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Molecular and Cellular Endocrinology Apr 2014Parathyroid neoplasia is most commonly due to benign parathyroid adenoma but rarely can be caused by malignant parathyroid carcinoma. Evidence suggests that parathyroid... (Review)
Review
Parathyroid neoplasia is most commonly due to benign parathyroid adenoma but rarely can be caused by malignant parathyroid carcinoma. Evidence suggests that parathyroid carcinomas rarely, if ever, evolve through an identifiable benign intermediate, with the notable exception of carcinomas associated with the familial hyperparathyroidism-jaw tumor syndrome. Several genes have been directly implicated in the pathogenesis of typical sporadic parathyroid adenoma; somatic mutations in the MEN1 tumor suppressor gene are the most frequent finding, and alterations in the cyclin D1/PRAD1 oncogene are also firmly established molecular drivers of sporadic adenomas. In addition, good evidence supports mutation in the CDKN1B/p27 cyclin-dependent kinase inhibitor (CDKI) gene, and in other CDKI genes as contributing to disease pathogenesis in this context. Somatic defects in additional genes, including β-catenin, POT1 and EZH2 may contribute to parathyroid adenoma formation but, for most, their ability to drive parathyroid tumorigenesis remains to be demonstrated experimentally. Further, genetic predisposition to sporadic presentations of parathyroid adenoma appears be conferred by rare, and probably low-penetrance, germline variants in CDKI genes and, perhaps, in other genes such as CASR and AIP. The HRPT2 tumor suppressor gene is commonly mutated in parathyroid carcinoma.
Topics: Epigenesis, Genetic; Genetic Predisposition to Disease; Humans; Mutation; Neoplasm Proteins; Parathyroid Neoplasms
PubMed: 24035866
DOI: 10.1016/j.mce.2013.09.005 -
European Review For Medical and... Oct 2021Parathyroid carcinoma is a rare etiology of primary hyperparathyroidism (PHPT) and subsequent hypercalcemia. Among clinical manifestations of hypercalcemia, acute... (Review)
Review
OBJECTIVE
Parathyroid carcinoma is a rare etiology of primary hyperparathyroidism (PHPT) and subsequent hypercalcemia. Among clinical manifestations of hypercalcemia, acute pancreatitis is very uncommon. Nevertheless, acute pancreatitis may be an initial clinical manifestation of parathyroid cancer.
PATIENTS AND METHODS
We present a case report and literature review on hypercalcemia-induced acute pancreatitis secondary to parathyroid carcinoma.
RESULTS
A 56 years-old man, who had previously received a diagnosis of pancreatic cancer with peritoneal and bone metastasis, complained of persistent postprandial epigastric pain, weight loss (12 kg) and hypercalcemia. He underwent endoscopic ultrasound, which did not identify any solid masses, but a pseudocyst of the pancreas body consistent with a local complication of acute pancreatitis. Plasma levels of parathyroid hormone were markedly increased, and neck ultrasound and scintigraphy confirmed the diagnosis of PHPT. Parathyroidectomy was performed and histological examination revealed parathyroid carcinoma. Searching on PubMed for the keywords "parathyroid carcinoma" AND "acute pancreatitis", from 1969 to March 2021 we found only 12 case reports of acute pancreatitis due to parathyroid cancer. The causal relationship between PHPT and acute pancreatitis has been widely discussed in literature but is still a controversial issue.
CONCLUSIONS
Acute pancreatitis induced by primary hyperparathyroidism due to parathyroid carcinoma is an extremely rare condition. However, when hypercalcemia is found, serum PTH levels should always be determined in order to rule out PHPT and hypercalcemia-induced acute pancreatitis should be suspected in presence of hypercalcemia and abdominal symptoms.
Topics: Abdominal Pain; Humans; Hypercalcemia; Hyperparathyroidism, Primary; Male; Middle Aged; Pancreatitis; Parathyroid Hormone; Parathyroid Neoplasms; Parathyroidectomy; Radionuclide Imaging; Ultrasonography
PubMed: 34661256
DOI: 10.26355/eurrev_202110_26874 -
European Annals of Otorhinolaryngology,... Nov 2015Fine-needle aspiration cytology (FNAC) of thyroid nodules commonly reveals the presence of oncocytic cells (or Hürthle cells) in a follicular neoplasm. Histological...
INTRODUCTION
Fine-needle aspiration cytology (FNAC) of thyroid nodules commonly reveals the presence of oncocytic cells (or Hürthle cells) in a follicular neoplasm. Histological examination is necessary to determine the benign or malignant nature of the tumour. However, oncocytic cells are also normally present in the parathyroid glands.
CASE REPORT
A thyroid nodule was discovered on thyroid ultrasound in a woman with a history of left partial thyroid lobectomy. Fine-needle aspiration cytology revealed a follicular neoplasm comprising oncocytic cells (Hürthle cells). This woman also presented features of hyperparathyroidism with hypercalcaemia. (123)I/(99m)Tc-sestamibi and (18)F-fluorocholine PET-CT scan revealed increased uptake over the remaining left thyroid lobe. Left lobectomy was completed together with thyroid exploration. Histological examination revealed a parathyroid adenoma in the residual thyroid tissue. Parathyroid hormone levels subsequently returned to normal.
DISCUSSION
Cytomorphological similarities are often observed between parathyroid and Hürthle cell thyroid tumours. The parathyroid rather than thyroid nature of the tumour must be strongly suspected preoperatively in the presence of hyperparathyroidism.
Topics: Adenoma; Female; Humans; Hyperparathyroidism; Middle Aged; Multimodal Imaging; Oxyphil Cells; Parathyroid Neoplasms; Positron-Emission Tomography; Tomography, X-Ray Computed
PubMed: 26364541
DOI: 10.1016/j.anorl.2015.08.033 -
International Journal of Molecular... Sep 2021Tumors of the parathyroid glands are common endocrine diseases almost always characterized by parathyroid hormone hypersecretion that determines the clinical... (Review)
Review
Tumors of the parathyroid glands are common endocrine diseases almost always characterized by parathyroid hormone hypersecretion that determines the clinical manifestations of primary hyperparathyroidism, such as fatigue, kidney problems, weakness, brittle bones, and other symptoms. Most parathyroid neoplasia are benign adenomas, although rare malignant forms have been described. They are heterogeneous in terms of clinical presentation and the associated signs and symptoms overlap with those of disease and aging. Furthermore, most patients with hypercalcemia are discovered during routine blood tests for other reasons. Surgical removal is considered the main therapeutic option to cure these endocrine tumors and, therefore, innovative therapeutic approaches are actively required. Recently, a growing number of studies have suggested that alterations to the epigenetic mechanisms could play a pivotal role in parathyroid tumorigenesis. Most of the attention has been focused on non-coding RNAs (ncRNAs) (i.e., miRNAs, lncRNAs, and circRNAs) whose expression profile has been found to be deregulated in parathyroid tumors. The aim of the present paper is to give an insight into the ncRNAs involved in parathyroid tumorigenesis, which could be used in the future either as innovative diagnostic biomarkers or as therapeutic targets for the treatment of this endocrine neoplasia.
Topics: Biomarkers, Tumor; Epigenesis, Genetic; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs; Parathyroid Neoplasms; RNA, Circular; RNA, Long Noncoding; RNA, Untranslated
PubMed: 34638805
DOI: 10.3390/ijms221910465 -
Endocrinology and Metabolism (Seoul,... Apr 2021We investigated the clinical characteristics of parathyroid adenomas according to radioactivity on 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) single-photon emission...
BACKGROUND
We investigated the clinical characteristics of parathyroid adenomas according to radioactivity on 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) single-photon emission computed tomography/computed tomography (SPECT/CT) in primary hyperparathyroidism (PHPT) patients.
METHODS
The study included 217 patients diagnosed with PHPT from 2000 to 2019 at Seoul National University Hospital who underwent 99mTc-MIBI SPECT/CT scans. On SPECT/CT, the radioactivity of parathyroid adenomas was measured as the ratio of the mean radioactivity count of the parathyroid adenoma to that of the contralateral thyroid.
RESULTS
Tumors were localized by MIBI scans in 190 patients (MIBI [+] group) and by ultrasound or parathyroid four-dimensional CT in 27 patients (MIBI [-] group). The mean age was 55 years, and mean body mass index was 23.4 kg/m2. Patients in the MIBI (+) group had higher parathyroid hormone (iPTH) and lower 25-hydroxy vitamin D levels than those in the MIBI (-) group (168.0 pg/mL [interquartile range, IQR, 111.0 to 250.7] vs. 134.7 pg/mL [IQR, 98.2 to 191.2], P=0.049; 15.4 ng/mL [IQR, 11.1 to 20.8] vs. 21.2 ng/mL [IQR, 13.9 to 24.8], P=0.012, respectively). Patients in the MIBI (+) group had larger tumor volumes, but lower iPTH/volume ratios than those in the MIBI (-) group (1,216.66 [IQR, 513.40 to 2,663.02], 499.82 mm3 [IQR, 167.77 to 1,229.80], P=0.002; 0.18 [IQR, 0.08 to 0.46], 0.40 pg/mL/mm3 [IQR, 0.16 to 1.29], P=0.016, respectively). Adenoma radioactivity was positively correlated with calcium, iPTH, and volume (r=0.180, P=0.020; r=0.208, P=0.006; r=0.288, P<0.001, respectively), but not with iPTH/volume.
CONCLUSION
Parathyroid adenomas with positive MIBI scans had larger volumes and higher iPTH than adenomas with negative scans, but lower iPTH per unit volume.
Topics: Humans; Middle Aged; Parathyroid Glands; Parathyroid Hormone; Parathyroid Neoplasms; Radioactivity; Technetium Tc 99m Sestamibi
PubMed: 33820395
DOI: 10.3803/EnM.2020.823 -
Journal of Bone and Mineral Research :... Dec 2008
Review
Topics: Adult; Aged; Disease Progression; Female; Gene Expression Regulation, Neoplastic; Humans; Hypercalcemia; Immunohistochemistry; Male; Medical Oncology; Middle Aged; Models, Genetic; Mutation; Parathyroid Neoplasms; Tumor Suppressor Proteins
PubMed: 19016595
DOI: 10.1359/jbmr.081018 -
The Journal of Clinical Endocrinology... Jun 2023To define somatic variants of parathyroid adenoma (PA) and to provide novel insights into the underlying molecular mechanism of sporadic PA.
OBJECTIVE
To define somatic variants of parathyroid adenoma (PA) and to provide novel insights into the underlying molecular mechanism of sporadic PA.
METHODS
Basic clinical characteristics and biochemical indices of 73 patients with PA were collected. Whole-exome sequencing was performed on matched tumor-constitutional DNA pairs to detect somatic alterations. Functional annotation was carried out by ingenuity pathway analysis afterward. The protein expression of the variant gene was confirmed by immunohistochemistry, and the relationship between genotype and phenotype was analyzed.
RESULTS
Somatic variants were identified in 1549 genes, with an average of 69 variants per tumor (range, 13-2109; total, 9083). Several novel recurrent somatic variants were detected, such as KMT2D (15/73), MUC4 (14/73), POTEH (13/73), CD22 (12/73), HSPA2 (12/73), HCFC1 (11/73), MAGEA1 (11/73), and SLC4A3 (11/73), besides the previously reported PA-related genes, including MEN1 (11/73), CASR (6/73), MTOR (4/73), ASXL3 (3/73), FAT1 (3/73), ZFX (5/73), EZH1 (2/73), POT1 (2/73), and EZH2 (1/73). Among them, KMT2D might be the candidate driver gene of PA. Crucially, 5 patients carried somatic mutations in CDC73, showed an aggressive phenotype similar to that of parathyroid carcinoma (PC), and had a decreased expression of parafibromin. Pathway analysis of recurrent potential PA-associated driver variant genes revealed functional enrichments in the signaling pathway of Notch.
CONCLUSION
Our study expanded the pathogenic variant spectrum of PA and indicated that KMT2D might be a novel candidate driver gene and be considered as a diagnostic biomarker for PA. Meanwhile, CDC73 mutations might be an early developmental event from PA to PC. The results provided insights into elucidating the pathogenesis of parathyroid tumorigenesis and a certain basis for clinical diagnosis and treatment.
Topics: Humans; East Asian People; Genomics; Mutation; Parathyroid Neoplasms
PubMed: 36611251
DOI: 10.1210/clinem/dgad002 -
Journal of the National Medical... 2001Parathyroid carcinoma is a rare entity accounting for 0.5% to 5% of parathyroid neoplasia. Most of these malignancies present as functional hormone-producing masses with... (Review)
Review
Parathyroid carcinoma is a rare entity accounting for 0.5% to 5% of parathyroid neoplasia. Most of these malignancies present as functional hormone-producing masses with elevated serum levels of parathormone and calcium. These tumors may also be nonfunctional. Clinical detection of nonfunctioning parathyroid malignancies preoperatively is primarily based on symptoms of an expanding neck mass. This ominous complaint is typically accompanied with an advanced stage of the disease at initial diagnosis. Because there is a paucity of data in the literature regarding nonfunctioning parathyroid carcinoma, prognosis can not be readily assessed. In both functional and nonfunctional parathyroid carcinoma, early surgery has proven to be the only curative treatment approach whereas both chemotherapy and radiation therapy fail to produce systemic or regional benefit when used alone. Hence, parathyroid cancer should be considered in every patient evaluated for a neck mass regardless of the blood calcium and blood parathormone level.
Topics: Carcinoma; Humans; Parathyroid Neoplasms; Prognosis
PubMed: 11491274
DOI: No ID Found -
Medicina (Kaunas, Lithuania) Feb 2023: Parathyroid cancer is a very rare endocrine tumor, especially in patients with secondary hyperparathyroidism due to end stage renal disease failure. This pathology is...
: Parathyroid cancer is a very rare endocrine tumor, especially in patients with secondary hyperparathyroidism due to end stage renal disease failure. This pathology is difficult to diagnose preoperatively because it has nonspecific clinical manifestations and paraclinical aspects. Our study of the literature identified 34 reported cases of parathyroid carcinoma over the last 40 years in patients undergoing dialysis. We present our experience as illustrative of the features of clinical presentation and histopathological findings of parathyroid carcinoma and assess its management considering the recent relevant literature. : From January 2012 to November 2022, 650 patients with secondary hyperparathyroidism undergoing dialysis were treated at our academic Department of General Surgery and only two cases of parathyroid carcinoma were diagnosed on histopathological examination. : All patients presented with symptomatic hypercalcemia, with no clinical or imaging suspicion of malignant disease and were surgically treated by total parathyroidectomy. Histopathological examination revealed morphologic aspects of parathyroid carcinoma in two cases and immunostaining of Ki-67 was performed for diagnostic confirmation. Postoperative follow-up showed no signs of recurrence and no oncological adjuvant treatment or surgical reinterventions were needed. : Parathyroid neoplasia is a particularly rare disease, that remains a challenge when it comes to diagnosis and proper management. Surgical approach is the only valid treatment to remove the malignant tissue and thus improve the patient's prognosis. Medical and oncologic treatment may be beneficial to control hypercalcemia in case of tumor recurrence.
Topics: Humans; Parathyroid Neoplasms; Parathyroidectomy; Hypercalcemia; Neoplasm Recurrence, Local; Renal Dialysis; Hyperparathyroidism, Secondary; Parathyroid Hormone
PubMed: 36984449
DOI: 10.3390/medicina59030448 -
Langenbeck's Archives of Surgery Oct 2023Despite advances in biochemical and radiological identification of parathyroid gland enlargement, primary hyperparathyroidism (PHPT) due to sporadic multigland... (Review)
Review
BACKGROUND
Despite advances in biochemical and radiological identification of parathyroid gland enlargement, primary hyperparathyroidism (PHPT) due to sporadic multigland parathyroid disease (MGPD) remains a perioperative diagnostic dilemma. Failure to recognise MGPD pre- or intraoperatively may negatively impact surgical cure rates and result in persistent PHPT and ongoing patient morbidity.
METHODS
We have conducted a comprehensive review of published literature in attempt to determine factors that could aid in reliably diagnosing sporadic MGPD pre- or intraoperatively. We discuss preoperative clinical features and examine pre- and intraoperative biochemical and imaging findings concentrating on those areas that give practicing surgeons and the wider multi-disciplinary endocrine team indications that a patient has MGDP. This could alter surgical strategy.
CONCLUSION
Biochemistry can provide diagnosis of PHPT but cannot reliably discriminate parathyroid pathology. Histopathology can aid diagnosis between MGPD and adenoma, but histological appearance can overlap. Multiple negative imaging modalities indicate that MGPD may be more likely than a single parathyroid adenoma, but the gold standard for diagnosis is still intraoperative identification during BNE. MGPD remains a difficult disease to both diagnose and treat.
Topics: Humans; Parathyroid Hormone; Parathyroidectomy; Parathyroid Diseases; Parathyroid Glands; Parathyroid Neoplasms; Hyperparathyroidism, Primary; Retrospective Studies
PubMed: 37806985
DOI: 10.1007/s00423-023-03087-w