptomatic form of PHPT was identified in 310 patients (69%), while 139 were asymptomatic. 4.2% of patients had PHPT as part of MEN syndrome. Almost half of the male population had urolithiasis and 45% of women had osteoporosis. Cardiovascular diseases were present in 64.4% of cases. 25(OH)D level was determined only in 20% of cases and was higher in asymptomatic patients (32.2 & 18.6 ng/ml, p = 0.003). Normocalcemic form of PHPT was diagnosed in 37 patients (8.2%) and was characterized not only by normocalcemia and lower PHT level, but also by smaller adenoma size ( p = 0.01) and hypocalcemic syndrome after surgery. Conclusions: Study results showed that symptomatic PHPT is more prevalent in the Russian population, that there are gender distinctions affecting the clinical presentation, and that the frequency of cardiovascular disease is high in this patient population. PHPT as part of MEN syndrome was detected in 4.2% of cases and required molecular genetic testing. Normocalcemic form of PHPT with postoperative hypocalcemia was present in every fourth patient. Rare determination of 25(OH)D level imposes the need of mandatory assessment of vitamin D supplementation and the reduction of its deficiency as part of the preoperative preparation of PHPT patients.

Circular RNAs (circRNAs) are a recently identified class of non-coding RNAs that participate in multiple biological processes and tumour progression. However, circRNA expression pattern in parathyroid neoplasms remains unknown. The circRNA profile of 6 parathyroid carcinomas (PCs), 6 parathyroid adenomas (PAs) and 4 normal parathyroid tissues was assessed by a microarray. Bioinformatic analyses were performed to investigate potential core circRNAs via co-expression network. CircRNA and corresponding mRNA expression were validated in a cohort of parathyroid neoplasms by RT-qPCR and fluorescence in situ hybridization (FISH). Compared to normal parathyroid, 5310 and 1055 circRNAs were differentially expressed in PC and PA tissues, respectively. The differential expression of 4 circRNAs (hsa_circRNA_0035563 (p = 0.006), hsa_circRNA_0017545 (p = 0.009), hsa_circRNA_0001687 (p = 0.005) and hsa_circRNA_0075005 (p = 0.001)) and 4 mRNAs (MYC, FSCN1, ANXA2 and AKR1C3) between PC and PA tissues were confirmed by RT-qPCR. In addition, high expression of hsa_circ_0035563 was related to CDC73 mutations (p = 0.022) and recurrence in PC patients (p = 0.042). Furthermore, hsa_circ_0075005 helped distinguish PCs from benign lesions using FISH, and the area under the curve was 0.779 (p = 0.013). Our findings describe the circRNA profile of PC for the first time and suggest that circRNAs and mRNAs interact in parathyroid tumourigenesis. This study demonstrates that hsa_circ_0075005 and MYC mRNA may be used for the differential diagnosis of PC and PA. The expression levels of hsa_circ_0035563 are related to CDC73 mutations and recurrence in malignancy, highlighting the significance of this parameter in prognosis of PC patients.

We report an ectopic mediastinal parathyroid adenoma in a patient with chronic kidney disease who presented with refractory hypercalcemia. Technetium-99m-sestamibi scintigraphy is a valuable imaging technique for the detection of an ectopic parathyroid adenoma in the mediastinum. The combination of intense contrast enhancement and the identification of a polar vessel on a computed tomography scan will ensure that a radiologist can differentiate a parathyroid adenoma from other pathologies in the mediastinum. By virtue of the advancement of imaging modalities, localization of an ectopic mediastinal parathyroid adenoma prior to surgery is possible and unnecessary neck exploration is avoidable.

Objective: To evaluate the relationship between various biochemical parameters in patients with primary hyperparathyroidism (PHPT) with positive and negative technetium-99 sestamibi (Tc) parathyroid scans performed with single-photon emission computed tomography/computed tomography (SPECT/CT). Methods: This retrospective analysis was used to develop a logistic probability model. It included 218 patients with PHPT. The main outcome measures were serum total calcium, ionized calcium, intact parathyroid hormone (PTH), albumin, alkaline phosphatase, phosphate, 25-hydroxy vitamin D, 1,25-dihydroxy vitamin D, 24-h urinary calcium levels, and parathyroid adenoma weight. Results: Individually, using cut-off levels of 6.0 mg/dL for ionized calcium, 3.0 mg/dL for phosphate, and 90 pg/mL for intact PTH, we found that 91.3% (P = .005), 70.7% (P = .004) and 87.90% (P = .023) of the patients had a positive Tc scan with their corresponding strengths of associations in the parentheses. Similar significant associations were sustained in multivariate setting for serum ionized calcium (P = .015), phosphate (P = .016), and intact PTH (P = .028). A logistic probability model was designed to predict the probability of being positive for Tc scan given a set of covariates. Conclusion: There are significant associations between the levels of serum ionized calcium, phosphate, intact PTH, and Tc scan positivity. Further studies with larger patient populations are needed. Abbreviations: BMI = body mass index; CT = computed tomography; CV = coefficient variation; DXA = dual-energy x-ray absorptiometry; MRI = magnetic resonance imaging; PHPT = primary hyperparathyroidism; PPV = positive predictive value; PTH = parathyroid hormone; SPECT = single-photon emission computed tomography; Tc = technetium-99 sestamibi

Objective The aim of this study was to evaluate the value of technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) imaging and ultrasound in preoperative localization of parathyroid adenoma (PA) and parathyroid hyperplasia (PH). Participants and methods A retrospective study of 99mTc-MIBI double-phase scintigraphy (DPS) was performed in 187 hyperparathyroidism cases with pathologically diagnosed PA or PH. Of these patients, 167 cases underwent ultrasound, and 146 cases underwent 99mTc-MIBI single-photon emission computed tomography/computed tomography (SPECT/CT). The sensitivity and diagnostic accuracy of ultrasound, 99mTc-MIBI DPS, and SPECT/CT were compared between PA and PH. Differences in 99mTc-MIBI DPS, serum parathyroid hormone (PTH), serum calcium and phosphorus, as well as the weight and longest diameter of lesion between PA and PH were also compared. Results As per patient-based analysis, the sensitivity of ultrasound, 99mTc-MIBI DPS, and SPECT/CT was 90.70% (39/43), 95.56% (43/45), and 100.00% (30/30), respectively, for PA, and 93.55% (116/124), 90.85% (129/142), and 93.10% (108/116), respectively, for PH. There were no significant differences in sensitivity of these three imaging methods between PA and PH. However, per lesion-based analysis, the accuracy of ultrasound, 99mTc-MIBI DPS, and SPECT/CT in detecting PA was 78.43% (40/51), 86.79% (46/53) and 96.88% (31/32), respectively, and the accuracy of 99mTc-MIBI DPS was higher than that of ultrasound (χ2=6.507, P=0.011), and for PH, it was 49.69% (160/322), 40.71% (171/420), and 43.80% (152/347), respectively. The accuracy of ultrasound was higher than that of 99mTc-MIBI DPS (χ2=5.940, P=0.015). The accuracy of a combination of all three examinations of ultrasound+99mTc-MIBI DPS, ultrasound+99mTc-MIBI SPECT/CT, 99mTc-MIBI DPS+SPECT/CT, and ultrasound+99mTc-MIBI DPS+99mTc-MIBI SPECT/CT was 51.51% (154/299), 53.85% (161/299), 50.17% (150/299), and 54.18% (162/299), respectively, which was higher than that of ultrasound (χ2=5.273, P=0.022; χ2=8.226, P=0.004; χ2=3.880, P=0.049; χ2=8.702, P=0.003, respectively). Serum levels of PTH and phosphorus were lower in patients with PA than in patients with PH (P

A 45-year-old gentleman presented to hospital with vomiting. Bloods demonstrated a corrected calcium of 4.48 and PTH of 979. CT neck showed a right sided thyroid lesion, which on FNA was reported as a possible thyroid or parathyroid neoplasm. A NM scan showed an enhancing nodule in the right thyroid gland and lytic vertebral and pelvic lesions. Bone biopsy showed parathyroid carcinoma. He underwent palliative total thyroidectomy and right superior and inferior parathyroidectomy under the ENT team. His thyroidectomy specimen was reported as right inferior parathyroid carcinoma, infiltrating into the thyroid gland. His calcium levels did not normalise post-surgery and corrected levels were consistently above 3, with PTH > 5000 despite fluid and calcimimetic therapy with only temporary normalisation with bisphosphonates and denosumab. This refractory hypercalcaemia is due to the bony metastases producing PTH, which represents a primary cause of mortality. He is currently being managed with regular fluid infusions and bisphosphonates, with view to commence palliative chemotherapy. Parathyroid carcinoma is extremely rare, and rarer still to present with metastatic disease. Treatment options are limited, with poor evidence behind chemoradiation and immunotherapy. Clinicians should be aware of the complications and management of refractory hypercalcaemia linked to this disease entity.

Patient: Female, 51-year-old (was first diagnosed as 23-year-old) Final Diagnosis: Parathyroid carcinoma Symptoms: Hypercalcemia • hypercalcemic shock • nephrolithiasis Medication: — Clinical Procedure: Pharmacological treatment • surgery and radiotherapy Specialty: Endocrinology and Metabolic • Oncology Objective: Rare disease Background: Parathyroid carcinoma (PC), accounting for 0.005% of all cancers, is responsible for less than 1% of all cases of primary hyperparathyroidism, and equally affects males and females, usually in 4th or 5th decades of life. PC can occur sporadically and can be associated with congenital genetic syndromes such as hyperparathyroidism-jaw tumor syndrome (HPT-JT), isolated familial hyperparathyroidism, or multiple endocrine neoplasia 1 and 2 syndromes. Surgery is the main treatment, with a limited role of radio- and chemotherapy, which allows 49–77% of patients to survive 10 years. In this work we report the case of a patient with parathyroid carcinoma, whose treatment required 13 surgeries over a period of 27 years, together with radiotherapy and pharmacological treatment. Case Report: A 51-year-old woman was first diagnosed with primary hyperparathyroidism in 1993 at the age of 23. From 1993 to present, she underwent 13 surgeries and 33 courses of radiotherapy due to recurrent lesions, which initially had a character of parathyroid adenomas, then parathyromatosis, and finally were diagnosed as parathyroid carcinoma. The patient also required and currently requires complex pharmacological treatment to control the calcemia and manage the complications of the primary disease. Supervision by the multidisciplinary professional medical team allows the patient to lead a normal life with good control of the disease. Conclusions: Parathyroid carcinoma is a rare disease with a number of complications; however, obtaining satisfactory long-term survival with acceptable quality of life is achievable.

Background Primary hyperparathyroidism is characterized by an autonomous hypersecretion of parathyroid hormone by one or more parathyroid glands. Preoperative localization of the affected gland(s) is of key importance in order to allow minimally invasive surgery. At the moment, 11C-Methionine and 18F-Fluorocholine PET studies appear to be among the most promising second-line localization techniques; their comparative diagnostic performance, however, is still unknown. Methods PubMed/Medline and Embase databases were searched up to October 2020 for studies estimating the diagnostic accuracy of 11C-Methionine PET or 18F-Fluorocholine PET for parathyroid localization in patients with primary hyperparathyroidism. Pooled sensitivity and positive predictive value were calculated for each tracer on a 'per-lesion' basis and compared using a random-effect model subgroup analysis. Results In total, 22 studies were finally considered in the meta-analysis. Of these, 8 evaluated the diagnostic accuracy of 11C-Methionine and 14 that of 18F-Fluorocholine. No study directly comparing the two tracers was found. The pooled sensitivity of 18F-Fluorocholine was higher than that of 11C-Methionine (92% vs 80%, P < 0.01), while the positive predictive value was similar (94% vs 95%, P = 0.99). These findings were confirmed in multivariable meta-regression models, demonstrating their apparent independence from other possible predictors or confounders at a study level. Conclusion This was the first meta-analysis that specifically compared the diagnostic accuracy of 11C-Methionine and 18F-Fluorocholine PET for parathyroid localization in patients with primary hyperparathyroidism. Our results suggested a superior performance of 18F-Fluorocholine in terms of sensitivity, while the two tracers had comparable accuracy in terms of positive predictive value.

Case summary A 16-year-old neutered female Korat cat presented with chronic vomiting, mild azotaemia and mild hypercalcaemia. Physical examination revealed bilateral palpable masses on each side of the trachea. Laboratory results were consistent with primary hyperparathyroidism, diagnostic imaging findings with cystic thyroid or parathyroid masses, and fine-needle aspiration cytology with thyroid hyperplasia or adenoma. In order to confirm whether one or two of the masses were the cause of the hyperparathyroidism, cystic fluid was aspirated from both for parathyroid hormone concentration measurement. The concentration was shown to exceed that of the serum manyfold in both samples, confirming both masses to be functional and of parathyroid origin. A total parathyroidectomy and thyroidectomy were performed on the right side, and a subtotal thyroidectomy and a subtotal to total parathyroidectomy on the left, without any major postoperative complications. Histopathology was consistent with bilateral parathyroid carcinoma. Relevance and novel information To our knowledge, this report is the first to describe a rare case of bilateral parathyroid cystic carcinoma in a cat. It highlights the usefulness of determining parathyroid hormone concentration in the cystic fluid of a suspected neoplastic parathyroid mass preoperatively. It also demonstrates that it may be possible to remove most of the cervical parathyroid and thyroid tissue of a cat without causing any clinically relevant hypocalcaemia or iatrogenic hypothyroidism. However, serum concentrations of ionised calcium, thyroxine and creatinine should be closely monitored in the postoperative period in order to detect and control possible complications.

Standardized pathologic reporting for cancers improves patient care and prognostic determination. However, access in many countries is limited. To address this issue, the International Collaboration on Cancer Reporting (ICCR), a not-for-profit organization, has the mission to develop and disseminate standardized data sets for global use. Within endocrine organs, the parathyroid gland has rarely been included in formal pathologic data sets. Utilizing an expert international panel of eleven members, an evidence-based data set was developed for parathyroid carcinoma and atypical parathyroid neoplasms. This data set consists of sixteen core (required) elements viewed as essential for documentation of these conditions. Characterizing parathyroid carcinomas and atypical neoplasms begins with correlative clinical information, the operative procedure, specimens submitted, and site of the disease. The pathologic features essential to document include parathyroid weight, size, classification, and, when a carcinoma, the tumor grade. Histologic grade of parathyroid carcinoma incorporates other core elements including necrosis, mitotic count, perineural invasion, and lymphovascular invasion. Documenting the extent of disease locally into adjacent organs, regionally, and distally is critical for staging. Pathologic staging is now included as part of the American Joint Committee on Cancer 8th edition and is included in this data set. Ancillary studies should be recorded when performed as noncore elements. Standardized pathologic data sets for endocrine organs including the parathyroid gland are now available through the ICCR website. These essential resources enhance international standardization for documenting these rare tumors for both patient care and future guidelines.

Purpose: The occurrence of parathyroid carcinoma (PC) and atypical parathyroid neoplasm (APN) in multiple endocrine neoplasia type 1 (MEN1) is rare. The present paper reports the cases of 3 MEN1-PC/APN patients at our center and discusses the prevalence in a Chinese MEN1 cohort.Methods: This report is a retrospective analysis of 153 MEN1-associated primary hyperparathyroidism (MEN1-HPT) patients at our center, which included 3 MEN1-associated PC/APN (MEN1-PC/APN) patients. The clinical manifestations, biochemical indices, pathological findings, and therapy have been summarized along with the report of the genetic testing of the 3 patients.Results: Of the 153 MEN1-HPT patients, 1 (0.7%) was histopathologically diagnosed with PC and 2 (1.3%) with APN. Three heterozygous mutations were identified in the 3 MEN1-PC/APN patients (c.917 T > G, c.431T > C, and c.549 G > C). The cumulative findings of 3 cases with 18 previously reported MEN1-PC/APN cases revealed that the mean serum calcium (Ca) level was 3.15 ± 0.44 mmol/L and the median parathyroid hormone (PTH) level was 327 pg/mL (214.1, 673.1), both of which were significantly higher as compared to the respective levels in non-PC/APN MEN1 patients at our center [Ca: 2.78 mmol/L [2.61, 2.88], PTH: 185.5 pg/mL [108.3, 297.0]; P = 0.0003, 0.0034, respectively].Conclusion: MEN 1-PC/APN is a rare disease, with a prevalence of only 2.0% among the MEN1-HPT cohort at our center. The affected patients recorded higher serum Ca level and PTH levels than those with MEN1-associated benign tumors. However, the diagnosis of MEN1-PC/APN is based upon pathology most of the times.

The thyroid and adjacent parathyroid glands demonstrate a variety of benign and malignant pathology, with nodular thyroid disease being the most common pathology encountered in most routine head and neck imaging practice. A variety of thyroid cancers exist, and imaging strategy for staging, surveillance and follow-up depend upon the cancer type. The importance of parathyroid gland imaging in both benign disease, primary hyperparathyroidism (HPT), and the less common parathyroid carcinoma has seen recent advances. An understanding of the available imaging modalities, pathologies and options for imaging thyroid and parathyroid disorders is essential.

ABS TRACT Objective: Primary hyperparathyroidism (PHPT) is characterized by hypercalcemia and elevated parathyroid hormone (PTH) levels. In this study, we aimed to report our clinical experience by presenting the demographic, laboratory, and clinical features of our PHPT patients. Material and Methods: A total of 217 patients who underwent parathyroidectomy from 2010 to 2018 at Ondokuz Mayıs University General Surgery Clinic were retrospectively reviewed, and PHPT patients who were diagnosed with parathyroid adenoma were further evaluated. Results: In total, 136 patients (85.3% females) with a mean age of 52.6±12.66 years were included. The prevalence of osteoporosis, nephrolithiasis, hypercalciuria, and vitamin D deficiency were 45.3%, 21.7%, 59.0%, and 63.8%, respectively. Postoperative hypocalcemia (21.3%) was only related with low preoperative calcium levels (p=0.002). Preoperative calcium was positively correlated with age (p=0.029), parathyroid adenoma weight (PAW) (p=0.009), and preoperative PTH (p

Parathyroid tumors are the second most common endocrine neoplasia, and it is almost always associated with hypersecretion of the parathormone (PTH), involved in calcium homeostasis, causing primary hyperparathyroidism (PHPT). Parathyroid neoplasia has a stromal component particularly represented in atypical adenomatous and carcinomatous lesions. Recently, data about the features and the function of the parathyroid tumor microenvironment (TME) have been accumulated. Parathyroid TME includes heterogeneous cells: endothelial cells, myofibroblasts, lymphocytes and macrophages, and mesenchymal stem cells have been identified, each of them presenting a phenotype consistent with tumor-associated cells. Parathyroid tumors overexpress proangiogenic molecules including vascular endothelial growth factor (VEGF-A), fibroblast growth factor-2 (FGF-2), and angiopoietins that promote both recruitment and proliferation of endothelial cell precursors, thus resulting in a microvessel density higher than that detected in normal parathyroid glands. Moreover, parathyroid tumor endocrine cells operate multifaceted interactions with stromal cells, partly mediated by the CXCL12/CXCR4 pathway, while, at present, the immune landscape of parathyroid tumors has just begun to be investigated. Studies about TME in parathyroid adenomas provide an example of the role of TME in benign tumors, whose molecular mechanisms and functions comprehension are limited.

Patient: Female, 73 Final Diagnosis: Primary hyperparathyroidism Symptoms: Bone fractures • nephrolithiasis • palpable mass • weakness Medication: — Clinical Procedure: Operation Specialty: Surgery Objective: Rare disease 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.

In this study, echogenicity and histopathological projections of parathyroid neoplasia in grey mode ultrasonography were compared with whole side imaging (WSI). The utility of the data obtained for clinical assessment was evaluated.In 57 patients operated for hyperparathyroidism, the parathyroid gland was sampled in the sagittal plane. The lesion slides were scanned. The WSI was rendered digital. The histopathological slide images scanned with USG images were matched. With the İmage J program, the areas of cell types and morphological changes were measured.In parathyroid neoplasms, hypoechoic areas were found to be matched with 21% [55.3%] chief cell, 2 [5.0%] oncocytic cell and 8%[20.0%] cystic morphology. Of the 57 patients, 26 [45.61%] had a cystic area. It was seen that hyperechogenic areas match more connective tissue areas than chef cell [p 0.05]. There was less clear cell in hyperechogenic areas than iso-hyperechogenic areas [p 0.05]. The ratio of fat tissue echogenicity was lower in hypoechoic areas than hyperechoic [p 0.05]. There was a positive correlation between PTH and the entire tissue area [r = 0.377, p = 0.004]. A positive directional moderate linear relationship was found between blood calcium level and parathyroid adenoma [rho = 0.530, p = 0.009] and percentage [rho = 0.416, p = 0.048]. When atypical adenomas and adenoma cases were compared, no significant difference was found between the cystic and chief cell areas [p 0.05].The hypoechogenicity seen in USG was observed to be compatible with chief cell, hyperechogenic areas in USG were compatible with connective tissue and fat tissue. As the cystic area increased, blood calcium levels were higher in adenomas. We think that the results of this study will be guiding to evaluate the reflections of the detailed morphometric studies.

Transoral robotic surgery (TORS) has become an increasingly popular option for early malignancies of the oropharynx. It offers superior visualization and has been proven to have acceptable functional and oncologic outcomes. Additionally, indications in head neck have expanded to manage tumors of the thyroid, neck, parapharyngeal space and salivary glands. A 58-year-old female had an incidental finding on CT imaging of a retropharyngeal mass at the level of the hyoid bone. She was referred to a tertiary medical center for further workup and removal of this mass. Due to the midline position of the mass, favorable access and potentially decreased surgical morbidity, TORS excision of the mass was performed for diagnosis and treatment. Histopathology confirmed this to be a hypercellular parathyroid mass consistent with parathyroid adenoma. We report a relatively unusual location of parathyroid adenoma in an asymptomatic patient with normal parathyroid and calcium levels. TORS proves to be a feasible and safe method for complete surgical excision of retropharyngeal parathyroid adenoma without tumor spillage or violation.

Introduction Highly specific preoperative localizing test is required to select patients for minimally invasive parathyroidectomy (MIP) in lieu of traditional four-gland exploration. We hypothesized that Tc-99m sestamibi scan interpretation incorporating numerical measurements on the degree of asymmetrical activity from bilateral thyroid beds can be useful in localizing single adenoma for MIP. Methods We devised a quantitative interpretation method for Tc-99m sestamibi scan based on the numerically graded asymmetrical activity on early phase. The numerical ratio value of each scan was obtained by dividing the number of counts from symmetrically drawn regions of interest (ROI) over bilateral thyroid beds. The final pathology and clinical outcome of 109 patients were used to perform receiver operating curve (ROC) analysis. Results Receiver operating curve analysis revealed the area under the curve (AUC) was calculated to be 0.71 (P = 0.0032), validating this method as a diagnostic tool. The optimal cut-off point for the ratio value with maximal combined sensitivity and specificity was found with corresponding sensitivity of 67.9% (56.5-77.2%, 95% CI) and specificity of 75.0% (52.8-91.8%, 95% CI). An additional higher cut-off with higher specificity with minimal possible sacrifice on sensitivity was also selected, yielding sensitivity of 28.6% (18.8-38.6%, 95% CI) and specificity of 90.0% (69.6-98.8%, 95% CI). Conclusions Our results demonstrated that the more asymmetrical activity on the initial phase, the more successful it is to localize a single parathyroid adenoma on sestamibi scans. Using early-phase Tc-99m sestamibi scan only, we were able to select patients for minimally invasive parathyroidectomy with 90% specificity.

Introduction Intraoperative parathyroid hormone (ioPTH) testing is a widely accepted standard for assessing the parathyroid gland function. A decline of preoperative parathyroid hormone (PTH) levels by more than 50% is one accepted measure of parathyroid surgery adequacy. However, there may be a variation between preoperative PTH levels obtained at a clinic visit and pre-excisional ioPTH. Objective Our study explores the differences between preoperative PTH and pre-excisional ioPTH levels, and the potential impact this difference has on determining the adequacy of parathyroid surgery. Methods A retrospective study that consisted of 33 patients that had undergone parathyroid resection between September 2009 and March 2016 at a tertiary academic center was performed. Each subject's preoperative PTH levels were obtained from clinic visits and pre-excisional ioPTH levels were recorded along with the time interval between the measurements. Results There was a significant difference between the mean preoperative PTH and the pre-excisional ioPTH levels of 147 pg/mL (95% confidence interval [CI] 11.43 to 284.47; p = 0.0396). The exclusion of four outliers revealed a further significant difference with a mean of 35.09 pg/mL (95% CI 20.27 to 49.92; p Conclusion Our study reveals a significant difference between the preoperative PTH levels obtained at clinic visits and the pre-excisional intraoperative PTH levels. We recommend routine pre-excisional intraoperative PTH levels, despite evidence of elevated preoperative PTH levels, in order to more accurately assess the adequacy of surgical resection.

Objective We tested the hypothesis that a single-phase neck computed tomography (CT) is not inferior to multiphase neck CT (MPNCT), ultrasound, or nuclear medicine sestamibi scan in identifying parathyroid adenomas (PAs). Methods A total of 29 patients who had an MPNCT for the evaluation of a PA were identified; 11 patients met the inclusion criteria. During the 30-second arterial phase CT (APNCT), a normalized Hounsfield unit of suspected PA was compared to Hounsfield unit of a normal-appearing level I and a level II lymph node. A PA was defined as a lesion with a ratio of greater than 1.4 when compared to the level I and level II lymph node. This cutoff was determined based on the normalized ratios between level II and level I lymph nodes. Results of intraoperative parathyroid hormone assays and surgical pathology were used to validate the accuracy of this technique. Results The sensitivity of this method in APNCT is 90.9% whereas positive predictive value is 100%. The sensitivity or positive predictive value of ultrasound and nuclear medicine are 60% or 100% and 90% or 100%, respectively. Conclusion The sensitivity of APNCT is equivalent to that of MPNCT in identifying PA.