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).

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

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

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

Boaventura P, Pereira D, Mendes A, et al.
Thyroid and parathyroid tumours in patients submitted to X-ray scalp epilation during the tinea capitis eradication campaign in the North of Portugal (1950-1963).
Virchows Arch. 2014; 465(4):445-52 [PubMed] Related Publications
Tinea capitis attained epidemical proportions in the fifth and sixth decades in Portugal, as in other countries. Before starting the utilization of griseofulvin in 1959, the best approach to treat tinea capitis infection was X-ray scalp epilation combined with topical antimycotic ointments. A long-term side effect of this therapy is thyroid disease, namely thyroid cancer; data on parathyroid lesions (hyperplasia, adenoma and carcinoma) are scarce. We observed clinically 1,375 individuals irradiated in childhood for tinea capitis treatment in the North of Portugal with the main purpose of evaluating thyroid and parathyroid tumours as possible sequelae of the irradiation treatment. For each individual, a cervical ultrasound and a serum calcium measurement were proposed. Fine needle aspiration cytology was suggested whenever ultrasound thyroid nodules presented suspicious features. We observed a 54 % frequency of thyroid nodules and a 2.8 % frequency of thyroid carcinoma (38/1,375). Nineteen of the 38 (50 %) carcinomas were diagnosed by us, whereas the remaining 19 carcinomas had been diagnosed and treated prior to our observation. The carcinomas were significantly more frequent in women than in men. Benign excised lesions were also significantly more frequent in women and in patients irradiated at younger ages. Seven women, considered asymptomatic until our clinical observation, had laboratory signs of hyperparathyroidism. The data we have obtained, namely high thyroid cancer frequency, corroborate previous data from childhood irradiated cohorts and highlight the need for the close follow-up of these populations in order to identify and treat early undiagnosed head and neck lesions. No evidence of increased parathyroid disease was found in this cohort of head and neck X-irradiated patients.

Related: Thyroid Cancer

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.

Nagar S, Walker DD, Embia O, et al.
A novel technique to improve the diagnostic yield of negative sestamibi scans.
Surgery. 2014; 156(3):584-90 [PubMed] Related Publications
INTRODUCTION: Minimally invasive parathyroidectomy is successful in achieving cure for most patients with primary hyperparathyroidism. Most surgeons rely on preoperative imaging as part of the workup for localization. Ultrasonography and sestamibi are the 2 most commonly used preoperative imaging studies. When these 2 studies are positive and concordant the preoperative localization is straightforward. However, when ≥1 of these studies is negative, the preoperative localization is suspect. We hypothesize that the yield of useful localizing information from "negative" sestamibi scans can be increased in certain situations. Specifically, in cases where the thyroid lobe length seen on sestamibi is discordant from the lobe length of the ultrasonography, this often represents a "hidden" parathyroid adenoma. If our hypothesis is correct, this could lead to decreased resource utilization in cases of nonlocalized parathyroid adenomas.
METHODS: We retrospectively analyzed our database of patients with primary hyperparathyroidism who underwent parathyroidectomy from 2005 to 2011. The anteroposterior views of early phase sestamibi were analyzed for thyroid lobe lengths. A ratio of the length of the right lobe to left lobe was calculated. The thyroid lobe lengths on ultrasonography were measured and similar ratios were calculated. The difference in ratios between sestamibi and ultrasonography was calculated for each patient. A difference in ratios from sestamibi and ultrasonography that corresponded with a "hidden" parathyroid on the side of the additional length on sestamibi at the time of surgery was considered a positive finding. When the difference in ratios from the 2 images did not correspond with a "hidden" parathyroid at the time of operation, it was considered a negative finding.
RESULTS: There were 59 patients with single-gland disease, negative sestamibi, and images available for review. There were 32 patients (54%) with the positive finding of a "hidden" parathyroid corresponding with a difference in thyroid lobe length ratios from sestamibi and ultrasonography. The overall mean difference in ratios between sestamibi and ultrasonography was 0.37 ± 0.32. The mean ratio difference in the group of patients with a negative "hidden" parathyroid was 0.11 ± 0.02, and the mean ratio difference in the group of patients with a positive "hidden" parathyroid was 0.58 ± 0.05 (P < .001). When a difference in ratios of ≥0.23 was obtained, this predicted a "hidden" parathyroid with a sensitivity of 93.8% and specificity of 85.2%. There were 39 patients with multigland disease, negative sestamibi, and images available for review. None of these patients had a ratio difference of ≥0.23. The mean ratio difference for patients with multigland disease was significantly lower than that of the single-gland disease (0.08 ± 0.06 vs 0.37 ± 0.32; P < .001).
CONCLUSION: Discordance between thyroid lobe lengths on the early phase sestamibi compared with ultrasonography has led to successful preoperative identification of parathyroid adenomas, even though the sestamibi was traditionally read as negative. This finding has not been previously described, seems to be reliable, and can lead to improved preoperative localization and decreased resource utilization in this subset patients.

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.

Korpi-Hyövälti E, Cranston T, Ryhänen E, et al.
CDC73 intragenic deletion in familial primary hyperparathyroidism associated with parathyroid carcinoma.
J Clin Endocrinol Metab. 2014; 99(9):3044-8 [PubMed] Free Access to Full Article Related Publications
CONTEXT: CDC73 mutations frequently underlie the hyperparathyroidism-jaw tumor syndrome, familial isolated hyperparathyroidism (FIHP), and parathyroid carcinoma. It has also been suggested that CDC73 deletion analysis should be performed in those patients without CDC73 mutations.
OBJECTIVE: To investigate for CDC73 deletion in a family with FIHP previously reported not to have CDC73 mutations.
PATIENTS AND METHODS: Eleven members (six affected with primary hyperparathyroidism and five unaffected) were ascertained from the family, and multiplex ligation-dependent probe amplification was performed to detect CDC73 deletion using leukocyte DNA.
RESULTS: A previously unreported deletion of CDC73 involving exons 1-10 was detected in five affected members and two unaffected members who were 26 and 39 years of age. Two affected members had parathyroid carcinomas at the ages of 18 and 32 years, and they had Ki-67 proliferation indices of 5 and 14.5% and did not express parafibromin, encoded by CDC73. Primary hyperparathyroidism in the other affected members was due to adenomas and atypical adenomas, and none had jaw tumors. Two affected members had thoracic aortic aneurysms, which in one member occurred with parathyroid carcinoma and renal cysts.
CONCLUSION: A previously unreported intragenic deletion of exons 1 to 10 of CDC73 was detected in a three-generation family with FIHP, due to adenomas, atypical adenomas, and parathyroid carcinomas. In addition, two affected males had thoracic aortic aneurysms, which may represent another associated clinical feature of this disorder.

Related: CDC73

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.

Al-Kurd A, Mekel M, Mazeh H
Parathyroid carcinoma.
Surg Oncol. 2014; 23(2):107-14 [PubMed] Related Publications
Parathyroid carcinoma is a rare form of endocrine malignancy accounting for only a small minority of cancer cases. Due to the rarity of this cancer, there are no generalized guidelines for its management; however, surgery remains to be the mainstay therapy. The purpose of this article is to review and summarize the available literature on parathyroid carcinoma, while discussing proposed staging systems and the role of available adjuvant therapies.

Dekaken A, Gouri A, Bentorki AA, Yakhlef A
Knee brown tumor revealing a primary hyperparathyroidism: a case report.
Ann Biol Clin (Paris). 2014 Mar-Apr; 72(2):245-8 [PubMed] Related Publications
Primary hyperparathyroidism is a common endocrine disorder, asymptomatic and diagnosed through a fortuitous hypercalcemia. Brown tumors are exceptional but severe hyperparathyroidism bone complications. We report in this paper an original observation of hyperparathyroidism due to a parathyroid adenoma presenting as a brown tumor. A 28 year-old girl admitted for a bone tumor of the knee, the blood test shows hypercalcemia with hyperparathyroidism, bone biopsy revealed giant cell lesions characteristic of brown tumors.

Kentwell J, Gundara JS, Sidhu SB
Noncoding RNAs in endocrine malignancy.
Oncologist. 2014; 19(5):483-91 [PubMed] Article available free on PMC after 01/05/2015 Related Publications
Only recently has it been uncovered that the mammalian transcriptome includes a large number of noncoding RNAs (ncRNAs) that play a variety of important regulatory roles in gene expression and other biological processes. Among numerous kinds of ncRNAs, short noncoding RNAs, such as microRNAs, have been extensively investigated with regard to their biogenesis, function, and importance in carcinogenesis. Long noncoding RNAs (lncRNAs) have only recently been implicated in playing a key regulatory role in cancer biology. The deregulation of ncRNAs has been demonstrated to have important roles in the regulation and progression of cancer development. In this review, we describe the roles of both short noncoding RNAs (including microRNAs, small nuclear RNAs, and piwi-interacting RNAs) and lncRNAs in carcinogenesis and outline the possible underlying genetic mechanisms, with particular emphasis on clinical applications. The focus of our review includes studies from the literature on ncRNAs in traditional endocrine-related cancers, including thyroid, parathyroid, adrenal gland, and gastrointestinal neuroendocrine malignancies. The current and potential future applications of ncRNAs in clinical cancer research is also discussed, with emphasis on diagnosis and future treatment.

Related: MicroRNAs Thyroid Cancer

Daliakopoulos SI, Chatzoulis G, Lampridis S, et al.
Gamma probe-assisted excision of an ectopic parathyroid adenoma located within the thymus: case report and review of the literature.
J Cardiothorac Surg. 2014; 9:62 [PubMed] Article available free on PMC after 01/05/2015 Related Publications
Primary hyperparathyroidism due to parathyroid adenomas may be associated with ectopic parathyroid gland localization in 20-25% of the patients. We report herein the excision of an ectopic parathyroid adenoma which was detected in the thymus gland by gamma probe intraoperatively. A 38-year-old patient presented to our clinic with a history of bilateral nephrolithiasis, chronic hypercalcaemia, and PTH elevation. A combination of Technetium-99 m sestamibi scintigraphy and Computed Tomography scan of the chest and neck revealed an ectopic parathyroid adenoma of 8.5 mm in its greatest dimension. The patient underwent sternotomy and the adenoma was found within the right lobe of the thymus gland with the intraoperative use of gamma probe. PTH detection and frozen biopsy were performed during surgery and confirmed the successful excision of the adenoma, while mild hypocalcaemia was noticed postoperatively. We conclude that accurate preoperative and intraoperative localization of an ectopic parathyroid adenoma is crucial to successful surgery. The use of at least two diagnostic modalities before surgical excision minimizes the risk of re-operation for recurrent hyperparathyroidism, while the intraoperative use of gamma probe offers a significant advantage over conventional techniques by reducing surgical time, morbidity and/or complications associated with surgical exploration.

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.

Noureldine SI, Lewing N, Tufano RP, Kandil E
The role of the robotic-assisted transaxillary gasless approach for the removal of parathyroid adenomas.
ORL J Otorhinolaryngol Relat Spec. 2014; 76(1):19-24 [PubMed] Related Publications
BACKGROUND: We sought to describe a robotic technique of transaxillary gasless parathyroidectomy for the management of primary hyperparathyroidism (PHPT) due to a parathyroid adenoma.
METHODS: All consecutive patients who underwent robotic parathyroidectomy for a parathyroid adenoma by a single surgeon were included. Data was obtained by a retrospective review of patients' medical charts.
RESULTS: Nine patients with confirmed PHPT underwent robotic parathyroidectomy. Curative resection was established in all patients with the aid of intraoperative parathyroid hormone monitoring. One patient required bilateral cervical exploration of multiglandular disease. There were no complications. Patients were followed up for a period exceeding 6 months without any evidence of persistent or recurrent hyperparathyroidism.
CONCLUSIONS: Our initial experience demonstrates that this technique is safe and effective for the treatment of PHPT. We believe that the use of robotic technology for endoscopic parathyroid surgeries could overcome the limitations of conventional techniques in the management of parathyroid lesions.

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.

Im HJ, Lee IK, Paeng JC, et al.
Functional evaluation of parathyroid adenoma using 99mTc-MIBI parathyroid SPECT/CT: correlation with functional markers and disease severity.
Nucl Med Commun. 2014; 35(6):649-54 [PubMed] Related Publications
OBJECTIVES: In parathyroid adenoma, uptake of technetium-99m-methoxyisobutylisonitrile ((99m)Tc-MIBI) has been suggested to have a correlation with functional markers. The purpose of this study was to evaluate the feasibility of (99m)Tc-MIBI parathyroid single photon emission computed tomography/computed tomography (SPECT/CT) in evaluating the function and disease severity of parathyroid adenoma.
PATIENTS AND METHODS: Twenty-three patients with surgically confirmed parathyroid adenoma were retrospectively enrolled. A parathyroid planar scan and SPECT/CT were performed before parathyroidectomy. Functional and clinical makers reflecting the disease severity of parathyroid adenoma were also evaluated, including serum intact parathyroid hormone, calcium, bone mineral density, and creatinine clearance. The pathologic volume (V(P)) of the adenoma was measured after parathyroidectomy. On parathyroid SPECT/CT, metabolic volume (V(M)) was measured using an isocontour method. Maximum uptakes of parathyroid adenoma and mean uptakes of contralateral thyroid tissue were measured to calculate the parathyroid adenoma-to-background ratio on parathyroid SPECT/CT (PBR(SCT)) and planar scan (PBR(PL)).
RESULTS: V(M) significantly correlated with V(P) (r=0.669, P=0.0005). Serum intact parathyroid hormone level significantly correlated with PBR(PL), PBR(SCT), V(M), and V(P) (P=0.0004, 0.005, 0.003, and 0.025, respectively). However, serum calcium level correlated only with V(M) (P=0.012). Regarding the surgical indication criteria, PBR(SCT) and PBR(PL) were significantly higher in the young-aged group (P=0.0004 and 0.024, respectively) and V(M) was significantly higher in the high calcium level group (P=0.049), whereas V(P) was not different between groups on the basis of any criteria.
CONCLUSION: Quantitative indices of parathyroid SPECT/CT closely correlate with laboratory functional markers and disease severity of parathyroid adenoma. Thus, parathyroid SPECT/CT could be used for evaluation of the underlying functional state and disease severity of parathyroid adenoma, particularly for decision pertaining to surgical treatment.

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] Article available free on PMC after 01/05/2015 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.

McCoy KL, Chen NH, Armstrong MJ, et al.
The small abnormal parathyroid gland is increasingly common and heralds operative complexity.
World J Surg. 2014; 38(6):1274-81 [PubMed] Related Publications
BACKGROUND: Over decades, improvements in presymptomatic screening and awareness of surgical benefits have changed the presentation and management of primary hyperparathyroidism (PHPT). Unrecognized multiglandular disease (MGD) remains a major cause of operative failure. We hypothesized that during parathyroid surgery the initial finding of a mildly enlarged gland is now frequent and predicts both MGD and failure.
METHODS: A prospective database was queried to examine the outcomes of initial exploration for sporadic PHPT using intraoperative PTH monitoring (IOPTH) over 15 years. All patients had follow-up ≥6 months (mean = 1.8 years). Cure was defined by normocalcemia at 6 months and microadenoma by resected weight of <200 mg.
RESULTS: Of the 1,150 patients, 98.9 % were cured and 15 % had MGD. The highest preoperative calcium level decreased over time (p < 0.001) and varied directly with adenoma weight (p < 0.001). Over time, single adenoma weight dropped by half (p = 0.002) and microadenoma was increasingly common (p < 0.01). MGD risk varied inversely with weight of first resected abnormal gland. Microadenoma required bilateral exploration more often than macroadenoma (48 vs. 18 %, p < 0.01). When at exploration the first resected gland was <200 mg, the rates of MGD (40 vs. 11 %, p = 0.001), inadequate initial IOPTH drop (67 vs. 79 %, p = 0.002), operative failure (6.6 vs. 0.7 %, p < 0.001), and long-term recurrence (1.6 vs. 0.3 %, p = 0.007) were higher.
CONCLUSIONS: Single parathyroid adenomas are smaller than in the past and require more complex pre- and intraoperative management. During exploration for sporadic PHPT, a first abnormal gland <200 mg should heighten suspicion of MGD and presages a tenfold higher failure rate.

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.

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