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Parathyroid Cancer

The parathyroid gland is located at the base of the neck near the thyroid gland. It produces a hormone called parathyroid hormone (PTH), which controls how the body stores and uses calcium. Parathyroid cancer is a condition where the cells of the parathyroid gland become malignant (cancerous). Parathyroid cancers are rare; while problems with the parathyroid gland are common, these are not usually cancer related.

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    MeSH term: Parathyroid Neoplasms
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Latest Research Publications

This list of publications is regularly updated (Source: PubMed).

Inic Z, Inic M, Jancic S, et al.
The relationship between proliferation activity and parathyroid hormone levels in parathyroid tumors.
J BUON. 2015 Mar-Apr; 20(2):562-6 [PubMed] Related Publications
PURPOSE: This article examines as to whether the Ki-67 index may be useful as a marker for cell proliferation, as well as to whether Ki-67 immunohistochemical expression and parathyroid hormone (PTH) levels are useful in distinguishing between parathyroid carcinoma (PC) and adenoma.
METHODS: A retrospective analysis of 50 patients (10 with PC and 40 with adenoma) who had been previously diagnosed with primary hyperparathyroidism (PHPT) was conducted. Normal parathyroid glands served as the control group. Immunostaining of Ki-67 was estimated through image analysis and the results were statistically analyzed.
RESULTS: Ki-67 was higher in PC patients (median 785.15) compared to adenoma patients (median 297.41; Mann-Whitney U-test p<0.001). ROC analysis confirmed that Ki-67 has a positive predictive marker in diagnosing cancer. Mann-Whitney U-test confirmed a highly statistically significant difference in the preoperative PTH levels between the PC and adenoma group (p <0.001). The PTH serum preoperative level was higher in PC patients (median 1721) than in those with adenoma (median 189.5). A highly significant correlation was also found between Ki-67 and preoperative PTH levels (p <0.001).
CONCLUSION: A higher rate of cellular proliferation was noted in malignant tumors as compared to benign tumors. Moreover, the expression profile of Ki-67 and high PTH levels in this study indicates a role for them as potential markers of malignancy.

Diaconescu MR, Glod M, Costea I, et al.
Clinicopathological phenotype of parathyroid carcinoma: therapeutic and prognostic aftermaths.
Chirurgia (Bucur). 2015 Jan-Feb; 110(1):66-71 [PubMed] Related Publications
Parathyroid carcinomas (PC) are rare and "devastating"€ causes of hyperparathyroidism (HP), frequently discovered fortuitously,with not always doubtless pathological confirmation, and dissociate post-therapeutic outcomes and prognosis even after well-performed surgery. We herein report four PT neoplasms,three of them proving to be authentic PCs, and one an atypical parathyroid adenoma. There were three females and one male, aged 32-49 (mean 44) years. In three circumstances PC was associated with primary HP and in one case the tumor had developed on a CKD-BMD (renal HP) background. All patients presented marked clinical and biochemical phenomena related to hypercalcemia with greater intensity of renal, bone, neuromuscular and psychological signs and symptoms to which in one observation specific uremic manifestations were added. Preoperative and intraoperative diagnosis was suspected only in two cases (one of them being in fact an atypical PT adenoma), but in the other two it was established by paraffin section on histological evidence of definitive stigma of malignancy. Our little experience underlines the wide and protean range of the origins, clinical aspects, course and prognosis of PC, which adds to the difficulties of pre- and intraoperative diagnosis. Awareness of this lesion must be permanent to detect its presence in any unusual eventuality, imposing a radical en bloc resection at the initial operation, assuring the best chance of cure.

Saifuddin M, Selim S, Haq T, et al.
A middle aged lady with recurrent low trauma fracture due to parathyroid adenoma.
Mymensingh Med J. 2015; 24(1):191-4 [PubMed] Related Publications
A 48 year old lady was referred to BIRDEM Hospital, Dhaka, Bangladesh by her local physician for evaluation of hypercalcaemia and increased serum parathyroid hormone (PTH) in the background history of low trauma fracture. Ultrasound of neck and parathyroid scintigraphy with 99mTc-MIBI revealed a parathyroid adenoma. Parathyroidectomy was done. Histopathology report showed features consistent with parathyroid adenoma. Primary hyperparathyroidism should be kept in mind in all patients presenting with history of bone problems ranging from simple bone pain to spontaneous or low trauma fracture associated with hypercalcemia. By the help of appropriate localization technique it can be localized and cured by parathyriodectomy.

Mandal R, Muthukrishnan A, Ferris RL, et al.
Accuracy of early-phase versus dual-phase single-photon emission computed tomography/computed tomography in the localization of parathyroid disease.
Laryngoscope. 2015; 125(6):1496-501 [PubMed] Related Publications
OBJECTIVES/HYPOTHESIS: Preoperative localization for parathyroid disease has improved in recent years with the advent of dual-phase (99m) Tc-sestamibi single-photon emission computed tomography/computed tomography (SPECT/CT) imaging. However, dual-phase imaging is associated with increased cost, time, and radiation dose. The aim of this study was to investigate the need for late-phase imaging when using SPECT/CT for the preoperative localization of parathyroid disease.
STUDY DESIGN: Retrospective chart analysis.
METHODS: A retrospective review of 75 patients who underwent preoperative imaging localization and subsequent surgical resection for parathyroid disease at a tertiary referral center was performed. Of these, 50 patients met study criteria including preoperative SPECT/CT imaging and specific reporting of early- and late-phase focal radiotracer uptake. Localization accuracy was verified with definitive surgical findings confirmed by histological analysis and evidence of biochemical cure.
RESULTS: Accurate localization of adenoma(s) was seen in 78.0% of patients using dual-phase SPECT/CT. Early-phase imaging alone localized 76.0%, whereas late-phase imaging alone localized 74.0%. Sensitivity and specificity for dual-phase imaging was 84.8% and 89.6%, respectively. In comparison, early-phase localization alone was found to have a sensitivity/specificity of 84.4%/89.4%; sensitivity/specificity of late-phase scanning alone was found to be 80.4%/89.1%. Dual-phase SPECT/CT scanning did not provide a statistically significant improvement in adenoma localization when compared to early-phase scanning alone.
CONCLUSIONS: Although further investigation is needed, the results of this study suggest that early-phase SPECT/CT scanning alone may obviate the need for dual-phase SPECT/CT scanning in the initial preoperative localization workup of parathyroid disease.

Guerin C, Lowery A, Gabriel S, et al.
Preoperative imaging for focused parathyroidectomy: making a good strategy even better.
Eur J Endocrinol. 2015; 172(5):519-26 [PubMed] Related Publications
OBJECTIVE: Surgical treatment for primary hyperparathyroidism (pHPT) has undergone a major paradigm shift during the last decades from bilateral cervicotomy with four-gland neck exploration to image-guided focused approaches. The primary objective of the present study was to compare the performances of parathyroid scintigraphy (PS), parathyroid ultrasonography (US), and the combination of both procedures for guiding a focused approach on the basis of modified interpretation criteria.
METHODS: Data from 199 patients operated for apparent sporadic pHPT and evaluated with US and PS using dual-isotope (123)I/(99m)Tc-sestamibi planar pinhole and single-photon emission computed tomography (SPECT) acqusitions were evaluated.
RESULTS: A total of 127 patients underwent a focused approach and the remainder had bilateral cervicotomy. In 42 cases, a focused approach was not performed due to the absence of concordant results between US and PS for a single-gland abnormality. Four patients had persistent disease and three had recurrent disease. A localizing preoperative PS had a sensitivity of 93.3%, positive predictive value of 85.8%, negative predictive value of 73.0%, and accuracy of 83.4% for predicting uniglandular disease. Additional SPECT images accurately localize posterior adenomas that are often missed by US. Compared with PS, US had a lower sensitivity (P<0.01). Our imaging protocol also enabled diagnosis of multiglandular disease in 60.6%.
CONCLUSIONS: PS using a highly sensitive dual-tracer subtraction method is the most accurate technique for directing a focused approach. PS could be sufficient for directing a focused approach in the presence of a negative US in two major circumstances: posterior locations due to acquired ectopia that could be missed by US, and previous history of thyroidectomy due to interpretation difficulties.

Mori H, Okada Y, Arao T, Tanaka Y
Case of parathyroid carcinoma with a highly aggressive clinical course.
J UOEH. 2014; 36(4):243-9 [PubMed] Related Publications
We describe a 59-year-old woman who presented with pathological osteoporosis, cerebral infarction, hypercalcemia, and markedly high parathyroid hormone levels. The diagnosis was primary hyperparathyroidism, and parathyroidectomy was performed. Histopathological examination showed parathyroid adenoma. Surgical exploration for recurrent parathyroid carcinoma was undertaken at 2 and 3 years after the initial neck resection. Pulmonary metastasis was diagnosed at 4 years after the initial surgery.Despite treatment with intravenous bisphosphonates, her calcium and parathyroid hormone (PTH) levels remained elevated, and leg amputation was performed following the development of arteriosclerosis obliterans at 6 years after the initial neck resection. The prognosis for parathyroid carcinoma is often difficult to predict due to recurrence.

Shifrin A, LiVolsi V, Shifrin-Douglas S, et al.
Primary and metastatic parathyroid malignancies: a rare or underdiagnosed condition?
J Clin Endocrinol Metab. 2015; 100(3):E478-81 [PubMed] Related Publications
OBJECTIVE: Parathyroid gland malignancies are considered rare. The most common of these tumor types is primary parathyroid carcinoma. Metastatic spread from other cancers may also occur with up to 10% of cancers from other sites showing parathyroid involvement at autopsy. Tumor-to-tumor metastases (metastatic spread to parathyroid neoplasm) from remote cancers to the parathyroid gland have been described.
METHODS: We did a PubMed literature review and analysis of our own experience of 392 consecutive parathyroidectomies.
RESULTS: Primary and secondary parathyroid malignancies can be grouped into three categories: primary parathyroid carcinoma (PPCa), spread of carcinoma into parathyroid glands by contiguous extension from the thyroid gland or other head and neck cancer, and metastatic disease to the parathyroid gland from distant cancers. Studies of tumor-to-tumor spread indicate a predilection of spread to endocrine tumors possibly because of the rich blood supply that is present in endocrine tumors. Two of our 392 parathyroidectomies (0.5%) had cancer: one metastatic (thymic neuroendocrine tumor) and another PPCa.
CONCLUSION: Metastatic disease to the parathyroid gland is poorly documented. When performing surgery for primary thyroid cancer, the search for parathyroid gland metastases is often overlooked because of the desire to preserve parathyroid function. Metastatic disease from other cancers to a benign parathyroid gland or to a parathyroid adenoma probably suggests a grave prognosis because it likely indicates widespread metastatic disease; however, isolated metastases to the parathyroid may occur. Although these lesions may be uncommon they may not be as rare as once thought.

Quinn CE, Healy J, Lebastchi AH, et al.
Modern experience with aggressive parathyroid tumors in a high-volume New England referral center.
J Am Coll Surg. 2015; 220(6):1054-62 [PubMed] Related Publications
BACKGROUND: Parathyroid carcinoma (PTCA) is an exceptionally rare malignancy, often with a clinical presentation similar to that of benign atypical parathyroid adenoma. Its low incidence portends unclear guidelines for management. Accordingly, thorough examination of clinical and pathologic variables was undertaken to distinguish between PTCA and atypical adenomas.
STUDY DESIGN: This was a retrospective analysis of a prospective database at a tertiary academic referral center. Between September 2001 and April 2014, 3,643 patients were referred for surgical treatment of PHPT. Of these, 52 harbored aggressive parathyroid tumors: parathyroid carcinomas (n=18) and atypical adenomas (n=34). We analyzed the surgical and clinicopathologic tumor characteristics, and did a statistical analysis. We measured preoperative and intraoperative variables, and postoperative and pathologic outcomes.
RESULTS: Parathyroid carcinoma patients present with significantly increased tumor size (3.5 cm vs 2.4 cm, respectively; p=0.002), mean serum calcium (13.0 vs 11.8 mg/dL, respectively; p=0.003) and intact parathyroid hormone (iPTH) levels (489 vs 266 pg/mL, respectively; p=0.04), and a higher incidence of hypercalcemic crisis, compared with patients with atypical adenomas (50% vs 19%, respectively; p=0.072). Parathyroid carcinoma more frequently lacks a distinct capsule (47.1% vs 12.9%, respectively; p=0.03) and adheres to adjacent structures (77.8% vs 20.6%, respectively; p=0.017). Of note, there was no significant difference in loss of parafibromin expression between groups.
CONCLUSIONS: Clinical distinction between PTCA and atypical adenomas is of critical importance in determining the appropriate extent of resection and follow-up. Loss of parafibromin has not been shown to distinguish between PTCA and atypical adenoma; clearer definition of clinicopathologic criteria for PTCA is warranted and may lead to improved postoperative management.

James BC, Nagar S, Tracy M, et al.
A novel, ultrarapid parathyroid hormone assay to distinguish parathyroid from nonparathyroid tissue.
Surgery. 2014; 156(6):1638-43 [PubMed] Related Publications
BACKGROUND: Frozen section is the gold standard for distinguishing parathyroid tissue from lymph nodes, thyroid nodules, or fat during parathyroidectomy and thyroidectomy. Although a very accurate procedure, it can be time-consuming and costly. We hypothesize that the extremely high concentrations of parathyroid hormone (PTH) in parathyroid tissue allow for modification of a standard PTH assay that would distinguish parathyroid from nonparathyroid tissue in substantially less time than frozen section or any currently available PTH assay.
METHODS: A prospective, single-institution study using a modified PTH assay protocol and a manual luminometer was undertaken by testing 20 parathyroid adenomas and 9 control tissues. Analyses were performed simultaneously by the modified PTH protocol and the conventional intraoperative PTH assay.
RESULTS: PTH luminescence values from parathyroid tissue and control tissue aspirates were significantly different at 60 seconds (P = .015). ROC curve analysis showed the assay to be 100% sensitive and 100% specific in differentiating parathyroid from nonparathyroid tissue.
CONCLUSION: Our novel PTH assay accurately and reliably differentiates parathyroid from nonparathyroid tissue within 60 seconds of measurement onset. This assay provides a great advantage in time savings compared with frozen section as well as any currently existing PTH assays.

Sadler C, Gow KW, Beierle EA, et al.
Parathyroid carcinoma in more than 1,000 patients: A population-level analysis.
Surgery. 2014; 156(6):1622-9; discussion 1629-30 [PubMed] Related Publications
BACKGROUND: Parathyroid carcinoma (PC) is a rare malignancy with a moderate prognosis. The staging system, prognostic indicators, and optimal surgical management are still under debate. This large cohort explores prognostic factors for PC.
METHODS: 1,022 cases of PC in the 1998-2011 National Cancer Data Base that underwent surgery were examined for predictors of lower overall survival (OS) and relative risk (RR) of death at 5 years.
RESULTS: The 5-year OS was 81.1% in 528 patients with ≥ 60 months of follow-up. The overall cohort was mainly non-Hispanic (96.5%), white (77.4%), and insured (94.3%), with a median age of 57 years. Mean OS was lower and RR of death greater in older (P < .001), black (P = .007) patients with a secondary malignancy (P = .015) and ≥ 2 comorbidities (P = .005), whose surgical specimen had positive surgical margins (P = .026) or positive lymph nodes (P < .001). Multivariate cox regression demonstrated that positive lymph nodes (hazard ratio [HR], 6.47; 95% CI, 1.81-23.11) and older age (HR, 2.35; 95% CI, 1.25-4.43) were associated with lower OS.
CONCLUSION: PC is a rare malignancy with a 5-year OS of 81.1%. Positive lymph nodes and older age predict lower OS and an increased risk of death.

Hsu KT, Sippel RS, Chen H, Schneider DF
Is central lymph node dissection necessary for parathyroid carcinoma?
Surgery. 2014; 156(6):1336-41; discussion 1341 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Parathyroid carcinoma is a rare cancer. Unlike other more common malignancies, the importance of lymph node (LN) status remains controversial. The purpose of this study was to determine the relative importance of LN metastases in disease-specific survival (DSS).
METHODS: A retrospective review of the Surveillance, Epidemiology, and End Result database was performed on parathyroid carcinoma cases diagnosed between 1988 and 2010.
RESULTS: We identified 405 parathyroid carcinoma patients. Among 114 patients with LNs examined at operation, only 12 (10.5%) had positive LNs. Sensitivity analysis found that a tumor size threshold of 3 cm best divided the cohort by DSS. Only tumors ≥ 3 cm and distant metastasis but not LN metastases were independent prognostic factors on multivariate analysis. When examining factors associated with LN status, only tumors ≥ 3 cm predicted LN metastasis. LN metastases were 7.5 times more likely in patients with tumors ≥ 3 cm than those with tumors <3 cm.
CONCLUSION: Tumors ≥ 3 cm were associated with LN metastases in parathyroid carcinoma, but positive LN status was not associated with DSS. Tumor size can potentially risk stratify patients by their risk of LN metastases.

Villar-del-Moral J, Jiménez-García A, Salvador-Egea P, et al.
Prognostic factors and staging systems in parathyroid cancer: a multicenter cohort study.
Surgery. 2014; 156(5):1132-44 [PubMed] Related Publications
BACKGROUND: Parathyroid carcinoma (PC) is an uncommon disease that generally is detected postoperatively and traditionally is associated with a poor prognosis. Our purpose was to evaluate treatment outcomes, prognostic factors, and usefulness of some proposed staging systems for this disease.
METHODS: A multicenter review of patients with surgically resected PC was performed, led by the Spanish Association of Surgery. All surgical units affiliated with its endocrine surgery section were invited to answer a questionnaire that collected several hospital-related, clinical, biochemical, operative, pathologic, and follow-up data. Their relationships with prognosis were assessed by both univariate and multivariate analysis, as well as the effectiveness of three staging systems for parathyroid carcinoma.
RESULT: Of the 6,863 patients undergoing parathyroidectomy, 62 (0.9%) had PC. Of them, 12 (19.3%) died, in 5 cases (8%) because of disease, and 14 (22.6%) suffered recurrence, after a median follow-up of 55 months. The most predictive independent variables on tumor recurrence were intraoperative tumor rupture (hazard ratio [HR] 6.22; 95% confidence interval [CI] 1.19-32.36; P = .030); the presence of mitotic figures within tumor parenchyma cells (HR 4.76; 95% CI 1.24-18.21; P = .022); and allocation in class III according to Schulte differentiated staging classification (HR 5.23; 95% CI 1.41-19.31; P = .013). As to disease-specific survival, poor outcomes were associated with intraoperative tumor rupture (HR 58.71; 95% CI 2.39-1,439.96; P = .013) and distant recurrence (HR 38.74; 95% CI 3.44-435.62; P = .003).
CONCLUSION: In addition to factors associated with tumor histopathology and stage, prognosis of PC is greatly influenced by surgeon's performance, which emphasizes the importance of preoperative diagnosis.

Mehta A, Patel D, Rosenberg A, et al.
Hyperparathyroidism-jaw tumor syndrome: Results of operative management.
Surgery. 2014; 156(6):1315-24; discussion 1324-5 [PubMed] Article available free on PMC after 01/12/2015 Related Publications
BACKGROUND: Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a rare, autosomal-dominant disease secondary to germline-inactivating mutations of the tumor suppressor gene HRPT2/CDC73. The aim of the present study was to determine the optimal operative approach to parathyroid disease in patients with HPT-JT.
METHODS: A retrospective analysis of clinical and genetic features, parathyroid operative outcomes, and disease outcomes in 7 unrelated HPT-JT families.
RESULTS: Seven families had 5 distinct germline HRPT2/CDC73 mutations. Sixteen affected family members (median age, 30.7 years) were diagnosed with primary hyperparathyroidism (PHPT). Fifteen of the 16 patients underwent preoperative tumor localization studies and uncomplicated bilateral neck exploration at initial operation; all were in biochemical remission at most recent follow-up. Of these patients, 31% had multiglandular involvement; 37.5% of the patients developed parathyroid carcinoma (median overall survival, 8.9 years; median follow-up, 7.4 years). Long-term follow-up showed that 20% of patients had recurrent PHPT.
CONCLUSION: Given the high risk of malignancy and multiglandular involvement in our cohort, we recommend bilateral neck exploration and en bloc resection of parathyroid tumors suspicious for cancer and life-long postoperative follow-up.

Wang X, Wang M, Zhang J, et al.
Humeral brown tumor as first presentation of primary hyperparathyroidism caused by ectopic parathyroid adenomas: report of two cases and review of literature.
Int J Clin Exp Pathol. 2014; 7(10):7094-9 [PubMed] Article available free on PMC after 01/12/2015 Related Publications
Two cases of brown tumor of the humerus caused by ectopic parathyroid adenomas were presented, which to our knowledge has not been previously documented in the international literature. There are two highlights in these two cases. First, brown tumors of the long bones may commonly involve femur and tibia, rarely involve humerus in association with primary hyperparathyroidism. Second, ectopic parathyroid adenomas of our patient had an unusual location of this disorder. We explored the role of ultrasound, MIBI scintigraphy as well as FNAB (fine needle aspiration biopsy) in diagnosis of brown tumor especially simultaneously occurrence of ectopic parathyroid adenomas and the importance of a thorough diagnostic work-up. The contemporary diagnosis and treatment options will be emphasized.

Gedik GK, Ata O, Karabagli P, Sari O
Differential diagnosis between secondary and tertiary hyperparathyroidism in a case of a giant-cell and brown tumor containing mass. Findings by (99m)Tc-MDP, (18)F-FDG PET/CT and (99m)Tc-MIBI scans.
Hell J Nucl Med. 2014 Sep-Dec; 17(3):214-7 [PubMed] Related Publications
Brown tumor is one of the skeletal manifestations of hyperparathyroidism. It is a benign but locally aggressive bone lesion and its differential diagnosis with giant cell containing skeletal tumors or metastases may be complicated. We present a male patient with chronic renal failure who was initially misdiagnosed as having a giant-cell rich neoplasm of bone in his right thumb. Diffusely increased fluorine-18 fluorodeoxyglucose ((18)F-FDG) uptake in the axial and appendicular skeleton and multiple (18)F-FDG avid lytic lesions suggesting multiple metastases were observed on the (18)F-FDG positron emission tomography/computed tomography (PET/CT) scan. On the usual technetium-99m methylene diphosphonate ((99m)Tc-MDP) bone scan we noticed diffusely increased uptake in the skeleton and two focuses with very much increased uptake, which suggested a metabolic bone disease rather than a multiple metastatic giant cell tumor or bone metastases. Additional investigation documentated increased levels of parathyroid hormone. Parathyroid hyperplasia was finally diagnosed with (99m)Tc-methoxyisobutylisonitrile (MIBI) parathyroid scintigraphy. Fluorine-18-FDG avid lytic lesions were attributed to hyerparathyroidism associated brown tumors instead of multiple metastases. In conclusion, we present a patient with chronic renal insufficiency, who suffered from secondary and later from tertiary HPT with polyostotic brown tumors, which were best shown by the (18)F-FDG PET/CT than by the (99m)Tc-MDP or the (99m)Tc-MIBI scans.

Yu W, McPherson JR, Stevenson M, et al.
Whole-exome sequencing studies of parathyroid carcinomas reveal novel PRUNE2 mutations, distinctive mutational spectra related to APOBEC-catalyzed DNA mutagenesis and mutational enrichment in kinases associated with cell migration and invasion.
J Clin Endocrinol Metab. 2015; 100(2):E360-4 [PubMed] Related Publications
CONTEXT: Cell division cycle 73 (CDC73), encoding the protein parafibromin, is the most prevalent mutated gene in familial and sporadic parathyroid carcinoma (PC).
OBJECTIVE: To identify additional genetic abnormalities in PCs.
DESIGN: Whole-exome sequencing was performed using DNA from seven pairs of matched PCs and one triplet containing double primary tumor and normal leukocyte. Somatic variants were confirmed using Sanger sequencing and recurrently mutated genes were assessed in 13 additional PCs as well as 40 parathyroid adenomas (PA).
RESULTS: PC had an average of 51 somatic variants/tumor (range 3-176) with approximately 58% of variants occurring as nonsynonymous single nucleotide variants. The importance of CDC73 in PC is reinforced with a remarkable preferential amplification of the mutant CDC73 allele. Furthermore, recurrent germ line and somatic mutations in prune homolog 2 [Drosophila] (PRUNE2) were found in PC and computationally predicted to be deleterious; in addition, recurrent mutations in kinase genes related to cell migration and invasion were found. PRUNE2 showed recurrent mutations in 18% (4/22) of PCs with additional screening in 40 PAs revealing only one rare missense polymorphism (Asp1677Asn). For the first time, the mutational signature associated with apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC)-catalyzed cytosine-to-uracil deamination is found in a subset of PC.
CONCLUSION: This study outlines the genetic landscape of PC and attempts to characterize the mutational processes shaping the PC genome.

Karras SN, Koutelidakis I, Anagnostis P, et al.
A rare case of a parathyroid adenoma inside a parathyroid cyst.
Arq Bras Endocrinol Metabol. 2014; 58(7):776-8 [PubMed] Related Publications
Parathyroid cysts (PCs) are rare lesions, located in the neck and anterior mediastinal region. The vast majority are non-functioning, presented as nodular cervical lesions. Large, non-functioning PCs can manifest with compressive symptoms of the surrounding tissues. Rarely, PCs produce excessive amounts of parathyroid hormone (PTH), resulting in primary hyperparathyroidism. We report a case of functional PC, describing its diagnostic and therapeutic approach.

Barker HS, Podoll MB, Parker JR, et al.
Parathyroid carcinoma with intracranial metastasis at diagnosis in a patient with uncontrolled hypercalcemia.
Ann Clin Lab Sci. 2014; 44(4):484-8 [PubMed] Related Publications
Parathyroid carcinoma is an uncommon malignancy and a rare cause of primary hyperparathyroidism. Although this tumor is capable of metastasis, metastatic disease is very uncommon intracranially, with only seven cases reported in the literature. When intracranial metastases occur, they typically present months to years following the diagnosis of the primary tumor with hypercalcemia refractory to medical conservative treatment. Aggressive surgical resection of all metastases is necessary for control of the disease. We report a case of metastatic parathyroid carcinoma with two intracranial metastatic foci (in the left frontal lobe and left cerebellar hemisphere) identified at the time of the primary tumor diagnosis in a patient who presented with symptomatic hypercalcemia.

Aliabadi-Wahle S, Kelly TL, Rozenfeld Y, et al.
Treatment strategies for primary hyperparathyroidism: what is the cost?
Am Surg. 2014; 80(11):1146-51 [PubMed] Related Publications
Primary hyperparathyroidism (HPT) contributes to the onset of many chronic conditions. Although parathyroidectomy is the only definitive treatment, observation remains a valid option. Over a 3-year span, a major health plan was queried for HPT and benign parathyroid neoplasm. Patients with secondary and tertiary HPT, Stage III to V kidney disease, and prior renal transplant were excluded. Patients were divided into: observation (Group 1), parathyroidectomy during the study period (Group 2), and parathyroidectomy before the study group (Group 3), and were compared with a control group of 27,092 adult members without HPT using analysis of variance. The 3-year mean total allowed expenditure for Group One (n = 559), Group Two (n = 93), and Group Three (n = 48) were $21,267, $37,043, and $14,702, respectively. Groups One and Two had significantly higher use than the nonparathyroid group (P < 0.0001), whereas that of Group Three was comparable. Group Two had the highest cost, whereas Group Three had a significantly lower cost than Group One (P 0.0001). Primary hyperparathyroidism is associated with a higher use of healthcare resources. Patients observed incurred a higher allowed expenditure than those with prior parathyroidectomy. Surgical treatment may represent a cost-effective strategy for treatment of hyperparathyroidism, although more comprehensive studies are needed to confirm these findings.

Zein RK, Jolepalem P, Wong CO
Implications of unexpected diffuse lung uptake on a 99mTc-sestimibi parathyroid scan.
J Nucl Med Technol. 2015; 43(1):64-5 [PubMed] Related Publications
Diffuse (99m)Tc-sestimibi uptake in the lungs is a sign of serious pathology and merits further work-up. We present a case in which diffuse lung uptake was incidentally found on a parathyroid scan.

Forde HE, Hill AD, Smith D
Parathyroid adenoma in a patient with familial hypocalciuric hypercalcaemia.
BMJ Case Rep. 2014; 2014 [PubMed] Related Publications
A 57-year-old man with symptoms of fatigue, joint pains and insomnia was found to have hypercalcaemia secondary to hyperparathyroidism with a corrected calcium of 2.61 mmol/L (2.2-2.6 mmol/L) and a serum parathyroid hormone (PTH) of 86 pg/mL (10-65 pg/mL). Preoperative workup demonstrated a parathyroid adenoma in the right upper position and he proceeded to surgery. Postoperatively, however, his symptoms remained unchanged and the corrected calcium remained elevated at 2.87 mmol/L with a PTH of 59 pg/mL. He had no family history of hypercalcaemia. Further investigations revealed low 24 h urinary calcium level and a low urine calcium to creatinine ratio. Genetic testing revealed a mutation in exon 4 of the calcium sensing receptor (CaSR) confirming a diagnosis of familial hypocalciuric hyercalcaemia (FHH). The case is an example of a rare phenomenon when a parathyroid adenoma develops in patients with FHH.

Sayar H, Sahin M, Dogan PO, et al.
Immunohistochemical expression of Insulin-like growth factor-1, Transforming growth factor-beta1, and Vascular endothelial growth factor in parathyroid adenoma and hyperplasia.
Indian J Pathol Microbiol. 2014 Oct-Dec; 57(4):549-52 [PubMed] Related Publications
BACKGROUND: Insulin-like growth factor (IGF), transforming growth factor-beta1 (TGF-β1), and vascular endothelial growth factor (VEGF) are commonly studied growth factors, but little data are available on the immunohistochemical expression of these factors in parathyroid lesions.
MATERIALS AND METHODS: Tissue specimens from 36 patients with primary hyperparathyroidism (P-HPT) (26 adenomas and 10 primary hyperplasias) were examined. Normal parathyroid tissue adjacent to the adenoma or area of hyperplasia was used as control tissue. Preoperative laboratory testing [serum Ca and P, creatinine and parathormone levels (PTH)] which led to the diagnosis of P-HPT had been performed, the size and weight of the parathyroid glands measured, and postoperative serum PTH levels determined. Paraffin-embedded parathyroid tissue specimens were stained with antibodies to IGF-1, VEGF, and TGF-β1 using standard immunohistochemical procedures.
RESULTS: IGF-1 immunoreactivity was seen in 50% of hyperplasia and in 46% of adenoma samples, but in 87% of normal parathyroid tissue in the vicinity of the adenomas (P = 0.005). TGF-β1 immunoreactivity was observed in 90% of hyperplasia, in 92% of adenoma samples, and in 95% of normal tissues around adenomas. VEGF immunoreactivity was observed in 70% of hyperplastic and 65% of adenomatous tissues, as well as in 54% of normal tissues in the vicinity of the adenoma. No significant differences in the expression of IGF-1, TGF-β1, and VEGF were observed between primary adenomas compared to hyperplasia samples (P > 0.05).
CONCLUSIONS: Parathyroid tissue is clearly a site for production of IGF-1, TGF-β1, and VEGF. IGF-1 receptor activity was higher in normal parathyroid tissue compared to hyperplastic and adenomatous tissue.

Orevi M, Freedman N, Mishani E, et al.
Localization of parathyroid adenoma by ¹¹C-choline PET/CT: preliminary results.
Clin Nucl Med. 2014; 39(12):1033-8 [PubMed] Related Publications
PURPOSE: This prospective pilot study was aimed to evaluate ¹¹C-choline PET/CT (choline) as a tool for localization of parathyroid adenoma (PTA).
METHODS: Forty patients with biochemical hyperparathyroidism underwent choline and ⁹⁹mTc-MIBI imaging within a median interval of 56 days. Choline and MIBI images were analyzed and correlated with each other, with additional modalities such as ultrasound, CT, MRI, and with surgical findings, when available.
RESULTS: Thirty-seven of forty cases were choline-positive, and 3 were choline-negative. Choline uptake on PET was identified with corresponding nodules on CT of the PET/CT, yielding precise localization. Twenty of thirty-seven foci were located in typical sites in the neck, and 17 were ectopic. Clear visualization of PTA was achieved in 33 of 37, whereas findings in 4 cases were suspicious for PTA. MIBI was positive in 33 of 40 cases (22 clearly positive, 11 suspicious). In 29 of 40 cases, choline and MIBI were concordant, but choline findings were clearer in 9 of these 29 studies.At the time of writing, 27 patients had undergone surgery. In 24 cases, there was complete matching of choline with surgical findings of PTA. Overall in 23 cases, both choline and MIBI matched surgical findings of PTA. In 1 case, PTA was correctly localized on choline but not on MIBI, and in 2 cases, neither choline nor MIBI corresponded to the surgical findings.
CONCLUSIONS: These preliminary results indicate that the combined functional and anatomical modality of choline PET/CT is a promising tool for PTA localization, providing clearer images than MIBI, equal or better accuracy, and quicker and easier acquisition.

Noureldine SI, Aygun N, Walden MJ, et al.
Multiphase computed tomography for localization of parathyroid disease in patients with primary hyperparathyroidism: How many phases do we really need?
Surgery. 2014; 156(6):1300-6; discussion 13006-7 [PubMed] Related Publications
BACKGROUND: Multiphase computed tomography (CT) involves multiple cervical CT acquisitions to accurately identify hyperfunctional parathyroid glands, thus increasing radiation exposure to the patient. We hypothesized that only 2 cervical acquisitions, instead of the conventional 4, would provide equivalent localization information and halve the radiation exposure.
METHODS: We identified 53 consecutive patients with primary hyperparathyroidism who underwent multiphase CT before parathyroidectomy. All scans were reinterpreted first using 2 phases then using all 4 phases. The accuracies of interpretations were determined with surgical findings serving as the standard of reference.
RESULTS: Sixty-four hyperfunctional parathyroid glands were resected with a mean weight of 394.3 mg. Two-phase CT lateralized the hyperfunctional glands in 38 patients with a sensitivity, positive predictive value (PPV), and accuracy of 100%, 71.7%, and 71.7%, respectively. Four-phase CT lateralized the hyperfunctional glands in 39 patients with a sensitivity, PPV, and accuracy of 95.1%, 76.5%, and 73.6%, respectively. For quadrant localization, the accuracy of 2-phase and 4-phase CT was 50.9% and 52.8%, respectively.
CONCLUSION: Our results suggest that 2-phase and 4-phase CT provide an equivalent diagnostic accuracy in localizing hyperfunctional parathyroid glands. The reduced radiation exposure to the patient may make 2-phase acquisitions a more acceptable alternative for preoperative localization.

Salido S, Gómez-Ramírez J, Bravo JM, et al.
Parathyroid adenoma in third pharyngeal pouch cyst as a rare case of primary hyperparathyroidism.
Ann R Coll Surg Engl. 2014; 96(7):e8-10 [PubMed] Related Publications
The primitive thymus and inferior parathyroid derive from the third branchial cleft. During embryonic development, these structures descend, reaching their final localisation. Third branchial cleft anomalies present usually as a fistula, abscess or cyst. However, there are no reports on parathyroid adenomas in the literature other than as a morphological possibility. We describe the case of a 47-year-old man, who had been diagnosed with arterial hypertension and who presented with a cervical mass at the edge of the lower third of the sternocleidomastoid muscle. On ultrasonography, the mass had a cystic walled appearance. Laboratory analysis only revealed an intact parathyroid hormone level of 140.5 pg/ml. Sestamibi imaging showed a probable parathyroid adenoma in the anterior mediastinum. During surgery, a tract running from beyond the superior thyroid pedicle to the superior mediastinum was dissected and removed. In the inferior end of the tract, a brown mass was visible. Pathological examination revealed a thymus cyst surrounding a parathyroid adenoma. The primal alteration was the lack of division between the thymus and inferior parathyroid gland, and the prompt prevention of their development. In the case of our patient, a parathyroid adenoma had grown by chance.

Hayakawa N, Nakamoto Y, Kurihara K, et al.
A comparison between 11C-methionine PET/CT and MIBI SPECT/CT for localization of parathyroid adenomas/hyperplasia.
Nucl Med Commun. 2015; 36(1):53-9 [PubMed] Related Publications
OBJECTIVE: The purpose of this study was to compare the sensitivity of single-photon emission computed tomography/computed tomography (SPECT/CT) using 99mTc-sestamibi (MIBI) with that of PET/CT using 11C-methionine (MET) for localization of parathyroid adenomas/hyperplasia in primary hyperparathyroidism.
MATERIALS AND METHODS: Twenty-three patients with primary hyperparathyroidism were analyzed. Fifteen patients underwent surgery, and the remaining eight did not, but these patients were clinically diagnosed as having primary hyperparathyroidism. Patients underwent both MET PET/CT and MIBI SPECT/CT scanning. The sensitivities of both modalities were evaluated on a per-patient basis, and on a per-lesion basis for parathyroid lesions detected by surgery. The size of the parathyroid adenoma/hyperplasia and serum intact parathyroid hormone levels were compared with the results of each of the two modalities.
RESULTS: Per-patient sensitivities of MET PET/CT and MIBI SPECT/CT were 65 and 61%, respectively. Per-lesion sensitivities of MET PET/CT and MIBI SPECT/CT were 91 and 73% for histologically confirmed adenomas and 30 and 30% for hyperplastic glands, respectively. No significant differences were observed between the two modalities. The size of uptake-positive lesions was significantly larger than that of uptake-negative lesions in both modalities. Intact parathyroid hormone levels showed no significant difference between uptake-positive and uptake-negative patients in both modalities.
CONCLUSION: The sensitivities of MET PET/CT and MIBI SPECT/CT were comparable. MET PET/CT has a complementary role in localizing parathyroid adenomas/hyperplasia when MIBI SPECT/CT is inconclusive.

Chiriac A, Stanciu R, Brzezinski P, Feldman SR
Not French manicure but onycholysis.
Dermatol Online J. 2014; 20(9) [PubMed] Related Publications
French manicure, a simple and elegant manicure style, caught the public's attention by the 19th century in French nail salons. Now this style has spread all over the world and is the first choice of 80% of women in the USA and Europe. It consists of a natural, pink, beige, or nude base tipped with pure white at the distal end.Onycholysis is a disease of the nails characterized by separation of the nail plate from the nail bed, with variable causes. We present 2 cases of onycholysis that resemble the beautiful and elegant French manicure.

Rajaei MH, Oltmann SC, Adkisson CD, et al.
Is intraoperative parathyroid hormone monitoring necessary with ipsilateral parathyroid gland visualization during anticipated unilateral exploration for primary hyperparathyroidism: a two-institution analysis of more than 2,000 patients.
Surgery. 2014; 156(4):760-6 [PubMed] Related Publications
INTRODUCTION: Intraoperative parathyroid hormone (ioPTH) monitoring during focused parathyroidectomy for primary hyperparathyroidism (PHPT) is used commonly, but some argue that ioPTH adds little if a normal ipsilateral parathyroid gland (IPG) is visualized. This hypothesis was tested for validity.
METHODS: The prospective databases of consecutive patients with PHPT undergoing initial parathyroidectomy with ioPTH at two academic institutions were queried. Patients with ectopic adenoma, familial PHPT, previous parathyroidectomy, planned bilateral exploration, or <6 months follow-up were excluded. Persistence was defined as hypercalcemia at <6 months.
RESULTS: From 1998 to 2013, 2,162 patients met inclusion criteria, and the rate of persistent disease was 1.5%. Most (n = 1,353; 63.5%) underwent single-gland resection with ioPTH and no IPG visualization, with 1% persistence. Among patients with a single adenoma resected and a normal IPG visualized, 15.2% had contralateral disease. Resection based on IPG appearance alone would have resulted in 13% persistent disease.
CONCLUSION: In PHPT, the cure rate for initial unilateral exploration guided by ioPTH is 98.5% versus a predicted rate of 87% when decision making is based on IPG appearance alone. Routine visualization of IPG is not necessary during exploration for suspected single adenoma guided by ioPTH. ioPTH remains useful in optimizing outcomes.

Neagoe RM, Sala DT, Borda A, et al.
Clinicopathologic and therapeutic aspects of giant parathyroid adenomas - three case reports and short review of the literature.
Rom J Morphol Embryol. 2014; 55(2 Suppl):669-74 [PubMed] Related Publications
In the last decade, the clinical picture of primary hyperparathyroidism has changed, with the majority of patients being diagnosed while asymptomatic and the "classical" clinical pattern characterized by bone disease, recurrent nephrolithiasis, peptic ulcer disease, neurological or psychiatric disorders being rarely encountered. In this context, most patients have minimal hypercalcemia and small parathyroid adenomas. Not surprisingly, giant parathyroid adenomas have seldom been described in the literature. We herein report three cases of giant parathyroid adenomas weighing more than 30 g and discuss their clinicopathological and therapeutic particularities. We also review the relevant literature, with the principal aim of outlining the rarity of these giant parathyroid adenomas and the issues concerning their diagnosis and treatment.

Pimentel L, Portela S, Loureiro A, Bandeira F
Normocalcemic primary hyperparathyroidism: long-term follow-up associated with multiple adenomas.
Arq Bras Endocrinol Metabol. 2014; 58(5):583-6 [PubMed] Related Publications
Normocalcemic primary hyperparathyroidism (NPHPT) is a condition characterized by elevation of the parathyroid hormone (PTH) in the presence of normal serum calcium and the absence of secondary causes. The case described illustrates the long-term follow-up of a postmenopausal woman with NPHPT patient who progressed with multiple adenomas. This case reports a 77-year-old female who has chronic generalized pain and osteoporosis. Her initial serum PTH was 105 pg/mL, with total serum calcium of 9.6 mg/dL, albumin 4.79 g/dL, phosphorus 2.8 mg/dL, and 25OHD after supplementation was 34.6 ng/mL. The bone densitometry (BMD) results were as follows: lumbar spine: T-score -3.0, femoral neck: T-score -2.6 and distal radius: -4.2. Other causes of secondary hyperparathyroidism were ruled out and cervical ultrasound and Tc-99-Sestamibi scan were negative. She used oral alendronate and three infusions of zoledronic acid for treatment of osteoporosis. In the 10th year of follow-up, after successive negative cervical imaging, ultrasound showed a nodule suggestive of an enlarged right inferior parathyroid gland. PTH levels in fluid which was obtained during fine-needle aspiration (FNA) were over 5,000 pg/mL and a Sestamibi scan was negative. The patient underwent parathyroidectomy, and a histological examination confirmed parathyroid adenoma. Post-operatively serum PTH remained elevated in the presence of normal serum calcium levels. A follow-up cervical ultrasound showed a new solid nodule suggestive of an enlarged right superior parathyroid gland. PTH levels in the aspiration fluid were remarkably high. A second parathyroidectomy was performed, with the excision of a histologically confirmed parathyroid adenoma. In conclusion, this is an unusual presentation of NPHPT and highlights the long-term complications.

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