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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 -
TouchREVIEWS in Endocrinology Jul 2023Parathyroid carcinoma is a rare endocrine neoplasm that accounts for <1% of cases of primary hyperparathyroidism. The management of parathyroid carcinoma is a challenge... (Review)
Review
Parathyroid carcinoma is a rare endocrine neoplasm that accounts for <1% of cases of primary hyperparathyroidism. The management of parathyroid carcinoma is a challenge due to the high rate of local recurrence of the tumour. We report the case of a middle-aged north Indian woman who presented with recurrent primary hyperparathyroidism due to parathyroid carcinoma. She presented with a recurrent palpable hard neck mass and underwent radical dissection of the neck six times. At the time of writing this report, she was referred for external beam radiotherapy to the neck. Parathyroid carcinoma is a rare malignancy with an indolent but tenacious course. Complete resection at the time of initial surgery determines the prognosis of the neoplasm. Chemotherapy and radiotherapy are usually ineffective. Hypercalcaemia needs to be aggressively managed. A multidisciplinary team is required to effectively manage parathyroid carcinoma.
PubMed: 38046185
DOI: 10.17925/EE.2023.19.2.6 -
Frontiers in Endocrinology 2023
Topics: Humans; Hypercalcemia; Cinacalcet; Calcium; Neoplasms
PubMed: 37780626
DOI: 10.3389/fendo.2023.1281731 -
American Journal of Otolaryngology 2023Parathyroid carcinoma is rarely encountered in clinical practice. When faced with this clinical challenge, there is currently a paucity of evidence available for the... (Review)
Review
OBJECTIVE
Parathyroid carcinoma is rarely encountered in clinical practice. When faced with this clinical challenge, there is currently a paucity of evidence available for the optimal management of patients with parathyroid carcinoma. This systematic review synthesizes the available literature to evaluate the optimal management approach, thus providing guidance for future management.
METHODS
A systematic review was conducted according to PRISMA guidelines using Ovid MEDLINE, EMBASE, and PubMed databases for studies, published in English, reporting on parathyroid carcinoma. Full text of potentially eligible articles were reviewed by two authors independently and eligible studies selected. Treatment options and associated outcomes were evaluated. Descriptive statistics were used to describe pooled patient cohorts.
RESULTS
3203 articles were initially identified using the search criteria with 59 full-text articles then screened for eligibility. Seven articles, all retrospective studies, concerning 2307 patients (median 224/study). Parathyroidectomy alone was the most frequently utilised surgical approach across all studies, followed by en-bloc resection (with adjacent thyroid and/or nodal tissue). There was no difference in post-operative morbidity, mortality or survival between surgical approaches (p < 0.005). Patients who underwent either form of surgery had longer overall survival than those managed non-operatively (p < 0.005).
CONCLUSION
Surgical resection is the optimal treatment of parathyroid carcinoma. However there remains no consensus on the optimal extent of surgery, and as such future randomised prospective studies are necessary to evaluate the effects of different surgical approaches on morbidity, mortality and oncologic outcomes. Following resection, long-term surveillance with PTH is advised.
Topics: Humans; Parathyroid Neoplasms; Prospective Studies; Retrospective Studies
PubMed: 36989753
DOI: 10.1016/j.amjoto.2023.103843 -
Frontiers in Endocrinology 2023
Topics: Humans; Thyroid Neoplasms; Endocrinology
PubMed: 37484953
DOI: 10.3389/fendo.2023.1236887 -
Hormones (Athens, Greece) Mar 2024Primary hyperparathyroidism (PHPT), a relatively common disorder characterized by hypercalcemia with raised or inappropriately normal serum parathyroid hormone (PTH)... (Review)
Review
Primary hyperparathyroidism (PHPT), a relatively common disorder characterized by hypercalcemia with raised or inappropriately normal serum parathyroid hormone (PTH) concentrations, may occur as part of a hereditary syndromic disorder or as a non-syndromic disease. The associated syndromic disorders include multiple endocrine neoplasia types 1-5 (MEN1-5) and hyperparathyroidism with jaw tumor (HPT-JT) syndromes, and the non-syndromic forms include familial hypocalciuric hypercalcemia types 1-3 (FHH1-3), familial isolated hyperparathyroidism (FIHP), and neonatal severe hyperparathyroidism (NS-HPT). Such hereditary forms may occur in > 10% of patients with PHPT, and their recognition is important for implementation of gene-specific screening protocols and investigations for other associated tumors. Syndromic PHPT tends to be multifocal and multiglandular with most patients requiring parathyroidectomy with the aim of limiting end-organ damage associated with hypercalcemia, particularly osteoporosis, nephrolithiasis, and renal failure. Some patients with non-syndromic PHPT may have mutations of the MEN1 gene or the calcium-sensing receptor (CASR), whose loss of function mutations usually cause FHH1, a disorder associated with mild hypercalcemia and may follow a benign clinical course. Measurement of the urinary calcium-to-creatinine ratio clearance (UCCR) may help to distinguish patients with FHH from those with PHPT, as the majority of FHH patients have low urinary calcium excretion (UCCR < 0.01). Once genetic testing confirms a hereditary cause of PHPT, further genetic testing can be offered to the patients' relatives and subsequent screening can be carried out in these affected family members, which prevents inappropriate testing in normal individuals.
Topics: Infant, Newborn; Humans; Hyperparathyroidism, Primary; Calcium; Hypercalcemia; Adenoma; Fibroma; Hyperparathyroidism; Jaw Neoplasms
PubMed: 38038882
DOI: 10.1007/s42000-023-00508-9