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).

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.

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.

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.

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] Free Access to Full Article 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.

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] Free Access to Full Article 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.

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.

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.

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.

Burke JF, Jacobson K, Gosain A, et al.
Radioguided parathyroidectomy effective in pediatric patients.
J Surg Res. 2013; 184(1):312-7 [PubMed] Article available free on PMC after 01/09/2014 Related Publications
BACKGROUND: Radioguided parathyroidectomy (RGP) has been shown to be effective in adult patients with hyperparathyroidism (HPT), but the utility of RGP in pediatric patients has not been systematically examined. It is not known if adult criteria for radioactive counts can accurately detect hyperfunctioning parathyroid glands in pediatric patients. The purpose of our study was to determine the utility of RGP in children with primary HPT.
MATERIALS AND METHODS: A retrospective review of our prospectively maintained single-institution database for patients who underwent a RGP for primary HPT identified 1694 adult and 19 pediatric patients aged 19 y or younger. From the adult population, we selected a control group matched three to one for gland weight and gender and compared pre- and postoperative laboratory values, surgical findings, pathology, and radioguidance values between the control and the pediatric groups.
RESULTS: Excised glands from pediatric patients were smaller than those in the total adult population (437 ± 60 mg versus 718 ± 31 mg, P = 0.0004). When controlled for gland weight, ex vivo counts as a percentage of background were lower in the pediatric group (51% ± 5% versus 91% ± 11%, P = 0.04). However, ex vivo radionuclide counts >20% of the background were found in 100% of pediatric patients and 95% of the adult-matched control group.
CONCLUSIONS: All pediatric patients met the adult detection criteria for parathyroid tissue removal when a RGP was performed, and 100% cure was achieved. We conclude that RGP is a useful treatment option for pediatric patients with primary HPT.

Ezzat T, Maclean GM, Parameswaran R, et al.
Primary hyperparathyroidism with water clear cell content: the impact of histological diagnosis on clinical management and outcome.
Ann R Coll Surg Engl. 2013; 95(3):e60-2 [PubMed] Related Publications
Water clear cell hyperplasia (WCCH) and water clear cell adenomas (WCCA) of the parathyroid glands are rare causes of primary hyperparathyroidism. We report in this series one case of WCCH and two cases of WCCA representing 0.3% of patients with primary hyperparathyroidism presenting to our institution. Increased parathyroid cellular water content was responsible for relatively larger parathyroid gland sizes. However, this was not associated with higher biochemical markers or more severe clinical presentations. Histological distinction between WCCH and WCCA is difficult but important since patients with WCCH who have had a parathyroidectomy via a unilateral neck exploration may carry an increased risk of future disease recurrence.

Suzuki K, Sakuta A, Aoki C, Aso Y
Hyperparathyroidism caused by a functional parathyroid cyst.
BMJ Case Rep. 2013; 2013 [PubMed] Related Publications
A 67-year-old Japanese woman was admitted to our hospital for malaise and loss of appetite. Relevant biochemical examinations showed definite hypercalcaemia and elevated serum levels of intact parathyroid hormone (PTH). We performed thyroid ultrasonography and CT of the neck, which revealed a cystic lesion in the right lower lobe of the thyroid glands. Ultrasound-guided fine-needle aspiration was performed, and PTH level of the cystic fluid was markedly elevated. Technetium-99m-hexakis 2-methoxyisobutyi isonitrile sesta scintigraphy showed intense ring-shaped accumulation of radioactivity in the wall of the cyst. The patient underwent a right lobectomy to resect the cystic parathyroid adenoma. After surgery, her serum calcium and PTH level returned to normal ranges.

Philip George AJ, Banerji JS
Brown tumor and staghorn calculi in primary hyperparathyroidism.
Urology. 2013; 82(2):e13-4 [PubMed] Related Publications
A case of primary hyperparathyroidism with bilateral renal staghorn calculi and brown tumor right thumb is reported in these images, along with the appropriate sequential management. Percutaneous nephrolithotomy (PCNL)was done after management of hypercalcemia and after parathyroidectomy. This case highlights the need for urologists and general practitioners to have a holistic approach in patient management.

Sulaiman L, Juhlin CC, Nilsson IL, et al.
Global and gene-specific promoter methylation analysis in primary hyperparathyroidism.
Epigenetics. 2013; 8(6):646-55 [PubMed] Article available free on PMC after 01/06/2014 Related Publications
Epigenetic mechanisms involved in primary hyperparathyroidism are poorly understood as studies are limited. In order to understand the role of aberrant DNA promoter methylation in the pathogenesis of parathyroid tumors, we have quantified the CpG island promoter methylation density of several candidate genes including APC (promoter 1A and 1B), β-catenin (CTNNB1), CASR, CDC73/HRPT2, MEN1, P16 (CDKN2A), PAX1, RASSF1A, SFRP1 and VDR in 72 parathyroid tumors and 3 normal parathyroid references using bisulfite pyrosequencing. Global methylation levels were assessed for LINE-1. We also compared methylation levels with gene expression levels measured by qRT-PCR for genes showing frequent hypermethylation. The adenomas displayed frequent hypermethylation of APC 1A (37/66; 56%), RASSF1A (34/66; 52%) and β-catenin (19/66; 29%). One of the three atypical adenomas was hypermethylated for APC 1A. The three carcinomas were hypermethylated for RASSF1A and SFRP1, and the latter was only observed in this subtype. The global methylation density was similar in tumors (mean 70%) and parathyroid reference samples (mean 70%). In general, hypermethylated genes had reduced expression in the parathyroid adenomas using qRT-PCR. Among the adenomas, methylation of APC 1A correlated with adenoma weight (r = 0.306, p < 0.05). Furthermore, the methylation status of RASSF1A correlated with each of APC 1A (r = 0.289, p < 0.05) and β-catenin (r = 0.315, p < 0.01). Our findings suggest a role for aberrant DNA promoter methylation of APC 1A, β-catenin and RASSF1A in a subset of parathyroid tumors.

Lee SH, Kim BH, Bae MJ, et al.
Concurrence of primary hyperparathyroidism and metastatic breast carcinoma affected a parathyroid gland.
J Clin Endocrinol Metab. 2013; 98(8):3127-30 [PubMed] Related Publications
OBJECTIVE: Involvement of the parathyroid glands by metastatic tumor is rare. Breast is 1 of the primary sites in metastatic cancers. We introduce a rare case of metastatic breast carcinoma affecting a parathyroid gland, which was clinically combined with parathyroid gland hyperplasia.
CASE REPORT: A 65-year-old woman was referred due to hypercalcemia and constipation. The patient had a history of left breast carcinoma. She was admitted to the hospital because of the recent discovery of hypercalcemia and elevation of PTH. A Tc99m-sestamibi scan showed retained uptake in the right thyroid and in the lower pole of the left thyroid gland. Aspiration biopsy results revealed that the nodule in the posterior portion of the right thyroid was metastatic breast cancer and the nodule in the left thyroid gland was the hyperplastic parathyroid gland.
CONCLUSION: This case illustrates that hyperparathyroidism caused by parathyroid hyperplasia was concurrent with metastatic breast cancer to a parathyroid gland without disseminated systemic metastasis. Although this case is very uncommon and it is not clear whether there is a relationship between breast cancer and primary hyperparathyroidism, that possibility should always be considered as the cause of hypercalcemia in patients with breast cancer.

Related: Breast Cancer

Sabetkish N, Tavangar SM
An unusual combination of parathyroid adenoma, medullary and papillary thyroid carcinoma.
Acta Med Iran. 2013; 51(5):337-40 [PubMed] Related Publications
The coexistence of medullary thyroid carcinoma (MTC), papillary thyroid carcinoma (PTC) and parathyroid adenoma is an uncommon clinical entity. Here, we report a case of MTC, PTC, and parathyroid adenoma diagnosed incidentally on a routine physical examination of the neck for the work-up of diabetes. The patient had neither symptoms of hypercalcemia nor those related to MTC and PTC.

Related: Multiple Endocrine Neoplasia Thyroid Cancer

Razib FA, Mannan M, Biswas AK, et al.
Presentation of primary hyperparathyroidism due to adenoma.
Mymensingh Med J. 2013; 22(2):320-4 [PubMed] Related Publications
This descriptive study was done to evaluate the clinical, biochemical and radiological findings of primary hyperthyroidism (pHPT) patients with parathyroid adenoma. This study was done in the department of Otolaryngology and Head-Neck surgery, BIRDEM, Dhaka from July 2000 to June 2007. We retrospectively reviewed the clinical presentation, biochemical and radiological features from the case records from the last 7 years of 32 patients at a tertiary care centre in Dhaka who had documented pHPT due to adenoma. Of them 18 were male and 14 were female. Mean age±SD of the patients was 42.16±11.64 years. Median preoperative serum calcium, serum phosphate and serum parathyroid hormone (PTH) levels were 11.42 mg/dL (range 8.4-14.0mg/dL), 3.11 mg/dL (range 2.5-4.5) and 293.22 pg/mL (range 65-700 pg/mL), respectively. Of all patients 75% had raised serum calcium level and 100.0% had raised serum PTH levels but all had normal serum phosphate level. Common radiological features were nephrocalcinosis, renal calculi, osteopenic changes in finger and toe, Brown tumour in forearm, 'Salt and pepper' appearance in skull, fracture of femur, fracture radius. pHPT due to adenoma in Bangladesh continues to be a symptomatic disorder with skeletal and renal manifestations.

D'Agostino J, Wall J, Soler L, et al.
Virtual neck exploration for parathyroid adenomas: a first step toward minimally invasive image-guided surgery.
JAMA Surg. 2013; 148(3):232-8; discussion 238 [PubMed] Related Publications
OBJECTIVE: To evaluate the performance of 3-dimensional (3D) virtual neck exploration (VNE) as a modality for preoperative localization of parathyroid adenomas in primary hyperparathyroidism and assess the feasibility of using augmented reality to guide parathyroidectomy as a step toward minimally invasive imageguided surgery.
DESIGN: Enhanced 3D rendering methods can be used to transform computed tomographic scan images into a model for 3D VNE. In addition to a standard imaging modality, 3D VNE was performed in all patients and used to preoperatively plan minimally invasive parathyroidectomy. All preoperative localization studies were analyzed for their sensitivity, specificity, positive predictive value, and negative predictive value for the correct side of the adenoma(s) (lateralization) and the correct quadrant of the neck (localization). The 3D VNE model was used to generate intraoperative augmented reality in 3 cases.
SETTING: Tertiary care center.
PATIENTS: A total of 114 consecutive patients with primary hyperparathyroidism were included from January 8, 2008, through July 26, 2011.
RESULTS: The accuracy of 3D VNE in lateralization and localization was 77.2% and 64.9%, respectively. Virtual neck exploration had superior sensitivity to ultrasonography (P.001), sestamibi scanning (P=.07), and standard computed tomography (P.001). Use of the 3D model for intraoperative augmented reality was feasible.
CONCLUSIONS: 3-Dimensional VNE is an excellent tool in preoperative localization of parathyroid adenomas with sensitivity, specificity, and diagnostic accuracy commensurate with accepted first-line imaging modalities. The added value of 3D VNE includes enhanced preoperative planning and intraoperative augmented reality to enable less-invasive image-guided surgery.

Dasgupta DJ, Navalkissoor S, Ganatra R, Buscombe J
The role of single-photon emission computed tomography/computed tomography in localizing parathyroid adenoma.
Nucl Med Commun. 2013; 34(7):621-6 [PubMed] Related Publications
With hybrid imaging playing an increasingly important role in nuclear medicine, this article reviews the literature on single-photon emission computed tomography/computed tomography (SPECT/CT) in parathyroid scintigraphy. An understanding of parathyroid and neck anatomy is important for accurate reporting of these scans, as this can have an impact on the surgical approach used. The contribution of SPECT/CT over and above SPECT alone is greatest in terms of localization, particularly for ectopic tumours. There remains controversy on the role of SPECT/CT in eutopic tumours, especially when considering such factors as imaging time and the additional radiation dose.

Varshney S, Bhadada SK, Saikia UN, et al.
Simultaneous expression analysis of vitamin D receptor, calcium-sensing receptor, cyclin D1, and PTH in symptomatic primary hyperparathyroidism in Asian Indians.
Eur J Endocrinol. 2013; 169(1):109-16 [PubMed] Related Publications
BACKGROUND: To explore underlying molecular mechanisms in the pathogenesis of symptomatic sporadic primary hyperparathyroidism (PHPT).
MATERIALS AND METHODS: Forty-one parathyroid adenomas from patients with symptomatic PHPT and ten normal parathyroid glands either from patients with PHPT (n=3) or from euthyroid patients without PHPT during thyroid surgery (n=7) were analyzed for vitamin D receptor (VDR), calcium-sensing receptor (CASR), cyclin D1 (CD1), and parathyroid hormone (PTH) expressions. The protein expressions were assessed semiquantitatively by immunohistochemistry, based on percentage of positive cells and staining intensity, and confirmed by quantitative real-time PCR.
RESULTS: Immunohistochemistry revealed significant reductions in VDR (both nuclear and cytoplasmic) and CASR expressions and significant increases in CD1 and PTH expressions in adenomatous compared with normal parathyroid tissue. Consistent with immunohistochemistry findings, both VDR and CASR mRNAs were reduced by 0.36- and 0.45-fold change (P<0.001) and CD1 and PTH mRNAs were increased by 9.4- and 17.4-fold change respectively (P<0.001) in adenomatous parathyroid tissue. PTH mRNA correlated with plasma PTH (r=0.864; P<0.001), but not with adenoma weight, while CD1 mRNA correlated with adenoma weight (r=0.715; P<0.001). There were no correlations between VDR and CASR mRNA levels and serum Ca, plasma intact PTH, or 25-hydroxyvitamin D levels. In addition, there was no relationship between the decreases in VDR and CASR mRNA expressions and the increases in PTH and CD1 mRNA expressions.
CONCLUSIONS: The expression of both VDR and CASR are reduced in symptomatic PHPT in Asian Indians. In addition, CD1 expression was greatly increased and correlated with adenoma weight, implying a potential role for CD1 in adenoma growth and differential clinical expression of PHPT.

Hendy GN, Cole DE
Genetic defects associated with familial and sporadic hyperparathyroidism.
Front Horm Res. 2013; 41:149-65 [PubMed] Related Publications
Primary hyperparathyroidism (PHPT) occurs sporadically, but occasionally it may be a feature of a familial condition, such as multiple endocrine neoplasia type 1 (MEN1), MEN2A, or the HPT-jaw tumor syndrome (HPT-JT), and familial hypocalciuric hypercalcemia/neonatal severe hyperparathyroidism (FHH/NSHPT). PHPT may also occur as familial isolated hyperparathyroidism (FIHP), and has been observed as a consequence of mutations in the CDKN1B gene (MEN4). Tumorigenesis in these conditions may be the result of protooncogene activation (e.g. RET in MEN2) or two-hit losses of a tumor suppressor (e.g. MEN1, HPT-JT). In patients with MEN1, HPT-JT or FHH/NSHPT, the hyperparathyroidism manifests at a younger age and affects both sexes equally. In MEN1, mutations of the MEN1 gene also cause enteropancreatic and anterior pituitary tumors. In MEN2, activating mutations in the RET protooncogene also cause medullary thyroid carcinoma and pheochromocytoma. In HPT-JT, mutations of CDC73/HRPT2 are associated with parathyroid carcinoma, but tumors of the kidneys and uterus are additional features. In some FIHP families, a CASR mutation may be identified. In parathyroid carcinoma, even if sporadic, molecular diagnostics for CDC73/HRPT2 should be considered, as it should be for younger patients. Further exploration of these hereditary syndromes may shed light on the molecular mechanisms giving rise to nonhereditary PHPT.

Related: BCL1 Gene (CCND1) MEN1 RET

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