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Parathyroid Cancer

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).

Lalire P, Ly S, Deguelte S, et al.
Incremental Value of 18F-Fluorocholine PET/CT in the Localization of Double Parathyroid Adenomas.
Clin Nucl Med. 2017; 42(3):218-220 [PubMed] Related Publications
A 73-year-old man displaying primary hyperparathyroidism with severe hypercalcemia (Ca: 4.1 mmol/l, PTH > 600 pmol/l) was referred for preoperative localization of a parathyroid adenoma. Tc-pertechnetate and Tc-sestaMIBI dual tracer scintigraphy displayed a mild focal uptake in the projection of the right thyroid lobe with negative ultrasonography. F-Fluorocholine PET/CT was quickly performed considering this discrepancy and not only confirmed the scintigraphic findings but also revealed a second contralateral focus of increased uptake, both later confirmed by operative consideration (the two other parathyroid glands are considered normal by the surgeon), pathology, and intraoperative parathyroid hormone assessment.

Vellani C, Hodolič M, Chytiris S, et al.
Early and Delayed 18F-FCH PET/CT Imaging in Parathyroid Adenomas.
Clin Nucl Med. 2017; 42(2):143-144 [PubMed] Related Publications
Preoperative localization with Tc-sestaMIBI or ultrasound is a common prerequisite for successful minimally invasive parathyroid adenoma (PA) surgery. SPECT/CT with Tc-sestaMIBI and PET/CT with F-FCH offer the possibility of attenuation correction and coregistration of functional and anatomical images providing more accurate PA localization. F-FCH PET/CT is used predominantly in patients with prostate cancer and is under investigation in PA. We report the case of a 43-year-old man with early FCH uptake in a cystic PA with delayed washout at 60 minutes.

Listewnik MH, Piwowarska-Bilska H, Kurantowicz M, et al.
Semi-quantitative method for the assessment of focal lesions in parathyroid scintigraphy with relation to histopathology: a prospective study.
Nucl Med Rev Cent East Eur. 2017; 20(1):18-24 [PubMed] Related Publications
BBACKGROUND: The aim of this paper was to analyse our own semi-quantitative method of assessing focal lesions localised in pre-operative diagnostic scintigraphy of primary hyperparathyroidism (PHPT) using 99mTc-MIBI with washout and comparing these data with the result of the histopathological examination (HP).
MATERIAL AND METHODS: A total of 40 (37 female, 3 male, average age 58.7 years) patients with a suspicion of PHPT were enrolled for prospective analysis. Dual phase planar and SPECT/CT examination with 99mTc-MIBI were performed. The tumour to background ratios in the 10th and 120th minute were calculated (TBR10 and TBR120) on the basis of the planar acquisition. PTH, ionised calcium and phosphate levels were measured. Parathyroid surgery alone or combined with subtotal/total thyreoidectomy was conducted in 23 (57.5%) and 17 (42.5%) patients, respectively. A HP was performed in all patients.
RESULTS: Average concentration of PTH in the whole group was 243.95 pg/ml. There was a statistically significant correlation between medians of PTH concentration and parathyroid histopathological results (p = 0.01). A total of 45 lesions of increased uptake were found in 32 (80.0%) and 34 (85%) patients in the early phase and the delayed phase, respectively. The post-operative material contained 20 (44.5%) parathyroid adenomas, 11 (24.5%) cases of hyperplasia, 2 (4.4%) cancers, 4 (8.9%) cases of normal parathyroid tissue, 2 (4.4%) lymph nodes and 6 (13.3%) cases of thyroid gland tissue. The medians of TBR10 and TBR120 for lesions examined in the HP were respectively: 3.64 and 2.59 for adenoma; 3.08 and 2.18 for hyperplasia; 7.7 and 5.5 for parathyroid cancer, 4.89 and 3.16 for normal tissue and 5.26 and 2.95 for lymph nodes or thyroid gland tissue. A high correlation coefficient of TBR10 to TBR120 in the parathyroid adenoma and parathyroid hyperplasia groups was observed with r = 0.867 and r = 0.964, respectively. The ρr correlation coefficient of TBR10 to TBR120 for normal parathyroid was 0.4. There was a statistically significant association between the HP and TBR10 medians (p = 0.047), but not between histopathology and TBR120 medians (p = 0.840).
CONCLUSIONS: The washout technique in pre-operative 99mTc-MIBI scintigraphy is effective in detecting lesions of the parathyroid (cancer, adenoma, hyperplasia, normal tissue of the parathyroid). Parathyroid cancers in semi-quantitative analysis were characterised by a slightly higher TBR. However, it is impossible to differentiate lesions based on this data. Histopathology results are significantly associated with TBR and PTH.

Christakis I, Silva AM, Kwatampora LJ, et al.
Oncologic progress for the treatment of parathyroid carcinoma is needed.
J Surg Oncol. 2016; 114(6):708-713 [PubMed] Related Publications
BACKGROUND AND OBJECTIVES: Parathyroid carcinoma (PC) is rare but potentially lethal. No standardized staging system or treatment guidelines have been established. We aimed to determine whether management of PC and patient outcomes have changed at our institution over the past 35 years.
METHODS: Retrospective review of patients with PC at our institution between 1980 and 2015. Patients were grouped by date of initial surgery: group 1, 1980-2001; group 2, 2002-2015.
RESULTS: About 57 patients (26 in group 1; 31 in group 2) were included. Group 2 had more female patients (61%) than group 1 (31%; P = 0.033). Patients in group 2 were older at the time of initial operation (mean age 48 years in group 1 (SD:14.3) and 56 years (SD:14.6) in group 2; P = 0.034). The 5-year OS rates were 82% (95%CI 59.6%, 93%) for group 1 and 72% (95%CI 45.0%, 87.7%) for group 2. The 5-year DFS rates were 62% (95%CI 36.4%, 79.9%) for group 1 and 66% (95%CI 40.6%, 82.2%) for group 2.
CONCLUSION: Management of PC and patient outcomes (OS and DFS) have not significantly changed over the past 35 years at our institution. This rare malignancy needs oncologic improvement. J. Surg. Oncol. 2016;114:708-713. © 2016 Wiley Periodicals, Inc.

Zhou W, Chen M
A case report of mediastinal ectopic parathyroid adenoma presented as parathyroid crisis localized by SPECT/CT.
Medicine (Baltimore). 2016; 95(41):e5157 [PubMed] Free Access to Full Article Related Publications
INTRODUCTION: Parathyroid crisis due to ectopic parathyroid adenomas can pose diagnostic and management challenges, since it is quite rare in clinical practice.
CLINICAL FINDINGS/PATIENT CONCERNS: A 67-year-old Chinese male presented as a parathyroid crisis due to an ectopic mediastinal parathyroid adenoma with his serum calcium and PTH markedly increased in short time. An ultrasonography and computed tomography (CT) scan of the neck did not reveal any parathyroid adenoma. Thoracic CT detected a contrast-enhanced mass in the mediastinum. Although the ectopic location is difficult to appreciate on anterior planar technetium-99m-sestamibi scintigraphy views but has been accurately localized with single photon-emission computed tomography/computed tomography. After fluid resuscitation, loop diuretic, and calcitonin treatment, a thoracoscope surgery was performed. The histopathology of the mediastinal nodule was consistent with a parathyroid adenoma. Hypocalcemia due to hungry bone syndrome occurred after surgery and was resolved quickly with large-dose calcium and calcitriol supplementation. He is asymptomatic and has normal serum calcium and PTH levels on regular follow-up.
DIAGNOSES: The ultrasonography, CT, sestamibi, and single photon-emission computed tomography/computed tomography provide limited sensitivity in the detecting ectopic parathyroid adenomas alone. The combination of these techniques has incremental value in localizing ectopic parathyroid adenomas over either technique alone.
CONCLUSION: Any parathyroid crisis without parathyroid adenoma in the neck should alert physicians to search for ectopic locations through combination of imaging techniques.

Abu Abeeleh M, Bani Hani A, Ghaith A, et al.
Aortopulmonary ectopic parathyroid gland and concurrent thymolipoma.
Asian Cardiovasc Thorac Ann. 2016; 24(8):822-824 [PubMed] Related Publications
Ectopic parathyroid adenomas are considered the main cause of primary hyperparathyroidism. However, concurrent parathyroid and thymic pathologies are rarely diagnosed in the same patient. A 47-year-old man with history of diabetes mellitus, hypertension, and myasthenia gravis presented with persistent hypercalcemia. Laboratory investigations, computed tomography, and technetium-99 m sestamibi scintigraphy revealed ectopic parathyroid glands, a mediastinal mass, and an enlarged thymus. The patient underwent thymectomy and mass excision via a median sternotomy. Histopathology was consistent with ectopic parathyroid adenoma and thymolipoma. The serum calcium and parathormone concentrations normalized within 48 hours after surgery.

Sharma S, Dey P, Gude G, Saikia UN
Parathyromatosis-A rare occurrence along the endoscopic tract detected on fine needle aspiration cytology.
Diagn Cytopathol. 2016; 44(12):1125-1127 [PubMed] Related Publications
Parathyromatosis is a rare cause of recurrent or persistent hyperparathyroidism after parathyroidectomy. The knowledge of such an entity is essential for clinical suspicion as well as cytological diagnosis and can be confirmed by ancillary techniques. We report a case, previously operated endoscopically for parathyroid adenoma, who presented with recurrent hyperparathyroidism and was found to have multiple tiny subcutaneous chest wall nodules along the endoscopic tract. Fine needle aspiration cytology coupled with immunocytochemistry confirmed parathyroid tissue. Clinical awareness of this entity can help in early detection of the cause of persistent hyperparathyroidism in these patients. Diagn. Cytopathol. 2016;44:1125-1127. © 2016 Wiley Periodicals, Inc.

Mossinelli C, Saibene AM, De Pasquale L, Maccari A
Challenging neck mass: non-functional giant parathyroid adenoma.
BMJ Case Rep. 2016; 2016 [PubMed] Related Publications
A 46-year-old man was referred to our ear, nose and throat department after the accidental discovery of a large retrotracheal mass. In order to obtain the diagnosis and to plan treatment he underwent a full battery of tests (CT, MRI, blood tests, hormonal assays, ultrasounds, thyroid scintigraphy, urine tests and fine-needle aspiration of the mass), but none of these was able to define the true nature of such cervical mass. Only after surgical excision and histological evaluation, it was diagnosed as an exceptional case of giant non-functional parathyroid adenoma.

Azizi G, Piper K, Keller JM, et al.
Shear wave elastography and parathyroid adenoma: A new tool for diagnosing parathyroid adenomas.
Eur J Radiol. 2016; 85(9):1586-93 [PubMed] Related Publications
OBJECTIVES: This study prospectively determines the shear wave elastography characteristics of parathyroid adenomas using virtual touch imaging quantification, a non-invasive ultrasound based shear wave elastography method.
METHODS: This prospective study examined 57 consecutive patients with biochemically proven primary hyperparathyroidism and solitary parathyroid adenoma identified by ultrasound and confirmed by at least one of the following: surgical resection, positive Technetium-99m Sestamibi Scintigraphy (MIBI) scan, or fine needle aspiration biopsy with positive PTH washout (performed only in MIBI negative patients). Vascularity and shear wave elastography were performed for all patients. Parathyroid adenoma stiffness was measured as shear wave velocity in meters per second.
RESULTS: The median (range) pre-surgical value for PTH and calcium were 58pg/mL (19, 427) and 10.8mg/dL (9.5, 12.1), respectively. 37 patients had positive MIBI scan. 20 patients had negative MIBI scan but diagnosis was confirmed with positive PTH washout. 42 patients underwent parathyroidectomy, and an adenoma was confirmed in all. The median (range) shear wave velocity for all parathyroid adenomas enrolled in this study was 2.02m/s (1.53, 2.50). The median (range) shear wave velocity for thyroid tissue was 2.77m/s (1.89, 3.70). The shear wave velocity of the adenomas was independent of adenoma size, serum parathyroid hormone concentration, or plasma parathyroid hormone concentration.
CONCLUSIONS: Tissue elasticity of parathyroid adenoma is significantly lower than thyroid tissue. B-mode features and distinct vascularity pattern are helpful tools in diagnosing parathyroid adenoma with ultrasound. Shear wave elastography may provide valuable information in diagnosing parathyroid adenoma.

Touska P, Srikanthan A, Amarasinghe K, Jawad S
Parathyroid adenoma arising within the sternocleidomastoid muscle: a rare complication of autotransplantation.
BMJ Case Rep. 2016; 2016 [PubMed] Related Publications
A 19-year-old patient presented with slowly enlarging, painless, left-sided cervical mass. She had a background of multiple endocrine neoplasia 2B and had undergone a total thyroidectomy for medullary thyroid carcinoma during childhood. A cervical recurrence was therefore suspected. Ultrasonographic and MRI examination revealed a well-defined lesion within the left sternocleidomastoid muscle. Further evaluation with sestamibi and single-photon emission CT revealed elevated tracer uptake within the lesion. Cytological analysis, following ultrasound-guided sampling, revealed absent staining for calcitonin and blood samples confirmed a normal serum calcitonin level; however, the serum parathyroid hormone level was elevated. Overall, summative findings were consistent with a diagnosis of a parathyroid adenoma arising within the left sternocleidomastoid muscle. Given that this is not a location for a physiological parathyroid tissue, the adenoma might have arisen within the autotransplanted parathyroid tissue, injected into the muscular sheath during thyroidectomy. The clinical, radiological and pathological features are considered in this article.

Shi C, Guan H, Qi W, et al.
Intrathyroidal parathyroid adenoma: Diagnostic pitfalls on fine-needle aspiration: Two case reports and literature review.
Diagn Cytopathol. 2016; 44(11):921-925 [PubMed] Related Publications
Parathyroid adenomas may occur within the thyroid, clinically simulating thyroid nodules. Fine-needle aspiration (FNA) of these presumably "thyroid nodules" can lead to misinterpretation of cytomorphological findings because of similarities in cytological features of parathyroid and thyroid lesions. Here, we reported two cases of intrathyroidal parathyroid adenomas. One of them was misinterpreted as thyroid lesions. The other was composed exclusively of oncocytic cells and had a correct cytological diagnosis. In this study, both cases showed a new cytological feature which has not been reported in the literature: many capillaries protruding outside the three-dimensional fragments without epithelial cells around. Diagn. Cytopathol. 2016;44:921-925. © 2016 Wiley Periodicals, Inc.

Tan MZ, Ng JC, Eisman JA, et al.
A Retrospective Review of Imaging and Operative Modalities Performed in Patients with Primary Hyperparathyroidism at a Mid-Volume Surgical Centre in Southeast Asia.
Ann Acad Med Singapore. 2016; 45(5):191-7 [PubMed] Related Publications
INTRODUCTION: A paradigm shift appears to have occurred worldwide in surgery for primary hyperparathyroidism with the advent of sensitive preoperative imaging techniques. Preoperative imaging for parathyroid adenoma localisation was not found to be useful in a study conducted in Singapore in the 1990s. This study aimed to explore what the change has been in preoperative localisation tools compared to the previous study and if the ability of these tools to correctly localise pathologic parathyroid glands has improved.
MATERIALS AND METHODS: A retrospective review of patients who had surgery for primary hyperparathyroidism at our institution during the period 2005 to 2014 was carried out. Individuals with positive, as opposed to those with negative preoperative imaging, were compared with regard to whether they underwent limited focal or bilateral neck exploration. Length of hospital stay (LOHS) was also compared between patients who underwent limited versus bilateral exploration.
RESULTS: Fifty-eight patients who had preoperative imaging and surgery were evaluated. True positive rates of sestamibi, ultrasound and 4-dimensional (4D) computed tomography (CT) scans were 63.8%, 72.4% and 90%, respectively. Eighty percent of patients who had positive localisation had limited exploration. LOHS was 2.8 days (1.6, 4.8) and 4.3 days (2.1, 9.0) for limited and bilateral exploration respectively, P = 0.011.
CONCLUSION: Our study highlights the marked change in the surgical landscape for primary hyperparathyroidism in the last 2 decades in Singapore. Improved preoperative localisation has resulted in a swing from predominantly bilateral, to limited exploration in almost all cases of primary hyperparathyroidism due to solitary adenoma. LOHS was significantly shorter in patients who had limited as compared to those who had bilateral exploration.

Dagang DJ, Gutierrez JB, Sandoval MA, Lantion-Ang FL
Multiple brown tumours from parathyroid carcinoma.
BMJ Case Rep. 2016; 2016 [PubMed] Related Publications
We report a case of a 29-year-old woman who suffered from severe bilateral inguinal pain and left mandibular mass. CT scan showed innumerable expansile osteolytic bone masses on the iliac wings, femur, ribs and vertebral bodies, diffuse skeletal osteopaenia, calyceal lithiasis on the right kidney and a left thyroid mass. Ionised calcium and intact parathyroid hormone (PTH) were elevated. Parathyroid sestamibi scan showed a hyperfunctioning left inferior parathyroid gland. Biopsy of the left mandibular mass was consistent with brown tumour. The patient underwent parathyroidectomy of the enlarged parathyroid gland. Final histopathology, however, revealed parathyroid carcinoma, 4.7 cm in widest dimension, with capsular and vascular space invasion. The patient underwent repeat surgery, specifically, left thyroid lobectomy, isthmectomy and central node dissection. Intact PTH decreased from 681.3 to 74 pg/mL (normal range: 10-65) 24 hours postoperatively. Follow-up at 6 months showed normal serum calcium levels, size reduction of bone lesions and improvement of quality of life.

do Vale RH, Queiroz MA, Coutinho AM, et al.
18F-FDG PET/CT Osteometabolic Activity in Metastatic Parathyroid Carcinoma.
Clin Nucl Med. 2016; 41(9):724-5 [PubMed] Related Publications
Parathyroid cancer is an uncommon type of malignancy, which is frequently associated with poor prognosis. Clinical manifestations are caused by elevated serum calcium and parathyroid hormone (PTH). Diagnostic imaging studies as neck ultrasonography, technetium Tc Tc-sestamibi whole body scintigraphy, CT, and MR are already established tools for this malignancy. Nevertheless, the role of F-FDG PET/CT remains unknown in this scenario, with few published studies in literature. Hence, in this article, we aimed to report an illustrative case of increased skeletal FDG uptake associated with high calcium and PTH levels.

Niramitmahapanya S, Deerochanawong C, Sarinnapakorn V, et al.
Somatic HRPT2 Mutation (Arg234X) of Parathyroid Carcinoma Associated with Slipped Capital Femoral Epiphysis: A First Case Report.
J Med Assoc Thai. 2016; 99 Suppl 2:S201-5 [PubMed] Related Publications
A 14-year-old boy was admitted to the orthopedic clinic of Rajavithi Hospital complaining of pain in the left hip. A year earlier, pain had developed in his left joint and had gradually increased in intensity in both hips. A month before he was referred, radiographs obtained at another hospital showed bilateral slipped capital femoral epiphysis (SCFE). The patient's biochemical laboratory data showed hypercalcemia, hypophosphatemia, and a high level of intact parathyroid hormone (iPTH) compatible with primary hyperparathyroidism. HRPT2 gene analysis found heterozygosity for c. 700 C > T mutation (Arg234X) of HRPT2 gene at exon 7. This is the first report in the literature about somatic mutation of the HRPT2 gene of parathyroid carcinoma associated with slipped capital femoral epiphysis.

Agarwal C, Kaushal M
Parathyroid lesions: Difficult diagnosis on cytology.
Diagn Cytopathol. 2016; 44(8):704-9 [PubMed] Related Publications
Cytology of parathyroid lesion (PL) is often confused with that of thyroid lesions. Differentiation between thyroid and PL is very difficult on cytomorphology because of their similar features and close anatomical proximity. Three cases of PLs reported on cytology in last one year were retrieved from archives of cytology department. Their cytomorphological details were studied and were correlated with the available biochemical parameters. Histopathology was available in two cases. Radiological assistance and parathyroid hormone (PTH) assessment in our cases formed the basis of diagnosing PLs on cytology. We discuss the differential diagnosis and pitfalls in cytological diagnosis of PLs. However, histopathology remains the gold standard for diagnosis. Interpretation of PLs on cytology remains problematic due to its rarity and limited available literature. The cytomorphology combined with clinical and biochemical data supported by histopathology are necessary to improve the diagnostic sensitivity of PLs. Diagn. Cytopathol. 2016;44:704-709. © 2016 Wiley Periodicals, Inc.

Wong YP, Sharifah NA, Tan GC, et al.
Intrathyroidal oxyphilic parathyroid carcinoma: A potential diagnostic caveat in cytology?
Diagn Cytopathol. 2016; 44(8):688-92 [PubMed] Related Publications
Oxyphilic (oncocytic) parathyroid lesions are very uncommon and their cytological features are rarely described. Due to the similarities in anatomical location and indistinguishable cytomorphological features, these lesions are easily confused with neoplastic and non-neoplastic thyroid lesions on fine needle aspiration (FNA). The diagnosis becomes more challenging in cases of unusual intrathyroidal location of the parathyroid lesions in the absence of clinical evidence of hyperparathyroidism, which simulate thyroid nodules clinically. We describe a case of intrathyroidal oxyphilic parathyroid carcinoma in a 66-year-old female, who presented with a dominant left "thyroid" nodule. FNA smears were cellular, comprising predominantly of oxyphilic cells arranged in papillary-like architecture with occasional nuclear grooves, which was mistaken for oncocytic variant of papillary carcinoma of the thyroid. The histological diagnosis of oxyphilic parathyroid "adenoma" was made following total thyroidectomy. The tumor, unfortunately, recurred 7 years later with associated multiple lung metastases. When dealing with thyroid lesions comprising predominantly of oncocytic cells, one should consider oxyphilic parathyroid neoplasms as one of the differential diagnosis. In difficult equivocal cases, a panel of immunocytochemical stains (PTH, GATA3, TTF-1, PAX8, and thyroglobulin) can be helpful. In addition, a combination of valuable clinical, radiological, and laboratory data, including serum calcium and parathyroid hormone levels are key to arriving at an accurate cytological diagnosis. Diagn. Cytopathol. 2016;44:688-692. © 2016 Wiley Periodicals, Inc.

Forghani R, Roskies M, Liu X, et al.
Dual-Energy CT Characteristics of Parathyroid Adenomas on 25-and 55-Second 4D-CT Acquisitions: Preliminary Experience.
J Comput Assist Tomogr. 2016 Sep-Oct; 40(5):806-14 [PubMed] Related Publications
OBJECTIVE: The objective of this study was to compare the dual-energy computed tomography (CT) characteristics of parathyroid adenomas (PAs), thyroid tissue, and lymph nodes (LNs) and assess whether the spectral information can improve distinction of these tissues.
METHODS: Dual-energy CT scans from 20 patients with pathologically proven PAs were retrospectively evaluated, identifying 19 eligible PAs and region of interest analysis used for spectral characterization.
RESULTS: There was a significant difference in multiple spectral parameters between PAs, LNs, and the thyroid gland (P < 0.05-0.0001). The greatest difference in spectral characteristics of PAs compared with that of LNs was on the 25-second acquisition, whereas the 55-second acquisition was better for distinguishing PAs from the thyroid gland.
CONCLUSIONS: Four-dimensional CT acquired in dual-energy CT mode has the potential to further enhance diagnostic accuracy for PA identification on individual phases of the perfusion study.

Siddiqi MS, Al Badai Y, Al Kemyani NA, Al Kindi AH
Combined transcervical and thoracoscopic mediastinal parathyroid adenoma resection.
Asian Cardiovasc Thorac Ann. 2016; 24(6):593-6 [PubMed] Related Publications
The routine approach for excision of a parathyroid adenoma is transcervical, but this approach is inadequate when the gland is located in the mediastinum. Traditionally, these cases have required a sternotomy or thoracotomy. We used a combined transcervical and video-assisted thoracoscopic surgery approach to resect a parathyroid adenoma that extended to the middle mediastinum.

Ozaki A, Tanimoto T, Yamagishi E, et al.
Finger Fractures as an Early Manifestation of Primary Hyperparathyroidism Among Young Patients: A Case Report of a 30-Year-Old Male With Recurrent Osteoporotic Fractures.
Medicine (Baltimore). 2016; 95(20):e3683 [PubMed] Free Access to Full Article Related Publications
Osteoporosis and osteoporotic fractures represent a substantial health burden, and predominantly affect the elderly. Younger generations may also develop these conditions because of various predisposing conditions, including primary hyperparathyroidism. However, little information is available regarding early skeletal manifestations of primary hyperparathyroidism.A 30-year-old Japanese male presented with pain in his left wrist, and was diagnosed with a distal radius fracture. During surgery, we noticed decreased bone strength of the fracture site. Further investigation found osteoporosis and primary hyperparathyroidism owing to a solitary parathyroid adenoma, which was resected without significant complications. History revealed that the patient suffered a metacarpal bone fracture of his right fifth bone 6 months earlier. Although serial x-rays at that time had shown rapidly developed cortical bone erosion around the fractured finger, the possibility of primary hyperparathyroidism was overlooked because of poor awareness of the condition, leading to a 6-month delay in the diagnosis of primary hyperparathyroidism.Clinicians should be aware that finger fractures may be an early skeletal manifestation of primary hyperparathyroidism that can help achieve a prompt diagnosis of the condition, especially when they occur in young adults in the absence of major trauma.

Grozavu C, Pantile D
Primary Hyperparathyroidism Through an Ectopic Parathyroid Adenoma.
Chirurgia (Bucur). 2016 Mar-Apr; 111(2):156-60 [PubMed] Related Publications
INTRODUCTION: Parathyroid glands, usually four, are localized at the anterior cervical level, in several positions, on the posterior side of the thyroid gland. Parathyroid glands participate to calcium level regulations by producing the parathormone as a response to hypocalcemia. Hyperparathyroidism is defined as the excess secretion of the parathormone.
MATERIAL AND METHOD: We present the case of 48 year-old women, admitted with intense bone pain, headache and dizziness. Imaging studies performed identified a small nodule localized in the anterior mediastinum. This nodule was positive for high levels of tracer fixation. Surgery was performed and the nodule was identified as a small parathyroid adenoma.
RESULTS AND DISCUSSIONS: The outcome of the surgical intervention was favorable, without any postoperative complications. We suggest for the imaging diagnostic procedure to include: ultrasonography, scintigraphy, computed tomography, MRI. Using nuclear medicine, the sensibility for the imagistic identification of parathyroid adenomas increased to approximately 90%. The approach for mediastinal ectopic parathyroid glands is controversial, but their preoperative localization is mandatory.
CONCLUSIONS: Primary hyperparathyroidism is a rare, important disease, with severe clinical manifestations. The diagnosis must be based on imaging finding, with mandatory surgical treatment, and in most cases, with the remission of the severe clinical manifestation.

Kamenický P, Lecoq AL, Chanson P
Primary hyperparathyroidism in pregnancy.
Ann Endocrinol (Paris). 2016; 77(2):169-71 [PubMed] Related Publications
Primary hyperparathyroidism (PHPT) is one of the most common endocrine disorders in the general population but is rarely diagnosed during pregnancy. Symptoms of gestational PHPT may be unrecognized, or masked by physiological changes in calcium homeostasis associated with pregnancy. Gestational PHPT may have severe consequences for both mother and fetus. However, nowadays, gestational PHPT is usually diagnosed in earlier stages and milder forms, with low complication rates. Treatment should be individually tailored according to gestational age, the severity of hypercalcemia, and the risk-benefit balance. The conservative approach is preferred in mild forms, whereas surgery, usually performed during the second trimester, is reserved for symptomatic hypercalcemic PHPT. Given the young age of the patients, genetic causes should be considered.

Dhiwakar M, Damodharan S, Rajeshwari KM, Mehta S
Ectopic parathyroid adenoma presenting as facial expansile growths.
B-ENT. 2016; 12(1):73-6 [PubMed] Related Publications
BACKGROUND: Giant cell reparative granuloma of the facial skeleton is a rare presentation of hyperparathyroidism.
METHODOLOGY: A 17-year-old girl presented with progressive expansile bony growths of the mandible and maxilla. The case was investigated using biopsies, blood tests, imaging, and surgery.
RESULTS: Biopsies confirmed giant cell reparative granuloma. Blood testing revealed very high parathyroid hormone levels, and brown tumours due to primary hyperparathyroidism weresuspected. Surgical removal of an ectopic adenoma led to correction of the endocrine condition.
CONCLUSIONS: To our knowledge, this is the first reported case of multiple brown tumours of the facial skeleton due to an ectopic parathyroid adenoma. Diagnostic pitfalls and therapeutic challenges are described.

Kitada M, Yasuda S, Nana T, et al.
Surgical treatment for mediastinal parathyroid adenoma causing primary hyperparathyroidism.
J Cardiothorac Surg. 2016; 11:44 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Primary hyperparathyroidism is a rare disease characterized by excessive secretion of parathyroid hormone from parathyroid adenoma, hyperplasia, or malignancy. The clinical symptoms of the condition are those of hypercalcemia. Although the lesions are commonly located in the neck region, in about 1-2 % of cases, the lesions are ectopically located within the mediastinum, where surgical excision using the cervical approach is difficult. The principal treatment of the condition is surgical excision of the lesion. However, some patients require additional surgery because of recurrence due to intraoperative dissemination. Therefore, safe and accurate excision is essential for the treatment. We reviewed the surgical treatment used at our institution for mediastinal parathyroid adenoma that caused primary hyperparathyroidism.
METHOD: The subjects were four patients with primary hyperparathyroidism due to mediastinal parathyroid adenoma who underwent surgery at our institution within a period of 10 years, between January 2005 and December 2014. All of the patients were female, with a mean age of 64.5 years (range, 55-74 years). The examined variables included background factors, clinical condition, surgical method, and clinical outcome.
RESULT: In all of the patients, primary hyperparathyroidism was detected with symptoms of hypercalcemia. Laboratory tests revealed a mean serum calcium level of 11.85 mg/dL (range, 11.2-13.2 mg/dL) and a mean parathyroid hormone (intact PTH) level of 304.8 pg/mL (range, 126-586 pg/mL), indicating elevated levels for all patients. Chest computed tomography (CT) revealed tumors with a mean diameter of 2.8 cm (range, 10-45 mm) in the anterior mediastinum in all of the patients. On 99mTC-methoxy isobutyl isonitrile (MIBI) scintigraphy, abnormal accumulation was observed in all of the patients. Regarding the surgical methods, median sternotomy was used for three cases and upper partial sternotomy was used for one case. The surgery was safely and accurately performed, without postoperative complications. After surgery, the serum calcium levels immediately returned to normal and the symptoms improved.
CONCLUSION: We performed excision safely and accurately in all of the patients. In tumor identification, 99mTC-MIBI scintigraphy was useful. Accurate tumor identification and selection of the optimal surgical method are important for prevention of recurrence due to intraoperative dissemination.

Kamali D, Sharpe A, Nagarajan S, Elsaify W
Non-functioning parathyroid adenoma: a rare differential diagnosis for vocal-cord paralysis.
Ann R Coll Surg Engl. 2016; 98(6):e94-6 [PubMed] Free Access to Full Article Related Publications
Introduction Adenomas of the parathyroid gland typically present with symptoms of hyperparathyroidism, manifested by fatigue, bone pain, abdominal pain, weakness, dyspepsia, nephrolithiasis and skeletal bone disease. Here, we describe, for the first time, a case of a non-functioning benign tumour of the parathyroid gland presenting as vocal-cord paralysis. Case History A 49-year-old male presented with a 10-week history of dysphonia and the feeling of having 'something stuck in my throat'. History-taking elicited no other associated symptoms. Flexible nasal endoscopy demonstrated paralysis of the left vocal cord. Computed tomography of the neck revealed a cystic lesion, 18mm in diameter adjacent to the oesophagus. After more rigorous tests, a neck exploration, left hemithyroidectomy, excision of the left paratracheal mass and level-VI neck dissection was undertaken, without incident to the patient or surgical team. Histology was consistent with a parathyroid adenoma. Conclusions This case emphasises the importance of including adenomatous disease of the parathyroid gland in the differential diagnosis despite normal parathyroid status as a cause of vocal cord palsy.

Kumari N, Chaudhary N, Pradhan R, et al.
Role of Histological Criteria and Immunohistochemical Markers in Predicting Risk of Malignancy in Parathyroid Neoplasms.
Endocr Pathol. 2016; 27(2):87-96 [PubMed] Related Publications
Parathyroid carcinoma (PC) is a rare neoplasm accounting for 0.5-6 % of primary hyperparathyroidism. Histological criteria are currently considered as established means to diagnose malignancy in parathyroid neoplasms; however, it does not accurately predict the risk of aggressive behaviour of PC. Immunohistochemical (IHC) markers have been used in the literature with variable results. This work was planned to study whether IHC markers would have any added advantage over histology in predicting outcome in parathyroid neoplasms. Two hundred twenty-seven parathyroid neoplasms were reviewed according to older and revised histological criteria. IHC was performed for parafibromin, APC, galectin-3, PGP9.5 and Ki67. Diagnostic categories were correlated with clinical, biochemical, histological features and IHC markers. Chi-square test was used to analyse categorical variables. Review of histology by earlier and revised criteria showed a change in diagnosis of five cases of atypical adenoma (15.1 %), all of which were diagnosed as carcinoma according to earlier criteria. Change in diagnosis did not affect behaviour of disease as none of the cases showed recurrence or metastasis on follow-up. Combination of PF, Gal-3 and PGP9.5 showed 50 % sensitivity, 97.9 % specificity and 95.4 % predictive accuracy for PC. Histological criteria still remains the most established method for predicting risk of malignancy in parathyroid neoplasms irrespective of whether old or revised criteria are used. Combination of positive (Gal-3, PGP9.5) and negative (PF) IHC markers may be used as an adjunct to histology in histological, atypical and malignant parathyroid neoplasms to obviate the need for repeated follow-up.

Barazeghi E, Gill AJ, Sidhu S, et al.
5-Hydroxymethylcytosine discriminates between parathyroid adenoma and carcinoma.
Clin Epigenetics. 2016; 8:31 [PubMed] Free Access to Full Article Related Publications
BACKGROUND: Primary hyperparathyroidism is characterized by enlarged parathyroid glands due to an adenoma (80-85 %) or multiglandular disease (~15 %) causing hypersecretion of parathyroid hormone (PTH) and generally hypercalcemia. Parathyroid cancer is rare (<1-5 %). The epigenetic mark 5-hydroxymethylcytosine (5hmC) is reduced in various cancers, and this may involve reduced expression of the ten-eleven translocation 1 (TET1) enzyme. Here, we have performed novel experiments to determine the 5hmC level and TET1 protein expression in 43 parathyroid adenomas (PAs) and 17 parathyroid carcinomas (PCs) from patients who had local invasion or metastases and to address a potential growth regulatory role of TET1.
RESULTS: The global 5hmC level was determined by a semi-quantitative DNA immune-dot blot assay in a smaller number of tumors. The global 5hmC level was reduced in nine PCs and 15 PAs compared to four normal tissue samples (p < 0.05), and it was most severely reduced in the PCs. By immunohistochemistry, all 17 PCs stained negatively for 5hmC and TET1 showed negative or variably heterogeneous staining for the majority. All 43 PAs displayed positive 5hmC staining, and a similar aberrant staining pattern of 5hmC and TET1 was seen in about half of the PAs. Western blotting analysis of two PCs and nine PAs showed variable TET1 protein expression levels. A significantly higher tumor weight was associated to PAs displaying a more severe aberrant staining pattern of 5hmC and TET1. Overexpression of TET1 in a colony forming assay inhibited parathyroid tumor cell growth.
CONCLUSIONS: 5hmC can discriminate between PAs and PCs. Whether 5hmC represents a novel marker for malignancy warrants further analysis in additional parathyroid tumor cohorts. The results support a growth regulatory role of TET1 in parathyroid tissue.

Pramono LA, Larasati D, Yossy Y, et al.
Recurrent Bilateral Staghorn Stones as a Manifestation of Primary Hyperparathyroidism due to Parathyroid Adenoma.
Acta Med Indones. 2015; 47(4):348-51 [PubMed] Related Publications
Primary hyperparathyroidism is a medical condition caused by overactive of parathyroid gland. It is most commonly caused by solitary adenoma of the parathyroid gland. Other causes of this condition are hyperplasia, multiple adenomas, and parathyroid cancer. Primary hyperparathyroidism has some metabolic consequences in the calcium metabolism. Hypercalcemia in patient with primary hyperparathyroidism will resulted to the most important comorbidity that is chronic deposition of calcium in the kidney forming nephrolithiasis or other urolithiasis. It is not uncommon, patient with parathyroid adenoma come to health care professionals with the chief complain of recurrence nephrolithiasis.

Haglund F, Juhlin CC, Kiss NB, et al.
Diffuse parathyroid hormone expression in parathyroid tumors argues against important functional tumor subclones.
Eur J Endocrinol. 2016; 174(5):583-90 [PubMed] Free Access to Full Article Related Publications
OBJECTIVE: Primary hyperparathyroidism is usually characterized by a monoclonal parathyroid tumor secreting excess parathyroid hormone (PTH). The main regulator of PTH secretion is calcium and the calcium-PTH set point is shifted in parathyroid tumor cells. We sought to investigate the relationship between tumor PTH and PTH mRNA expression and clinical presentation as well as the regulatory factors including phosphate, vitamin D, and fibroblast growth factor 23.
DESIGN: A total of 154 parathyroid tumors were analyzed by PTH immunohistochemistry and chromogenic in situ hybridization of PTH mRNA. A subset of samples (n = 34) was analyzed using quantitative real-time PCR.
RESULTS: Low tumor PTH mRNA level was significantly associated with low tumor PTH immunoreactivity (P = 0.026), but the two did not correlate with regard to histological distribution within individual tumors. Tumors displaying reduced PTH mRNA levels as compared with normal rim were significantly larger (P = 0.013) and showed higher expression of the calcium-sensing receptor (CASR) (P = 0.046). Weaker tumor PTH mRNA level was significantly associated with higher concentration of circulating 25-hydroxyvitamin D (P = 0.005). No significant correlation was seen between PTH immunoreactivity and patient biochemistry. Tumor weight was strongly associated with circulatory concentrations of calcium and PTH.
CONCLUSIONS: No areas with apparently higher PTH expression were identified, perhaps suggesting that hyper functioning parathyroid tumor subclones should be rare. Circulating 25-hydroxyvitamin D levels may influence tumor PTH expression in vivo. If PTH immunoreactivity reflects the tumor calcium-PTH set point, our data imply that the main determinant of disease severity should be tumor weight.

Sanders CD, Kirkland JD, Wolin EA
Ectopic Parathyroid Adenoma in the Carotid Sheath.
J Nucl Med Technol. 2016; 44(3):201-2 [PubMed] Related Publications
Primary hyperparathyroidism is predominantly caused by a single parathyroid adenoma. Knowledge of normal and ectopic locations of parathyroid glands is crucial to help guide surgeons who plan targeted unilateral parathyroidectomy to reduce surgical time and risk. We describe a female patient with clinical primary hyperparathyroidism who underwent a failed initial parathyroidectomy, with subsequent imaging localizing an ectopic parathyroid adenoma in the carotid sheath.

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