Oxyphil Cells Research Articles

Near-infrared autofluorescence pattern in parathyroid gland adenoma

BackgroundParathyroid gland (PG) surgery is often challenging due to the small size and indistinct nature of these glands. The introduction of intraoperative near-infrared autofluorescence (NIRAF) has shown promise in localizing parathyroid tissue. However, the NIRAF features of parathyroid adenomas remain unclear. The aim of this study is to assess the NIRAF pattern of parathyroid adenomas.MethodsPatients who underwent surgery for primary hyperparathyroidism at the University Hospital of Pisa, Endocrine Surgery Unit, between December 2021 and February 2022 were enrolled in this study. Intraoperative NIRAF patterns of suspected parathyroid adenomas were evaluated, with particular attention given to the presence of a bright cap.ResultsA retrospective study was conducted on 11 patients with primary hyperparathyroidism who underwent parathyroidectomy at our institution. Histopathological examination of the 15 resected specimens confirmed 14 parathyroid adenomas (12 chief cell parathyroid adenomas, 1 oxyphil cell parathyroid adenoma, and 1 mixed cell parathyroid adenoma) and one schwannoma. All adenomas exhibited a heterogeneous NIRAF pattern, distinct from the homogeneous pattern observed in the schwannoma. A bright cap was identified in 9 out of 14 (64.3%) parathyroid adenomas (all chief cell adenomas). On the contrary, all 9 macroscopically normal PGs identified during surgery presented an homogeneous pattern.ConclusionOur findings support the integration of NIRAF into parathyroid surgical procedures. The heterogeneous NIRAF pattern observed in parathyroid adenomas, often accompanied by a bright cap, offers a promising intraoperative diagnostic tool to differentiate hyperfunctioning from normal parathyroid tissue. Larger-scale randomized trials are warranted to further validate these findings.

Correlation Between Near-Infrared Autofluorescence Properties and Sestamibi Uptakes of Parathyroid Glands in Primary Hyperparathyroidism.

Near-infrared autofluorescence (NIRAF) characteristics of parathyroid glands in primary hyperparathyroidism (pHPT) vary, with unclarity regarding the underlying mechanism. Similarly, 99mTc-sestamibi uptake in diseased parathyroid glands is variable. There is a suggestion that oxyphilic cell content may influence both imaging modalities. This study aims to analyze the relationship between NIRAF imaging characteristics, 99mTc-sestamibi uptake, and cellular composition in pHPT. Retrospective analysis of an Institutional Review Board-monitored prospective database. Single tertiary referral center. NIRAF characteristics of parathyroid glands of patients with pHPT between 2019 and 2024 were compared with 99mTc-sestamibi scan findings from a prospective database. Using third-party software, brightness intensity and heterogeneity index (HI) of the glands were calculated. A subgroup of parathyroid glands obtained from consecutive patients with pHPT in 2020 to 2021 underwent histological analysis. A total of 428 patients with 638 diseased parathyroid glands were analyzed. Forty-seven percent of the glands showed an uptake on 99mTc-sestamibi scans. The brightness intensity of the NIRAF signals from parathyroid glands that were seen versus not seen on sestamibi was 2.1 versus 2.3 (P = .002) and HI 0.18 versus 0.17 (P = .35), respectively. On multivariate analysis, low autofluorescence intensity, high gland volume, and single adenoma were associated with detectability on 99mTc-sestamibi scan (P < .0001). Intraglandular adipose tissue content was lower in diseased glands that were detected on 99mTc-sestamibi scans (0% vs 5%, P < .0001). Our findings indicate an inverse relationship between autofluorescence intensity and detectability on 99mTc-sestamibi scans and a lack of correlation between different cell types and autofluorescence properties.

Single-cell analysis reveals transcriptional dynamics in healthy primary parathyroid tissue.

Studies on human parathyroids are generally limited to hyperfunctioning glands owing to the difficulty in obtaining normal human tissue. We therefore obtained non-human primate (NHP) parathyroids to provide a suitable alternative for sequencing that would bear a close semblance to human organs. Single-cell RNA expression analysis of parathyroids from four healthy adult M. mulatta reveals a continuous trajectory of epithelial cell states. Pseudotime analysis based on transcriptomic signatures suggests a progression from GCM2 hi progenitors to mature parathyroid hormone (PTH)-expressing epithelial cells with increasing core mitochondrial transcript abundance along pseudotime. We sequenced, as a comparator, four histologically characterized hyperfunctioning human parathyroids with varying oxyphil and chief cell abundance and leveraged advanced computational techniques to highlight similarities and differences from non-human primate parathyroid expression dynamics. Predicted cell-cell communication analysis reveals abundant endothelial cell interactions in the parathyroid cell microenvironment in both human and NHP parathyroid glands. We show abundant RARRES2 transcripts in both human adenoma and normal primate parathyroid cells and use coimmunostaining to reveal high levels of RARRES2 protein (also known as chemerin) in PTH-expressing cells, which could indicate that RARRES2 plays an unrecognized role in parathyroid endocrine function. The data obtained are the first single-cell RNA transcriptome to characterize nondiseased parathyroid cell signatures and to show a transcriptomic progression of cell states within normal parathyroid glands, which can be used to better understand parathyroid cell biology.

Sporadic Parathyroid Adenoma: A Pilot Study of Novel Biomarkers in Females.

Background and Objectives: Parathyroid adenoma is a distinct cause of primary hyperparathyroidism, with the vast majority being sporadic ones. Proteomic analysis of parathyroid adenomas has proposed a large number of related proteins. The aim of this study is to evaluate the immunohistochemical staining of ANXA2, MED12, MAPK1 and VDR in parathyroid adenoma tissue. Materials and Methods: Fifty-one parathyroid adenomas were analyzed for ANXA2, MED12, MAPK1 and VDR expressions. Tissue was extracted from formalin-fixed paraffin-embedded parathyroid adenoma specimens; an immunohistochemical study was applied, and the percentage of allocation and intensity were evaluated. Results: ANXA2 stained positively in 60.8% of all cell types, while MED12 had positive staining in 66%. MAPK1 expression was found to be negative in total, although a specific pattern for oxyphil cells was observed, as they stained positive in 17.7%. Finally, VDR staining was positive at 22.8%, based on nuclear staining. Conclusions: These immunohistochemical results could be utilized as biomarkers for the diagnosis of sporadic parathyroid adenoma. It is of great importance that a distinct immunophenotype of nodule-forming cells in a positive adenoma could suggest a specific pattern of adenoma development, as in hereditary patterns.

TRPC3 Is Downregulated in Primary Hyperparathyroidism.

Transient receptor potential canonical sub-family channel 3 (TRPC3) is considered to play a critical role in calcium homeostasis. However, there are no established findings in this respect with regard to TRPC6. Although the parathyroid gland is a crucial organ in calcium household regulation, little is known about the protein distribution of TRPC channels-especially TRPC3 and TRPC6-in this organ. Our aim was therefore to investigate the protein expression profile of TRPC3 and TRPC6 in healthy and diseased human parathyroid glands. Surgery samples from patients with healthy parathyroid glands and from patients suffering from primary hyperparathyroidism (pHPT) were investigated by immunohistochemistry using knockout-validated antibodies against TRPC3 and TRPC6. A software-based analysis similar to an H-score was performed. For the first time, to our knowledge, TRPC3 and TRPC6 protein expression is described here in the parathyroid glands. It is found in both chief and oxyphilic cells. Furthermore, the TRPC3 staining score in diseased tissue (pHPT) was statistically significantly lower than that in healthy tissue. In conclusion, TRPC3 and TRPC6 proteins are expressed in the human parathyroid gland. Furthermore, there is strong evidence indicating that TRPC3 plays a role in pHPT and subsequently in parathyroid hormone secretion regulation. These findings ultimately require further research in order to not only confirm our results but also to further investigate the relevance of these channels and, in particular, that of TRPC3 in the aforementioned physiological functions and pathophysiological conditions.

Advancing parathyroid anatomy understanding through single-cell RNA sequencing in uremic secondary hyperparathyroidism

This commentary explores the recent application of single-cell RNA sequencing in the study of uremic secondary hyperparathyroidism, shedding light on the cellular dynamics within parathyroid glands. The use of single-cell RNA sequencing reveals new insights into the differentiation processes of chief and oxyphil cells, challenging traditional views and highlighting the potential of this technology in advancing our understanding of parathyroid anatomy.

Single-cell RNA sequencing reveals transdifferentiation of parathyroid chief cells into oxyphil cells in patients with uremic secondary hyperparathyroidism

The parathyroid gland is one of the main organs that regulate calcium and phosphorus metabolism. It is mainly composed of chief cells and oxyphil cells. Oxyphil cell counts are low in the parathyroid glands of healthy adults but are dramatically increased in patients with uremia and secondary hyperparathyroidism (SHPT). Increased oxyphil cell counts are related to drug treatment resistance, but the origin of oxyphil cells and the mechanism of proliferation remain unknown. Herein, three types of parathyroid nodules (chief cell nodules, oxyphil cell nodules and mixed nodules, respectively) excised from parathyroid glands of uremic SHPT patients were used for single-cell RNA sequencing (scRNA-seq), other molecular biology studies, and transplantation into nude mice. Through scRNA-seq of parathyroid mixed nodules from three patients with uremic SHPT, we established the first transcriptomic map of the human parathyroid and found a chief-to-oxyphil cell transdifferentiation characterized by gradual mitochondrial enrichment associated with the uremic milieu. Notably, the mitochondrial enrichment and cellular proliferation of chief cell and oxyphil cell nodules decreased significantly after leaving the uremic milieu via transplantation into nude mice. Remarkably, the phenotype of oxyphil cell nodules improved significantly in the nude mice as characterized by decreased mitochondrial content and the proportion of oxyphil cells to chief cells. Thus, our study provides a comprehensive single-cell transcriptome atlas of the human parathyroid and elucidates the origin of parathyroid oxyphil cells and their underlying transdifferentiating mechanism. These findings enhance our understanding of parathyroid disease and may open new treatment perspectives for patients with chronic kidney disease.

Experimental rat models for Hashimoto's thyroiditis.

Hashimoto's thyroiditis (HT) is an autoimmune thyroid disease characterized by T lymphocyte-mediated destruction of thyroid follicles. To study the pathogenesis of HT and the efficacy of new substances for its treatment, an easily obtained and adequate to the human disease experimental model is needed. The aim of our study was to find out whether it is possible to induce experimental autoimmune thyroiditis (EAT) similar to Hashimoto's thyroiditis by injecting with thyroglobulin (Tg) without using agents that enhance its thyroiditogenicity and without taking into account the genetic sensitivity of animals. Wistar rats were immunized with freshly isolated rat Tg or porcine Tg. In 8weeks, histological studies of the thyroid and parathyroid glands were performed. Thyroid function and total serum calcium level were also evaluated. Immunization with both rat and porcine freshly isolated Tg caused T lymphocytic infiltration of the thyroid gland, thyroid follicle atrophy and degradation in Wistar rats. EAT caused by porcine Tg was characterized by greater severity than EAT induced with rat Tg. In 55% of rats with porcine Tg-induced EAT, oxyphilic metaplasia was detected in the parathyroid glands. In addition, low total serum calcium was observed in these rats. Two rat models of autoimmune thyroiditis were obtained. EAT caused in Wistar rats by immunization with rat Tg is similar to Hashimoto's thyroiditis. EAT induced with porcine Tg was accompanied by oxyphil cell metaplasia in the parathyroids and hypocalcemia.

Are 99mTC-Sestamibi Single Photon Emission Computed Tomography Scan Results Associated to the Parathyroid Cell Type in Primary Hyperparathyroidism?

Introduction99mTC-sestamibi scintigraphy (SPECT-CT) is a common imaging modality for parathyroid localization in primary hyperparathyroidism (PHPT). Prior studies have suggested that the cellular composition of parathyroid adenomas influences SPECT-CT imaging results. Other biochemical and anatomical factors may also play a role in false negative results. Therefore, after controlling for confounding variables, we sought to determine whether the histologic composition of parathyroid adenomas is associated to SPECT-CT results in patients with single gland disease causing PHPT. MethodsA retrospective review of patients with PHPT due to confirmed single gland disease was performed over a 2-y period. A 1:1 propensity score matching was done between patients with positive and negative SPECT-CT results with regard to demographical, biochemical, and anatomical characteristics followed by blinded pathologic examination of cell composition in the matched pairs. ResultsFive hundred forty two patients underwent routine four gland exploration and 287 (53%) patients were found to have a single adenoma. Of those, 26% had a negative SPECT-CT result. There were significant differences between groups with regards to biochemical profile, gland location, and gland size. All of which became nonsignificant after propensity score matching. Adenomas were primarily composed of chief cells, with no difference between groups (95% versus 97%, P = 0.30). In the positive SPECT-CT group, chief cells were the dominant cell type in 68% of the cases, followed by mixed type (13%), oxyphil cells (12%), and clear cells (7%). This was similar to the negative SPECT-CT group (P = 0.22). ConclusionsWhile certain patient’s clinical characteristics are associated with SPECT-CT imaging results, histologic cell type is not significantly associated.

SAT193 Double Trouble: A Case of Ipsilateral Double Parathyroid Adenoma

Abstract Disclosure: J.P. Suelto: None. G.D. Wassmer: None. Background: Eighty percent of the cases of Primary Hyperparathyroidism is caused by a single adenoma and only about 15% are multiglandular adenoma. Parathyroid imaging like Sestamibi is less sensitive in detecting multiglandular disease. Clinical Case: A 63 year-old female presented with intermittent left lower back pain for 7 years. There was no joint pain, weakness, urinary symptoms, constipation and abdominal pain. In 2019, due to persistence of left back pain, abdominal ultrasound done showed a right non-obstructing nephrolithiasis. Ionized and total calcium were elevated at 1.53 meq/L (NV 1.12-1.32 meq/L) and 11.35 ng/dl (NV 8.42-10.23 ng/dl) respectively with normal creatinine, phosphorus and albumin. PTH was elevated at 116.6 pg/ml (NV 10-65 pg/ml). Primary Hyperparathyroidism probably secondary to parathyroid adenoma was considered. Thyroid ultrasound showed right thyroid cyst but no enlarged parathyroid gland. Parathyroid imaging using Dual Isotope Subtraction Method neither showed evidence of adenoma. Patient was advised parathyroidectomy but did not consent hence started on Cinacalcet. In 2021, ionized calcium was still elevated to 1.58 meq/L with elevated PTH 151 pg/ml and low Vitamin D level 22.76 ng/ml (&amp;gt;30 ng/mL). Patient was given Vitamin D3 2000 IU daily and Cinacalcet was up-titrated to 60mg daily. Sestamibi/SPECT CT showed faint focus of radioactivity in the right thyroidal bed area suspicious for parathyroid adenoma or hyperplasia. She then agreed to have parathyroidectomy. There was no decrease in PTH after removal of the right inferior parathyroid gland (measuring 1.8x0.6x0.6cm, weighs 500mg), hence re-exploration was done. It was only after the removal of the right superior parathyroid gland (measuring 2.8x0.9x0.7cm, weighs 1 gram) when the 5 and 10 minute post excision PTH decreased to 123.91 and 76.01 pg/ml respectively from preincision PTH of 407.19 pg/ml. Histopathology showed Parathyroid adenoma of right inferior and superior parathyroid glands. No further evidence of hypercalcemia was noted at 6-month follow-up. Conclusion: Double adenoma is reported in 2% to 12% of patients with primary hyperparathyroidism. This occurs predominantly as bilateral superior in 45% and on same side of the neck in 18%. Sestamibi scanning is poor in the presence of multiglandular disease. It was observed that the presence of oxyphil cells may cause longer sestamibi retention in parathyroid tissues. Given the same amount of oxyphil cells in ipsilateral adenomas, the tracer may be distributed hence faintly seen on imaging. Addition of SPECT/CT/4D CT may improve the anatomical localization. Another reason for false negative imaging in this patient can be due to use of Cinacalcet which may decrease scintigraphy uptake of parathyroid adenoma. The combination of preoperative imaging localization and intraoperative PTH monitoring permits successful surgical outcome. Presentation: Saturday, June 17, 2023

THU396 Digital Spatial Profiling Of Human Parathyroid Tumors Reveals Distinct Cellular And Molecular Alterations Linked To Vitamin D Deficiency

Abstract Disclosure: C. Tu: None. W. Chang: None. J.A. Sosa: Advisory Board Member; Self; Novo Nordisk, AstraZeneca, Eli Lilly &amp; Company. Grant Recipient; Self; Exelixis, Inc., Eli Lilly &amp; Company. J. Koh: None. Primary hyperparathyroidism (PHPT) is a common endocrine neoplastic disorder characterized by disrupted calcium homeostasis secondary to inappropriately elevated parathyroid hormone (PTH) secretion. Low levels of serum 25-hydroxyvitamin D (25OHD) are significantly more prevalent in PHPT patients than in the general population, but the pathophysiological basis for this association remains unclear. We employed a spatially defined in situ whole-transcriptomics and selective proteomics profiling approach to compare gene expression patterns and cellular composition in parathyroid adenomas from 9 vitamin D-deficient or 34 vitamin D-replete PHPT patients with 12 eucalcemic cadaveric donor parathyroid glands as normal tissue controls. Parathyroid oxyphil cell content is markedly higher in tumors from vitamin D-deficient PHPT patients (Def-Ts) relative to tumors from vitamin D-replete PHPT patients (Rep-Ts) (47.8% vs 17.8%, respectively; p &amp;lt;0.0001) and normal donor parathyroid glands (7.7%). Def-Ts display increased expression of genes encoding electron transport chain (corr. coefficient=0.546), proteasomal catabolism (corr. coefficient=0.587), and oxidative phosphorylation (corr. coefficient=0.982) pathway components. In contrast, Rep-Ts are characterized by upregulation of the ras (corr. coefficient=0.632) and myc (corr. coefficient=0.811) signaling pathways, suggestive of an oncogene-driven etiology. Parathyroid oxyphil cells are comparable to chief cells at the transcriptional level, and vitamin D-status is reflected in the transcriptional profiles of both cell types in a similar manner. Among PHPT patients who did not present as vitamin D deficient, three distinct tumor transcriptional profile clusters showed a dose-dependent relationship to pre-operative 25OHD levels (p &amp;lt;0.0001 by ANOVA). Relative to normal tissue, the abundance of calcium sensing receptor (CaSR) protein is reduced in Def-Ts (mean protein count 253.6 vs 492.3, respectively; p=0.039 for difference), while the type B γ-aminobutyric acid receptor 1 (GABAB1R) is increased (mean protein count 114.5 vs 64.65, respectively; p=0.0099 for difference). These expression changes resulted in a vitamin D dose-dependent reduction in the ratio of CaSR to GABAB1R receptors in Def-T tumor cells (r2 = 0.218, p&amp;lt;0.0001), favoring the formation of calcium sensing-attenuated CaSR:GABAB1R heteromers. The abundance of the amyloid precursor protein (APP) peptide derivative Aβ1-42, a putative GABAB1R ligand, is preferentially increased in Def-Ts compared to normal tissue (mean protein count 5797 vs 4500, respectively; p=0.0318). Collectively, these findings suggest a novel mechanism where chronic vitamin D deficiency can contribute to tonic PTH hypersecretion in PHPT patients by increasing GABAB1R-mediated antagonism of CaSR activity in parathyroid adenomas. Presentation: Thursday, June 15, 2023

Spontaneous necrosis of parathyroid adenoma: clinical observation

Fine needle aspiration biopsy is a routinely used technique to determine the nature of thyroid and parathyroid nodules. The complications and side effects associated with this procedure are minimal. At the same time, the histological alterations resulting from its use are well documented. Their range is quite w, however, from a clinical point of view, the most striking and catastrophic in their consequences are extensive heart attacks and necrosis. Such changes more often than in formations of a different morphological nature occur in tumors from oxyphilic cells. It should be noted that a lot of works devoted to post-biopsy changes are naturally focused on the morphological aspects of this problem, or are presented in the form of a presentation of individual clinical observations.This report presents the observation of necrosis in the parathyroid adenoma, which developed before fine needle aspiration biopsy.

Why does diseased parathyroid appear weak or heterogenous intensity during intraoperative near-infrared autofluorescence?

During intraoperative autofluorescence, the imaging intensity of diseased parathyroid glands is often lower than that of normal parathyroid glands, and some diseased glands especially those in secondary hyperparathyroidism (HPT) show heterogeneous intensities. This study aimed to investigate the reasons for these findings. After formalin and paraffin fixation and bivalve cutting, 18 diseased glands from patients with primary HPT, 35 diseased parathyroid glands from patients with uremic HPT, and the surrounding thyroid and thymus tissues were measured using near-infrared autofluorescence with a Fluorobeam imaging system (Fluoptics, France). None of the tissues were stained with indocyanine green. Hematoxylin and eosin staining matched the intensity of the autofluorescence. Using the bright white intensity of the adult normal parathyroid gland as a reference (index score of 2), the chief cells and oxyphilic cell tissues of the diseased parathyroid had the same intensity score of 2 as that of the normal parathyroid gland, and the clear water parathyroid cell had a weaker intensity score (1-1.5). Their glandular architecture, including the trabecular, follicular, or solid arrangements, did not affect the level of intensity. The thymus, thyroid, fat, fibrosis, and necrosis had very low intensities (scores of 0). The red blood cell-hemorrhage appeared dark black (intensity score -1). The thickness of the fibrotic capsule varied in the diseased parathyroid glands; however, only a very thin capsule was observed in the normal parathyroid glands. Various degrees of fibrotic capsules in the diseased parathyroid gland may be the main factor contributing to the lower intensity during autofluorescence, and different cell types, necrosis, fibrosis, and hemorrhage may explain the appearance of heterogeneous intensity in the diseased parathyroid glands.

Abstract #1398160: A Rare Case of Water Clear Cell Parathyroid Adenoma Escaping Sestamibi Scan and Neck Ultrasound – A Diagnostic Conundrum of a Rare Pathological Intity with a Rare Presentation

Parathyroid water-clear cell hyperplasia (WCCH) and water-clear cell adenoma (WCCA) are extremely rare causes of primary hyperparathyroidism (PHPT). WCCH contributes to < 1% of all PHPT however WCCA is exceptionally rare and has been reported only in less than 30 case reports. We are presenting a very rare indolent pathological entity with a very rare presentation escaping common diagnostic measures of Sestamibi scan and neck ultrasound. A 63-year-old female presented for evaluation of severe osteoporosis with a T-score of -3.6. Laboratory workup revealed elevated parathyroid hormone (PTH) of 122 pg/ml (reference range 12-88 pg/ml), Normal calcium 9.8 mg/dl, Normal vitamin D 50 ng/ml, and normal magnesium 2.2 mg/dl. 24-hour urine calcium was 421 mg/24H. Diagnosis was consistent with normocalcemic PHPT and meeting surgical criteria with osteoporosis and high urine calcium. Sestamibi scan did not identify any focal activity. CT H&N revealed an 8 mm mass inferior and posterior to right thyroid lobe with partial washout and slightly different enhancement compared to thyroid gland. Neck ultrasound (US) reported that previously noted tissue activity on the CT H&N is not visualized and most likely represents normal thyroid tissue. Patient was referred to otolaryngology surgery and underwent four gland explorations, including right inferior and left superior parathyroidectomy. Pathology of superior parathyroid gland revealed parathyroid water clear cell adenoma. 3-month Postoperative PTH 29.4 pg/ml and calcium level of 9.3 mg/dl. Solitary parathyroid adenoma (SPA) attributes to 80-85% of PHPT. Majority of cases is due to Chief cell adenomas, less frequent pathologies include oxyphil cell adenoma, lipoadenoma, WCCA or mixed type. Scientific literature regarding WCCA presentation and diagnosis is blurred due to its rarity. Clinical presentation of WCCA resembles other etiologies of PHPT, though some data suggest that is frequently indolent and manifests with mild PHPT. Literature suggests that WCCA has low biochemical activity and most cases had normal to mildly elevated calcium-our patient support this hypothesis-. Hypercalcemia does not manifest until significant growth of the adenoma, though few reported cases manifested with hypercalcemia. Unlike other SPA where Sestamibi scan sensitivity is 91%, literature suggests possibility of false-negative results with WCCA which is hypothesized to be attributed to its different histology of glycogen-rich vacuolized cytoplasm that leads to fast Sestamibi wash-out, for the same reason data suggest that US is more decisive given high water content of cells -Our patient didn’t follow this rule and escaped Sistamibi and US though seen on CT- which still makes the diagnosis of WCCA a conundrum. Some cases underwent surgical excision based on clinical diagnosis which led to revision of PHPT and/or hypercalcemia. There is no available data suggesting different long-term follow-up regimens for WCCA compared to other SPA. Further literature with longer follow-up is needed for this extremely rare entity for a comprehensive understanding of its natural course.

Single-cell RNA sequencing reveals the role of cell heterogeneity in the sex difference in primary hyperparathyroidism.

To explore the difference in parathyroid tissue-derived cells between male and female PHPT patients. Resected parathyroid tissues were collected from PHPT patients of both sexes. Single cells were isolated and sequenced for RNA expression profiles. The cell sequencing data were annotated by cell type, followed by population analysis, functional analysis, pathway analysis, cell communication analysis, differential gene expression analysis, and pseudotime trajectory analysis. The subcluster analyses were also performed in the parathyroid cells. No substantial difference in the cell population, function, or communication is found between the two sexes. The interferon-a response, oxidative phosphorylation, and reactive oxygen species pathways are up-regulated in females than in male patients, mainly contributed by fibroblast cells, endothelial cells, parathyroid cells, and myeloid cells, which also have significantly more up-regulated pathways and cellular interactions than the other three cell types. The subcluster analysis of parathyroid cells identified five subpopulations: SPARCL1-OC and ISG15-OC are predominant in females, while more S100A13-PCC and PTHLH-OC are found in males. The cellular functions are also elevated in females compared with males. Cells from female patients show a higher expression level of parathyroid hormone (PTH) but a lower expression level of parathyroid hormone-like hormone (PTHLH). The cell pseudotime trajectory and pathway analyses show that the oxyphil cells may be more mature and functionally active than the chief cells in both sexes. These findings suggest that the sex difference in PHPT may be caused by the differentially expressed genes and activated pathways in different cell types in the parathyroid tissue. The heterogeneity of parathyroid cell subpopulations, especially in oxyphil cells, may be associated with the sex differences in PHPT pathogenesis.

Digital spatial profiling of human parathyroid tumors reveals cellular and molecular alterations linked to vitamin D deficiency.

Primary hyperparathyroidism (PHPT) is a common endocrine neoplastic disorder characterized by disrupted calcium homeostasis secondary to inappropriately elevated parathyroid hormone (PTH) secretion. Low levels of serum 25-hydroxyvitamin D (25OHD) are significantly more prevalent in PHPT patients than in the general population (1-3), but the basis for this association remains unclear. We employed a spatially defined in situ whole-transcriptomics and selective proteomics profiling approach to compare gene expression patterns and cellular composition in parathyroid adenomas from vitamin D-deficient or vitamin D-replete PHPT patients. A cross-sectional panel of eucalcemic cadaveric donor parathyroid glands was examined in parallel as normal tissue controls. Here, we report that parathyroid tumors from vitamin D-deficient PHPT patients (Def-Ts) are intrinsically different from those of vitamin D-replete patients (Rep-Ts) of similar age and preoperative clinical presentation. The parathyroid oxyphil cell content is markedly higher in Def-Ts (47.8%) relative to Rep-Ts (17.8%) and normal donor glands (7.7%). Vitamin D deficiency is associated with increased expression of electron transport chain and oxidative phosphorylation pathway components. Parathyroid oxyphil cells, while morphologically distinct, are comparable to chief cells at the transcriptional level, and vitamin D deficiency affects the transcriptional profiles of both cell types in a similar manner. These data suggest that oxyphil cells are derived from chief cells and imply that their increased abundance may be induced by low vitamin D status. Gene set enrichment analysis reveals that pathways altered in Def-Ts are distinct from Rep-Ts, suggesting alternative tumor etiologies in these groups. Increased oxyphil content may thus be a morphological indicator of tumor-predisposing cellular stress.

A case of thyroid oxyphilic cell follicular carcinoma followed-up by fine needle aspiration cytology

A case of thyroid oxyphilic cell follicular carcinoma followed-up by fine needle aspiration cytology

ODP098 Hyperparathyroidism Caused by Two Large Water Clear Cell Adenomas

Abstract Background In ambulatory settings, primary hyperparathyroidism is the most prevalent cause of hypercalcemia. Approximately 85% of primary hyperparathyroidism cases are caused by a solitary parathyroid adenoma; other causes include diffuse parathyroid hyperplasia, multiple parathyroid adenomas, and parathyroid cancer. Chief cell adenomas are the most prevalent; adenomas can also consist of oxyphil cell adenomas, lipoadenomas, or mixed cell adenomas. Water clear cell adenoma (WCCA) is a rare tumor formed of large clear cells with foamy pink cytoplasm. Fewer than 30 cases have been recorded in the literature. Case A 52-year-old male with polyuria and polydipsia, diagnosed with hypercalcemia was referred to an endocrinologist. His calcium was 10.9 mg/dl, corresponding parathyroid hormone (PTH) 74 pg/ml, 24-hour urine calcium 818 mg/24hr, vitamin D 25–hydroxy 24.2 ng/ml. He was referred to an endocrine surgeon. A 4-dimensional CT scan revealed soft tissue masses posterior to the thyroid and in the tracheoesophageal groove, consistent with potential parathyroid masses. In the operating room, baseline intraoperative PTH (ioPTH) was 371 pg/ml. A large left superior gland was removed from its normal position, and the ioPTH dropped to 104 pg/ml at 10 minutes post-resection, followed by a rise to 525 pg/ml. A large descended (ectopic) right superior gland was then identified and resected, and the ioPTH decreased to 72, 44, and 57 pg/ml at 10, 15 and 20 minutes post-resection. The remaining parathyroid glands were not identified due to adipose tissue in the neck and likely gland suppression in the setting of high PTH. The pathology report of the two excised glands (left superior 3.2×1.7×0.5cm and 3.703g, right superior 3.4×1.3×0.4cm and 1.86g) demonstrated water clear cell tissue. Post-operatively, patient's polyuria and polydipsia resolved. Labs collected 3 months after surgery demonstrated normalization of the calcium and PTH. The patient was advised to continue follow up every six months. Conclusion Water clear cell parathyroid adenomas are extremely rare. Water clear-cell lesions are considered indolent because excised adenomas are markedly larger than conventional adenomas and grow to a considerable size before becoming biochemically active and diagnosed. Clinical presentation of water clear cell parathyroid lesion is like other causes of primary hyperparathyroidism. The only way to diagnose is via histopathological examination. In rare cases, clear cell renal carcinoma can metastasize to the parathyroid gland causing a similar presentation. Additionally, the rate of hypercalcemia recurrence is higher in WCCA as compared to chief cell adenoma. Therefore, closer follow up of these patients is recommended. Reporting additional cases will aid in our understanding of this uncommon entity, elucidating possible causes/associations, natural history, typical appearances, and post-treatment prognosis. Presentation: No date and time listed

Integrated transcriptomic and proteomic analyses for the characterization of parathyroid oxyphil cells in uremic patients.

Chief cells are the predominant cells in parathyroid glands of healthy adults; however, parathyroid oxyphil cells, whose function is unknown, increase dramatically in patients with secondary hyperparathyroidism (SHPT). Calcitriol and calcimimetics are the most powerful treatments for SHPT, while the mechanisms leading to calcitriol or calcimimetic resistance in oxyphil cell-predominant SHPT are unknown. Here we used transcriptomic and proteomic techniques to characterize oxyphil cells by comparing the differences between chief and oxyphil cell nodules of parathyroid glands in uremic patients. Compared to chief cell nodules, the most marked expression increases in oxyphil cell nodules were for mitochondrion-associated proteins. The mitochondria number and mitochondrial DNA content were also significantly increased in oxyphil cell nodules. Moreover, oxyphil cell nodules expressed parathyroid-specific factors, and exhibited lower levels of proliferation-related proteins but higher synthesis and secretion level of parathyroid hormone (PTH). The protein expression of SHPT-regulating factors, including vitamin-D receptor, calcium-sensing receptor and Klotho, were significantly downregulated in oxyphil cell nodules. Therefore, oxyphil cells characterized by enrich mitochondria in uremic patients showed higher synthesis and secretion of PTH but lower expression of SHPT regulators than chief cells, which may contribute to the pathophysiology of SHPT and the treatment resistance to calcitriol and calcimimetics.

Involvement of Parathyroid Gland in COVID-19

<strong>Introduction:</strong> Parathyroid glands are yellow brown, small and soft. Typically four parathyroids are present in posterior surface of thyroid. Parathyroid’s numeral, size and site is inconstant. Corona virus disease-19(COVID-19) is a major problem all over world and aim of this study is to discuss possible involvement of parathyroid in COVID-19.<strong></strong> <strong><br /></strong> <strong>Materials and methods:</strong> The previous studies were used for this review study.<strong></strong> <strong><br /></strong> <strong>Results and discussions:</strong> The COVID-19 mainly causes pulmonary injury and respiratory failure. Virus was chiefly detected in respiratory pathway, gastrointestinal tract, sweat gland, pituitary, pancreas, adrenal, renal, parathyroid, liver and cerebrum. Nearly 65% of COVID-19 patients had hypocalcaemia. Advanced age and hypocalcaemia were bad prognostic factors for COVID-19 patients. Hypocalcaemia might be due to vitamin-D deficit, decreased bowel absorption of calcium, diminished secretion or response to parathyroid hormone (PTH). The PTH rises serum calcium by discharge calcium by osteoclastic activity, calcium reabsortion in nephron. Vitamin-D encourage reabsorption of dietary calcium. Thus inadequate Vitamin-D excites parathyrood to discharge more PTH. Normal and abnormal parathyroids are identified by their size, form, consistency and histological judgments. There was association between size of parathyroid and PTH level. Glands of black populations were longer than white groups. Larger parathyroid secrets more PTH and might has greater number of chief cells. Microscopically quantity of fatty tissues and oxyphil cells rise in elders. Both transitional and oxyphil cells secrets PTH to extensive parathyroid stimulation.<strong></strong> <strong><br /></strong> <strong>Conclusion:</strong> Size of all parathyroids, patient’s age, oxyphil cells amount, ethnicity, amount of PTH and Vitamin-D determines the serum calcium level in COVID-19.