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Surgical Pathology Clinics Dec 2019Proliferative pathologic lesions of parathyroid glands encompass a spectrum of entities ranging from benign hyperplastic processes to malignant neoplasia. This review... (Review)
Review
Proliferative pathologic lesions of parathyroid glands encompass a spectrum of entities ranging from benign hyperplastic processes to malignant neoplasia. This review article outlines the pathophysiologic classification of parathyroid disorders and describes histologic, immunohistochemical, and molecular features that can be assessed to render accurate diagnoses.
Topics: Adenoma; Humans; Hyperparathyroidism; Immunohistochemistry; Parathyroid Glands; Parathyroid Neoplasms
PubMed: 31672291
DOI: 10.1016/j.path.2019.08.006 -
British Journal of Hospital Medicine... Nov 2020Lithium is a mood stabiliser widely used in the treatment and prophylaxis of mania, bipolar disorders and recurrent depression. Treatment with lithium can give rise to... (Review)
Review
Lithium is a mood stabiliser widely used in the treatment and prophylaxis of mania, bipolar disorders and recurrent depression. Treatment with lithium can give rise to various endocrine and metabolic abnormalities, including thyroid dysfunction, nephrogenic diabetes insipidus and hypercalcaemia. Lithium may induce hypercalcaemia through both acute and chronic effects. The initial acute effects are potentially reversible and occur as a result of lithium's action on the calcium-sensing receptor pathway and glycogen synthase kinase 3, giving rise to a biochemical picture similar to that seen in familial hypocalciuric hypercalcaemia. In the long term, chronic lithium therapy leads to permanent changes within the parathyroid glands by either unmasking hyperparathyroidism in patients with a subclinical parathyroid adenoma or possibly by initiating multiglandular hyperparathyroidism. The latter biochemical picture is identical to that of primary hyperparathyroidism. Lithium-associated hyperparathyroidism, especially in patients on chronic lithium therapy, is associated with increased morbidity. Hence, regular monitoring of calcium levels in patients on lithium therapy is of paramount importance as early recognition of lithium-associated hyperparathyroidism can improve outcomes. This review focuses on the definition, pathophysiology, presentation, investigations and management of lithium-associated hyperparathyroidism.
Topics: Humans; Hypercalcemia; Hyperparathyroidism; Lithium; Parathyroid Glands; Parathyroid Neoplasms
PubMed: 33263481
DOI: 10.12968/hmed.2020.0457 -
Endocrine Pathology Mar 2022The 2022 WHO classification reflects increases in the knowledge of the underlying pathogenesis of parathyroid disease. In addition to the classic characteristic features... (Review)
Review
The 2022 WHO classification reflects increases in the knowledge of the underlying pathogenesis of parathyroid disease. In addition to the classic characteristic features of parathyroid neoplasms, subtleties in histologic features which may indicate an underlying genetic abnormality reflect increased understanding of the clinical manifestations, histologic, and genetic correlation in parathyroid disease. The importance of underlying genetic aberrancies is emphasized due to their significance to the care of the patient. Traditionally, the term "parathyroid hyperplasia" has been applied to multiglandular parathyroid disease; however, the concept of hyperplasia is generally no longer supported in the context of primary hyperparathyroidism since affected glands are usually composed of multiple "clonal" neoplastic proliferations. In light of these findings and management implications for patient care, the 2022 WHO classification endorses primary hyperparathyroidism-related multiglandular parathyroid disease (multiglandular multiple parathyroid adenomas) as a germline susceptibility-driven multiglandular parathyroid neoplasia. From such a perspective, pathologists can provide additional value to genetic triaging by recognizing morphological and immunohistochemical harbingers of MEN1, CDKN1B, MAX, and CDC73-related manifestations. In the current WHO classification, the term "parathyroid hyperplasia" is now used primarily in the setting of secondary hyperplasia which is most often caused by chronic renal failure. In addition to expansion in the histological features, including those that may be suggestive of an underlying genetic abnormality, there are additional nomenclature changes in the 2022 WHO classification reflecting increased understanding of the underlying pathogenesis of parathyroid disease. The new classification no longer endorses the use of "atypical parathyroid adenoma". This entity is now being replaced with the term of "atypical parathyroid tumor" to reflect a parathyroid neoplasm of uncertain malignant potential. The differential diagnoses of atypical parathyroid tumor are discussed along with the details of worrisome clinical and laboratory findings, and also features that define atypical histological and immunohistochemical findings to qualify for this diagnosis. The histological definition of parathyroid carcinoma still requires one of the following findings: (i) angioinvasion (vascular invasion) characterized by tumor invading through a vessel wall and associated thrombus, or intravascular tumor cells admixed with thrombus, (ii) lymphatic invasion, (iii) perineural (intraneural) invasion, (iv) local malignant invasion into adjacent anatomic structures, or (v) histologically/cytologically documented metastatic disease. In parathyroid carcinomas, the documentation of mitotic activity (e.g., mitoses per 10mm) and Ki67 labeling index is recommended. Furthermore, the importance of complete submission of parathyroidectomy specimens for microscopic examination, and the crucial role of multiple levels along with ancillary biomarkers have expanded the diagnostic workup of atypical parathyroid tumors and parathyroid carcinoma to ensure accurate characterization of parathyroid neoplasms. The concept of parafibromin deficiency has been expanded upon and term "parafibromin deficient parathyroid neoplasm" is applied to a parathyroid neoplasm showing complete absence of nuclear parafibromin immunoreactivity. Nucleolar loss is considered as abnormal finding that requires further molecular testing to confirm its biological significance. The 2022 WHO classification emphasizes the role of molecular immunohistochemistry in parathyroid disease. By adopting a question-answer framework, this review highlights advances in knowledge of histological features, ancillary studies, and associated genetic findings that increase the understanding of the underlying pathogenesis of parathyroid disease that are now reflected in the updated classification and new entities in the 2022 WHO classification.
Topics: Humans; Hyperparathyroidism, Primary; Parathyroid Glands; Parathyroid Neoplasms; Tumor Suppressor Proteins; World Health Organization
PubMed: 35175514
DOI: 10.1007/s12022-022-09709-1 -
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 -
Radiologic Clinics of North America Nov 2020Primary hyperparathyroidism (PHPT) is a common endocrine abnormality, caused in most cases by a single parathyroid adenoma. Surgery remains the first-line curative... (Review)
Review
Primary hyperparathyroidism (PHPT) is a common endocrine abnormality, caused in most cases by a single parathyroid adenoma. Surgery remains the first-line curative therapy in PHPT. Imaging plays a vital role in presurgical localization of parathyroid adenomas. Ultrasound provides a safe and quick imaging modality free of ionizing radiation, but is operator dependent. Sestamibi scan offers comparable sensitivity to ultrasound, improved with concurrent tomographic imaging. 4DCT remains a problem-solving technique in challenging cases and after failed neck exploration. We present an overview of various parathyroid imaging modalities, including protocols and findings, in addition to relevant pearls and pitfalls.
Topics: Diagnostic Imaging; Female; Humans; Hyperparathyroidism, Primary; Imaging, Three-Dimensional; Male; Parathyroid Glands; Parathyroid Neoplasms; Parathyroidectomy; Prognosis; Radiographic Image Enhancement; Radiopharmaceuticals; Tomography, X-Ray Computed; Treatment Outcome; Ultrasonography, Doppler
PubMed: 33040849
DOI: 10.1016/j.rcl.2020.07.006 -
Seminars in Nuclear Medicine Jul 2023Primary hyperparathyroidism (1° HPT) is a relatively common endocrine disorder usually caused by autonomous secretion of parathormone by one or several parathyroid... (Review)
Review
Primary hyperparathyroidism (1° HPT) is a relatively common endocrine disorder usually caused by autonomous secretion of parathormone by one or several parathyroid adenomas. 1° HPT causing hypercalcemia, kidney stones and/or osteoporosis should be treated whenever possible by parathyroidectomy. Accurate preoperative location of parathyroid adenomas is crucial for surgery planning, mostly when performing minimally invasive surgery. Cervical ultrasonography (US) is usually performed to localize parathyroid adenomas as a first intention, followed by Tc- sestamibi scintigraphy with SPECT/CT whenever possible. 4D-CT is a possible alternative to Tc- sestamibi scintigraphy. Recently, F-fluorocholine positron emission tomography/computed tomography (F-FCH PET/CT) has made its way in the clinics as it is the most sensitive method for parathyroid adenoma detection. It can eventually be combined to 4D-CT to increase its diagnostic performance, although this results in higher dose exposure to the patient. Other forms of hyperparathyroidism consist in secondary (2° HPT) and tertiary hyperparathyroidism (3° HPT). As parathyroidectomy is not usually part of the management of patients with 2° HPT, parathyroid imaging is not routinely performed in these patients. In patients with 3° HPT, total or subtotal parathyroidectomy is often performed. Localization of hyperfunctional glands is an important aid to surgery planning. As F-FCH PET/CT is the most sensitive modality in multigland disease, it is the preferred imaging technic in 3° HPT patients, although its cost and availability may limit its widespread use in this setting.
Topics: Humans; Positron Emission Tomography Computed Tomography; Parathyroid Neoplasms; Parathyroid Glands; Hyperparathyroidism; Technetium Tc 99m Sestamibi; Radiopharmaceuticals
PubMed: 36922339
DOI: 10.1053/j.semnuclmed.2023.02.004 -
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 -
Mayo Clinic Proceedings Nov 2022
Topics: Humans; Parathyroid Neoplasms; Adenoma, Oxyphilic; Adenoma
PubMed: 36333022
DOI: 10.1016/j.mayocp.2022.09.015 -
Academic Radiology May 2023
Topics: Humans; Parathyroid Neoplasms; Tomography, X-Ray Computed; Tomography, Emission-Computed, Single-Photon; Mass Screening; Technetium Tc 99m Sestamibi
PubMed: 36941157
DOI: 10.1016/j.acra.2023.02.021 -
Advances in Anatomic Pathology Jan 2023Hyperparathyroidism is a common endocrine disorder characterized by elevated levels of parathyroid hormone and hypercalcemia and is divided into 3 types: primary,... (Review)
Review
Hyperparathyroidism is a common endocrine disorder characterized by elevated levels of parathyroid hormone and hypercalcemia and is divided into 3 types: primary, secondary, and tertiary. Distinction between these types is accomplished by correlation of clinical, radiologic, and laboratory findings with pathologic features. Primary hyperparathyroidism occurs sporadically in 85% of cases with the remaining cases associated with multiple familial syndromes. The pathologic manifestations of primary hyperparathyroidism include parathyroid adenoma, parathyroid hyperplasia, and parathyroid carcinoma. Recent advances in the understanding of the pathogenesis of parathyroid disease has helped to refine the diagnosis and classification of parathyroid lesions. The identification of multiple clonal proliferations in traditional multiglandular parathyroid hyperplasia has led to the adoption by the World Health Organization (WHO) of the alternate term of primary hyperparathyroidism-related multiglandular parathyroid disease. Additional nomenclature changes include the adoption of the term atypical parathyroid tumor in lieu of atypical parathyroid adenoma to reflect the uncertain malignant potential of these neoplasms. Clinical and morphologic features characteristic of familial disease have been described that can help the practicing pathologist identify underlying familial disease and provide appropriate management. Use of ancillary immunohistochemistry and molecular studies can be helpful in classifying parathyroid neoplasms. Parafibromin has proven useful as a diagnostic and prognostic marker in atypical parathyroid tumors and parathyroid carcinomas. This review provides an update on the diagnosis and classification of parathyroid lesions considering the recent advances in the understanding of the molecular and clinical features of parathyroid disease and highlights the use of ancillary studies (immunohistochemical, and molecular) to refine the diagnosis of parathyroid lesions.
Topics: Humans; Hyperparathyroidism, Primary; Hyperplasia; Parathyroid Glands; Parathyroid Neoplasms; Adenoma
PubMed: 36315270
DOI: 10.1097/PAP.0000000000000379