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Journal of Internal Medicine Dec 2016Primary hyperparathyroidism (PHPT), due to parathyroid tumours, may occur as part of a complex syndrome or as an isolated (nonsyndromic) disorder, and both forms can... (Review)
Review
Primary hyperparathyroidism (PHPT), due to parathyroid tumours, may occur as part of a complex syndrome or as an isolated (nonsyndromic) disorder, and both forms can occur as familial (i.e. hereditary) or nonfamilial (i.e. sporadic) disease. Syndromic PHPT includes multiple endocrine neoplasia (MEN) types 1 to 4 (MEN1 to MEN4) and the hyperparathyroidism-jaw tumour (HPT-JT) syndrome. Syndromic and hereditary PHPT are often associated with multiple parathyroid tumours, in contrast to sporadic PHPT, in which single parathyroid adenomas are more common. In addition, parathyroid carcinomas may occur in ~15% of patients with the HPT-JT syndrome. MEN1 is caused by abnormalities of the MEN1 gene which encodes a tumour suppressor; MEN2 and MEN3 are due to mutations of the rearranged during transfection (RET) proto-oncogene, which encodes a tyrosine kinase receptor; MEN4 is due to mutations of a cyclin-dependent kinase inhibitor (CDNK1B); and HPT-JT is due to mutations of cell division cycle 73 (CDC73), which encodes parafibromin. Nonsyndromic PHPT, which may be hereditary and referred to as familial isolated hyperparathyroidism, may also be due to MEN1, CDC73 or calcium-sensing receptor (CASR) mutations. In addition, ~10% of patients presenting below the age of 45 years with nonsyndromic, sporadic PHPT may have MEN1, CDC73 or CASR mutations, and overall more than 10% of patients with PHPT will have a mutation in one of 11 genes. Genetic testing is available and of value in the clinical setting, as it helps in making the correct diagnosis and planning the management of these complex disorders associated with parathyroid tumours.
Topics: Genetic Therapy; Humans; Hypercalcemia; Hyperparathyroidism, Primary; Parathyroid Neoplasms; Proto-Oncogene Mas
PubMed: 27306766
DOI: 10.1111/joim.12523 -
Annals of the Royal College of Surgeons... May 2015Primary hyperparathyroidism is a relatively common problem encountered by any endocrine surgical unit. Ectopic parathyroid adenomas have been known to be a common cause... (Review)
Review
Primary hyperparathyroidism is a relatively common problem encountered by any endocrine surgical unit. Ectopic parathyroid adenomas have been known to be a common cause of persistent hyperparathyroidism after surgery. A common site of the missed ectopic gland will be that in the mediastinum. However, with the increasing improvement in available imaging, it is likely that this can be diagnosed preoperatively. The surgical approach to the mediastinal parathyroid has also changed vastly over the last decade from maximally invasive to minimally invasive with minimal complications. We provide a review on the entity of mediastinal parathyroid adenomas and their surgical implications.
Topics: Adenoma; Humans; Mediastinal Neoplasms; Parathyroid Neoplasms
PubMed: 26263931
DOI: 10.1308/003588415X14181254789088 -
Archives of Pathology & Laboratory... Aug 2008Primary hyperparathyroidism (P-HPT) is one of the most common of all endocrine disorders. Eighty percent to 85% of cases are due to parathyroid adenomas while... (Review)
Review
CONTEXT
Primary hyperparathyroidism (P-HPT) is one of the most common of all endocrine disorders. Eighty percent to 85% of cases are due to parathyroid adenomas while hyperplasia and carcinoma account for 10% to 15% and less than 1%, of cases, respectively. The past decade has witnessed remarkable advances in the understanding of the molecular basis of parathyroid hyperplasia and neoplasia. Additionally, imaging studies and the development of the intraoperative assay for parathyroid hormone have transformed the diagnosis and management of patients with these disorders.
OBJECTIVE
To review the pathology of parathyroid lesions associated with P-HPT, their molecular and genetic bases, including heritable hyperparathyroidism syndromes, and their clinical diagnosis and management.
DATA SOURCES
Review of pertinent epidemiology, pathology, radiology, and surgery literature on the diagnosis, classification, and treatment of P-HPT.
CONCLUSIONS
Although heritable causes of P-HPT including multiple endocrine neoplasia 1 and 2A and hyperparathyroidism-jaw tumor syndrome account for a minority of cases of P-HPT, advances in the characterization of the affected genes have provided insights into the genetic basis of sporadic parathyroid neoplasms. Alterations in cyclin D1 and loss of heterozygosity of chromosome 11q in adenomas and hyperplasias have provided support for clonality of these lesions. Parafibromin, the protein product of the HRPT2 gene responsible for hyperparathyroidism-jaw tumor syndrome, has been implicated in the development of sporadic parathyroid carcinomas and loss of immunohistochemical expression of this protein has been suggested to be of value in making the diagnosis of parathyroid carcinoma. Sestamibi scanning and ultrasound have revolutionized the planning of surgical approaches and the intraoperative parathyroid hormone assay has become the standard in guiding completion or extension of surgery.
Topics: Adenoma; Carcinoma; Humans; Hyperparathyroidism, Primary; Hyperplasia; Incidence; Parathyroid Glands; Parathyroid Neoplasms; Syndrome
PubMed: 18684024
DOI: 10.5858/2008-132-1251-PHACP -
Journal of Medical Case Reports Apr 2022Giant parathyroid adenoma is a type of parathyroid adenoma weighing > 3.5 g and having a size of more than 2 cm.
BACKGROUND
Giant parathyroid adenoma is a type of parathyroid adenoma weighing > 3.5 g and having a size of more than 2 cm.
CASE PRESENTATION
This report describes giant primary parathyroid adenoma with reference to the literature. We report the case of a 48-year-old Persian man referred to the clinic with knee and lower back pain. He had a history of mitral valve replacement and several episodes of bilateral nephrolithiasis. After a thorough assessment, a neck mass with a possible thyroid origin was detected, but further assessment showed it was of parathyroid origin. The resected mass was 9 × 6× 4 cm and weighed 122 g, and histopathology showed a giant parathyroid adenoma.
CONCLUSION
Giant parathyroid adenomas that weigh more than 110 g and are larger than 8 cm can lead to significant hypercalcemia. Despite giant parathyroid adenomas and high parathyroid hormone levels, a calcium crisis may not always occur in these patients, and the masses may be initially misdiagnosed as a thyroid mass.
Topics: Adenoma; Humans; Hypercalcemia; Male; Middle Aged; Parathyroid Hormone; Parathyroid Neoplasms; Thyroid Gland
PubMed: 35414046
DOI: 10.1186/s13256-022-03401-y -
Journal of Internal Medicine Dec 2016Primary hyperparathyroidism (pHPT) is a common endocrine disease characterized by excessive secretion of parathyroid hormone and an increased level of serum calcium.... (Review)
Review
Primary hyperparathyroidism (pHPT) is a common endocrine disease characterized by excessive secretion of parathyroid hormone and an increased level of serum calcium. Overall, 80-85% of pHPT cases are due to a benign, single parathyroid adenoma (PA), and 15% to multiglandular disease (multiple adenomas/hyperplasia). Parathyroid carcinoma (PC) is rare, accounting for <0.5-1% of pHPT cases. Secondary hyperparathyroidism (sHPT) is a complication of renal failure, with the development of parathyroid tumours and hypercalcaemia. Recurrent mutations in the MEN1 gene have been confirmed by the whole-exome sequencing in 35% of PAs, suggesting that non-protein-coding genes, regulatory elements or epigenetic derangements may also have roles in the majority of PAs. DNA translocations with cyclin D1 overexpression occur in PAs (8%). In PCs, mutations in CDC73/HRPT2 are common. Activation of the WNT/β-catenin signalling pathway (accumulation of nonphosphorylated β-catenin) by an aberrantly truncated LRP5 receptor has been seen for the majority of investigated PAs and sHPT tumours, and possibly by APC inactivation through promoter methylation in PCs. Promoter methylation of several other genes and repressive histone H3 lysine 27 trimethylation by EZH2 of the HIC1 gene may also contribute to parathyroid tumorigenesis. It is possible that a common pathway exists for parathyroid tumour development. CCND1 (cyclin D1) and EZH2 overexpression, accumulation of nonphosphorylated β-catenin and repression of HIC1 have all been observed to occur in PAs, PCs and sHPT tumours. In addition, hypermethylation has been observed for the same genes in PAs and PCs (e.g. SFRP1, CDKN2A and WT1). Whether β-catenin represents a 'hub' in parathyroid tumour development will be discussed.
Topics: Epigenesis, Genetic; Humans; Hyperparathyroidism, Primary; Jumonji Domain-Containing Histone Demethylases; MicroRNAs; Mutation; Parathyroid Neoplasms; Wnt Signaling Pathway
PubMed: 27071708
DOI: 10.1111/joim.12458 -
International Journal of Molecular... Jun 2022Immunohistochemistry remains an indispensable tool in diagnostic surgical pathology. In parathyroid tumours, it has four main applications: to detect (1) loss of... (Review)
Review
Immunohistochemistry remains an indispensable tool in diagnostic surgical pathology. In parathyroid tumours, it has four main applications: to detect (1) loss of parafibromin; (2) other manifestations of an aberrant immunophenotype hinting towards carcinoma; (3) histogenesis of a neck mass and (4) pathogenetic events, including features of tumour microenvironment and immune landscape. Parafibromin stain is mandatory to identify the new entity of parafibromin-deficient parathyroid neoplasm, defined in the WHO classification (2022). Loss of parafibromin indicates a greater probability of malignant course and should trigger the search for inherited or somatic mutations. Aberrant immunophenotype is characterised by a set of markers that are lost (parafibromin), down-regulated (e.g., APC protein, p27 protein, calcium-sensing receptor) or up-regulated (e.g., proliferation activity by Ki-67 exceeding 5%) in parathyroid carcinoma compared to benign parathyroid disease. Aberrant immunophenotype is not the final proof of malignancy but should prompt the search for the definitive criteria for carcinoma. Histogenetic studies can be necessary for differential diagnosis between thyroid vs. parathyroid origin of cervical or intrathyroidal mass; detection of parathyroid hormone (PTH), chromogranin A, TTF-1, calcitonin or CD56 can be helpful. Finally, immunohistochemistry is useful in pathogenetic studies due to its ability to highlight both the presence and the tissue location of certain proteins. The main markers and challenges (technological variations, heterogeneity) are discussed here in the light of the current WHO classification (2022) of parathyroid tumours.
Topics: Adenoma; Carcinoma; Humans; Immunohistochemistry; Parathyroid Neoplasms; Tumor Microenvironment; Tumor Suppressor Proteins
PubMed: 35805976
DOI: 10.3390/ijms23136981 -
Journal of Ayub Medical College,... 2006Parathyroid carcinoma is a very rare cause of primary hyperparathyroidism and these tumors are usually hyper-functioning as compared to other malignant endocrine tumors....
Parathyroid carcinoma is a very rare cause of primary hyperparathyroidism and these tumors are usually hyper-functioning as compared to other malignant endocrine tumors. Surgery is the only effective primary treatment. We report a patient, who presented with pathological fracture of femur, hypercalcemia, bilateral renal stones, markedly raised Parathormone levels and palpable mass in the neck. Parathyroid adenoma was initially diagnosed and localized at left lower gland by Sestamibi scan and ultrasonography. She underwent surgery and enlarged parathyroid gland was removed. Intra operatively there was no evidence of local invasion or lymph nodes involvement but biopsy report suggested malignancy.
Topics: Adenoma; Diagnosis, Differential; Female; Humans; Middle Aged; Parathyroid Neoplasms
PubMed: 16977824
DOI: No ID Found -
Endocrine-related Cancer Sep 2016The vagus nerve (cranial nerve X) is the main nerve of the parasympathetic division of the autonomic nervous system. Vagal paragangliomas (VPGLs) are a prime example of... (Review)
Review
The vagus nerve (cranial nerve X) is the main nerve of the parasympathetic division of the autonomic nervous system. Vagal paragangliomas (VPGLs) are a prime example of an endocrine tumor associated with the vagus nerve. This rare, neural crest tumor constitutes the second most common site of hereditary head and neck paragangliomas (HNPGLs), most often in relation to mutations in the succinate dehydrogenase complex subunit D (SDHD) gene. The treatment paradigm for VPGL has progressively shifted from surgery to abstention or therapeutic radiation with curative-like outcomes. Parathyroid tissue and parathyroid adenoma can also be found in close association with the vagus nerve in intra or paravagal situations. Vagal parathyroid adenoma can be identified with preoperative imaging or suspected intraoperatively by experienced surgeons. Vagal parathyroid adenomas located in the neck or superior mediastinum can be removed via initial cervicotomy, while those located in the aortopulmonary window require a thoracic approach. This review particularly emphasizes the embryology, molecular genetics, and modern imaging of these tumors.
Topics: Cranial Nerve Neoplasms; Humans; Paraganglioma; Parathyroid Neoplasms; Vagus Nerve; Vagus Nerve Diseases
PubMed: 27406876
DOI: 10.1530/ERC-16-0241 -
Endocrinology and Metabolism (Seoul,... Oct 2022Parathyroidectomy is the treatment of choice for primary hyperparathyroidism when the clinical criteria are met. Although bilateral neck exploration is traditionally the... (Review)
Review
Parathyroidectomy is the treatment of choice for primary hyperparathyroidism when the clinical criteria are met. Although bilateral neck exploration is traditionally the standard method for surgery, minimally invasive parathyroidectomy (MIP), or focused parathyroidectomy, has been widely accepted with comparable curative outcomes. For successful MIP, accurate preoperative localization of parathyroid lesions is essential. However, no consensus exists on the optimal approach for localization. Currently, ultrasonography and technetium-99m-sestamibi-single photon emission computed tomography/computed tomography are widely accepted in most cases. However, exact localization cannot always be achieved, especially in cases with multiglandular disease, ectopic glands, recurrent disease, and normocalcemic primary hyperparathyroidism. Therefore, new modalities for preoperative localization have been developed and evaluated. Positron emission tomography/computed tomography and parathyroid venous sampling have demonstrated improvements in sensitivity and accuracy. Both anatomical and functional information can be obtained by combining these methods. As each approach has its advantages and disadvantages, the localization study should be deliberately chosen based on each patient's clinical profile, costs, radiation exposure, and the availability of experienced experts. In this review, we summarize various methods for the localization of hyperfunctioning parathyroid tissues in primary hyperparathyroidism.
Topics: Humans; Hyperparathyroidism, Primary; Parathyroid Neoplasms; Tomography, Emission-Computed, Single-Photon; Radiopharmaceuticals; Parathyroid Glands
PubMed: 36327985
DOI: 10.3803/EnM.2022.1589 -
Endocrine Pathology Mar 2021The majority of parathyroid disease encountered in routine practice is due to single parathyroid adenoma, of which the majority arise as sporadic tumors. This is usually... (Review)
Review
The majority of parathyroid disease encountered in routine practice is due to single parathyroid adenoma, of which the majority arise as sporadic tumors. This is usually a straightforward diagnosis in endocrine pathology when in the appropriate clinical setting, although subsets of cases will exhibit atypical histological features that may warrant additional immunohistochemical and genetic analyses to estimate the malignant potential. Parathyroid carcinomas on the other hand, are bona fide malignant tumors characterized by their unequivocal invasion demonstrated through routine histology or metastasis. The ultimate endpoint for any molecular marker discovered through laboratory investigations is to be introduced in clinical routine practice and guide the surgical pathologist in terms of diagnostics and prognostication. For parathyroid tumors, the two main diagnostic challenges include the distinction between parathyroid adenoma and parathyroid carcinoma, as well as the pinpointing of hereditable disease for familial screening purposes. While numerous markers on genetic, epigenetic, and protein levels have been proposed as discriminative in these aspects, this review aims to condense the scientific coverage of these enigmatic topics and to propose a focused surgical pathology approach to the subject.
Topics: Animals; Epigenesis, Genetic; Epigenomics; Genomics; Humans; Parathyroid Neoplasms; Pathology, Surgical
PubMed: 33269427
DOI: 10.1007/s12022-020-09656-9