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Biomedical Optics Express Feb 2022Primary hyperparathyroidism, often caused by a single adenoma (80-85%) or four-gland hyperplasia (10-15%), can lead to elevated parathyroid hormone (PTH) levels and...
Primary hyperparathyroidism, often caused by a single adenoma (80-85%) or four-gland hyperplasia (10-15%), can lead to elevated parathyroid hormone (PTH) levels and resultant hypercalcemia. Surgical excision of offending lesions is the standard of care, as the removal of pathologic adenomas reduces PTH and calcium values to baseline. The small size, variable location, and indistinct external features of parathyroid glands can make their identification quite challenging intraoperatively. Our group has developed the dynamic optical contrast imaging (DOCI) technique, a novel realization of dynamic temporally dependent measurements of tissue autofluorescence. In this study, we evaluated the efficacy of using the DOCI technique and normalized steady-state fluorescence intensity data for differentiating types of human parathyroid and thyroid tissues. We demonstrate that the DOCI technique has the capability to distinguish normal parathyroid tissue from diseased parathyroid glands as well as from adjacent healthy thyroid and adipose tissue across 8 different spectral channels between 405nm-600nm (). Patient tissue DOCI data was further analyzed with a logistic regression classifier trained across the 8 spectral channels. After computer training, the computer-aided identification was able to accurately locate hypercellular parathyroid tissue with 100% sensitivity and 98.8% specificity within the captured DOCI image.
PubMed: 35284177
DOI: 10.1364/BOE.443671 -
The Journal of Surgical Research May 2015Tertiary hyperparathyroidism (3HPT) is defined as the persistent hyperproduction of parathyroid hormone and resulting hypercalcemia after renal transplantation. Here, we...
BACKGROUND
Tertiary hyperparathyroidism (3HPT) is defined as the persistent hyperproduction of parathyroid hormone and resulting hypercalcemia after renal transplantation. Here, we examine the utility of radioguided parathyroidectomy (RGP) in patients with 3HPT.
MATERIALS AND METHODS
We reviewed a prospective surgery database containing 80 3HPT patients who underwent RGP from January 2001-July 2014 at our institution. We evaluated patient demographics, operative management, radioguided neoprobe utilization, and operative outcomes. Data are reported as mean ± standard error of the mean.
RESULTS
The mean age of the patients was 52 ± 1 y, and 46% were male. A total of 69 patients had hyperplasia and received subtotal parathyroidectomy, whereas 5 patients had double adenomas and 6 patients had single adenomas. The average calcium level among 3HPT patients was 10.8 ± 0.1 mg/dL preoperatively and 8.7 ± 0.1 mg/dL postoperatively. In vivo radioguided counts normalized to background counts averaged 145 ± 4%, whereas ex vivo counts normalized to background counts averaged 69 ± 5%. All but one ex vivo count was >20%. Ectopically located glands were successfully localized in 38 patients using the gamma probe. Ex vivo percentage did not correlate with parathyroid gland weight, preoperative parathyroid hormone, or preoperative calcium. Our radioguided approach achieved normocalcemia in 96% of 3HPT patients undergoing RGP; two patients developed recurrent disease.
CONCLUSIONS
In this series, all enlarged parathyroid glands were localized and resected using the gamma probe. Thus, RGP reliably localizes adenomatous, hyperplastic, and ectopically located glands in patients with 3HPT, resulting in high cure rate after resection.
Topics: Female; Humans; Hyperparathyroidism; Male; Middle Aged; Parathyroid Hormone; Parathyroidectomy; Radiopharmaceuticals; Technetium Tc 99m Sestamibi
PubMed: 25770735
DOI: 10.1016/j.jss.2015.02.015 -
Frontiers in Endocrinology 2023We evaluated the difference in parathyroid visualization on F-FCH PET/CT images obtained at 5 and 60 min, and quantitatively analyzed the mode of FCH uptake at...
OBJECTIVE
We evaluated the difference in parathyroid visualization on F-FCH PET/CT images obtained at 5 and 60 min, and quantitatively analyzed the mode of FCH uptake at different time points, to determine the best imaging time for FCH PET/CT.
METHODS
This retrospective study included 73 patients with hyperparathyroidism (HPT) who underwent F-FCH PET/CT imaging between December 2017 and December 2021. The diagnostic efficiency of 5- and 60-min dual time point imaging for the diagnosis of hyperparathyroidism and parathyroid adenoma and hyperplasia, were compared using visual and quantitative analyses.
RESULTS
Dual-time F-FCH PET/CT imaging visual analysis had diagnostic value for HPT. The receiver operating characteristic curve of PET/CT quantitative parameters for the diagnosis of HPT and lesions showed that the parathyroid/thyroid SUVmax ratio for 60-min imaging had a higher sensitivity and specificity (based on patient, sensitivity: 90.90% and specificity: 85.71%; based on focus, sensitivity: 83.06% and specificity: 85.71%) compared to that for 5-min imaging. PET/CT quantitative parameters can distinguish parathyroid adenoma and hyperplasia. The 60-min parathyroid SUVmax value had the highest diagnostic value (cutoff: 3.945; area under the curve: 0.783).
CONCLUSION
The quantitative parameters of 60min F-FCH PET/CT have more advantages in aiding in the pathologica diagnosis and clinical treatment of HPT.
Topics: Humans; Positron Emission Tomography Computed Tomography; Parathyroid Neoplasms; Retrospective Studies; Hyperplasia; Choline; Hyperparathyroidism
PubMed: 37113486
DOI: 10.3389/fendo.2023.1100056 -
Indian Journal of Endocrinology and... 2019Secondary Hyperparathyroidism (SHP) seen as a frequent complication in Chronic Kidney Disease (CKD) has many pathogenetic peculiarities that are still incompletely... (Review)
Review
Secondary Hyperparathyroidism (SHP) seen as a frequent complication in Chronic Kidney Disease (CKD) has many pathogenetic peculiarities that are still incompletely defined and understood. During the long course of chronic renal failure, SHP can also transform sometimes into the hypercalcemic state characterized by quasi-autonomous production of Parathyroid Hormone from the parathyroid glands: a disorder that is termed Tertiary Hyperparathyroidism. The clinical consequences of SHP in CKD are protean, encompassing bone and mineral abnormalities but as recently identified, also several metabolic and cardiovascular problems, the most important of which is vascular calcification. There have been several advances in the therapeutic armamentarium available for the treatment of SHP, though clear demonstration of a benefit regarding major clinical outcomes with any of the new agents is still lacking. This narrative review summarizes the current understanding about this disorder and highlights some of the recent research on the subject.
PubMed: 31741895
DOI: 10.4103/ijem.IJEM_292_19 -
Kidney International Sep 2003A high level of parathyroid hormone (PTH) is considered to be an indicator of poor prognosis and a poor quality of life of dialysis patients; therefore, an effective and... (Clinical Trial)
Clinical Trial
BACKGROUND
A high level of parathyroid hormone (PTH) is considered to be an indicator of poor prognosis and a poor quality of life of dialysis patients; therefore, an effective and safe therapy for secondary hyperparathyroidism (SHPT) has been developed.
METHODS
In 20 patients with SHPT resistant to maxacalcitol (OCT) intravenously administered, all detectably enlarged parathyroid glands were treated by percutaneous maxacalcitol injection therapy (PMIT) under ultrasonographic guidance consecutively 6 times, which was followed by OCT that was intravenously administered. The clinical effects of PMIT were evaluated based on the changes in the serum intact-PTH, adjusted Ca, phosphorus, and bone marker levels, and the parathyroid gland volume determined by ultrasonography. Morphologic examination, apoptosis analysis, and PTH mRNA expression level determination by reverse transcription-polymerase chain reaction (RT-PCR) using parathyroid tissues obtained by a biopsy technique were performed.
RESULTS
PMIT and subsequent intravenous OCT administrations significantly decreased the serum intact-PTH level and parathyroid gland volume for at least 12 weeks after PMIT without major complications. Parathyroid tissues obtained after PMIT exhibited some partial defects of parathyroid cells, a marked increase in the number of the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells, the ladder formation determined by DNA electrophoresis, and the decrease in the PTH mRNA expression level.
CONCLUSION
PMIT is effective and safe for the treatment of refractory SHPT, and a locally high level of OCT suppresses PTH secretion and regresses parathyroid hyperplasia, which is involved in the induction of apoptosis of parathyroid cells.
Topics: Administration, Cutaneous; Adult; Aged; Apoptosis; Calcitriol; Female; Humans; Hyperparathyroidism, Secondary; Hyperplasia; Injections, Intralesional; Male; Middle Aged; Parathyroid Glands; Parathyroid Hormone; RNA, Messenger; Reverse Transcriptase Polymerase Chain Reaction; Uremia
PubMed: 12911549
DOI: 10.1046/j.1523-1755.2003.00154.x -
Nephrology, Dialysis, Transplantation :... Mar 2015In chronic kidney disease (CKD), parathyroid hyperplasia contributes to high serum parathyroid hormone (PTH) and also to an impaired suppression of secondary...
BACKGROUND
In chronic kidney disease (CKD), parathyroid hyperplasia contributes to high serum parathyroid hormone (PTH) and also to an impaired suppression of secondary hyperparathyroidism by calcium, vitamin D and fibroblast growth factor 23 (FGF23). In rats, systemic inhibition of epidermal growth factor receptor (EGFR) activation markedly attenuated uremia-induced parathyroid hyperplasia and vitamin D receptor (VDR) loss, hence restoring the response to vitamin D. Therefore, we propose that parathyroid-specific EGFR inactivation should prevent CKD-induced parathyroid hyperplasia.
METHODS
A dominant-negative human EGFR mutant, which forms non-functional heterodimers with full-length endogenous EGFR, was successfully targeted to the parathyroid glands (PTGs) of FVB/N mice, using the 5' regulatory sequence of the PTH promoter. The parathyroid phenotype and serum chemistries of wild-type (WT) and transgenic mice were examined after 14 weeks of either sham operation or 75% renal mass reduction (NX).
RESULTS
Both genotypes had similar morphology and body weight, and NX-induction enhanced similarly serum blood urea nitrogen compared with sham-operated controls. However, despite similar serum calcium, phosphate and FGF23 levels in NX mice of both genotypes, parathyroid EGFR inactivation sufficed to completely prevent the marked increases in PTG enlargement, serum PTH and in parathyroid levels of transforming growth factor-α, a powerful EGFR-activator, and the VDR reductions observed in WT mice.
CONCLUSION
In CKD, parathyroid EGFR activation is essential for parathyroid hyperplasia and VDR loss, rendering this transgenic mouse a unique tool to scrutinize the pathogenesis of parathyroid and multiple organ dysfunction of CKD progression unrelated to parathyroid hyperplasia.
Topics: Animals; ErbB Receptors; Fibroblast Growth Factor-23; Humans; Hyperparathyroidism, Secondary; Hyperplasia; In Situ Hybridization; Male; Mice; Mice, Transgenic; Mutation; Parathyroid Glands; Parathyroid Hormone; Promoter Regions, Genetic; Rats; Receptors, Calcitriol; Renal Insufficiency, Chronic; Uremia
PubMed: 25324357
DOI: 10.1093/ndt/gfu318 -
Cirugia Pediatrica : Organo Oficial de... Apr 2021To determine whether combined ultrasonography and parathyroid scintigraphy improves hyperplastic parathyroid gland detection in the pediatric population for... (Observational Study)
Observational Study
OBJECTIVE
To determine whether combined ultrasonography and parathyroid scintigraphy improves hyperplastic parathyroid gland detection in the pediatric population for parathyroidectomy planning in patients with secondary or tertiary hyperparathyroidism.
MATERIAL AND METHODS
An observational and analytical retrospective cohort study was carried out. Patients diagnosed with secondary or tertiary hyperparathyroidism from 2011 to 2018 undergoing total or subtotal parathyroidectomy were included - provided there was information available on pathological examination and surgical protocol.
RESULTS
N = 15 patients. A total of 53 parathyroid glands diagnosed with hyperplasia using either of the imaging methods were analyzed. For each method (ultrasonography and scintigraphy) and the combination of both, sensitivity and area under the curve were calculated, using pathological examination result as a reference. Ultrasonography and scintigraphy diagnostic match was 66%.
DISCUSSION AND CONCLUSIONS
The intraoperative difficulty of parathyroid gland identification as well as the anatomical variation that these present is well-known. Ultrasonography detected more glands than scintigraphy when diagnosing parathyroid hyperplasia. The combination of both methods allows patients with a first negative study to be detected.
Topics: Child; Humans; Hyperparathyroidism; Radionuclide Imaging; Retrospective Studies; Technetium Tc 99m Sestamibi; Ultrasonography
PubMed: 33826257
DOI: No ID Found -
VideoEndocrinology 2016Subtotal parathyroid resection is indicated when secondary or tertiary hyperparathyroidism (HPT) develops and may be indicated also in patients with primary HPT and...
Subtotal parathyroid resection is indicated when secondary or tertiary hyperparathyroidism (HPT) develops and may be indicated also in patients with primary HPT and multiglandular disease. Three different surgical procedures are used to treat diffuse parathyroid hyperplasia: total parathyroidectomy with or without autotransplantation, and subtotal parathyroidectomy. One of the main complications is transient or persistent hypoparathyroidism. In this video, we show our technique of subtotal parathyroidectomy using a fluorescent dye (indocyanine green [ICG]) to check for the vascularization of the parathyroid remnant, to avoid definitive postoperative hypoparathyroidism. We present a 64-year-old man with end-stage chronic kidney disease dialyzed since 2008. His parathyroid hormone (PTH) level was 106 pmol/L, corrected calcium level was 2.29 mmol/L and phosphate 1.63 mmol/L under maximal medical treatment, and he had significant bone disease. A subtotal parathyroidectomy was scheduled. After reclining pre-thyroid muscles, we medialized the right thyroid lobe to expose the right parathyroid glands. The superior one was a good candidate to be preserved partially because it looked hyperplastic, but without a macroscopic nodule and was the smallest of the four parathyroid glands. The inferior one was located deep in the mediastinum, in the thymus, and was therefore not suitable for subtotal resection. The procedure was the same for the left side. The inferior parathyroid gland harbored nodular hyperplasia and, therefore, was not very suitable for partial resection, but the superior one looked as a good candidate for subtotal resection too. We started reducing the volume of the parathyroid glands with clips, preserving carefully each parathyroid's vascular pedicle. Then, we intravenously injected 3.5 mL of indocyanine green solution to check the perfusion of the parathyroid remnant, using a fluorescent imaging camera (PINPOINT camera; Novadaq, Mississauga, ON, Canada). The perfusion can be seen as green or white, depending on the selected image mode. We finally chose the right superior parathyroid gland and resected the gland outside of the clips. The other glands have finally been entirely removed. The postoperative course was uneventful except for hypocalcemia needing intravenous calcium for 48 hours. On the first postoperative day, corrected calcium level was 1.93 mmol/L and PTH level was 8 pmol/L. The two inferior parathyroid glands showed nodular hyperplasia at pathologic examination and the two superior glands showed diffuse hyperplasia without nodules. With this new procedure, subtotal parathyroidectomy under ICG angiography, we can check for the good vascularization of the parathyroid remnant before resecting the other parathyroid glands. Therefore, we can intraoperatively guarantee the absence of definitive hypoparathyroidism. This technique is safe, reproducible, and its easy use makes it the procedure of choice in these situations, when the device is available. No competing financial interests exist. Runtime of video: 6 mins 33 secs.
PubMed: 32025526
DOI: 10.1089/ve.2015.0056 -
Bioscience Reports Apr 2019The aim of the present study was to elucidate the diagnostic and prognostic implications of parafibromin immunohistochemistry (IHC) in parathyroid carcinoma (PC). We... (Meta-Analysis)
Meta-Analysis
The aim of the present study was to elucidate the diagnostic and prognostic implications of parafibromin immunohistochemistry (IHC) in parathyroid carcinoma (PC). We performed a meta-analysis to examine the rate of loss of parafibromin expression from 18 eligible studies. In addition, a diagnostic test accuracy review was conducted to investigate the diagnostic role of parafibromin in PC. The rates of loss of parafibromin expression were 0.522 (95% CI: 0.444-0.599), 0.291 (95% CI: 0.207-0.391), 0.027 (95% CI: 0.011-0.064), and 0.032 (95% CI: 0.008-0.119) in PC, atypical parathyroid adenoma (APA), parathyroid adenoma (PA), and parathyroid hyperplasia, respectively. In the diagnostic test accuracy review for diagnosis of PC, the pooled sensitivity and specificity of parafibromin IHC was 0.53 (95% CI: 0.46-0.59) and 0.96 (95% CI: 0.95-0.97), respectively. The diagnostic odds ratio and the area under curve on summary receiver operating characteristic curve was 25.31 (95% CI: 8.91-71.87) and 0.7954, respectively. In addition, the meta-analysis demonstrated that loss of parafibromin expression was significantly correlated with worse disease-free survival (hazard ratio: 2.832; 95% CI: 1.081-7.421). Loss of parafibromin IHC expression was significantly higher in PC than in APA, PA, and parathyroid hyperplasia. Parafibromin IHC could be useful for diagnosis and prediction of prognosis of PC in daily practice.
Topics: Biomarkers, Tumor; Disease-Free Survival; Humans; Hyperplasia; Immunohistochemistry; Parathyroid Glands; Parathyroid Neoplasms; Prognosis; ROC Curve; Tumor Suppressor Proteins
PubMed: 30926677
DOI: 10.1042/BSR20181778 -
Monoclonality of parathyroid tumors in chronic renal failure and in primary parathyroid hyperplasia.The Journal of Clinical Investigation May 1995The pathogeneses of parathyroid disease in patients with uremia and nonfamilial primary parathyroid hyperplasia are poorly understood. Because of multigland involvement,... (Comparative Study)
Comparative Study
The pathogeneses of parathyroid disease in patients with uremia and nonfamilial primary parathyroid hyperplasia are poorly understood. Because of multigland involvement, it has been assumed that these common diseases predominantly involve polyclonal (non-neoplastic) cellular proliferations, but an overall assessment of their clonality has not been done. We examined the clonality of these hyperplastic parathyroid tumors using X-chromosome inactivation analysis with the M27 beta (DXS255) DNA polymorphism and by searching for monoclonal allelic losses at M27 beta and at loci on chromosome band 11q13. Fully 7 of 11 informative hemodialysis patients (64%) with uremic refractory hyperparathyroidism harbored at least one monoclonal parathyroid tumor (with a minimum of 12 of their 19 available glands being monoclonal). Tumor monoclonality was demonstrable in 6 of 16 informative patients (38%) with primary parathyroid hyperplasia. Histopathologic categories of nodular versus generalized hyperplasia were not useful predictors of clonal status. These observations indicate that monoclonal parathyroid neoplasms are common in patients with uremic refractory hyperparathyroidism and also develop in a substantial group of patients with sporadic primary parathyroid hyperplasia, thereby changing our concept of the pathogenesis of these diseases. Neoplastic transformation of preexisting polyclonal hyperplasia, apparently due in large part to genes not yet implicated in parathyroid tumorigenesis and possibly including a novel X-chromosome tumor suppressor gene, is likely to play a central role in these disorders.
Topics: Adult; Aged; Blotting, Southern; Chromosome Deletion; Chromosome Mapping; Chromosomes, Human, Pair 11; DNA; DNA, Neoplasm; Female; Humans; Hyperplasia; Kidney Failure, Chronic; Middle Aged; Neoplasms, Second Primary; Parathyroid Glands; Parathyroid Neoplasms; Polymorphism, Genetic; Restriction Mapping; Sex Chromosome Aberrations; X Chromosome
PubMed: 7738171
DOI: 10.1172/JCI117890