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Mediastinal parathyroid carcinoma (PC) is a rare entity in primary hyperparathyroidism. The aim of this report is to demonstrate a case of mediastinal PC, and to provide a systemic literature review of this rare condition. A 34-year-old woman who had already undergone two cervical operations for hyperparathyroidism suffered from another recurrence, presenting with recurrent acute pancreatitis and persistent hypercalcemic crisis. Technetium-99 methoxyisobutylisonitrile imaging (MIBI) and computed tomography scanning (CT) identified three possible parathyroid tumors, one of which was the recurrence of residual tumor locating in the thyroid region, while the other two were ectopic tumors locating in the suprasternal fossa and thymus region, respectively. Pathological examination confirmed the diagnosis of PC. We conducted a systemic literature review by searching the PubMed MEDLINE from 1951 to 2019 for studies of all types in the English language only, using terms "mediastinal, mediastinum, parathyroid, carcinoma." Including our reported case, a total of 21 cases with ectopic mediastinal PCs were assessed for demographic data, tumor location and size, biochemical findings, and symptomatology, etc. Two thirds of the patients were men, with a mean age of 44 years old, a mean serum calcium of 14.2 mg/dl, and a mean serum intact parathyroid hormone of 1,216 pg/ml. We identified 89.5% of carcinomas in the anterosuperior mediastinum, and 10.5% in the middle mediastinum, with a mean diameter of 54 mm, and a mean weight of 216 g. MIBI and CT were the most commonly used methods to localize these mediastinal tumors, with 69.2 and 100% sensitivity, respectively. Half of the patients underwent more than one operation. Diagnosis and treatment of mediastinal PCs represent a challenge. Early suspicion, appropriate preoperative localization studies, and the cooperation of endocrinologists and surgeons are crucial in the effective management., (Copyright © 2020 Jiajue, Song, Wang and Li.)

This report summarizes published data on parathyroid cancer, with the inclusion of topics discussed at MEN2019: 16th International Workshop on Multiple Endocrine Neoplasia, 27-29 March 2019, Houston, TX, USA. An expert panel on parathyroid cancer was constituted by the Steering Committee to address key questions in the field. The objectives were to recap open forum discussion of interested parties from multiple disciplines. The expert panel met in a closed session to consult on the data to be highlighted on the evidence-based results and on the future directions. Preceding the Conference, members of the expert panel conducted an extensive literature search. All presentations were based upon the best peer-reviewed information taking into account the historical and current literature. Questions were developed by the expert panel on parathyroid carcinoma. A comprehensive literature search for relevant studies was undertaken. This report represents the expert panel's synthesis of the conference material placed in a context designed to be relevant to clinicians and those engaged in cutting-edge studies of parathyroid carcinoma. This document not only provides a summary of our current knowledge but also places recent advances in its management into a context that should enhance future advances in our understanding of parathyroid carcinoma.

Tc-99m sestamibi single-photon emission computed tomography/computed tomography (SPECT/CT) has been used to help surgeons explore the location of parathyroid diseases, but quantitative parameters have not been systemically investigated for this purpose. We aimed to establish objective criteria for adenoma and hyperplasia using the standardized uptake value (SUV) in patients with hyperparathyroidism.Thirty-nine hyperparathyroid patients (male/female: 17/22, age: 58.33 ± 11.69 years) with at least 1 uptake-positive lesion of any degree by visual assessment in preoperative Tc-99m sestamibi quantitative SPECT/CT were included from Oct 2015 to Oct 2017. Pathologically, 44 lesions (32 adenomas and 12 hyperplasia) were identified. All patients experienced normalized levels of intact parathyroid hormone immediately after surgery. Quantitative SPECT/CT was performed at 10 minute and 2 hour post injection of Tc-99m sestabmibi (dose = 740 MBq), and maximum SUV (SUVmax) was measured for the parathyroid lesions. Experienced pathologists evaluated the percentage cellular proportions of chief cells, oxyphil cells, and clear cells.SUVmax (g/mL) of adenomas, hyperplasia, and reference thyroid tissue were 12.92 ± 6.68, 7.90 ± 5.49, and 7.01 ± 2.62 at 10min (early phase), decreasing to 7.46 ± 5.66, 4.65 ± 3.14, and 2.21 ± 1.07 at 2 hour (delayed phase), respectively. The adenomas showed significantly higher SUVmax than both the hyperplasia (P = .0131) and reference thyroid tissue (P < .0001) along the early and delayed phases, but the SUVmax of the hyperplasia did not differ from that of the reference thyroid tissue (P = .4196). The adenomas and hyperplasia were discriminated from the reference thyroid tissue using a cutoff SUVmax of 3.26 at the delayed phase. The adenomas had lower %proportions of oxyphil cells than the hyperplasia (P = .0054), but its SUVmax at the delayed phase was positively correlated with the %proportions of mitochondria-abundant oxyphil cells (rho = 0.418, P = .0173). The hyperplasia showed no correlation between SUVmax and cellular proportions.SUVmax at the delayed phase in the Tc-99m sestamibi quantitative SPECT/CT was useful for the identification and differentiation of parathyroid lesions causing hyperparathyroidism.

Primary hyperparathyroidism is a common endocrinopathy that is mainly caused by benign parathyroid adenomas. The frequency, clinical presentation and complications of the disease show significant differences between genders, with the majority of cases being reported in postmenopausal women. Due to this gender predilection, several studies have investigated the role of sex hormones in the pathogenesis of the disease and their potential use as targets for optimal and gender-specific management. Epigenetic mechanisms that regulate gene transcription may also contribute to these differences between genders. In this review, we outline what is currently known regarding the role of sex hormones and the recent data on the role of non-coding RNAs in the differences between genders in primary hyperparathyroidism due to sporadic parathyroid adenomas., Competing Interests: The authors declare no conflict of interest.

A 77-year-old man with a history of hypertension, prostate hyperplasia, and urolithiasis was admitted for acute kidney injury caused by hypercalcemia. Neck ultrasonography showed a large cyst adjacent to the right lower thyroid lobe. Although a 99m technetium sestamibi scan was negative, an extremely high intracystic intact parathyroid hormone level suggested that the cyst had a parathyroid origin and that a functional parathyroid cyst was present. Immunohistochemical staining for the calcium-sensing receptor (CaSR) after right lower parathyroidectomy revealed CaSR-positive cells lining the cyst, indicating that the functional parathyroid cyst had originated from the hemorrhagic degeneration of a parathyroid adenoma.

Background: Secondary hyperparathyroidism is a common complication in patients with chronic kidney disease that requires vigilant treatment due to its high mortality rate. Pharmacologic therapy is recommended as an initial treatment; if there is no response, a total parathyroidectomy is performed. In some cases, surgery is accompanied by auto-transplantation of parathyroid tissue., Case Presentation: The patient was diagnosed with chronic kidney disease and received a kidney transplant. However, due to rejection of the transplanted kidney, medical nephrectomy was carried out and routine hemodialysis was initiated and observed. At this time, secondary hyperparathyroidism with elevated parathyroid hormone and hyperphosphatemia developed and pharmacologic treatment was applied. However, there was no response to pharmacologic treatment; therefore, total parathyroidectomy with auto-transplantation was performed. Eight years after surgery, a growing mass was observed in the transplantation site, accompanied by an elevation of parathyroid hormone. A complete resection of the mass was performed, and the patient was diagnosed with parathyroid carcinoma. Additional adjuvant radiation therapy was ordered, and the patient is being monitored., Conclusions: This is a rare but remarkable case of parathyroid carcinoma arising from auto-transplanted parathyroid tissue after total parathyroidectomy in a patient with secondary hyperparathyroidism. We suggest caution should be taken when choosing to auto- transplant parathyroid tissue and that careful postoperative observation should be performed.

Background: Parathyroid carcinoma is a rare neoplasm that may present sporadically or in the context of a genetic syndrome. Diagnosis and management are challenging due to the lack of clinical and pathological features that may reliably distinguish malignant from benign disease., Methods: From January 2013 to December 2017, from 358 consecutive patients affected by parathyroid diseases, 3 patients with parathyroid carcinoma were treated at our academic Department of General Surgery. We present our experience as illustrative of the different features of clinical presentation of parathyroid carcinoma and review its management considering the recent relevant literature., Results: Case 1: A 62-year-old man was hospitalized for left-sided palpable neck mass, hypercalcemia and elevated PTH. US-guided FNA was suspect for parathyroid carcinoma. A large cystic mass was excised in bloc with total thyroidectomy and central neck dissection. Genetic studies framed a pathologically confirmed parathyroid carcinoma within MEN1 syndrome. Case 2: A 48-year-old woman with hypothyroidism had total thyroidectomy performed for a suspect for right follicular thyroid lesion. Pathology revealed parathyroid carcinoma. Case 3: A 47 year-old man was admitted for hypercalcaemic crisis and renal failure in the context of PHPT. A lesion suggestive on US and MIBI scan for parathyroid adenoma in the right lower position was removed by mini-invasive approach. Pathology revealed parathyroid cancer and patient had completion hemythyroidectomy and central neck dissection., Conclusion: Parathyroid cancer is a particularly rare endocrine malignancy, however it should be suspected in patients with primary hyperparathyroidism when severe hypercalcemia is associated to cervical mass, renal and skeletal disease. Parathyroid surgery remains the mainstay of treatment. Radical tumour resection and expedited treatment in a dedicated endocrine Center represent crucial prognostic factors.

Background: Parathyroid tumors are mostly considered monoclonal neoplasms, the rationale for focused parathyroidectomy in primary hyperparathyroidism. We reported that flow sorting parathyroid tumor cells and methylation-sensitive polymerase chain reaction (me-PCR) of polymorphic human androgen receptor gene and phosphoglycerate kinase gene alleles in deoxyribonucleic acid reveals that ≤35% of parathyroid tumors are polyclonal. We sought to confirm these findings and assess for clinical relevance., Methods: Parathyroid tumors from 286 female primary hyperparathyroidism patients were analyzed for clonal status. Tumor clonal status was compared with clinical variables and operative findings. Statistical analysis was performed and significance was established at P < .05., Results: In the study, 176 (62%) patients were informative for human androgen receptor gene and/or phosphoglycerate kinase gene. Assignment of clonal status was made in 119 (68%) tumors, of which 64 (54%) were monoclonal and 55 (46%) were polyclonal. Comparison of tumor clonal status to clinical variables in patients with complete operative data (N = 82) showed that while clinical features were the same between tumor types, patients with polyclonal tumors more often had multiple gland disease (risk ratio 4.066, confidence interval, 1.016-16.26; P = .039) potentially missed at unilateral neck exploration., Conclusion: This work confirms that primary hyperparathyroidism is often the result of polyclonal tumors and that parathyroid tumor clonal status may be associated with multiple gland disease., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objective: Ultrasonography (US) and parathyroid scintigraphy (PS) with 99mTc-MIBI are common methods for preoperative localization of parathyroid adenomas but there discrepancies exist with regard to diagnostic accuracy. The aim of the study was to compare PS and US for localization of parathyroid adenoma with a systematic review and meta-analysis of the literature. Methods: Pub Med, Scopus (EMbase), Web of Science and the reference lists of all included studies were searched up to 1st January 2016. The search strategy was according PICO characteristics. Heterogeneity between the studies was accounted by P < 0.1. Point estimates were pooled estimate of sensitivity, specificity and positive predictive value of SPECT and ultrasonography with 99% confidence intervals (CIs) by pooling available data. Data analysis was performed using Meta-DiSc software (version 1.4). Results: Among 188 studies and after deletion of duplicated studies (75), a total of 113 titles and abstracts were studied. From these, 12 studies were selected. The meta-analysis determined a pooled sensitivity for scintigraphy of 83% [99% confidence interval (CI) 96.358 -97.412] and for ultra-sonography of 80% [99% confidence interval (CI) 76-83]. Similar results for specificity were also obtained for both approache. Conclusion: According this meta- analysis, there were no significant differences between the two methods in terms of sensitivity and specificity. There were overlaps in 99% confidence intervals. Also features of the two methods are similar., (Creative Commons Attribution License)

Aim: The main goal of our study was to confirm the usefulness of intra-operative parathyroid hormone (PTH) monitoring (ioPTH) when using minimally invasive techniques for treatment of sporadic Primary hyperparathyroidism (pHTP). Furthermore, we aimed to evaluate if ioPTH monitoring may help to predict the etiology of primary hyperparathyroidism, especially in malignant or multiglandular parathyroid disease., Methods: A retrospective review of 125 consecutive patients with pHPT who underwent parathyroidectomy between 2001 and 2016 at the Department of General Surgery was performed. For each patient, the specific preoperative work-up consisted of: high-resolution US of the neck by a skilled sonographer, sestamibi parathyroid scan, laryngoscopy, and serum measurement of PTH, serum calcium levels, and serum 25(OH)D levels., Results: The study included 125 consecutive patients who underwent surgery for pHPT. At the histological examination, we registered 113 patients with simple adenomatous pathology (90,4%), 5 atypical adenomas (4%), 3 cases of parathyroid carcinoma (2,4%),, , and 4 histological exams of different nature (3,2%). Overall, 6 cases (4,8%) of multiglandular disease were found. We reported 10 cases (8%) of recurrent/persistent hyperparathyroidism: 1/10 in a patient affected by atypical adenoma, 9/10 in patients with benign pathology. Regarding these 10 cases, in three (30%) patients, ioPTH wasn't dosed (only frozen section (FS) exam was taken), in 5 cases (50%) ioPTH dropped more than 50% compared to basal value (false negative results), and in 2 (20%) cases, ioPTH did not drop >50% from the first samples taken, the extemporary exam had confirmed the presence of adenoma and the probable second hyperfunctioning adenoma was not found., Conclusions: IoPTH determinations ensure operative success of surgical resection in almost all hyperfunctioning tissue; in particular it is very important during minimally invasive parathyroidectomy, as it allows avoiding bilateral neck exploration. The use of ioPTH monitoring offer increased sensitivity in detecting multiglandular disease and can minimize the need and risk associated with recurrent operations, and may facilitate cost-effective minimally invasive surgery. Moreover, intraoperative PTH monitoring could be a reliable marker to predict a malignant disease during parathyroidectomy, showing higher ioPTH baseline value and superior drop compared to benign disease., (Copyright © 2017 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.)

Parathyroid tumors display reduced sensitivity to extracellular calcium ([Ca 2+ ] o ). [Ca 2+ ] o activates calcium-sensing receptor (CASR), which interacts with the scaffold protein filamin A (FLNA). The study aimed to investigate: (1) the FLNA expression in human parathyroid tumors, (2) its effects on the CASR mRNA and protein expression, and (3) on ERK signaling activation, (4) the effect of the carboxy-terminal CASR variants and (5) of the treatment with the CASR agonist R568 on FLNA-mediated ERK phosphorylation in HEK293 cells. Full-length FLNA immunostaining was variably reduced in parathyroid tumors. Immunofluorescence showed that FLNA localized in membrane and cytoplasm and co-localized with CASR in parathyroid adenomas (PAds)-derived cells. Cleaved C-terminus FLNA fragment could also be detected in PAds nuclear protein fractions. In HEK293 cells transfected with 990R-CASR or 990G-CASR variants, silencing of endogenous FLNA reduced CASR mRNA levels and total and membrane-associated CASR proteins. In agreement, FLNA mRNA levels positively correlated with CASR expression in a series of 74 PAds; however, any significant correlation with primary hyperparathyroidism severity could be detected and FLNA transcript levels did not differ between PAds harboring 990R or 990G CASR variants. R568 treatment was efficient in restoring 990R-CASR and 990G-CASR sensitivity to [Ca 2+ ] o in the absence of FLNA. In conclusion, FLNA is downregulated in parathyroid tumors and parallels the CASR expression levels. Loss of FLNA reduces CASR mRNA and protein expression levels and the CASR-induced ERK phosphorylation. FLNA is involved in receptor expression, membrane localization and ERK signaling activation of both 990R and 990G CASR variants., (© 2017 Society for Endocrinology.)

Multiple Endocrine Neoplasia (MEN) is a condition in which several endocrine organs of an individual are affected by adenoma, hyperplasia and less often carcinoma, either simultaneously or at different stages of life. Two existing syndromes, MEN1 and MEN2 (2A, 2B), in literature is also mentioned MEN4, are associated also with other non-endocrine disorders. MEN1 (Wermer syndrome) affects the pituitary, parathyroid, and pancreatic area. 95 % of patients show very early manifestation of hyperparathyroidism, often before 40 years of age. Multiple adenomas gradually involve all four parathyroid glands. The first clinical sign of MEN1 includes recurrent nephrolithiasis. The second most frequent manifestation of MEN1 is pancreatic area (pancreas, stomach and duodenum), again multiple malignancies of varying degree which can metastasize. Most often gastrinomas and insulinomas are involved. Pituitary adenomas occur in about one third of MEN1 patients and tend to be larger and less responsive to treatment. Tumors appearing most often are prolactinomas, tumors producing growth hormone, or afunctional adenomas. The other endocrine tumors include carcinoids and adrenal lesions. In the last year we have registered four MEN1 syndrome patients in our center and one patient has been already followed since 2008. In four out of five patients, nephrolithiasis after 30 years of age was the first clinical symptom, but only one of theses cases resulted in MEN1 diagnosis. In all patients, the clinical symptoms intensified and the diagnosis was established between 36 and 40 years of age. A crutial factor is a cooperation with the urology examination of kidney stones formation in young individuals with nephrolithiasis in order to reveal the potential cases of MEN1 syndrome very early on. Consider the MEN1 genetic diagnostics if recurrent primary hyperparathyroidism or recurrent gastroduodenal ulcer disease appear in patients under 40 years of age.Key words: carcinoid - gastrinoma - hyperparathyroidism - insulinoma - MEN1 - multiple endocrine neoplasia - nefrolithiasis - neuroendocrine tumor - pancreatic area - pituitary gland.

The article describes two clinical cases of severe primary hyperparathyroidism (PHPT) caused by parathyroid carcinoma in young female patients who underwent molecular genetic testing to rule out the hereditary forms of PHPT. In both patients, heterozygous germline nonsense mutations of tumor suppressor gene CDC73 encoding parafibromin (p.R91X and p.Q166X) were identified using next-generation sequencing with Ion Torrent Personal Genome Machine (Thermo Fisher Scientific - Life Technologies, USA). It is the first description of CDC73 mutations in Russia, one of the mutations is described for the first time in the world. Identification of germline mutations in the CDC73 gene in patients with PHPT necessitates regular lifelong screening for other manifestations of hyperparathyroidism-jaw tumor syndrome (HPT-JT), PHPT recurrence due to parathyroid carcinoma as well, and identification of mutation carriers among first-degree relatives.

Graves' disease (GD) is frequently associated with mild hypercalcemia. The hypercalcemia may be due to the activation of osteoclastic bone resorption caused by the excess thyroid hormone. In some cases of GD, the hypercalcemia can be attributable to concomitant parathyroid diseases. In this study, 21 patients with a history of GD developed parathyroid adenoma based on histology, intraoperative parathyroid hormone (IOPTH) monitoring, and other clinical features. There were 11 patients with a history of radioactive iodine therapy (RAI) for GD. The latency time of RAI was from 12 to 41 years. The case cohort was divided into two groups: patients with (group GR: 11 patients) and patients without a history of RAI (group G: 10 patients). Mean age of patients in group GR was 54.8 years compared to 62.2 years of group G (P = 0.08). There were no statistically significant differences regarding the parathyroid weight, serum calcium, and pre- and post-parathyroidectomy PTH levels. There was no histopathologic difference between the two groups. In conclusion, we report 21 cases of parathyroid adenoma in patients with Graves' disease. There may be a possible link between GD patients with a RAI history and an increased risk of parathyroid adenoma. The parathyroid adenomas showed no clinicopathological differences between GD patient with and without a history of RAI.

Introduction: The purpose of the study was to assess the results of operative treatment of patients with tertiary hyperparathyroidism (tHPT) after kidney transplantation., Material and Methods: The study included 30 patients in whom kidney transplantation was performed between 2006 and 2013, and in whom parathyroidectomy had to be performed at a later time because of tHPT. There were 17 (56.7%) women and 13 (43,3%) men in the group, aged 18-64, mean 46.1 years. In order to locate the lesion before the operation, all patients had to undergo USG, and 14 had scintigraphy MIBI in addition. Serum levels of PTH, ionised calcium, and creatinine were determined together with glomerular filtration rate (GFR). The results of control tests were compared with those performed one day before parathyroidectomy (PTX) and three days after the operation., Results: Among 30 patients, 19 (63.3%) underwent total resection of three parathyroid glands and 3/4 of the fourth. Two parathyroid glands were resected in eight (26.7%) patients, and one in the remaining three (10%) patients. Histopathological examination showed one parathyroid adenoma in six (20%) patients, and one parathyroid adenoma and hyperplasia of the remaining glands in one (3.3%) patient. Five (16.7%) patients had hyperplasia of two parathyroid glands whereas no changes were observed in two patients. On the other hand, hyperplasia of all glands was noted in 18 (60%) patients. Serum PTH level was significantly lower compared to the level before operation (p < 0.001), being 5.5-58.5 pg/mL, on day 3 postoperatively. Differences in the levels of serum-ionised calcium were also significant (p < 0.0001) after eight months., Conclusions: Surgical resection of parathyroid glands is a management of choice in patients after kidney transplantation accompanied by hypercalcaemia lasting longer than one year. Resection of 3 3/4 parathyroid glands because of hyperplasia in patients with hyperparathyroidism after kidney transplantation enables restoration of normal calcium metabolism. Moreover, resection of 3 3/4 parathyroid glands can allow avoidance of autotransplantation, which is necessary in cases of total resection of parathyroid glands.

Aim: To investigate the efficacy of PET/CT with 11C-methionine for localizing parathyroid adenomas in patients with suspected primary hyperparathyroidism and inconclusive results of cervical ultrasonography and 99mTc-MIBI-SPECT/CT., Patients, Method: Retrospective analysis of imaging data of 18 patients and correlation with clinical outcome, in particular intraoperative findings and histopathology of excised tissue., Results: 12 of 18 patients received surgery. In 10 patients single parathyroid adenomas were found (diameter: 5-20 mm), 2 patients presented parathyroid hyperplasia (5 excised hyperplastic glands (diameter: 2-12 mm). PET/CT correctly localized all adenomas and 1 of 5 hyperplastic glands. The sensitivity per patient was 91.7% (11 of 12), the sensitivity per lesion 73.3% (11 of 15). All lesions missed by PET/CT had a size smaller than 9 mm and a volume of less than 0.2 ml. In 6 patients no surgery was performed. Five of them had a negative or atypical PET/CT. Further follow-up indicated familial hypocalciuric hypercalcemia in 3 of them (thus, PET/CT true negative), in the remaining 2 patients no validation is available. One patient with 2 highly suggestive lesions rejected surgery so far., Conclusion: PET/CT with 11C-methionine is a very sensitive method for the detection of parathyroid adenomas, even if they are too small to be visualized by 99mTc-MIBI-SPECT/CT.

Tinea capitis attained epidemical proportions in the fifth and sixth decades in Portugal, as in other countries. Before starting the utilization of griseofulvin in 1959, the best approach to treat tinea capitis infection was X-ray scalp epilation combined with topical antimycotic ointments. A long-term side effect of this therapy is thyroid disease, namely thyroid cancer; data on parathyroid lesions (hyperplasia, adenoma and carcinoma) are scarce. We observed clinically 1,375 individuals irradiated in childhood for tinea capitis treatment in the North of Portugal with the main purpose of evaluating thyroid and parathyroid tumours as possible sequelae of the irradiation treatment. For each individual, a cervical ultrasound and a serum calcium measurement were proposed. Fine needle aspiration cytology was suggested whenever ultrasound thyroid nodules presented suspicious features. We observed a 54 % frequency of thyroid nodules and a 2.8 % frequency of thyroid carcinoma (38/1,375). Nineteen of the 38 (50 %) carcinomas were diagnosed by us, whereas the remaining 19 carcinomas had been diagnosed and treated prior to our observation. The carcinomas were significantly more frequent in women than in men. Benign excised lesions were also significantly more frequent in women and in patients irradiated at younger ages. Seven women, considered asymptomatic until our clinical observation, had laboratory signs of hyperparathyroidism. The data we have obtained, namely high thyroid cancer frequency, corroborate previous data from childhood irradiated cohorts and highlight the need for the close follow-up of these populations in order to identify and treat early undiagnosed head and neck lesions. No evidence of increased parathyroid disease was found in this cohort of head and neck X-irradiated patients.

Brown tumors result from excess osteoclast activity and consist of collections of osteoclasts intermixed with fibrous tissue and poorly mineralized woven bone. They are secondary to hyperparathyroidism (HPT). Their incidence is higher in primary than in secondary hyperparathyroidism. We report a 69 years-old male, admitted in a state of confusion, lethargy and bedridden, with a pathological fracture of the femur caused by a brown tumor. The laboratory examination revealed a hypercalcemia (8.85 mEq/L), with high levels of ionized Ca (5.48 mEq/L), serum alkaline phosphatases (416 U/L) and serum parathormone (120 pg/mL). Ultrasound examination of the neck showed a large parathyroid tumor, probably corresponding to a carcinoma. A primary HPT was diagnosed. The patient was hydrated and high doses of diuretics and bisphosphonates were administered. After correction of serum calcium and neurologic symptoms, the patient was operated, performing an extensive resection of the tumor. The pathology report confirmed the diagnosis of parathyroid carcinoma.

Molecular epidemiological studies have shown that gene polymorphisms of estrogen receptor alpha gene (ESR-α) are associated with breast cancer risk. However, previous results from many molecular studies have been inconsistent. In this study, we examined two polymorphisms (PvuII and XbaI RFLPs) of the ESR-α gene in 542 breast cancer cases and 1,016 controls from China. Associations between the polymorphisms and breast cancer risk were calculated with an unconditional logistic regression model. Linkage disequilibrium and haplotypes were analyzed with the SHEsis software. In addition, we also performed a systematic meta-analysis of 24 published studies evaluating the association. No significant associations were found between the PvuII polymorphism and breast cancer risk. However, a significantly decreased risk of breast cancer was observed among carriers of the XbaI 'G' allele (age-adjusted OR = 0.80; 95% CI = 0.66- 0.97) compared with carriers of the 'A' allele. Haplotype analysis showed significantly decreased cancer risk for carriers of the 'CG' haplotype (OR = 0.79; 95% CI = 0.66- 0.96). In the systematic meta-analysis, the XbaI 'G' allele was associated with an overall significantly decreased risk of breast cancer (OR = 0.90, 95% CI = 0.82- 1.00). In addition, the PvuII 'C' allele showed a 0.96- fold decreased disease risk (95% CI = 0.92- 0.99). In subgroup analysis, an association between the PvuII 'C' and XbaI 'G' alleles and breast cancer risk was significant in Asians ('C' vs. 'T': OR = 0.93, 95% CI = 0.85- 1.00; 'G' vs. 'A': OR = 0.82, 95% CI = 0.68- 0.98), but not in Euro-Americans. Thus, our results provide evidence that ESR-α polymorphisms are associated with susceptibility to breast cancer. These associations may largely depend on population characteristics and geographic location.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal-dominant tumor syndrome characterized by the occurrence of tumors in multiple endocrine tissues and nonendocrine tissues. The three main endocrine tissues most frequently affected by tumors are parathyroid (95%), enteropancreatic neuroendocrine (50%) and anterior pituitary (40%). Tumors are caused by a heterozygous germline-inactivating mutation in the MEN1 gene (1st hit) followed by somatic inactivating mutation or loss of the normal copy of the gene (2nd hit), leading to complete loss of function of the encoded protein menin. Most of the disease features and tumors are recapitulated in mouse models with heterozygous germline loss of the Men1 gene. Also, tissue-specific tumors are observed in mouse models with homozygous somatic loss of the Men1 gene specifically in MEN1-associated endocrine tissues. Hence, mouse models could serve as possible surrogates for studying MEN1 and related states. To gain insights into MEN1 pathophysiology, menin-interacting partners and pathways have been identified to investigate its tumor suppressor and other functions. Also, the 3D crystal structure of menin has been deciphered which could be useful to reveal the relevance of MEN1 gene mutations and menin's interactions. This chapter covers clinical, genetic and basic findings about the MEN1 syndrome, MEN1 gene and its product protein menin., (Copyright © 2013 S. Karger AG, Basel.)

Parathyroid carcinoma is a malignant neoplasm affecting 0.5% to 5.0% of all patients with primary hyperparathyroidism. Since it was first described by De Quervain in 1904 to this day, it continues to defy diagnosis and treatment because of its rarity, overlapping features with benign parathyroid disease, and lack of distinct characteristics. En bloc surgical extirpation of the tumor with clear margins remains the best curative treatment. Although prolonged survival is possible with recurrent or metastatic disease, cure is rarely achievable. Efficacy of adjuvant therapies, such as radiotherapy and chemotherapy, in management of persistent, recurrent, or metastatic disease has been disappointing., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Recurrent laryngeal nerve (RLN) injury is a rare complication for patients undergoing neck exploration for primary hyperparathyroidism (pHPT). Distances between RLNs and parathyroid adenomas have not been previously published. In this study we used a RLN monitor to identify the RLN and to measure the proximity to parathyroid tumors., Methods: Patients with pHPT (n = 136) underwent neck exploration and had the clinical data recorded prospectively. Adenomas were recorded in 1 of 4 locations (right upper, right lower, left upper, left lower). Measurement of RLN to adenoma distances were recorded intraoperatively with the gland in situ. The RLN location was confirmed with a RLN monitor., Results: The average RLN to adenoma distance was 0.52 ± 0.52 cm. Adenomas in the right upper position were significantly closer to the nerve (0.25 ± 0.39 cm) compared with adenomas in the left upper (0.48 ± 0.61 cm, p = .03), left lower (0.70 ± 0.53 cm, p < .001), and right lower position (1.02 ± 0.56 cm, p < .001). Left upper adenomas were also significantly closer to the nerve compared with right lower adenomas (p < .001). Adenomas in the right upper position abutted the nerve more often (47 %) compared with adenomas in other positions (p = .001). There were no perioperative characteristics that predicted tumor abutment. There were no permanent RLN injuries., Conclusion: In patients with sporadic pHPT, parathyroid adenomas in the right upper location have, on average, greater proximity to the RLN and are more often directly abutting compared with adenomas in other locations.

Background: Prior head and neck irradiation is a known risk factor for hyperparathyroidism. It is not clear whether irradiation for breast cancer, which may expose the neck to radiation, is also a risk factor for hyperparathyroidism. The present study analyzes the association between the side of radiation to the chest following breast surgery and the side of subsequent parathyroid adenoma development., Methods: We analyzed a prospective database of 1,428 consecutive patients who underwent parathyroidectomy at our institution between November 2000 and August 2010. Patients who had previously undergone breast surgery were identified. Patients with multigland disease were excluded. Patients with bilateral breast surgery were counted as having had two separate procedures; one on each side. Patients who had radiation therapy following breast surgery (RadRx) were compared to those who had breast surgery without radiation treatment (No RadRx)., Results: A total of 146 breast procedures were performed in 121 patients. Forty procedures were in the RadRx group versus 106 cases in the No RadRx group. Patients with radiation therapy were older (68 ± 1.8 years versus 63 ± 1.2 years; P = 0.02) and had higher preoperative calcium levels (11.3 ± 0.1 mg/dl versus 10.9 ± 0.1 mg/dl; P = 0.001). However, there was no significant difference in either parathyroid hormone (PTH) level or gland weight. The latency period between breast irradiation and parathyroid surgery was 8 ± 0.9 years. Interestingly, the side of radiation therapy was associated with the side of the parathyroid adenoma in 76% of cases, compared to only 44% in those who had breast surgery without radiation exposure (P = 0.0004)., Conclusions: The present study demonstrates that, similar to prior head and neck radiation, prior breast irradiation correlates with the development of parathyroid disease. Specifically, there is a strong correlation between the side of the radiation therapy and the side of a subsequent parathyroid adenoma. Breast irradiation should therefore be considered a risk factor for the development of parathyroid adenomas.

Aim: To perform a genetic screening for the multiple endocrine neoplasia type 1 (MEN1) gene mutations in patients affected by an apparently sporadic form of the disease, referred to an internal medicine unit of a large general hospital., Subjects and Methods: In a group of 12 consecutive patients presenting clinical features of MEN type 1 syndrome, we performed a genetic screening for germline MEN1 gene mutations, including complete sequencing of the coding region (exons 2 to 10) and multiplex ligation-dependent probe amplification analysis for large deletion detection., Results: Among these patients affected by apparently sporadic MEN type 1 syndrome, a targeted clinical history could detect indirect support for a diagnosis of familial condition only in 2 cases. The genetic screening identified pathogenic germline MEN1 gene mutations in 3 patients (25%). A previously unknown 18 base-pair deletion within exon 3, c.564&#95;581delCAATGGGGAGCAGACAGC, resulting in loss of 6 amino acids (pAsp189&#95;Ala194del), was found in heterozygosis in a woman affected by primary hyperparathyroidism and multifocal pancreatic neoplasia., Conclusions: Our results underscore the importance of performing genetic testing also in apparently sporadic MEN1 patients and extend the list of molecular variants leading to inactivation of the MEN1 gene.

Background: Standard preoperative imaging for primary hyperparathyroidism usually includes sestamibi scanning (MIBI) and ultrasound (US). In a subset of patients with a positive MIBI and a negative US, we hypothesize that the parathyroid adenomas are more likely to be located posteriorly in the neck, where anatomically they are more difficult to detect by US., Methods: We retrospectively reviewed the records of 661 patients treated for primary hyperparathyroidism between 2004 and 2009 at a tertiary referral center. We included patients who for their first operation had a MIBI that localized a single lesion in the neck and an US that found no parathyroid adenoma. We excluded patients with persistent or recurrent hyperparathyroidism, and patients with MIBIs that were negative, that had more than one positive focus, or that had foci outside of the neck. Sixty-six cases were included in the final analysis., Results: A total of 54 patients (83%) had a single adenoma, 4 (6%) had double adenomas, and 7 (11%) had hyperplasia. Thirty-three patients (51%) had a single upper gland adenoma; 19 of these (58%) were posteriorly located upper gland adenomas (PLUGs). PLUGs occurred more often on the right side than on the left (P = 0.048, Fisher's test). PLUGs were also larger than other single adenomas (mean 1.85 vs. 1.48 cm, P = 0.021, t-test). Seventy-six percent of patients successfully underwent a unilateral or focused exploration. Six patients (9%) had persistent disease, which is double our group's overall average (4-5%)., Conclusions: Primary hyperparathyroid patients with preoperative positive MIBI and negative US are more likely to have PLUGs.

Brown tumor of hyperparathyroidism is a non-neoplastic osteoclastic process which results in cystic lesions that are often expansile. It occurs rarely and is often a late manifestation of primary hyperparathyroidism (PHPT). Multiple bone involvement is extremely rare. Because of its resemblance with benign tumors if it occurs as a solitary bone lesion and of metastatic bone lesion when it is multiple, differentiation is often difficult without biochemical analysis. Here we presented eight patients who visited Tikur Anbessa Specialized Hospital for the last 15 years with primary skeletal complaints. Out of these six were females and except one patient all had multiple brown tumors. Based on radiographic features only it is often difficult to diagnose the condition and biochemical tests and anterior neck sonography is usually crucial to reach at a definitive diagnosis. Although the occurrence of more than one separate bone lesion in the skeleton usually suggests metastasis, our cases shows that brown tumors should also be included in the differential diagnosis of such lesions, particularly in patients with hyperparathyroidism.

Objective: To review the current knowledge pertaining to the etiology, molecular pathogenesis, and management of parathyroid carcinoma, a rare presentation of primary hyperparathyroidism., Methods: The existing MEDLINE English-language literature was reviewed using the search terms "parathyroid" and "carcinoma" or "cancer.", Results: Parathyroid cancer is a rare endocrine tumor accounting for a small proportion of cases of primary hyperparathyroidism. Recent database studies indicate increasing incidence rates. Its etiology is unknown, although numerous molecular alterations have been described, and the tumors also occur in association with germline mutations in the CDC73 gene. Most affected patients present with severe hypercalcemia; however, the diagnosis can be challenging. Complete surgical resection remains the mainstay of treatment and provides the best chance of cure, although data from small series suggest that external beam radiation may also reduce the high recurrence rates. No effective chemotherapy regimens are currently available. A significant number of patients develop recurrent disease and need additional procedures; however, long-term survival is possible with palliative surgery. Medical management of chronic and debilitating hypercalcemia with calcimimetics is often necessary and is an important adjunct in patients with recurrent and metastatic disease., Conclusions: Further elucidation of the molecular pathogenesis of parathyroid carcinomas will enhance our understanding of etiology and behavior of this uncommon entity. Future research must be directed at identifying more effective therapies for this condition.

Tertiary hyperparathyroidism (tHPT) most commonly refers to a persistent secondary hyperparathyroidism even after successful renal transplantation. Parathyroidectomy (PTX) is an efficient method for treatment of tHPT. In this study, we examined our 31-year experience with patients who underwent PTX for tHPT after KTX and assessed the effects of PTX on graft function according to the type of surgery. Among 2,981 recipients who underwent renal allograft between April 1979 and Dec. 2010, 15 patients (0.5%) were identified as having tHPT and underwent PTX. Levels of intact parathyroid hormone (iPTH) and serum calcium were measured before and after PTX for evaluation of the therapeutic effect, and glomerular filtration rate (GFR) using the Modification of Diet in Renal Disease (MDRD) equation for investigation of any effect on graft function. One patient showed persistent hyperparathyroidism and hypercalcemia after limited PTX. We experienced 14 successful PTXs, including 3 total PTX with autotransplantations, 8 subtotal PTXs, and 3 limited PTXs. Level of iPTH and serum calcium were at normal range after PTX. Estimated GFR decreased after PTX. Total PTX with autotransplantation showed a tendency of more decrease in the values of iPTH, and GFR after PTX than Subtotal PTX. PTX can cure tHPT-specific symptoms and signs by recovery of hypercalcemia, but may carry the risk of deterioration of kidney graft function. We suspect that subtotal PTX, rather than total PTX with AT, prevent any risk of kidney graft deterioration in surgical treatment of tHPT, and, in selective tHPT patients, limited PTX might be recommended.

Purpose: 25-OH D3 (D3) deficiency causes secondary hyperparathyroidism. Asymmetric gland hypertrophy may also lead to unnecessary parathyroid gland resection by mistaking these glands for parathyroid incidentalomas. We tested the hypothesis that D3 deficiency causes parathyroid gland hypertrophy., Method: This is a prospective study of 100 consecutive patients undergoing total thyroidectomy. Pre-operative D3 measurement was made at first presentation and on the day after surgery. During thyroidectomy, the parathyroid glands were searched for and measured. Using an ellipsoid volume calculator, the gland volume was calculated. This was correlated with D3 and other possible confounding factors., Results: Normal parathyroid volume is 25.1 mm(3). Parathyroid gland size correlated with D3 levels, p < 0.001. There is a greater asymmetry in gland volume in those patients with the lowest levels of D3 (Spearman's rank correlation coefficient r = -0.51). There was a significant difference in individual gland volume between D3 levels >30 ng/ml and those <30 ng/ml. However, there was no difference in mean gland volume between these groups. There was no difference in correlation according to pathology or thyroid specimen weight., Conclusion: There is a significant difference in both individual gland volume and variation in parathyroid gland volume according to D3 levels. Patients with a D3 level <30 ng/ml have a more asymmetrical hyperplasia corresponding with parathyroid incidentalomas. D3 levels should be measured pre-operatively in all patients undergoing total thyroidectomy to avoid unnecessary parathyroid resection.

Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disorder characterized in man by parathyroid, pancreatic, pituitary and adrenal tumours. The MEN1 gene encodes a 610-amino acid protein (menin) which is a tumour suppressor. To investigate the in vivo role of menin, we developed a mouse model, by deleting Men1 exons 1 and 2 and investigated this for MEN1-associated tumours and serum abnormalities. Men1(+/-) mice were viable and fertile, and 220 Men1(+/-) and 94 Men1(+/+) mice were studied between the ages of 3 and 21 months. Survival in Men1(+/-) mice was significantly lower than in Men1(+/+) mice (<68% vs >85%, P<0.01). Men1(+/-) mice developed, by 9 months of age, parathyroid hyperplasia, pancreatic tumours which were mostly insulinomas, by 12 months of age, pituitary tumours which were mostly prolactinomas, and by 15 months parathyroid adenomas and adrenal cortical tumours. Loss of heterozygosity and menin expression was demonstrated in the tumours, consistent with a tumour suppressor role for the Men1 gene. Men1(+/-) mice with parathyroid neoplasms were hypercalcaemic and hypophosphataemic, with inappropriately normal serum parathyroid hormone concentrations. Pancreatic and pituitary tumours expressed chromogranin A (CgA), somatostatin receptor type 2 and vascular endothelial growth factor-A. Serum CgA concentrations in Men1(+/-) mice were not elevated. Adrenocortical tumours, which immunostained for 3-beta-hydroxysteroid dehydrogenase, developed in seven Men1(+/-) mice, but resulted in hypercorticosteronaemia in one out of the four mice that were investigated. Thus, these Men1(+/-) mice are representative of MEN1 in man, and will help in investigating molecular mechanisms and treatments for endocrine tumours.

Background: The goal of the present study was to make our medical practice evidence-based for patients with parathyroid carcinoma., Methods: We posed six clinical questions relevant to the management of parathyroid cancer. A comprehensive search and critical appraisal of the literature was then carried out., Results: Most of the literature retrieved was retrospective in design and differed in the definition of carcinoma. The distinction between unequivocal and equivocal carcinoma (or atypical adenoma) was not always made for the study populations. None of the studies indicated reproducibility of outcome measures. Of the histopathological features described in the literature based on the description of Schantz and Castleman, capsular/vascular invasions and trabecular growth pattern were the most specific, and fibrous bands were the most sensitive. None of the patients with "atypical adenoma" developed recurrence, whereas 25% of those with "equivocal carcinoma" did. Mutations in HRPT2, the gene responsible for hereditary hyperparathyroidism with jaw-tumor syndrome, were strongly associated with sporadic parathyroid carcinoma. Severe hypercalcemia and its related clinical symptoms, extremely high levels of parathyroid hormone, osteitis fibrosa cystica, a palpable neck mass, and a relatively large depth-width ratio on ultrasonography, are the important features of parathyroid carcinoma. Disease-specific survival rates reported in the literature were varied, reflecting the differences in the definitions of carcinoma, study populations, and interventions., Conclusions: To establish valid evidence for patient management in the future, a collaboration of endocrine specialists is essential to conduct well-designed clinical studies for this rare disease.

Purpose: To examine the occurrence of hyperparathyroidism in a cohort of patients undergoing combined parathyroid and thyroid surgery after previous head-and-neck irradiation for childhood malignancy., Methods and Materials: This is a retrospective cohort study for the years 1996 to 2007. The study group comprised patients undergoing surgery in the University of Sydney Endocrine Surgical Unit who had received previous head-and-neck irradiation in childhood and who were identified as having pathologic thyroid and parathyroid characteristics., Results: A total of 53 patients were identified in whom head-and-neck irradiation for the treatment of childhood malignancy had been documented. In each of the cases, thyroid disease was the primary reason for referral for surgery. Five of these patients (10%) were found to exhibit coexisting hyperparathyroidism. The latency period for hyperparathyroidism was less than 20 years in 4 of the 5 cases. There were four conventional parathyroid adenomas and one parathyroid lipoadenoma. All patients exhibited a significant decrease in postoperative calcium levels after surgery., Conclusions: To our knowledge, this is the first study to document the significant risk of hyperparathyroidism after radiation exposure for childhood malignancy. The timeframe for development of disease is much shorter than that published for individuals who have undergone irradiation for benign diseases. High doses of therapeutic radiation at a young age make childhood survivors of malignancy at especially high risk for developing hyperparathyroidism.

We present the clinical, laboratory, radiological and pathological findings in the case and review the literature. Our patient, a 37-year-old woman of short stature, was referred because of musculoskeletal pain. After primary evaluation, she underwent treatment with calcium and vitamin D supplement with the diagnosis of osteomalacia in Turner's syndrome. The rise of serum calcium during medical therapy, which was an unusual finding, attracted the clinician's attention to another underlying disorder. Further evaluation revealed primary hyperparathyroidism due to an adenoma of the parathyroid gland. Even though this is a rare diagnosis, its presence should be considered in any patient with Turner's syndrome presenting with severe osteoporosis and a rise in serum calcium during treatment.

Objective: In order to analyze the differential diagnosis of giant-cell lesion in facial bones, we present a case of a patient without a previously diagnosed primary hyperparathyroidism that displayed multiple maxillofacial brown tumors as the initial clinical manifestation of the disease., Case Description: A 70 year-old female with amandible tumor and one year of disease progression. Tumor biopsy confirmed the presence of a giant-cell lesion. Radiologically, we confirmed the presence of another two lytic lesions in the maxillofacial region. During biochemical evaluation prior to surgery, the possibility of hyperparathyroidism was considered. Using computed tomography, we noted a parathyroid tumor in an atypical location. Surgical resection confirmed the presence of an adenoma. Postoperatively, the patient developed symptomatic hypocalcemia and was managed with calcium supplementation in addition to calcitriol. At 4 months after surgery mandibular swelling had regressed partially and serum calcium levels returned to normal levels., Conclusion: The detection of giant-cell bone lesions in the maxillofacial region is a strategic diagnostic finding as several entities, among these brown tumor hyperparathyroidism can display similar histologic imaging findings. Only systematic clinical, radiologic, and biochemical evaluation can allow for a definitive diagnosis. The presence of multiple simultaneous maxillofacial brown tumors in primary hyperparathyroidism is an infrequent ocurrence, and only on rare occasions can this be the first sign of the disease.

Brown tumor is a localized form of osteitis fibrosa cystica, being part of the hyperparathyroid bone disease. It rarely is the first manifestation of hyperparathyroidism, since nowadays, the diagnosis is made at an asymptomatic or minimally symptomatic stage. We present a case of a left superior maxillar brown tumor as the first manifestation of primary hyperparathyroidism due to a parathyroid adenoma. A parathyroidectomy was performed, and there was a regression of the bone lesion, without the need of performing other local surgical procedures.

Background: External radiation is associated with a risk of hyperparathyroidism. We reviewed the outcomes after operation for radiation-induced hyperparathyroidism (R-HPT)., Methods: We conducted a retrospective review of all patients who had operative therapy for R-HPT from 1980 to 2003 in our department with a minimum of 3 years of follow-up after operative therapy., Result: Between 1980 and 2003, 1932 patients underwent parathyroidectomy for primary hyperparathyroidism. Thirty-seven (1.92%) patients had a history of neck irradiation. Thirty-two patients underwent a bilateral exploration (BE), and 5 patients had a focused approach (FA). Thirty-five patients presented with single gland disease, and 2 patients had multiple gland disease. In the BE group, 26 patients remained cured biochemically after a median follow-up of 10.3 years (range, 3-21 years), and 6 patients had recurrence after a median of 13.2 years (range, 7-22 years). In the FA group, all 5 patients remained cured biochemically; however, the median follow-up remained shorter (6.4 years; range, 3-8 years)., Conclusion: In R-HPT, the incidence of multiple gland disease at the time of initial operation was comparable with sporadic HPT. In the absence of thyroid disease, an FA may be proposed for R-HPT. Metachronous pathologic glands may develop several years after successful parathyroidectomy in R-HPT. Hence, lifelong follow-up of these patients is essential.

A case of giant cell lesion as an initial feature of primary hyperparathyroidism is presented. A 55-year-old woman reported with a complaint of swelling and occasional pain in the upper-left posterior region with 2 months' duration. The diagnosis of a giant cell lesion with primary hyperparathyroidism was confirmed on the basis of radiological, biochemical, and histopathological investigative procedures.

Parathyroid carcinoma (PC) is an uncommon finding, accounting for only 1-2% of patients with primary hyperparathyroidism (HPT), but a relatively higher incidence has been reported in Italy and Japan. The etiology of the tumour remains unclear, but molecular analysis studies have hypothesised the involvement of mutations of several genes in the pathogenesis of PC, including the oncogene cyclin Dl or PRADI located at the chromosome 13, the retinoblastoma and the p53 tumour suppressor gene. The clinical presentation of patients with PC is mainly related to the increased secretion of PTH rather than to the tumour burden. The pre-operative diagnosis of malignancy is very difficult to obtain, and, thus, intra-operative recognition of PC is mandatory. However, reliable signs of malignancy are rarely detectable. Probably, only vascular invasion, that correlates with tumour recurrence and metastases, should be considered useful in confirming malignancy, although both Ki-67 and Cyclin D1 have been recently used to aid in the definitive diagnosis. The en bloc resection of the tumour, together with ipsilateral thyroid lobe and adjacent structures, only if involved, avoiding any capsular rupture of the mass, represents the gold standard of surgical treatment of patients. Although the PC has traditionally been considered as a radioresistant tumour, there are some retrospective data holding a possible benefit from post-operative irradiation. No cytotoxic regimen with proven efficacy is currently available for patients with PC, but since hypercalcemia is ultimately the most frequent cause of death, several studies have suggested the usefulness of bisphosphonates (i.e., clodronate, pamidronate and zoledronate), calcitonin, and calcimimetic agents (i.e., cinacalcet) in patients with PC and severe hypercalcemia. In conclusion, PC is a rare malignancy and the NCDB survey reports an overall five- and ten-year survival rate of 85% and 49%, respectively. However, it is very difficult to predict the clinical behaviour of patients with PC and probably the ultimate prognosis depends on successful resection of the tumour at the initial surgery.

External ionizing radiation is a risk factor for primary hyperparathyroidism. Whether exposure to radioactive iodine contributes to the risk of primary hyperparathyroidism is unknown. Patients with thyrotoxicosis are often treated with radioactive iodine and its accumulation in the thyroid gland exposes the adjacent parathyroid glands to radioactivity. Six thousand and eighty two patients with thyrotoxicosis (ICD-9 = 242) were identified from medical records. In a randomly selected subcohort we assessed the frequency of treatment with radioactive iodine to be 86%. The number of patient-years at risk was 77,118. Patients with parathyroid adenomas (ICD-9 = 195.1) were recruited from the Swedish Cancer Registry. Eleven patients with parathyroid adenomas following the diagnosis of thyrotoxicosis were identified. The standard incidence ratio (SIR) compared to the reference population of approximately 900,000 was 1.14 (95% CI 0.57-2.03). The median age at exposure was 59 years and the latency period between diagnosis of thyrotoxicosis and parathyroid adenoma was 7.4 years (range <1-19 years). This study does not indicate that patients with thyrotoxicosis treated with radioactive iodine in adult age have increased risk of developing parathyroid adenoma.

Background: Parathyroid carcinoma is a rare malignancy affecting 0.5-5 per cent of all patients with primary hyperparathyroidism. This article reviews the literature on the pathogenesis, pathology, clinical features, diagnosis and management of parathyroid carcinoma., Methods: A Medline search was performed and all relevant English language articles published between 1970 and 2005 were retrieved. The search words included 'parathyroid carcinoma', 'pathology', 'genetics', 'management' and 'radiotherapy'. Secondary references were obtained from key articles., Results and Conclusion: The exact aetiology of parathyroid carcinoma remains obscure. Recently, the HRPT2 gene has been implicated in its pathogenesis and may prove to be a genetic target in future. Surgical resection is the accepted 'gold standard'. There is now a growing consensus on the use of adjuvant radiotherapy as it has been shown to provide a survival benefit.

Background: Mechanisms for potential effects of extremely low frequency (ELF) magnetic fields on carcinogenesis have not been identified. A potential pathway could be an interaction with the endocrine system., Aims: To analyse occupational exposure to ELF magnetic fields from welding, and tumours of the endocrine glands., Methods: This case-control study was based on a cohort with an increased prevalence of high exposed individuals. A total of 174 incident cases of tumours of the endocrine glands, 1985-94, were identified and data were obtained from 140 (80%) of these cases; 1692 controls frequency matched on sex and age were selected, and information on 1306 (77%) individuals was obtained. A short questionnaire was sent to a work administrator at the workplaces of the cases and controls. The exposure assessment was based on questions about job tasks, exposure to different types of welding, and exposure to solvents., Results: There was an overall increased risk for all tumours of the endocrine glands for individuals who had been welding sometime during the follow up. The increased risk was attributable to arc welding; for resistance welding there was no clear evidence of an association. We found an increased risk for the adrenal glands in relation to arc welding, and for the parathyroid glands in relation to both arc welding and resistance welding. An imprecise increase in risk was also noted for tumours of the pituitary gland for arc welding. No confounding effect was found for solvent exposure, and there was no sign of biological interaction., Conclusion: The increased risks of endocrine gland tumours related to welding might be explained by exposure to high levels of ELF magnetic fields.

Parathyroid carcinoma is an uncommon malignancy. It accounts for less than 1% of cases of primary hyperparathyroidism (HPT). It is manifested by severe hypercalcemia and up to 50% of patients will have concomitant kidney or bone disease. The etiology of parathyroid carcinoma is unknown, however, the recently discovered HRPT2 gene, a tumor suppressor gene encoding for the protein parafibromin, has been implicated in the pathogenesis. Identification of inactivating germ-line mutations in HRPT2 has significant implications for diagnosis and management. This article summarizes the genetic aspects of parathyroid carcinoma, reviews its clinical manifestations, and outlines the principles of surgical therapy, the indications for adjuvant therapy, and the use of bisphosphonate and calcimimetic agents for management of hypercalcemia., ((c) 2005 Wiley-Liss, Inc.)

Purpose: Contrast enhancement patterns of parathyroid adenomas in the arterial and venous phases were evaluated with multidetector computed tomography and specificity of the method to characterize the lesions was investigated., Materials and Methods: Arterial and venous enhancement patterns of parathyroid adenomas were evaluated retrospectively with multidetector computed tomography in 12 patients. All adenomas were removed surgically and the diagnosis was confirmed histopathologically. An area from the mandibular angle to the aortic arch was scanned with 1.5 mm section thickness in the arterial phase (20 seconds delay time) and venous phase (70 seconds delay time) after bolus injection of 50 ml of iodinated contrast media. Arterial and venous contrast enhancement of parathyroid adenomas was evaluated in the axial and coronal reformat images., Results: Ten (83.3%) of 12 parathyroid adenomas showed a heterogeneous enhancement with a hypodense small central area in the arterial phase and a homogeneous enhancement in the venous phase. However, two small lesions, four and five mm in diameter respectively, showed homogeneous contrast enhancement in the arterial phase unlike the larger lesions which displayed a hypodense center in this phase., Conclusion: Dynamic scanning with multidetector computed tomography after contrast administration may be helpful in characterizing parathyroid adenomas.

Parathyroid carcinoma constitutes less than 1% of primary hyperparathyroidism. The exact etiology is not known. Prior radiation to neck, chronic renal failure and genetic factors are thought to play a role. The male to female ratio is one. Parathyroid carcinomas are slow growing, have a tendency to recur locally and metastasize late. 95% of parathyroid carcinomas are functioning. The major distinguishing features of malignant hyperparathyroidism are presence of a palpable mass in the neck and features of severe hypercalcemia. By far the most important test to diagnose primary hyperparathyroidism is serum level of Immunoreactive PTH. The diagnosis of primary hyperparathyroidism is essentially clinical and biochemical. Biopsy is not necessary before definitive surgery. CT scan appears to be the best investigation for detecting the primary tumor, its local extent and metastases. Most of the symptoms are attributable to hypercalcemia, which needs to be treated aggressively. Early surgery with 'en bloc' resection of the tumor is the only potentially curative treatment. Parathyroid carcinoma is traditionally said to be resistant to radiotherapy. Various chemotherapeutic agents have been used with partial anecdotal responses. The 5-year survival is about 50% and 10-year survival varies from 13-49%.