Parathyroid Cancer
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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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Latest Research Publications

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

Vandenbulcke O, Delaere P, Vander Poorten V, Debruyne F
Incidence of multiglandular disease in sporadic primary hyperparathyroidism.
B-ENT. 2014; 10(1):1-6 [PubMed] Related Publications
OBJECTIVES: Multiple, minimally invasive surgical techniques have been developed over the last few decades for the management of sporadic primary hyperparathyroidism (PHTP). However, in cases with multiglandular disease, bilateral cervical exploration remains the gold standard. Therefore, it is important to have an accurate estimation of the incidence of multiglandular disease in sporadic PHTP.
METHODOLOGY: 698 patients were treated for PHTP between 1993 and 2010 at the University Hospitals Leuven, using the bilateral cervical exploration method. After excluding cases of multiple endocrine carcinoma syndrome, the incidences of double adenoma and multiple gland hyperplasia were investigated in these patients. Age, gender, imaging results, serum calcium and parathyroid hormone concentrations were analyzed and compared to the data of 50 randomly-selected, PHTP patients with solitary adenomas.
RESULTS: 6.6% and 2.4% of the patients with sporadic PHTP had double adenomas and multiple gland hyperplasia, respectively. The female/male ratio was 4.8 (38/8) and 1.8 (11/6), and the average age was 63 and 52 yrs for patients with double adenomas and multiple gland hyperplasia, respectively. The patients with solitary adenomas had a female/male ratio of 3.5, and an average age of 60 yrs. There were no significant differences in serum calcium or parathyroid hormone concentrations between patients with multiglandular disease and those with solitary adenomas.
CONCLUSIONS: Multiglandular disease occurs in 9% of patients with sporadic PHTP, and cannot be excluded before surgery. This incidence must be considered when using minimally invasive techniques for treatment of sporadic PHTP. In cases of multiglandular disease, bilateral cervical exploration is indicated.

Meyer M, Timmerman GL, VanderWoude JC, Lovrien FC
Hyperparathyroidism: a rare mediastinal presentation of an ectopic adenoma.
S D Med. 2014; 67(3):101-3, 105, 107 [PubMed] Related Publications
The aortopulmonary window is a rare location of an ectopic parathyroid gland, but one that must be considered in persistent primary hyperparathyroidism despite previously attempted parathyroidectomy. Multiple diagnostic studies, including nuclear scans and anatomical imaging techniques, are crucial for identification of a parathyroid gland in the mediastinum and prevention of unnecessary exploratory surgical intervention. This case report presents a 55-year-old female patient with persistent hyperparathyroidism following a neck exploration and thyroidectomy for a parathyroid adenoma. Serial sestamibi scans and CT imaging over the subsequent few years were suggestive, but not diagnostic, of a mediastinal adenoma. Four years after the initial surgery, however, imaging studies identified the development of a soft tissue mass with increased uptake in the aortopulmonary window. A median sternotomy was performed at that time. An ectopic parathyroid gland was identified during surgery between the aortic arch and the bifurcation of the pulmonary artery, as demonstrated on imaging and confirmed by frozen section. Two years following the sternotomy, the patient remains symptom free with calcium and parathyroid hormone (PTH) levels within reference ranges.

Cunningham LC, Yu JG, Shilo K, et al.
Thymoma and parathyroid adenoma: false-positive imaging and intriguing laboratory test results.
JAMA Otolaryngol Head Neck Surg. 2014; 140(4):369-73 [PubMed] Related Publications
IMPORTANCE: Parathyroid hormone (PTH)-secreting thymomas are an exceedingly rare entity. A PTH-secreting thymoma was discovered in the workup of a patient with primary hyperparathyroidism. A concomitant parathyroid adenoma was removed from the same patient. We present the intriguing clinical course and review the literature on this rare entity. In addition, we discuss the use of scanning with technetium Tc 99m sestamibi, the PTH assay, and cervical ultrasonography in the workup of a parathyroid adenoma.
OBSERVATIONS: Scanning with technetium Tc 99m sestamibi demonstrated false-positive uptake of the mediastinal thymoma and false-negative uptake of the true cervical parathyroid adenoma. After removal of the thymoma, the parathyroid adenoma demonstrated appropriate uptake on a follow-up scan. After removal of the parathyroid adenoma, the hyperparathyroidism was cured.
CONCLUSIONS AND RELEVANCE: Given the extremely rare incidence of a PTH-secreting thymoma with a concurrent parathyroid adenoma, we do not recommend alterations in the diagnostic algorithm for primary hyperparathyroidism. However, in this case, the need for 2 separate operations may have been avoided by obtaining an ultrasonogram to further explore the findings on the technetium Tc 99m sestamibi scan. We recommend that both studies be considered in unclear cases of primary hyperparathyroidism.

Related: Thymoma and Thymic Carcinoma

Shi Y, Hogue J, Dixit D, et al.
Functional and genetic studies of isolated cells from parathyroid tumors reveal the complex pathogenesis of parathyroid neoplasia.
Proc Natl Acad Sci U S A. 2014; 111(8):3092-7 [PubMed] Article available free on PMC after 25/08/2014 Related Publications
Parathyroid adenomas (PAs) causing primary hyperparathyroidism (PHPT) are histologically heterogeneous yet have been historically viewed as largely monotypic entities arising from clonal expansion of a single transformed progenitor. Using flow cytometric analysis of resected adenomatous parathyroid glands, we have isolated and characterized chief cells, oxyphil cells, and tumor-infiltrating lymphocytes. The parathyroid chief and oxyphil cells produce parathyroid hormone (PTH), express the calcium-sensing receptor (CASR), and mobilize intracellular calcium in response to CASR activation. Parathyroid tumor infiltrating lymphocytes are T cells by immunophenotyping. Under normocalcemic conditions, oxyphil cells produce ∼50% more PTH than do chief cells, yet display significantly greater PTH suppression and calcium flux response to elevated calcium. In contrast, CASR expression and localization are equivalent in the respective parathyroid cell populations. Analysis of tumor clonality using X-linked inactivation assays in a patient-matched series of intact tumors, preparatively isolated oxyphil and chief cells, and laser-captured microdissected PA specimens demonstrate polyclonality in 5 of 14 cases. These data demonstrate the presence of functionally distinct oxyphil and chief cells within parathyroid primary adenomas and provide evidence that primary PA can arise by both clonal and polyclonal mechanisms. The clonal differences, biochemical activity, and relative abundance of these parathyroid adenoma subpopulations likely reflect distinct mechanisms of disease in PHPT.

Bohdanowicz-Pawlak A, Szymczak J, Jakubowska J, et al.
Parathyroid adenoma diagnosed on the basis of a giant cell tumor of parieto-occipital region and multifocal bone injuries.
Neuro Endocrinol Lett. 2013; 34(7):610-4 [PubMed] Related Publications
Brown tumors are rare skeletal manifestations of hyperparathyroidism (HPT) that may mimic cancer metastases. Histopathologically, they are difficult to differentiate from other giant cell lesions. A case is presented of 41-year-old woman with giant cell tumor in parieto-occipital region with injury of external bone lamina, growing into the skull cavity. The mass was suspected of being neoplastic. Numerous osteolytic lesions in the skull skeleton and multifocal bone injuries were observed, also. Elevation in calcium (5.91 mEq/L) and parathormone (1188 ng/mL) concentrations and hypercalciuria (52 mEq/24 h) suggested the diagnosis of HPT initially manifesting as a brown tumor of the skull. Further exploration confirmed the existence of parathyroid adenoma as a cause of the disease. The key treatment for the condition was surgical excision of the adenoma followed by the normalization of parathyroid function and significant reduction in size of skull tumor and other lesions.

Gungunes A, Sahin M, Gultekin SS, et al.
Nonadenomatous nonencapsulated thymic parathyroid tissue concomitant with primary hyperparathyroidism due to ectopic parathyroid adenoma.
Arq Bras Endocrinol Metabol. 2013; 57(9):739-42 [PubMed] Related Publications
Primary hyperparathyroidism due to ectopic parathyroid adenoma is not infrequent. Primary hyperparathyroidism caused by unusual thymic nonadenomatous nonencapsulated parathyroid tissue has been reported before. Both can cause unsuccessful neck explorations. Here we presented for the first time a patient with hyperparathyroidism due to ectopic parathyroid adenoma concomitant to the presence of thymic nonadenomatous nonencapsulated parathyroid tissue.

Deé E, Loghin A, Nechifor-Boilă A, et al.
Fibro-hyaline involution of a papillary thyroid carcinoma metastasis in a lymph node, consecutive to radioiodine therapy, mimicking a parathyroid adenoma. A case presentation.
Rom J Morphol Embryol. 2013; 54(4):1121-4 [PubMed] Related Publications
OBJECTIVE: The aim of the study is to present the unusual changes that a lymph node metastasis of papillary thyroid carcinoma (PTC) underwent after radioiodine therapy, leading to the confusion with a parathyroid adenoma (PA).
PATIENT AND METHODS: Eight years after a total thyroidectomy and radioiodine ablation with 73.35 mCurie 131I for PTC, a 67-year-old female presented with an enlarged, painless, nodular mass in the left lateral neck region. Clinical examination revealed a firm nodule located on the site of the left inferior parathyroid gland. Elevated serum parathyroid hormone level (120 pg/mL) and parathyroid scintigraphy led to a suspicion of PA. A minimally invasive surgical procedure was performed to remove the mass, which was sent to the Department of Pathology, Emergency County Hospital, Tirgu Mures, Romania, as left PA. It was fixed and processed for microscopic evaluation.
RESULTS: On macroscopic examination, the surgical specimen was oval; it had 13 mm at the largest diameter and weighted 2 g. On microscopy, the lesion appeared as a fibro-hyaline, intensely acidophilic, acellular mass, with calcifications. It was limited by a delicate capsule in which one typical psammoma body was present. At the periphery, on one single level, a small mass of cells of indefinite origin was noticed. Immunohistochemistry (IHC) was done to ascertain the origin of these cells: they were negative for Pan-Cytokeratin AE1/AE2, Parathormone and Thyroglobulin antibodies, but positive for Leukocyte Common Antigen (LCA) antibody, proving that they were lymphocytes, most likely residual from a lymph node.
CONCLUSIONS: These IHC data, together with the microscopic feature, the presence of the psammoma body and the patient's history, excluded a PA and led to a diagnosis of fibro-hyaline involution of a PTC metastasis in a lymph node, consecutive to radioiodine therapy. Without careful microscopic examination and accurate clinical information, this lesion could represent a real diagnostic challenge.

Related: Thyroid Cancer

Hoang JK, Sung WK, Bahl M, Phillips CD
How to perform parathyroid 4D CT: tips and traps for technique and interpretation.
Radiology. 2014; 270(1):15-24 [PubMed] Related Publications
Parathyroid four-dimensional (4D) computed tomography (CT) is an imaging technique for preoperative localization of parathyroid adenomas that involves multidetector CT image acquisition during two or more contrast enhancement phases. Four-dimensional CT offers an alternative or additional tool in the evaluation of primary hyperparathyroidism. The purpose of this article is to describe the 4D CT technique and provide a practical guide to the radiologist for imaging interpretation. The article will discuss the rationale for imaging, approach to interpretation, imaging findings, and pitfalls.

Zawawi F, Mlynarek AM, Cantor A, et al.
Intraoperative parathyroid hormone level in parathyroidectomy: which patients benefit from it?
J Otolaryngol Head Neck Surg. 2013; 42:56 [PubMed] Article available free on PMC after 25/08/2014 Related Publications
BACKGROUND: Intraoperative parathyroid hormone level (IOPTH) is withdrawn during parathyroidectomy to confirm the success of the procedure. Recently, the importance of IOPTH has been put to question. The purpose of this study is to determine whether IOPTH is necessary for all patients undergoing parathyroidectomy in the presence of frozen section.
MATERIALS AND METHODS: A cohort study of parathyroidectomies was performed in three university affiliated hospitals during 2007-2012. The patients were divided into two groups. Group 1: Patients with two preoperative concordant imaging localizing a hyperactive gland. Group 2: Patients without two concordant imaging. A comparison of benefit of IOPTH was carried out. Frozen section results were also analyzed to determine sensitivity and predictability of a parathyroid adenoma.
RESULTS: The study considered 221 patients having parathyroidectomies for primary hyperparathyroidism (PHPT). Of them, 10 were excluded due to incomplete data. Among the remaining, 186 had 2 concordant imaging preoperatively localizing an adenoma. 93.5% of whom were found intraoperatively in that location. IOPTH was not found to be of importance in 98.92% of the preoperative localized adenomas in the presence of frozen section. IOPTH added an estimate of 30.9 minutes on average to the surgery time.
CONCLUSION: This study demonstrates that the added operating time associated with IOPTH may not be justified for patients undergoing parathyroidectomy who have 2 concordant imaging preoperatively in the presence of frozen section. This study suggests a simple algorithm, The McGill Parathyroid Protocol (MPP), to help in approaching PHPT patients undergoing parathyroidectomy.

Fu QY, Ma L, Yang ZB, Pao T
Multiple organ dysfunction caused by parathyroid adenoma-induced primary hyperparathyroidism.
Niger J Clin Pract. 2014 Jan-Feb; 17(1):122-4 [PubMed] Related Publications
We present a 27-year-old male with multiple organ dysfunction caused by parathyroid adenoma-induced primary hyperparathyroidism (PHPT). Initially, the patient experienced a sudden onset of gastrointestinal symptoms, polyuria, polydipsia, bone pain, renal dysfunction, nephrolithiasis, and acute pancreatitis, symptoms associated with hypercalcemia. Biochemical findings suggested PHPT. Renal biopsy showed an acute tubular injury and massive calcium deposits in the tubular epithelial cells and tubular lumina. Moreover, neck ultrasonography suggested the possibility of a parathyroid tumor. We excised his right parathyroid gland. Histopathological analysis revealed features of a parathyroid adenoma. Post-operatively this patient had normal serum calcium concentration, but was renally insufficient. A recent repeat biopsy showed chronic renal tubular injury. Our findings illustrate the complications of various systems that can occur in patients with PHPT caused by a parathyroid adenoma.

Vellanki P, Lange K, Elaraj D, et al.
Denosumab for management of parathyroid carcinoma-mediated hypercalcemia.
J Clin Endocrinol Metab. 2014; 99(2):387-90 [PubMed] Article available free on PMC after 01/02/2015 Related Publications
CONTEXT: Most of the morbidity and mortality from parathyroid cancer is due to PTH-mediated hypercalcemia. Classically, management mainly consists of surgical resection, chemotherapy, and alleviation of hypercalcemia using bisphosphonates and calcium receptor agonists. The use of denosumab in the treatment of parathyroid cancer-mediated hypercalcemia has not been reported.
OBJECTIVE: The aim of this report is to describe the effect of denosumab on parathyroid cancer-induced hypercalcemia. SUBJECT, MEASURES, AND RESULT: The patient is a 39-year-old man with metastatic parathyroid cancer who presented at age 35. His calcium levels initially responded to surgery, bisphosphonates, calcium receptor agonist, and chemotherapy (dacarbazine). However, his disease progressed, and his hypercalcemia became refractory to these measures in the setting of rising PTH levels. The addition of denosumab, a humanized monoclonal antibody inhibiting receptor activator of nuclear factor κB ligand resulted in successful management of his hypercalcemia for an additional 16 months.
CONCLUSIONS: Denosumab can be effective in the treatment of refractory hypercalcemia in parathyroid cancer. It may also be of potential use in settings of benign hyperparathyroid-related hypercalcemia such as parathyromatosis, where hypercalcemia is not amenable to surgery or medical therapy with bisphosphonates and calcium receptor agonists.

Saguan N, Recabaren J
A unique use of intraoperative digital specimen radiography in the treatment of primary hyperparathyroidism.
Am Surg. 2013; 79(10):1098-101 [PubMed] Related Publications
Intraoperative evaluation of primary parathyroid specimens historically has been difficult. Frozen section diagnosis is not reliable and time-consuming. A visible rim of compressed normal parathyroid tissue is seen histologically surrounding a parathyroid adenoma and absent in parathyroid hyperplasia. Adjuncts such as radionuclide scanning and intraoperative parathyroid hormone levels help but are indirect methods of evaluation. Intraoperative digital specimen radiography (IDSR) of specimens is a novel technique that was compared with frozen section analysis. The study spanned a 12-month period. Thirty-six patients with primary hyperparathyroidism met eligibility criteria. Resected parathyroid specimens were evaluated with the Bioptics PiXarray100 digital radiograph system and pathologic evaluation. Thirty-nine specimens were evaluated with IDSR, reflecting three patients with multiple glands excised. Thirty patients were pathologically found to have adenomas (83%) and six were hyperplasia (17%). Twenty-seven of 30 adenoma specimens had an IDSR visible rim of compressed tissue (sensitivity 90%) and no hyperplasia specimens had an IDSR visible rim (specificity 100%). Fisher's exact test was significant (P = 0.000). Frozen section correctly diagnosed adenoma in only 16 of 30 specimens (sensitivity 53%). IDSR of parathyroid specimens is a powerful modality in the real-time differentiation of parathyroid adenomas from hyperplasia (sensitivity 90%). This technique is noninferior to the current "gold standard," frozen section (sensitivity 53%). We propose IDSR evaluation of all parathyroid surgical specimens for the immediate diagnosis of adenoma versus hyperplasia.

Goldner B, Lee B, Stabile BE
The unequal distribution of parathyroid neoplasms in male patients.
Am Surg. 2013; 79(10):1022-5 [PubMed] Related Publications
There is a known lesser incidence of primary hyperparathyroidism and parathyroid neoplasms in male patients. Any difference in the anatomic distribution between males and females has not been documented. Review of our institutional experience with 125 pathologically confirmed parathyroid adenomas (119) or carcinomas (six) from 2000 through 2012 was conducted. The anatomic location was identified from operative records and the distributions between males and females were compared. Ninety-two females with parathyroid neoplasms had equal anatomic distributions between left and right sides and no significant difference between superior and inferior locations (P = 0.381). In marked contrast, tumors in 33 male patients had a significant predilection for the right side (67%, P = 0.016) and inferior position (85%, P = 0.033) and most notably the right inferior position (64%, P = 0.026). For the group as a whole, inferior adenomas were significantly more common (70%, P = 0.044). All patients had postoperative normalization of serum calcium levels. Late biochemical recurrence was noted in two patients. This is the first operatively confirmed delineation of the anatomic distributions of parathyroid neoplasms in separate sexes. Based on the unexpected findings of this study, we recommend the right inferior cervical region be explored first in males with suspected parathyroid tumors of indeterminate location.

Ogrin C
A rare case of double parathyroid lipoadenoma with hyperparathyroidism.
Am J Med Sci. 2013; 346(5):432-4 [PubMed] Related Publications
A rare case of double lipoadenomas of parathyroid glands with hyperparathyroidism is described. A 56-year-old woman was referred for management of diabetes. Work up revealed: serum Calcium (Ca) =11.9 mg/dl, glomerular filtration rate (GFR) = 103 ml/min/m2, parathyroid hormone (PTH) = 60 pg/ml, Phosphorus = 3.0 mg/dl, 25 hydroxy vitamin D (25 OH D) =16.5 ng/ml, 24 h urine Calcium =179 mg/day. Parathyroid sestamibi scan showed increased activity in the left thyroid and right thyroid lobe. Single photon emission computed tomography demonstrated uptake in inferior left and right thyroid lobes. Her serum calcium following successful bilateral parathyroidectomy was 9.3 mg/dl. Pathology showed double parathyroid lipoadenomas. After surgery, her serum Calcium and PTH normalized to 9.8 mg/dl and 32 pg/ml respectively. Lipoadenoma has been described as a very rare lesion of the parathyroid gland and is most commonly non-functional. PubMed search failed to reveal any case of hyperparathyroidism due to double parathyroid lipoadenomas.

Olatoke SA, Agodirin OS, Rahman GA, et al.
Serial pathologic fractures of five long bones on four separate occasions in a patient with primary hyperparathyroidism, challenges of management in a developing country: a case report.
Pan Afr Med J. 2013; 15:45 [PubMed] Article available free on PMC after 01/02/2015 Related Publications
Multiple pathologic fractures secondary to parathyroid adenoma is rarely recognized and reported in the tropics. Inadequate evaluation causes worsened disability and increased psychological stress. We present a 27-year-old Nigerian male student with recurrent unexplained pathological fractures of the long bones. Primary Hyperparathyroidism was later diagnosed and he benefited from a unilateral parathyroidectomy. Primary hyperparathyroidism secondary to parathyroid adenoma is difficult to diagnose and needs a high index of suspicion. Surgery and good post-operative biochemical control of serum calcium produce satisfying outcomes.

Li M, Lu H, Gao Y
FDG-anorectic parathyroid carcinoma with FDG-avid bone metastasis on PET/CT images.
Clin Nucl Med. 2013; 38(11):916-8 [PubMed] Related Publications
A 53-year-old man complained of aggravated left hip pain of more than 2 months. Whole-body (18)F-FDG PET/CT revealed only 1 hypermetabolic lesion in the left ilium. Histopathologic examination of the lesion suggested metastatic disease. Blood tests documented mildly elevated blood calcium and parathyroid hormone. Subsequent neck ultrasonography, contrast-enhanced CT, and dual-phase scintigraphy with (99m)Tc-MIBI showed a right parathyroid tumor, which was confirmed to be a parathyroid carcinoma postoperatively. We report a case of parathyroid carcinoma rarely encountered with a FDG-negative primary but a FDG-positive metastasis on PET/CT images.

Tee MC, Chan SK, Nguyen V, et al.
Incremental value and clinical impact of neck sonography for primary hyperparathyroidism: a risk-adjusted analysis.
Can J Surg. 2013; 56(5):325-31 [PubMed] Article available free on PMC after 01/02/2015 Related Publications
BACKGROUND: Despite the different preoperative imaging modalities available for parathyroid adenoma localization, there is currently no uniform consensus on the most appropriate preoperative imaging algorithm that should be routinely followed prior to the surgical management of primary hyperparathyroidism (PHPT). We sought to determine the incremental value of adding neck ultrasonography to scintigraphy-based imaging tests.
METHODS: In a single institution, surgically naive patients with PHPT underwent the following localization studies before parathyroidectomy: 1) Tc-99m sestamibi imaging with single photon emission computed tomography/computed tomography (SPECT/CT) or Tc-99m sestamibi imaging with SPECT alone, or 2) ultrasonography in addition to those tests. We retrospectively collected data and performed a multivariate analysis comparing group I (single study) to group II (addition of ultrasonography) and risk of bilateral (BNE) compared with unilateral (UNE) neck exploration.
RESULTS: Our study included 208 patients. Group II had 0.45 times the odds of BNE versus UNE compared with group I (unadjusted odds ratio [OR] 0.45, 95% confidence interval [CI] 0.25-0.81, p = 0.008). When adjusting for patient age, sex, preoperative calcium level, use of intraoperative PTH monitoring, preoperative PTH level, adenoma size, and number of abnormal parathyroid glands, Group II had 0.48 times the odds of BNE versus UNE compared with group I (adjusted OR 0.48, 95% CI 0.23-1.03, p = 0.06). In a subgroup analysis, only the addition of ultrasonography to SPECT decreased the risk of undergoing BNE compared with SPECT alone (unadjusted OR 0.40, 95% CI 0.19-0.84, p = 0.015; adjusted OR 0.38, 95% CI 0.15-0.96, p = 0.043).
CONCLUSION: The addition of ultrasonography to SPECT, but not to SPECT/CT, has incremental value in decreasing the extent of surgery during parathyroidectomy, even after adjusting for multiple confounding factors.

French R, Oweis D, Kurup V
Bilateral femoral fractures in a 21-year-old man following a simple fall.
BMJ Case Rep. 2013; 2013 [PubMed] Related Publications
We present a case of a 21-year-old man with hip pain to the orthopaedic team. During the initial assessment he was found to be hypercalcaemic (adjusted calcium 3.55) due to the primary hyperparathoidism (PTH 1285), with all other screening for multiple endocrine neoplasia negative. During his time on the ward while being treated for the hypercalcaemia he had a fall resulting in bilateral femoral fractures, requiring surgical management. He underwent an emergency exploration of neck and excision of a large parathyroid adenoma, measuring 5.5 cm. He also developed renal failure as a result of nephrocalcinosis. This case highlights the importance of early detection and management of hyperparathyroidism with the aim of preventing long-term complications. This patient ultimately required a renal transplant and multiple orthopaedic procedures as a result of undiagnosed PTH and recently underwent excision of the remaining parathyroid glands.

Hunter GJ, Ginat DT, Kelly HR, et al.
Discriminating parathyroid adenoma from local mimics by using inherent tissue attenuation and vascular information obtained with four-dimensional CT: formulation of a multinomial logistic regression model.
Radiology. 2014; 270(1):168-75 [PubMed] Related Publications
PURPOSE: To identify a set of parameters, which are based on tissue enhancement and native iodine content obtained from a standardized triple-phase four-dimensional (4D) computed tomographic (CT) scan, that define a multinomial logistic regression model that discriminates between parathyroid adenoma (PTA) and thyroid nodules or lymph nodes.
MATERIALS AND METHODS: Informed consent was waived by the institutional review board for this retrospective HIPAA-compliant study. Electronic medical records were reviewed for 102 patients with hyperparathyroidism who underwent triple-phase 4D CT and parathyroid surgery resulting in pathologically proved removal of adenoma from July 2010 through December 2011. Hounsfield units were measured in PTA, thyroid, lymph nodes, and aorta and were used to determine seven parameters characterizing tissue contrast enhancement. These were used as covariates in 10 multinomial logistic regression models. Three models with one covariate, four models with two covariates, and three models with three covariates were investigated. Receiver operating characteristic (ROC) analysis was performed to determine how well each model discriminated between adenoma and nonadenomatous tissues. Statistical differences between the areas under the ROC curves (AUCs) for each model pair were calculated, as well as sensitivity, specificity, accuracy, negative predictive value, and positive predictive value.
RESULTS: A total of 120 lesions were found; 112 (93.3%) lesions were weighed, and mean and median weights were 589 and 335 mg, respectively. The three-covariate models were significantly identical (P > .65), with largest AUC of 0.9913 ± 0.0037 (standard error), accuracy of 96.9%, and sensitivity, specificity, negative predictive value, and positive predictive value of 94.3%, 98.3%, 97.1%, and 96.7%, respectively. The one- and two-covariate models were significantly less accurate (P < .043).
CONCLUSION: A three-covariate multinomial logistic model derived from a triple-phase 4D CT scan can accurately provide the probability that tissue is PTA and performs significantly better than models using one or two covariates.

Malm IJ, Olcott CM, Chan JY, et al.
A case of congenital agenesis of the common carotid artery associated with an ectopic parathyroid adenoma mimicking a carotid body tumor.
Am J Otolaryngol. 2013 Sep-Oct; 34(5):553-5 [PubMed] Related Publications
Ectopic parathyroid adenomas can be encountered during four gland explorations, but nearly 80% of adenomas are localized with ultrasound and sestamibi imaging. Ectopic adenomas are thought to arise from abnormal migration during development. As a cervical congenital anomaly, common carotid artery agenesis is an extremely rare anomaly characterized by separate origins of the internal and external carotid arteries directly from the aortic arch. Here we present a case of a 75 year old man with primary hyperparathyroidism who was found to have congenital agenesis of the common carotid artery associated with an ectopic parathyroid adenoma within the parapharyngeal space, which mimicked a carotid body tumor based on location and imaging. The successful identification and resection of the ectopic parathyroid adenoma presented here demonstrate the importance of preoperative imaging studies to allow appropriate operative planning as well as the utility of intraoperative parathyroid hormone assay in predicting cure during surgery.

Spanheimer PM, Stoltze AJ, Howe JR, et al.
Do giant parathyroid adenomas represent a distinct clinical entity?
Surgery. 2013; 154(4):714-8; discussion 718-9 [PubMed] Article available free on PMC after 01/10/2014 Related Publications
BACKGROUND: The size of abnormal parathyroid glands in patients with primary hyperparathyroidism (PHPT) is highly variable, but the clinical significance of giant glands is unknown.
METHODS: We reviewed 300 consecutive patients after parathyroidectomy for PHPT. We compared patients with giant parathyroid adenomas (weight ≥95th percentile) with the remaining patients.
RESULTS: Giant adenomas were defined as weight ≥95th percentile or 3.5 g (median, 0.61; range, 0.05-29.93). Patients with giant adenomas had a greater mean preoperative calcium level, greater mean parathyroid hormone (PTH) level, and were less likely to have multiglandular or symptomatic disease. Giant adenomas were successfully localized on imaging in 87% of patients, which was not increased over other patients (82%). There were no differences between the groups in age, gender, gland location, or the incidence of persistent or recurrent hyperparathyroidism. Finally, giant glands had an increased incidence of symptomatic postoperative hypocalcemia, including 1 patient who required rehospitalization after removal of a giant gland.
CONCLUSION: Giant parathyroid adenomas have a distinct presentation characterized by single gland disease and lower incidence of symptoms despite increased levels of calcium and PTH. Additionally, after resection of a giant adenoma, patients are more likely to develop symptomatic hypocalcemia.

Devcic Z, Jeffrey RB, Kamaya A, Desser TS
The elusive parathyroid adenoma: techniques for detection.
Ultrasound Q. 2013; 29(3):179-87 [PubMed] Related Publications
The success of minimally invasive surgery for hyperparathyroidism depends on accurate preoperative localization of the hyperfunctioning adenoma with imaging. Ultrasound is an excellent initial modality because it has a high positive predictive value, sensitivity, and specificity, while being inexpensive and noninvasive without use of ionizing radiation. Determining the exact location and number of adenomas is essential, because these factors guide the surgical approach. The goal of this review article was to discuss specific sonographic techniques that can be applied to find even the elusive adenoma, which include (1) compression scanning, (2) color Doppler, (3) scanning regions where ectopic glands may be located, and (4) evaluating intrathyroidal adenomas.

Piciu D, Irimie A, Kontogeorgos G, et al.
Highly aggressive pathology of non-functional parathyroid carcinoma.
Orphanet J Rare Dis. 2013; 8:115 [PubMed] Article available free on PMC after 01/10/2014 Related Publications
Parathyroid carcinoma is a rare malignant endocrine tumor accounting for only 0.5% to 5% of all primary hyperparathyroidism. Among these malignancies, only 10-25% are nonfunctioning. After the review of the literature we could only ascertain a number of 25 cases reported worldwide, since 1929, our case being the 26th, but the first with a very aggressive pathology, treated with chemotherapy scheme usually used for neuroendocrine tumors. Considering these facts, every single case presented is a step forward in defying the clinical presentation, for the awareness of the clinicians, and also in establishing standard adjuvant therapies.

Related: Carboplatin Etoposide

Varshney S, Bhadada SK, Sachdeva N, et al.
Methylation status of the CpG islands in vitamin D and calcium-sensing receptor gene promoters does not explain the reduced gene expressions in parathyroid adenomas.
J Clin Endocrinol Metab. 2013; 98(10):E1631-5 [PubMed] Related Publications
AIM: The exact mechanism causing decreased expression of the vitamin D receptor (VDR) and calcium-sensing receptor (CASR) genes in parathyroid adenoma is not known, but methylation of promoter regions is often detected during epigenetic downregulation of gene expression. We investigated whether epigenetic silencing is involved in the decreased expression of VDR and CASR.
EXPERIMENTAL DESIGN: Real-time PCR and immunohistochemistry confirmed the downregulation of the VDR and CASR genes at transcriptional and translational levels. Bisulfite-converted DNA samples from parathyroid adenomas with control samples were analyzed for methylation in the promoter region of VDR and CASR genes.
RESULTS: There was no significant methylation in the promoter regions of VDR and CASR genes in parathyroid adenomatous tissues.
CONCLUSIONS: Methylation-mediated silencing of VDR and CASR promoter does not appear to be associated with reduced expression, indicating the involvement of other factors in specific suppression of VDR and CASR in parathyroid adenomas.

Xu SY, Wang Y, Xie Q, Wu HY
Percutaneous sonography-guided radiofrequency ablation in the management of parathyroid adenoma.
Singapore Med J. 2013; 54(7):e137-40 [PubMed] Related Publications
Parathyroid adenoma is a major cause of primary hyperparathyroidism. Treatment usually involves the surgical removal of one or more parathyroid glands. However, specific localising techniques have boosted the development of nonsurgical, minimally invasive procedures, such as percutaneous radiofrequency ablation (RFA) under ultrasonographic guidance, which are gaining popularity as a method of treatment. This paper reports two male patients who presented with hypercalcaemia (highest serum calcium level 4.56 mmol/L and 4.57 mmol/L, respectively) and hyperparathyroidism (highest serum parathyroid hormone [PTH] level 772 ng/L and > 1,900 ng/L, respectively) due to solitary parathyroid adenoma. Four days after percutaneous RFA, the serum calcium levels in both patients decreased and PTH levels showed a significant decreasing trend. Both patients recovered well with normal levels of calcium and improvement of symptoms. Thus, we conclude that RFA may be a safe and effective therapeutic option in the treatment of parathyroid adenoma.

Mohammadi A, Moloudi F, Ghasemi-rad M
Spectral Doppler analysis of parathyroid adenoma: correlation between resistive index and serum parathyroid hormone concentration.
AJR Am J Roentgenol. 2013; 201(2):W318-21 [PubMed] Related Publications
OBJECTIVE: The purpose of this study was to evaluate the correlation between spectral wave analyses by measuring the resistive index and serum intact parathyroid hormone (iPTH) concentration in primary hyperparathyroidism.
SUBJECTS AND METHODS: From March 2008 to April 2012, 46 consecutively registered patients underwent color and spectral Doppler ultrasonography for determination of vascularity and vascular resistance of parathyroid adenoma. The color Doppler sonographic findings were compared with methoxyisobutylisonitrile (MIBI) scintigraphic findings, serum iPTH concentration, and the volume of the gland.
RESULTS: The mean resistive index in parathyroid adenoma was 0.69 ± 0.12. The study showed a strong negative relation between resistive index and serum iPTH concentration. There was a significant negative relation between the volume of the gland and the resistive index.
CONCLUSION: There is a relation between degree of perfusion in parathyroid adenoma and serum iPTH concentration. Resistive index may be an objective alternative parameter for determining the vascularity of adenoma for monitoring of response to alcohol ablation therapy and medical management.

Qiu ZL, Wu CG, Zhu RS, et al.
Unusual case of solitary functioning bone metastasis from a "parathyroid adenoma": imagiologic diagnosis and treatment with percutaneous vertebroplasty--case report and literature review.
J Clin Endocrinol Metab. 2013; 98(9):3555-61 [PubMed] Related Publications
BACKGROUND: Parathyroid carcinoma is a rare endocrine malignancy that accounts for a small percentage of patients with primary hyperparathyroidism. Here, an unusual patient with parathyroid carcinoma misdiagnosed as a parathyroid adenoma was reported. A solitary L4 vertebral metastasis, which was localized by technetium-99m-labelled methoxyisobutyl isonitrile ((99m)Tc-MIBI) single photon emission computed tomography (SPECT)/computed tomography (CT) fusing images, was successfully treated with percutaneous vertebroplasty (PVP) for the first time.
PATIENT AND METHODS: A 53-year-old man with primary hyperparathyroidism and a palpable mass in the right neck was referred. A right unilateral parathyroidectomy was performed. A pathological diagnosis of parathyroid adenoma was made; however, hyperparathyroidism persisted with a serum calcium of 4.51 mmol/L and a PTH of 3235 pg/mL. Early and delayed images of the (99m)Tc-MIBI whole-body scan revealed abnormal (99m)Tc-uptake in the lower abdomen. The delayed (99m)Tc-MIBI SPECT/CT fusion images found that the lower abnormal (99m)Tc-MIBI uptake was located in the area of osteolytic destruction of the L4 vertebra. A bone metastasis from parathyroid carcinoma was diagnosed based on histopathological evaluation and immunohistochemical staining. PVP was performed to treat the osteolytic destruction of the L4 vertebra. The PTH level decreased to normal within 1 week after PVP.
CONCLUSION: (99m)Tc-MIBI SPECT/CT scan may be a useful and suitable method by which to localize functioning distant metastases from the parathyroid cancer when serum PTH and calcium levels remain greatly elevated after parathyroidectomy. PVP may be an effective procedure in eliminating cancer cells, reducing serum PTH levels, preventing bone fractures, and improving the quality of life of patients.

Sim IW, Farrell S, Grodski S, et al.
Parathyromatosis following spontaneous rupture of a parathyroid adenoma: natural history and the challenge of management.
Intern Med J. 2013; 43(7):819-22 [PubMed] Related Publications
Parathyromatosis, the presence of small nodules of hyper-functioning parathyroid tissue scattered throughout the soft tissues of the neck and superior mediastinum, is a rare cause of persistent primary hyperparathyroidism. We report the first case of parathyromatosis secondary to spontaneous rupture of a parathyroid adenoma. Despite running an indolent course, this case highlights the potential challenges of management of parathyromatosis and the value of calcimimetic therapy as an adjunct to surgery for disease control.

Sturniolo G, Gagliano E, Tonante A, et al.
Parathyroid carcinoma: case report.
G Chir. 2013 May-Jun; 34(5-6):170-2 [PubMed] Article available free on PMC after 01/10/2014 Related Publications
The authors present a case of parathyroid carcinoma in a patient with primary hyperparathyroidism. Following a literature review, the clinical and diagnostic profile, treatment and prognosis of this rare disease are discussed.

Riss P, Krall C, Scheuba C, et al.
Risk factors for "PTH spikes" during surgery for primary hyperparathyroidism.
Langenbecks Arch Surg. 2013; 398(6):881-6 [PubMed] Related Publications
PURPOSE: Increased intraoperative parathyroid hormone excretion ("PTH spikes") due to unintended manipulation of parathyroid adenoma can be observed frequently during surgery for primary hyperparathyroidism. This may lead to difficulties in interpreting intraoperative PTH curves. The aim of this study was to elucidate possible risk factors for PTH spikes and to evaluate the impact on different interpretation criteria of intraoperative PTH curves.
METHODS: Eight hundred forty-seven patients with primary hyperparathyroidism were included. The probability of PTH spikes was analyzed regarding preoperative PTH- and creatinine levels, and size of adenoma and their impact on the Vienna, Miami, and Halle criteria was evaluated.
RESULTS: PTH spikes occurred in 102 patients (12 %) and revealed to be independent of PTH- and creatinine levels (p = 0.13) preoperatively. There was a significant negative correlation between "manipulation PTH" and "baseline PTH" values and the gland volume, respectively. Patients presenting with smaller adenomas and those with low-baseline PTH values show significantly higher manipulation values. No risk factor for manipulation was exposed and no significantly higher risk of misclassification as "false positive" in case of PTH spikes was detected for any interpretation criterion. For the "Vienna Criterion," however, a significant increase in the risk of "false negative" misclassification was observed with increasing manipulation values.
CONCLUSIONS: In patients with PTH spikes, none of the analyzed criteria show a significant increase in missed adenomas. Nevertheless, the Vienna criterion shows a higher rate of potentially unnecessary explorations with increasing manipulation values. Thus, caution is warranted in detecting PTH spikes and in individual interpretations of specific PTH curves is recommended. The Miami criterion seems to be favorable in this group of patients.

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