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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 -
Frontiers in Endocrinology 2023We successfully developed a broad spectrum of patient-derived endocrine organoids (PDO) from benign and malignant neoplasms of thyroid, parathyroid, and adrenal glands....
INTRODUCTION
We successfully developed a broad spectrum of patient-derived endocrine organoids (PDO) from benign and malignant neoplasms of thyroid, parathyroid, and adrenal glands. In this study, we employed functionally intact parathyroid PDOs from benign parathyroid tissues to study primary hyperparathyroidism (PHPT), a common endocrine metabolic disease. As proof of concept, we examined the utility of parathyroid PDOs for bioenergetic and metabolic screening and assessed whether parathyroid PDO metabolism recapitulated matched PHPT tissues.
METHODS
Our study methods included a fine-needle aspiration (FNA)-based technique to establish parathyroid PDOs from human PHPT tissues (n=6) in semi-solid culture conditions for organoid formation, growth, and proliferation. Mass spectrometry metabolomic analysis of PHPT tissues and patient-matched PDOs, and live cell bioenergetic profiling of parathyroid PDOs with extracellular flux analyses, were performed. Functional analysis cryopreserved and re-cultured parathyroid PDOs for parathyroid hormone (PTH) secretion was performed using ELISA hormone assays.
RESULTS AND DISCUSSION
Our findings support both the feasibility of parathyroid PDOs for metabolic and bioenergetic profiling and reinforce metabolic recapitulation of PHPT tissues by patient-matched parathyroid PDOs. Cryopreserved parathyroid PDOs exhibited preserved, rapid, and sustained secretory function after thawing. In conclusion, successful utilization of parathyroid PDOs for metabolic profiling further affirms the feasibility of promising endocrine organoid platforms for future metabolic studies and broader multiplatform and translational applications for therapeutic advancements of parathyroid and other endocrine applications.
Topics: Humans; Parathyroid Glands; Biopsy, Fine-Needle; Thyroid Gland; Organoids
PubMed: 37492197
DOI: 10.3389/fendo.2023.1223312 -
Journal of Bone and Mineral Research :... Jul 2023Primary hyperparathyroidism is typically characterized by monoclonal parathyroid tumors that secrete an excessive amount of parathyroid hormone (PTH). However, the...
Primary hyperparathyroidism is typically characterized by monoclonal parathyroid tumors that secrete an excessive amount of parathyroid hormone (PTH). However, the underlying pathogenesis of tumorigenesis remains unclear. We performed single-cell transcriptomic analysis on five parathyroid adenoma (PA) and two parathyroid carcinoma (PC) samples. A total of 63,909 cells were divided into 11 different cell categories; endocrine cells accounted for the largest proportion of cells in both PA and PC, and patients with PC had larger populations of endocrine cells. Our results revealed significant heterogeneity in PA and PC. We identified cell cycle regulators that may play a critical role in the tumorigenesis of PC. Furthermore, we found that the tumor microenvironment in PC was immunosuppressive, and endothelial cells had the highest interactions with other cell types, such as fibroblast-musculature cells and endocrine cells. PC development may be stimulated by fibroblast-endothelial cell interactions. Our study clarifies the transcriptional signatures that underlie parathyroid tumors and offer a potential significant contribution in the study of pathogenesis of PC. © 2023 American Society for Bone and Mineral Research (ASBMR).
Topics: Humans; Parathyroid Neoplasms; Transcriptome; Endothelial Cells; Adenoma; Carcinogenesis; Tumor Microenvironment
PubMed: 37191193
DOI: 10.1002/jbmr.4824 -
Endocrine Sep 2023Parathyroid carcinoma (PC) is an extremely rare malignant tumor of the parathyroid glands, accounting for less than 1% of primary hyperparathyroidism, commonly... (Review)
Review
Parathyroid carcinoma (PC) is an extremely rare malignant tumor of the parathyroid glands, accounting for less than 1% of primary hyperparathyroidism, commonly characterized by severe and unmanageable hypercalcemia, aggressive behavior, high metastatic potential, and poor prognosis. PC manifests prevalently as a sporadic tumor and only occasionally it is part of congenital syndromic and non-syndromic endocrine diseases. Molecular pathogenesis of this form of parathyroid tumor is not fully elucidated and it appears to be caused by multiple genetic and epigenetic drivers, differing among affected patients and not yet clearly stated in distinguishing PC from the benign parathyroid adenoma (PA). Congenital forms of PC have been prevalently associated with germline heterozygous loss-of-function mutations of the CDC73 tumor suppressor gene, both in the context of the hyperparathyroidism jaw-tumor syndrome (HPT-JT) and of the isolated familial hyperparathyroidism (FIPH). Currently, surgical en bloc resection of affected gland(s) and other involved structures is the elective therapy for both primary and recurrent PC. However, it usually results ineffective for advance and metastatic disease, and a high percentage of post-operative recurrence is reported. Targeted medical therapies for surgically untreatable PC, based on the molecular profile of PC samples, are, therefore, needed. The characterization of genetic and epigenetic alterations and deregulated pathways in PC samples will be of fundamental importance to tailor treatment for each patient. Here, we reviewed main findings on molecular pathogenetic aspects of PC, and the current state of the art of therapies.
Topics: Humans; Parathyroid Neoplasms; Tumor Suppressor Proteins; Neoplasm Recurrence, Local; Jaw Neoplasms; Hyperparathyroidism, Primary
PubMed: 37160841
DOI: 10.1007/s12020-023-03376-w -
Histopathology Jan 2024Mediastinal tumours represent a heterogeneous group of entities derived from the manifold structures located in or adjacent to the mediastinum. Due to the occurrence of... (Review)
Review
Mediastinal tumours represent a heterogeneous group of entities derived from the manifold structures located in or adjacent to the mediastinum. Due to the occurrence of some of these tumours in characteristic mediastinal compartments, an anatomical subdivision of the mediastinum in the prevascular (anterior), visceral (middle), and paravertebral (posterior) is helpful for the differential diagnosis. Benign anterior mediastinal tumours linked to an enlargement of the thymic gland mainly consist of thymic cysts and several types of thymic hyperplasia: true thymic hyperplasia, rebound hyperplasia, lymphofollicular hyperplasia, and so-called thymic hyperplasia with lymphoepithelial sialadenitis (LESA)-like features. Mature teratomas, ectopic (para)thyroid tissue, and benign thymic tumours such as thymolipoma or thymofibrolipoma represent further typical tumours of the anterior mediastinum. Pericardial, bronchogenic, or oesophageal duplication cysts predominate in the middle mediastinum, whereas neurogenic tumours and myelolipomas are characteristic findings in the posterior compartment. Vascular tumours, lipomas, adenomatoid tumours, Castleman disease, or mediastinitis are further examples of less frequent tumours or tumorous lesions affecting the mediastinum. This review focuses on benign mediastinal lesions with an emphasis on benign tumours of the thymus. Besides histology, characteristic epidemiological and clinical aspects prerequisite for the correct diagnosis and patient management are discussed.
Topics: Humans; Mediastinum; Mediastinal Neoplasms; Thymus Hyperplasia; Hyperplasia; Thymus Neoplasms
PubMed: 37988262
DOI: 10.1111/his.15088