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).

Saad AF, Pacheco LD, Costantine MM
Management of ectopic parathyroid adenoma in pregnancy.
Obstet Gynecol. 2014; 124(2 Pt 2 Suppl 1):478-80 [PubMed] Related Publications
BACKGROUND: During pregnancy, management of refractory hypercalcemia secondary to a parathyroid adenoma must include prompt localization and excision of the mass, irrespective of gestational age.
CASE: An 18-year-old woman at 23 weeks of gestation was found to have severe hypercalcemia secondary to primary hyperparathyroidism. She required aggressive intravenous hydration with the addition of furosemide to enhance calcium elimination. After localization of an ectopic adenoma in the mediastinum using nuclear medicine scanning, she underwent a video-assisted thoracoscopic resection of the mediastinal parathyroid adenoma. The patient subsequently had an uneventful delivery at term.
CONCLUSION: Physiologic changes during pregnancy may delay the diagnosis of severe hypercalcemia secondary to parathyroid adenomas. When conservative management fails, localization and surgical excision of the adenoma become imperative to achieve the best maternal and perinatal outcomes.

Related: Breast cancer in pregnancy

Haldar A, Thapar A, Khan S, Jenkins S
Day-case minimally invasive excision of a giant mediastinal parathyroid adenoma.
Ann R Coll Surg Engl. 2014; 96(5):e21-3 [PubMed] Related Publications
Inferior parathyroid adenomas in the mediastinum can be a troublesome cause for hypercalcaemia, requiring a full collar incision or, occasionally, a sternotomy. We report a case of a giant parathyroid adenoma in a 61-year-old woman on warfarin, which we excised via a minimally invasive transcervical approach after radiological localisation. The procedure was performed as a day case and, at six weeks, the patient had recovered fully with biochemical resolution of hypercalcaemia. This case demonstrates that focused transcervical excision of giant parathyroid adenomas is a viable option and should be considered prior to neck exploration or sternotomy.

Twigt BA, van Dalen T, Vroonhoven TJ, Consten EC
Recurrent hyperparathyroidism caused by benign neoplastic seeding: two cases of parathyromatosis and a review of the literature.
Acta Chir Belg. 2013 May-Jun; 113(3):228-32 [PubMed] Related Publications
BACKGROUND: Parathyromatosis is defined as small nodules of hyperfunctioning parathyroid tissue scattered in the soft tissues of the neck and/or mediastinum. Parathyromatosis may be primary, it may be aimed for when autotransplanting parathyroid tissue in secondary hyperparathyroidism, and it may occur after surgery for primary hyperparathyroidism (pHPT). In the latter cases parathyromatosis poses a diagnostic and therapeutic challenge.
METHODS: To illustrate the clinical problem of parathyromatosis as a rare cause of recurrent disease after an operation for pHPT we describe two patients and performed a review of the literature for contributing factors.
RESULTS: Two patients, previously treated for pHPT and having undergone multiple neck explorations had at their final operation numerous small nests of benign parathyroid tissue scattered throughout connective tissue of the neck. These findings concur with various previous cases reported in the reviewed literature.
CONCLUSIONS: These cases illustrate that meticulous handling of parathyroid adenomas during surgical excision is of the utmost importance. Regardless of which operating technique is utilised, great emphasis must be placed on precautions towards ensuring the complete and above all the intact removal of the affected gland without capsular rupture. As parathymatosis is caused by seeding, which although extremely rare, it might very well result in the need for extensive reexploration.

Buderi SI, Saleh HZ, Theologou T, Shackcloth M
Endobronchial ultrasound-guided biopsy to diagnose large posterior mediastinal parathyroid adenoma prior to video-assisted thoracoscopic resection.
BMJ Case Rep. 2014; 2014 [PubMed] Related Publications
A 65-year-old woman was referred with hypercalcaemia and found to have a four cm retrotracheal mass on CT. The patient also suffered from neurofibromatosis and a recently diagnosed gastric mass. Tc(99) sestamibi scintigraphy revealed an area of intense uptake in the right upper mediastinum. Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) was used to confirm the diagnosis of parathyroid adenoma and thoracoscopic resection was subsequently performed. EBUS-TBNA biopsy can be a helpful diagnostic tool to confirm diagnosis of mediastinal parathyroid masses in patients with atypical or complex clinical presentations.

Tonelli F, Giudici F, Giusti F, et al.
A heterozygous frameshift mutation in exon 1 of CDKN1B gene in a patient affected by MEN4 syndrome.
Eur J Endocrinol. 2014; 171(2):K7-K17 [PubMed] Related Publications
OBJECTIVE: Multiple endocrine neoplasia type 4 (MEN4) is an autosomal dominant disorder that presents with a spectrum of clinical manifestations overlapping with those of MEN1 syndrome. It is caused by inactivating mutations of the CDKN1B gene, encoding for p27(kip1) cyclin-dependent kinase 2 inhibitor, implicated in cell cycle control. Eight mutations of CDKN1B in MEN4 patients have been published so far. The aim of this study was to characterize the molecular basis of a case of MEN1-like syndrome with a neuroendocrine tumor and persistent primary hyperparathyroidism (PHPT).
METHODS: Clinical, biochemical, and genetic evaluation were undertaken in the proband (a 53-year-old Caucasian woman) and in one 34-year-old son. The proband was operated for recurrent PHPT. Sequence analysis of the MEN1 and CDKN1B genes was performed on constitutional and parathyroid tissue DNA. Staining for p27 was carried out in parathyroid tissue.
RESULTS: Neither MEN1 mutations nor large deletions encompassing the MEN1 gene on chromosome 11q13.1 could be detected in the proband. A germline frameshift mutation of CDKN1B (371delCT) was revealed, predicted to generate a truncated p27 (CDKN1B) protein. This mutation was confirmed on somatic DNA from the pathological parathyroid tissue, with the retention of the WT allele.
CONCLUSIONS: We report a germline heterozygote frameshift mutation of the CDKN1B gene in a Caucasian woman with a long clinical history of MEN1-like multiple endocrine tumors, along with the finding of the mutation in her son. This is the first report of positive CDKN1B mutation analysis in a male subject and also the first description of recurrent hyperparathyroidism in MEN4.

Related: CDKN1B Multiple Endocrine Neoplasia

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.

Schwarzlmüller T, Brauckhoff K, Løvås K, et al.
High cardiac background activity limits 99mTc-MIBI radioguided surgery in aortopulmonary window parathyroid adenomas.
BMC Surg. 2014; 14:22 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Radioguided surgery using 99m-Technetium-methoxyisobutylisonitrile (99mTc-MIBI) has been recommended for the surgical treatment of mediastinal parathyroid adenomas. However, high myocardial 99mTc-MIBI uptake may limit the feasibility of radioguided surgery in aortopulmonary window parathyroid adenoma.
CASE PRESENTATION: Two female patients aged 72 (#1) and 79 years (#2) with primary hyperparathyroidism caused by parathyroid adenomas in the aortopulmonary window were operated by transsternal radioguided surgery. After intravenous injection of 370 MBq 99mTc-MIBI at start of surgery, the maximum radioactive intensity (as counts per second) was measured over several body regions using a gamma probe before and after removal of the parathyroid adenoma. Relative radioactivity was calculated in relation to the measured ex vivo radioactivity of the adenoma, which was set to 1.0. Both patients were cured by uneventful removal of aortopulmonary window parathyroid adenomas of 4400 (#1) and 985 mg (#2). Biochemical cure was documented by intraoperative measurement of parathyroid hormone as well as follow-up examination. Ex vivo radioactivity over the parathyroid adenomas was 196 (#1) and 855 counts per second (#2). Before parathyroidectomy, relative radioactivity over the aortopulmonary window versus the heart was found at 1.3 versus 2.6 (#1) and 1.8 versus 4.8 (#2). After removal of the adenomas, radioactivity within the aortopulmonary window was only slightly reduced.
CONCLUSION: High myocardial uptake of 99mTc-MIBI limits the feasibility of radioguided surgery in aortopulmonary parathyroid adenoma.

Karuppiah D, Thanabalasingham G, Shine B, et al.
Refractory hypercalcaemia secondary to parathyroid carcinoma: response to high-dose denosumab.
Eur J Endocrinol. 2014; 171(1):K1-5 [PubMed] Related Publications
OBJECTIVE: Hypercalcaemia is an important cause of increased morbidity and mortality in patients with parathyroid carcinoma. Surgical resection is the mainstay of treatment but, equally, managing hypercalcaemia is of paramount importance. At present, few therapies have been shown to be effective in the most severe cases. This report describes the efficacy of denosumab in a patient with parathyroid carcinoma when conventional therapies had been shown to be relatively ineffective.SUBJECT, METHODS AND RESULTS: A 50-year-old man presented with symptomatic hypercalcaemia 1 year after the surgery for his parathyroid carcinoma. Investigations revealed raised serum calcium and parathyroid hormone concentrations consistent with the recurrence of the disease. Imaging failed to localise any surgically remediable foci. Medical management with loop diuretics, calcimimetics and bisphosphonates failed to provide a sustained response. Denosumab, as a monthly injection, led to a gradual decrement in his peak calcium concentrations with the values now persistently below 3 mmol/l.
CONCLUSIONS: Denosumab, a fully human MAB that binds to the 'receptor activator of nuclear factor κB ligand (RANKL)', was shown to have a profound effect in modulating malignant hypercalcaemia. This medication should be considered as an effective option in patients with refractory hypercalcaemia secondary to parathyroid carcinoma.

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.

Alhefdhi A, Schneider DF, Sippel R, Chen H
Recurrent and persistence primary hyperparathyroidism occurs more frequently in patients with double adenomas.
J Surg Res. 2014; 190(1):198-202 [PubMed] Related Publications
INTRODUCTION: The incidence of recurrent primary hyperparathyroidism (PHPT) had been reported to be between 1% and 10%. The purpose of this study was to examine if patients with multigland disease have a different recurrence rate.
METHODOLOGY: A retrospective analysis of a prospectively collected database was performed on patients with PHPT who underwent parathyroidectomy at one institution between 2001 and 2013. Patients who underwent initial parathyroidectomy with at least 6 mo of follow-up were included and were divided into three groups according to operative notes: single adenoma (SA), double adenoma (DA), and hyperplasia (HP). An elevated postoperative serum calcium level within 6 mo of surgery was defined as a persistent disease, whereas an elevated calcium after 6 mo was defined as a recurrence.
RESULTS: In total, 1402 patients met inclusion criteria, and the success rate of parathyroidectomy was 98.4%. The mean age was 60±14 y and 78.5% were female. Among them, 1097 patients (78%) had SA, 124 patients (9%) had DA, and 181 patients had HP (13%). The rate of persistent PHPT was higher among patients with DA (4%) versus SA (1.3%) and HP (2.2%) (P=0.0049). Moreover, the recurrence rate was higher among patients with DA (7.3%) versus SA (1.7%) and HP (4.4%) (P=0.0005) with identical median follow-up time. The median of the follow-up was 11 mo for patients with SA, 12.5 for patients with DA, and 12 for patients with HP (P=0.1603).
CONCLUSIONS: Recurrent and persistent PHPT occur more frequently in patients with DA. These data suggest that DA in some cases could represent asymmetric or asynchronous hyperplasia. Therefore, patients with DA may warrant more rigorous intraoperative scrutiny and more vigilant monitoring after parathyroidectomy.

Whitcroft KL, Sharma A
Sestamibi scintigraphy for parathyroid localisation: a reminder of the dangers of false positives.
BMJ Case Rep. 2014; 2014 [PubMed] Related Publications
Surgical parathyroidectomy is the only curative treatment for primary hyperparathyroidism. As minimally invasive parathyroidectomy increases in popularity, so does reliance on preoperative parathyroid localisation techniques. One such technique is sestamibi scintigraphy. We report a case of false-positive sestamibi scintigraphy caused by follicular variant of papillary thyroid carcinoma. Subsequent completion thyroidectomy was not possible due to widespread postoperative fibrosis. This case, therefore, highlights the potential dangers of false-positive results due to thyroid carcinoma and encourages surgeons to consider this possibility when faced with intrathyroidal or otherwise ambiguous parathyroid localisation results.

Related: Thyroid Cancer

Lachungpa T, Sarawagi R, Chakkalakkoombil SV, Jayamohan AE
Imaging features of primary hyperparathyroidism.
BMJ Case Rep. 2014; 2014 [PubMed] Related Publications
Hyperparathyroidism can be primary, secondary or tertiary depending on its aetiology. Parathyroid adenoma accounts for 80% of cases of primary hyperparathyroidism. We report a case of a 41-year-old female patient presented with severe osteoporosis and pathological fracture of right acetabulum and left intertrochanteric region. The patient had diffuse osteoporosis and multiple well-defined lytic lesions. A diagnosis of hyperparathyroidism apart from multiple myeloma and metastasis was made based on the findings of diffuse osteoporotic changes with multiple lytic lesions. A skeletal survey was performed in view of the pathological fracture of the femur; findings of the skeletal survey favoured the diagnosis of hyperparathyroidism. An ultrasound of the neck was performed to look for the cause and a parathyroid adenoma was picked up in the inferior aspect of the left lobe of the thyroid gland. CT of the neck was also performed for preoperative localisation of the lesion. Based on these findings diagnosis of primary hyperparathyroidism due to parathyroid adenoma was made. The patient underwent parathyroidectomy and perioperative and histopathological findings confirmed the preoperative diagnosis.

Guy MS, Jacob C, McDonald SD, et al.
18F-FDG PET/CT metabolic variability in functioning oncocytic parathyroid adenoma with brown tumors.
Clin Nucl Med. 2014; 39(4):393-5 [PubMed] Related Publications
A 29-year-old female patient exhibited a solitary neck mass, severe hypercalcemia, and multiple skeletal lytic lesions consistent with metastatic neoplastic disease. Fine-needle aspiration (FNA) cytology of the neck lesion indicated a follicular thyroid neoplasm. CT-guided bone biopsy was non-diagnostic. Subsequent 18F-FDG PET/CT examination demonstrated avid glucose uptake within the neck mass and diffuse bony lesions of variable metabolic activity. Repeat biopsy utilizing PET/CT guidance produced core tissue with classic histologic features of a brown tumor. Postoperative histology revealed an exclusively oncocytic parathyroid adenoma. Atypical radiotracer uptake of this rare functioning adenoma subtype is illustrated with discussion of improved procedural diagnostic yield utilizing PET/CT.

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

Vaishya R, Nyokabi DN, Vaish A
Bilateral hip arthritis in a case of renal osteodystrophy.
BMJ Case Rep. 2014; 2014 [PubMed] Related Publications
Chronic renal disease is often associated with secondary hyperparathyroidism (HPP) and rarely with tertiary HPP. Hip arthritis with protrusio acetabuli, secondary to tertiary HPP, is a rare case scenario and has not been described well in the literature. We present a rare case of bilateral hip arthritis with protrusio acetabuli secondary to renal osteodystrophy due to tertiary HPP. The diagnosis and aetiology of hip arthritis and its treatment have been discussed along with a detailed review of literature of skeletal lesions due to HPP.

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] Free Access to Full Article 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.

Cavalier E, Betea D, Schleck ML, et al.
The third/second generation PTH assay ratio as a marker for parathyroid carcinoma: evaluation using an automated platform.
J Clin Endocrinol Metab. 2014; 99(3):E453-7 [PubMed] Related Publications
BACKGROUND: Parathyroid carcinoma (PCa) is rare and often difficult to differentiate initially from benign disease. Because PCa oversecretes amino PTH that is detected by third-generation but not by second-generation PTH assays, the normal 3rd/2nd generation PTH ratio (<1) is inverted in PCa (ie, >1).
OBJECTIVE: The objective of the investigation was to study the utility and advantages of automated 3rd/2nd generation PTH ratio measurements using the Liaison XL platform over existing manual techniques.
SETTING: The study was conducted at a tertiary-referral academic center.
DESIGN: This was a retrospective laboratory study.
SUBJECTS: Eleven patients with advanced PCa (mean age 56.0 y). The controls were patients with primary-hyperparathyroidism (n = 144; mean age 53.8 y), renal transplantation (n = 41; mean age 50.6 y), hemodialysis (n = 80; mean age 65.2 y), and healthy elderly subjects (n = 40; mean age 72.6 y).
RESULTS: The median (interquartile range) 3rd/2nd generation PTH ratio was 1.16 (1.10-1.38) in the PCa group, which was significantly higher than the control groups: hemodialysis: 0.74 (0.71-0.75); renal transplant: 0.77 (0.73-0.79); primary hyperparathyroidism: 0.76 (0.74-0.78); healthy elderly: 0.80 (0.74-0.83). An inverted 3rd/2nd-generation PTH ratio (>1) was seen in 9 of 11 PCa patients (81.8%) and in 7 of 305 controls (2.3%): 3 of 80 hemodialysis (3.8%), and 4 of 144 primary-hyperparathyroidism patients (2.8%). Of four PCa patients who had a normal PTH ratio with the manual method, two had an inverted 3rd/2nd-generation PTH ratio with the automated method.
CONCLUSIONS: Study of the 3rd/2nd-generation PTH ratio in large patient populations should be feasible using a mainstream automated platform like the Liaison XL. The current study confirms the utility of the inverted 3rd/2nd-generation PTH ratio as a marker of PCa (sensitivity: 81.8%; specificity: 97.3%).

Máximo V, Rios E, Sobrinho-Simões M
Oncocytic lesions of the thyroid, kidney, salivary glands, adrenal cortex, and parathyroid glands.
Int J Surg Pathol. 2014; 22(1):33-6 [PubMed] Related Publications
Oncocytic cell represents a special phenotype of neoplastic cells reflecting a unique biologic process characterized by the huge proliferation of morphologically abnormal mitochondria in the cytoplasm of neoplastic cells. This phenotype is driven by quite specific molecular mechanisms that interfere with mitochondrial function and metabolism. The oncocytic phenotype is more common in tumors arising in tissues presenting low proliferative rate, such as thyroid, kidney, salivary glands, adrenal cortex, and parathyroid glands, and it is superimposed on the genotypic and conventional histologic features of the tumors. In this short review, we address the similarity of the molecular alterations and of the biological features of the neoplastic cells in the oncocytic tumors of the different organs. We also discuss the differential diagnosis of benign and malignant oncocytic tumors as well as the prognosis of the malignant ones. We conclude that this rather unique phenotype, which is observed in tumors from different organs, indicates common metabolic alterations that may represent a useful target for therapeutic purposes.

Related: Adrenocortical Cancer Adrenocortical Carcinoma - Molecular Biology Salivary Gland Cancer Thyroid Cancer

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

Ali M, Kumpe DA
Embolization of bronchial artery-supplied ectopic parathyroid adenomas located in the aortopulmonary window.
J Vasc Interv Radiol. 2014; 25(1):138-43 [PubMed] Related Publications
Ectopic parathyroid adenomas in the aortopulmonary window (APW) are extremely rare, constituting only 1% of ectopic mediastinal adenomas and 0.24% of all parathyroid adenomas. The authors have encountered three patients with ectopic adenomas in the APW. In each case, the primary arterial supply to the APW adenoma arose from the bronchial artery. In addition, there was a small anastomotic arterial channel connecting the bronchial artery supplying the adenoma to the left inferior thyroid. All three adenomas were treated with transcatheter embolization, with control of hyperparathyroidism in two of three patients. One patient required thoracoscopic removal of the adenoma. It is critical that the interventionalist be aware of this arterial supply pattern to allow successful embolization of an APW ectopic adenoma.

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] Free Access to Full Article 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.

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