-
Frontiers in Endocrinology 2021The goal of parathyroid imaging is to identify all sources of excess parathyroid hormone secretion pre-operatively. A variety of imaging approaches have been evaluated... (Review)
Review
The goal of parathyroid imaging is to identify all sources of excess parathyroid hormone secretion pre-operatively. A variety of imaging approaches have been evaluated and utilized over the years for this purpose. Ultrasound relies solely on structural features and is without radiation, however is limited to superficial evaluation. 4DCT and 4DMRI provide enhancement characteristics in addition to structural features and dynamic enhancement has been investigated as a way to better distinguish parathyroid from adjacent structures. It is important to recognize that 4DCT provides valuable information however results in much higher radiation dose to the thyroid gland than the other available examinations, and therefore the optimal number of phases is an area of controversy. Single-photon scintigraphy with 99mTc-Sestamibi, or dual tracer 99mTc-pertechnetate and 99mTc-sestamibi with or without SPECT or SPECT/CT is part of the standard of care in many centers with availability and expertise in nuclear medicine. This molecular imaging approach detects cellular physiology such as mitochondria content found in parathyroid adenomas. Combining structural imaging such as CT or MRI with molecular imaging in a hybrid approach allows the ability to obtain robust structural and functional information in one examination. Hybrid PET/CT is widely available and provides improved imaging and quantification over SPECT or SPECT/CT. Emerging PET imaging techniques, such as 18F-Fluorocholine, have the exciting potential to reinvent parathyroid imaging. PET/MRI may be particularly well suited to parathyroid imaging, where available, because of the ability to perform dynamic contrast-enhanced imaging and co-registered 18F-Fluorocholine PET imaging simultaneously with low radiation dose to the thyroid. A targeted agent specific for a parathyroid tissue biomarker remains to be identified.
Topics: Humans; Hyperparathyroidism, Primary; Parathyroid Glands; Parathyroid Neoplasms; Positron Emission Tomography Computed Tomography; Technetium Tc 99m Sestamibi
PubMed: 35283807
DOI: 10.3389/fendo.2021.760419 -
The Quarterly Journal of Nuclear... Jun 2022Parathyroid imaging is essential for the detection and localization of hyperfunctioning parathyroid tissue in patients with primary hyperparathyroidism (pHPT). Surgical...
Parathyroid imaging is essential for the detection and localization of hyperfunctioning parathyroid tissue in patients with primary hyperparathyroidism (pHPT). Surgical treatment of pHPT mainly consists of minimally invasive parathyroidectomy (MIP), as a single adenoma represents the most common cause of this endocrine disorder. Successful surgery requires an experienced surgeon and relies on the correct preoperative detection and localization of hyperfunctioning parathyroid glands. Failure to preoperatively identify the culprit parathyroid gland by imaging may entail a more invasive surgical approach, including bilateral open neck exploration, with higher morbidity compared to minimally invasive parathyroidectomy. Parathyroid imaging may be also useful before surgery in case of secondary hyperparathyroidism (sHPT) or hereditary disorders (MEN 1, 2, 4) as it enables correct localization of typically located parathyroid glands, detection of ectopic as well as supernumerary glands. It is now accepted by most surgeons experienced in parathyroid surgery that preoperative imaging plays a key role in their patients' management. Recently, the European Association of Nuclear Medicine (EANM) issued an updated version of its Guidelines on parathyroid imaging. Its aim is to precise the role and the advantages and drawbacks of the various imaging modalities proposed or well established in the preoperative imaging strategy. It also aims to favor high performance in indicating, performing, and interpreting those examinations. The objective of the present article is to offer a summary of those recent EANM Guidelines and their originality among other Guidelines in this domain issued by societies of nuclear medicine physicians or other disciplines.
Topics: Humans; Nuclear Medicine; Parathyroid Glands; Parathyroid Neoplasms; Parathyroidectomy; Radionuclide Imaging; Technetium Tc 99m Sestamibi
PubMed: 35166093
DOI: 10.23736/S1824-4785.22.03427-6 -
Archives of Endocrinology and Metabolism Nov 2022Primary hyperparathyroidism (PHPT) is a hypercalcemic disorder that occurs when one or more parathyroid glands produces excessive parathyroid hormone (PTH). PHPT is... (Review)
Review
Primary hyperparathyroidism (PHPT) is a hypercalcemic disorder that occurs when one or more parathyroid glands produces excessive parathyroid hormone (PTH). PHPT is typically treated with surgery, and it remains the only definitive therapy, whose techniques have evolved over previous decades. Advances in preoperative localization exams and the intraoperative PTH monitoring have become the cornerstones of recent parathyroidectomy techniques, as minimally invasive techniques are appropriate for most patients. Nevertheless, these techniques, are not suitable for PHPT patients who are at risk for multiglandular disease, especially in those who present with familial forms of PHPT that require bilateral neck exploration. This manuscript also explores other conditions that warrant special consideration during surgical treatment for PHPT: normocalcemic primary hyperparathyroidism, pregnancy, reoperation for persistent or recurrent PHPT, parathyroid carcinoma, and familial and genetic forms of hyperparathyroidism.
Topics: Humans; Hyperparathyroidism, Primary; Parathyroidectomy; Parathyroid Neoplasms; Parathyroid Hormone; Parathyroid Glands
PubMed: 36382757
DOI: 10.20945/2359-3997000000557 -
Current Opinion in Oncology Jan 2006This article reviews current knowledge on the etiology, diagnosis and treatment of parathyroid carcinoma. (Review)
Review
PURPOSE OF REVIEW
This article reviews current knowledge on the etiology, diagnosis and treatment of parathyroid carcinoma.
RECENT FINDINGS
Due to its rarity, research on the molecular etiology and treatment of parathyroid carcinoma has been slow. Mutations of the tumor suppressor gene, HRPT2, and resultant loss of expression of its gene product have been found in the majority of parathyroid cancers studied. Recent advances in the field have identified regions on several chromosomes that demonstrate loss of heterozygosity more commonly in parathyroid carcinoma than in benign parathyroid lesions. This has provided clues to the location and identity of additional tumor suppressor genes associated with the development of this cancer.
SUMMARY
Parathyroid carcinoma is an extremely rare cause of primary hyperparathyroidism, accounting for fewer than 1% of cases. The etiology of parathyroid cancer is largely unknown. Associations have been made with several inherited syndromes and with specific genetic lesions. Little is known about the most appropriate management of this disease. En bloc resection at the time of initial surgery appears to provide the best chance of cure. Anecdotal experience with adjuvant chemotherapy has shown a modest and short-lived effect. External beam radiation following surgical resection, however, may increase long-term survival compared with surgery alone. Bisphosphonates and a new class of drugs known as calcimimetics have been used effectively in some patients to control the symptoms of severe hypercalcemia in a palliative setting.
Topics: Chemotherapy, Adjuvant; Humans; Hypercalcemia; Hyperparathyroidism, Primary; Parathyroid Neoplasms; Radiotherapy, Adjuvant
PubMed: 16357559
DOI: 10.1097/01.cco.0000198019.53606.2b -
Seminars in Oncology Dec 2010Parathyroid cancer is an uncommon malignancy and rare cause of primary hyperparathyroidism (HPT) with a high morbidity and patient death in advanced cases usually... (Review)
Review
Parathyroid cancer is an uncommon malignancy and rare cause of primary hyperparathyroidism (HPT) with a high morbidity and patient death in advanced cases usually resulting from intractable hypercalcemia. Inactivation of the HRPT2/CDC73 gene, encoding the putative tumor-suppressor protein parafibromin and discovered in the context of the hyperparathyroidism-jaw tumor (HPT-JT) syndrome, is a common, somatic event in most parathyroid cancers. Approximately 25% of patients with apparently sporadic parathyroid cancer carry germline HRPT2/CDC73 mutation. Germline DNA analysis for HRPT2/CDC73 mutation is recommended in all patients with parathyroid cancer because of the potential benefit for first-degree relatives, who should nevertheless undergo serum calcium screening. The histopathologic diagnosis of parathyroid cancer is nonspecific unless vascular, lymphatic, capsular, or soft tissue invasion is seen, or metastases are clinically evident. Immunohistochemical analysis of parathyroid tumors for loss of parafibromin expression offers promise as a diagnostic tool. En bloc tumor resection offers the highest chance of cure in patients with suspected parathyroid carcinoma. No adjuvant chemotherapy regimen has yet proven effective, and the role of local adjuvant radiotherapy is being evaluated. Metastatic disease can be palliated with surgical debulking. Medical therapy with the calcimimetic cinacalcet and bisphosphonates can ameliorate hypercalcemia in patients with inoperable disease.
Topics: Biomarkers, Tumor; Disease Progression; Humans; Hypercalcemia; Mutation; Parathyroid Neoplasms; Parathyroidectomy; Prognosis; Tumor Suppressor Proteins
PubMed: 21167377
DOI: 10.1053/j.seminoncol.2010.10.013 -
International Journal of Molecular... Apr 2020Primary hyperparathyroidism is a common endocrinopathy that is mainly caused by benign parathyroid adenomas. The frequency, clinical presentation and complications of... (Review)
Review
Primary hyperparathyroidism is a common endocrinopathy that is mainly caused by benign parathyroid adenomas. The frequency, clinical presentation and complications of the disease show significant differences between genders, with the majority of cases being reported in postmenopausal women. Due to this gender predilection, several studies have investigated the role of sex hormones in the pathogenesis of the disease and their potential use as targets for optimal and gender-specific management. Epigenetic mechanisms that regulate gene transcription may also contribute to these differences between genders. In this review, we outline what is currently known regarding the role of sex hormones and the recent data on the role of non-coding RNAs in the differences between genders in primary hyperparathyroidism due to sporadic parathyroid adenomas.
Topics: Disease Susceptibility; Epigenesis, Genetic; Female; Gene Expression Regulation; Gene Expression Regulation, Neoplastic; Genetic Predisposition to Disease; Gonadal Steroid Hormones; Humans; Male; Parathyroid Hormone; Parathyroid Neoplasms; Prevalence; Sex Factors
PubMed: 32331456
DOI: 10.3390/ijms21082964 -
Turk Patoloji Dergisi 2015Parathyroid carcinoma is a rare type of endocrine cancer, with significant morbidity and mortality associated with parathyroid hormone (PTH)-mediated hypercalcemia.... (Review)
Review
Parathyroid carcinoma is a rare type of endocrine cancer, with significant morbidity and mortality associated with parathyroid hormone (PTH)-mediated hypercalcemia. Concerning clinical features for parathyroid cancer include severe hypercalcemia (albumin-corrected calcium > 3 mmol/L), a palpable neck mass ( > 3 cm), 3rd/2nd generation PTH assay ratio ( > 1), and intraoperative suspicion of local invasion or regional metastasis. A definite diagnosis of malignancy is rendered when a parathyroid tumor presents one of the following clinicopathological features: (1) vascular invasion, (2) perineural invasion, (3) gross invasion into adjacent anatomical structures, and/or (4) metastasis. In difficult cases, the use of ancillary biomarkers is critical to establish an accurate diagnosis. Recent advances in molecular pathology have uncovered the important role of CDC73/HRPT2, a tumor suppressor gene deregulated in parathyroid carcinomas. Loss of nuclear and/or nucleolar expression of parafibromin (the gene product of CDC73/HRPT2) is now regarded as a diagnostic, prognostic and predictive biomarker for parathyroid carcinoma. Furthermore, over 15-20% of seemingly sporadic parathyroid carcinomas have underlying germline CDC73/HRPT2 mutations. As a result, many centers have integrated the use of ancillary biomarkers, notably parafibromin staining, in their routine practise. Radical surgery with en bloc resection has emerged as a primary treatment modality in parathyroid cancer, achieving cure in some patients. However, in those with inoperable disease, there remains a dire need for new therapies, as current treatments are largely ineffective. This review provides an update on the current knowledge of parathyroid carcinoma and highlights its exciting changes in endocrine practice.
Topics: Biomarkers, Tumor; Biopsy; Carcinoma; DNA Mutational Analysis; Genetic Predisposition to Disease; Humans; Immunohistochemistry; Mutation; Neoplasm Invasiveness; Parathyroid Neoplasms; Phenotype; Predictive Value of Tests; Prognosis; Signal Transduction
PubMed: 26177319
DOI: 10.5146/tjpath.2015.01316 -
Endocrine Reviews Sep 2023Recent data suggest an increase in the overall incidence of parathyroid disorders, with primary hyperparathyroidism (PHPT) being the most prevalent parathyroid disorder....
Recent data suggest an increase in the overall incidence of parathyroid disorders, with primary hyperparathyroidism (PHPT) being the most prevalent parathyroid disorder. PHPT is associated with morbidities (fractures, kidney stones, chronic kidney disease) and increased risk of death. The symptoms of PHPT can be nonspecific, potentially delaying the diagnosis. Approximately 15% of patients with PHPT have an underlying heritable form of PHPT that may be associated with extraparathyroidal manifestations, requiring active surveillance for these manifestations as seen in multiple endocrine neoplasia type 1 and 2A. Genetic testing for heritable forms should be offered to patients with multiglandular disease, recurrent PHPT, young onset PHPT (age ≤40 years), and those with a family history of parathyroid tumors. However, the underlying genetic cause for the majority of patients with heritable forms of PHPT remains unknown. Distinction between sporadic and heritable forms of PHPT is useful in surgical planning for parathyroidectomy and has implications for the family. The genes currently known to be associated with heritable forms of PHPT account for approximately half of sporadic parathyroid tumors. But the genetic cause in approximately half of the sporadic parathyroid tumors remains unknown. Furthermore, there is no systemic therapy for parathyroid carcinoma, a rare but potentially fatal cause of PHPT. Improved understanding of the molecular characteristics of parathyroid tumors will allow us to identify biomarkers for diagnosis and novel targets for therapy.
Topics: Humans; Adult; Hyperparathyroidism, Primary; Parathyroid Neoplasms; Parathyroidectomy; Genetic Testing; Renal Insufficiency, Chronic
PubMed: 36961765
DOI: 10.1210/endrev/bnad009 -
Experimental & Molecular Medicine May 2023Genomic and transcriptomic profiling has enhanced the diagnostic and treatment options for many cancers. However, the molecular characteristics of parathyroid cancer...
Genomic and transcriptomic profiling has enhanced the diagnostic and treatment options for many cancers. However, the molecular characteristics of parathyroid cancer remain largely unexplored, thereby limiting the development of new therapeutic interventions. Herein, we conducted genomic and transcriptomic sequencing of 50 parathyroid tissues (12 carcinomas, 28 adenomas, and 10 normal tissues) to investigate the intrinsic and comparative molecular features of parathyroid carcinoma. We confirmed multiple two-hit mutation patterns in cell division cycle 73 (CDC73) that converged to biallelic inactivation, calling into question the presence of a second hit in other genes. In addition, allele-specific repression of CDC73 in copies with germline-truncating variants suggested selective pressure prior to tumorigenesis. Transcriptomic analysis identified upregulation of the expression of E2F targets, KRAS and TNF-alpha signaling, and epithelial-mesenchymal transition pathways in carcinomas compared to adenomas and normal tissues. A molecular classification model based on carcinoma-specific genes clearly separated carcinomas from adenomas and normal tissues, the clinical utility of which was demonstrated in two patients with uncertain malignant potential. A deeper analysis of gene expression and functional prediction suggested that Wilms tumor 1 (WT1) is a potential biomarker for CDC73-mutant parathyroid carcinoma, which was further validated through immunohistochemistry. Overall, our study revealed the genomic and transcriptomic profiles of parathyroid carcinoma and may help direct future precision diagnostic and therapeutic improvements.
Topics: Humans; Parathyroid Neoplasms; Transcriptome; Genomics; Carcinoma; Adenoma
PubMed: 37121965
DOI: 10.1038/s12276-023-00968-4 -
Clinical Oncology (Royal College of... Aug 2010Parathyroid carcinoma is a rare endocrine malignancy. The reported incidence is from 0.5 to 5% of primary hyperparathyroidism cases in various series. The cause is... (Review)
Review
Parathyroid carcinoma is a rare endocrine malignancy. The reported incidence is from 0.5 to 5% of primary hyperparathyroidism cases in various series. The cause is unknown, but clinical correlations with different genetic syndromes exist. Mutations in the HPRT2 gene seem to play a significant role in the pathogenesis of this disease. Men and women are equally affected, usually in the fourth or fifth decade of life. Most patients will present with signs and symptoms of hypercalcaemia. Cases of non-functioning carcinoma are exceedingly rare. Surgical resection is the most effective method of treatment and palliation. A significant proportion of patients will experience recurrence, and will need further surgical and, eventually, medical management of hypercalcaemia. The disease is progressive but slow growing. Most patients will require multiple operations to resect recurrent disease. The main cause of morbidity and mortality is the sequela of uncontrolled chronic hypercalcaemia rather than tumour burden. The current paper will review the epidemiology, pathogenesis, clinical presentation and diagnostic work-up of this disease. Surgical management in different scenarios is reviewed in detail, followed by other types of treatment and management of incurable disease.
Topics: Diagnosis, Differential; Female; Humans; Hypercalcemia; Hypoxanthine Phosphoribosyltransferase; Male; Middle Aged; Neoplasm Recurrence, Local; Parathyroid Neoplasms; Prognosis
PubMed: 20510594
DOI: 10.1016/j.clon.2010.04.007