-
The Journal of Clinical Endocrinology... Oct 2023Secondary hyperparathyroidism (SHPT) is a complication of chronic kidney disease (CKD) affecting mineral and bone metabolism and characterized by excessive parathyroid... (Meta-Analysis)
Meta-Analysis
CONTEXT
Secondary hyperparathyroidism (SHPT) is a complication of chronic kidney disease (CKD) affecting mineral and bone metabolism and characterized by excessive parathyroid hormone (PTH) production and parathyroid hyperplasia.
OBJECTIVE
The objective of this analysis was to compare the efficacy and adverse effects of extended-release calcifediol (ERC) and paricalcitol (PCT) by assessing their effect on the biomarkers PTH, calcium, and phosphate in patients with non-dialysis CKD (ND-CKD).
METHODS
A systematic literature research was performed in PubMed to identify randomized control trials (RCTs). Quality assessment was done with the GRADE method. The effects of ERC vs PCT were compared using random effects in a frequentist setting.
RESULTS
Nine RCTs comprising 1426 patients were included in the analyses. The analyses were performed on 2 overlapping networks, due to nonreporting of outcomes in some of the included studies. No head-to-head trials were identified. No statistically significant differences in PTH reduction were found between PCT and ERC. Treatment with PCT showed statistically significant increases in calcium compared with ERC (0.2 mg/dL increase; 95% CI, -0.37 to -0.05 mg/dL). No differences in effects on phosphate were observed.
CONCLUSION
This network meta-analysis showed that ERC is comparable in lowering PTH levels vs PCT. ERC displayed avoidance of potentially clinically relevant increases in serum calcium, offering an effective and well-tolerated treatment option for the management of SHPT in patients with ND-CKD.
Topics: Humans; Calcifediol; Calcium; Ergocalciferols; Hyperparathyroidism, Secondary; Network Meta-Analysis; Parathyroid Hormone; Phosphates; Renal Insufficiency, Chronic; Randomized Controlled Trials as Topic
PubMed: 37235771
DOI: 10.1210/clinem/dgad289 -
Journal of Bone and Mineral Research :... Sep 2023Primary hyperparathyroidism (PHPT) includes sporadic PHPT and hereditary PHPT. However, until now, there have been no exact data on the proportion and composition of...
Primary hyperparathyroidism (PHPT) includes sporadic PHPT and hereditary PHPT. However, until now, there have been no exact data on the proportion and composition of hereditary PHPT in the Chinese PHPT population. This study aimed to clarify the proportion and composition of hereditary PHPT in patients at a large academic center in Beijing, China, and to analyze genotype-phenotype characteristics. A total of 394 newly diagnosed Han PHPT patients who consented to genetic screening were enrolled. Targeted next-generation sequencing (T-NGS) (including for MEN1, RET, CDKN1B, CaSR, HRPT2/CDC73, GNA11, AP2S1, GCM2), combined with MEN1-multiplex ligation-dependent probe amplification (MLPA) and CDC73-MLPA, was used for genetic screening. Diagnosis of hereditary PHPT was based on clinical manifestations, family history, and genetic screening. Thirty-seven pathogenic (P)/likely pathogenic (LP) variants were detected in 41 patients via T-NGS, and three patients carried long-range deletions of MEN1 or CDC73 detected by MLPA, with a variant detection rate of 11.2% (44/394). In total, 30 patients were clinically diagnosed with MEN1. Combined with genetic and clinical screening, the rate of hereditary PHPT in this study was 18.8% (74/394). For purposes of comparison, the rate of unequivocal nonhereditary PHPT was 66.5% (262/394); 14.7% (58/394) did not exhibit the clinical features of hereditary PHPT but carried variants of uncertain clinical significance and so could not be clearly categorized. Both the age at hospital visit (43.6 ± 14.0 versus 53.7 ± 14.9 years) and age at onset (35.4 ± 13.8 versus 50.6 ± 14.8 years) in the hereditary group (n = 74) were significantly lower than those in the nonhereditary group (n = 262). Higher levels of ionized calcium and serum β-CTX were observed in the hereditary group; proportions of parathyroid hyperplasia and multigland involvement were also higher. In addition to multigland disease and positive family history, it is recommended that patients with an age of onset less than 38 should be screened for hereditary forms. © 2023 American Society for Bone and Mineral Research (ASBMR).
Topics: Humans; Adult; Middle Aged; Aged; Hyperparathyroidism, Primary; East Asian People; Genetic Testing; Multiple Endocrine Neoplasia Type 1; Calcium; Transcription Factors
PubMed: 37449924
DOI: 10.1002/jbmr.4883 -
Journal of Clinical Medicine Jul 2023(1) Background: Parathyroid cystic adenomas (PCA) are rare entities representing only 0.5-1% of parathyroid adenomas, accounting for 1-2% of cases of primary...
(1) Background: Parathyroid cystic adenomas (PCA) are rare entities representing only 0.5-1% of parathyroid adenomas, accounting for 1-2% of cases of primary hyperparathyroidism (PHPT). The purpose of this study was to compare classical and functional/secreting cystic parathyroid lesions and identify risk factors for severe hypercalcemia; (2) Methods: A total of 17 patients with PHPT and parathyroid cysts (study group) were compared with the group of 100 patients with hyperparathyroidism caused by adenoma or hyperplasia (control group). In both groups the majority were women (88% vs. 12%, with gender ratio 7, 3:1). The patients were examined preoperatively and postoperatively: PTH, creatine, calcium and phosphate serum and urine concentrations and calcidiol serum levels were assessed; (3) Results: Patients with parathyroid cyst had statistically higher PTH and calcium serum concentration, higher calciuria and lower serum phosphate concentration. There were no statistically significant differences in the concentration of creatine in serum and urine and tubular reabsorption of phosphorus (TRP); (4) Conclusions: Due to higher PTH and calcium levels, cystic parathyroid adenomas could be one of the rare risk factors for severe hypercalcemia and hypercalcemic crisis which can be life threatening.
PubMed: 37568342
DOI: 10.3390/jcm12154939 -
Renal Failure Dec 2023The assessment and prevention of mineral and bone disorder (MBD) in kidney transplant recipients (KTRs) have not been standardized. This study aimed to evaluate MBD one...
BACKGROUND
The assessment and prevention of mineral and bone disorder (MBD) in kidney transplant recipients (KTRs) have not been standardized. This study aimed to evaluate MBD one year after kidney transplantation (KT) and identify the influencing factors of MBD.
METHODS
A total of 95 KTRs in our center were enrolled. The changes in bone mineral density (BMD) and bone metabolism biochemical markers, including serum calcium (Ca), phosphorus(P), 25-hydroxyvitamin D(25(OH)vitD), intact parathyroid hormone (iPTH), bone alkaline phosphatase, osteocalcin (OC), type I collagen N-terminal peptide and type I collagen C-terminal peptide (CTx), over one year after KT were assessed. The possible influencing factors of BMD were analyzed. The relationships between bone metabolism biochemical markers were evaluated. The indicators between groups with or without iPTH normalization were also compared.
RESULTS
MBD after KT was manifested as an increased prevalence of hypophosphatemia and bone loss, persistent 25(OH)vitD deficiency, and partially decreased PTH and bone turnover markers (BTMs). Femoral neck BMD was positively correlated with body mass index (BMI) and postoperative 25(OH)vitD, and negatively correlated with postoperative PTH. Lumbar spine BMD was positively correlated with BMI and preoperative TG, and negatively correlated with preoperative OC and CTx. BMD loss was positively associated with glucocorticoid accumulation. Preoperative and postoperative iPTH was negatively correlated with postoperative serum P and 25(OH)vitD, and positively correlated with postoperative Ca and BTMs. The recipients without iPTH normalization, who accounted for 41.0% of all KTRs, presented with higher Ca, lower P, higher BTMs, advanced age, and a higher prevalence of preoperative parathyroid hyperplasia.
CONCLUSIONS
MBD persisted after KT, showing a close relationship with hyperparathyroidism, high bone turnover, and glucocorticoid accumulation.
Topics: Humans; Biomarkers; Bone Density; Bone Remodeling; Cohort Studies; Collagen Type I; Glucocorticoids; Kidney Transplantation; Parathyroid Hormone; Peptides; Hyperparathyroidism; Chronic Kidney Disease-Mineral and Bone Disorder; Osteoporosis
PubMed: 37183797
DOI: 10.1080/0886022X.2023.2210231 -
PeerJ 2023Secondary hyperparathyroidism (SHPT) is a frequent complication of chronic kidney disease (CKD) associated with morbidity and mortality. This study aims to identify...
OBJECTIVE
Secondary hyperparathyroidism (SHPT) is a frequent complication of chronic kidney disease (CKD) associated with morbidity and mortality. This study aims to identify potential biomarkers that may be used to predict the progression of SHPT and to elucidate the molecular mechanisms of SHPT pathogenesis at the transcriptome level.
METHODS
We analyzed differentially expressed genes (DEGs) between diffuse and nodular parathyroid hyperplasia of SHPT patients from the GSE75886 dataset, and then verified DEG levels with the GSE83421 data file of primary hyperparathyroidism (PHPT) patients. Candidate gene sets were selected by machine learning screens of differential genes and immune cell infiltration was explored with the CIBERSORT algorithm. RcisTarget was used to predict transcription factors, and Cytoscape was used to construct a lncRNA-miRNA-mRNA network to identify possible molecular mechanisms. Immunohistochemistry (IHC) staining and quantitative real-time polymerase chain reaction (qRT-PCR) were used to verify the expression of screened genes in parathyroid tissues of SHPT patients and animal models.
RESULTS
A total of 614 DEGs in GSE75886 were obtained as candidate gene sets for further analysis. Five key genes (USP12, CIDEA, PCOLCE2, CAPZA1, and ACCN2) had significant expression differences between groups and were screened with the best ranking in the machine learning process. These genes were shown to be closely related to immune cell infiltration levels and play important roles in the immune microenvironment. Transcription factor ZBTB6 was identified as the master regulator, alongside multiple other transcription factors. Combined with qPCR and IHC assay of hyperplastic parathyroid tissues from SHPT patients and rats confirm differential expression of USP12, CIDEA, PCOLCE2, CAPZA1, and ACCN2, suggesting that they may play important roles in the proliferation and progression of SHPT.
CONCLUSION
USP12, CIDEA, PCOLCE2, CAPZA1, and ACCN2 have great potential both as biomarkers and as therapeutic targets in the proliferation of SHPT. These findings suggest novel potential targets and future directions for SHPT research.
Topics: Animals; Rats; Biomarkers; Cell Proliferation; Hyperparathyroidism, Primary; Hyperparathyroidism, Secondary; Hyperplasia; Parathyroid Glands; Humans
PubMed: 37456892
DOI: 10.7717/peerj.15633 -
Indian Journal of Endocrinology and... 2023Primary hyperparathyroidism (PHPT) is rarely associated with the occurrence of acute or chronic pancreatitis, requiring complex perioperative management. This study...
BACKGROUND
Primary hyperparathyroidism (PHPT) is rarely associated with the occurrence of acute or chronic pancreatitis, requiring complex perioperative management. This study aimed to assess the prevalence and disease characteristics of pancreatitis in PHPT.
MATERIALS AND METHODS
This study is a clinicopathological analysis of the medical records of patients who were diagnosed with PHPT with pancreatitis between 1989 and 2021 in the Endocrine Surgery department, SGPGI, Lucknow.
RESULTS
Out of 548 PHPT cases, 44 (8.03%) were found to be associated with pancreatitis. The mean age was 33.57 years (15-65 years); 5 were ≤20 years, while 26 were ≤30 years of age. There were 27 males and 17 females. Twenty-one cases were of acute (11 acute, nine recurrent acute, one acute on chronic), whereas 23 were of chronic pancreatitis (six chronic calcific pancreatitis). The major clinical presentation of PHPT with pancreatitis was abdominal pain (65.91%). The mean number of attacks per patient in recurrent acute pancreatitis was two. Mean PTH levels were 68.19 pmol/L. The mean tumor size (in the largest dimension) was 2.79 ± 1.4 cm while the mean tumor weight was 4.91 g. Nephrolithiasis was associated with 25 cases. An association with multiple endocrine neoplasia type 1 syndrome was seen in one case. The final histopathological diagnosis was parathyroid carcinoma in two, hyperplasia in three, and parathyroid adenoma in 39 cases. Normocalcemia was seen in 27.2%, hypercalcemic crisis in 15.9%, and 25% of patients required semi-emergency parathyroidectomy. The outcome was favorable in all, as none had any further attacks of pancreatitis.
CONCLUSION
In our study, the prevalence of pancreatitis in PHPT cases was 8.03%. The majority of patients were young. Normocalcemia was seen in 12 patients, so even if calcium levels are normal, PHPT should be suspected in young patients with pancreatitis. Parathyroidectomy resulted in the complete resolution of symptoms of pancreatitis in all 44 patients.
PubMed: 38371176
DOI: 10.4103/ijem.ijem_169_23 -
Medicine Sep 2023We aimed to explore the value of ultrasonic elastic imaging in the diagnosis of parathyroid hyperplasia and adenoma in patients with secondary hyperparathyroidism and...
We aimed to explore the value of ultrasonic elastic imaging in the diagnosis of parathyroid hyperplasia and adenoma in patients with secondary hyperparathyroidism and provide more evidence for clinical treatment. Forty patients who were on dialysis and underwent parathyroid surgery were selected All patients underwent routine ultrasound, ultrasound elasticity examination and blood biochemical examination before surgery, including calcium, phosphorus, parathyroid hormone (PTH), etc. According to postoperative results, adenoma group and hyperplasia group were divided into 2 groups. Receiver operating characteristic curve was drawn to evaluate the diagnostic efficacy and combined diagnostic efficacy of each index. The PTH levels significantly differed between the adenoma and hyperplasia groups (P < .001). The volume and blood flow grades significantly differed between the adenoma and hyperplasia groups (P < .001) The minimum of the adenoma group was 14.62 ± 6.79 kPa, mean was 19.42 ± 6.29 kPa, and maximum was 24.25 ± 6.35 kPa which were significantly different from those in the hyperplasia group (P < .05). The combinations of more than 6 indicators in the diagnosis of parathyroid adenoma resulted in an area under the curve of 0.892 (P < .001), and the sensitivity and specificity were 78.9% and 97.4%, respectively. Shear wave elastography can be used as an effective tool to distinguish secondary parathyroid hyperplasia from adenoma. When combined with PTH, conventional ultrasound blood flow grading and volume measurement, it has higher diagnostic efficacy.
Topics: Humans; Diagnosis, Differential; Elasticity Imaging Techniques; Hyperplasia; Renal Dialysis; Hyperparathyroidism, Primary; Parathyroid Hormone; Adenoma
PubMed: 37713846
DOI: 10.1097/MD.0000000000035079 -
Quantitative Imaging in Medicine and... Dec 2023Exact preoperative localization is desirable to perform minimally invasive parathyroidectomy for hyperparathyroidism (HPT). This study aimed to evaluate the diagnostic...
BACKGROUND
Exact preoperative localization is desirable to perform minimally invasive parathyroidectomy for hyperparathyroidism (HPT). This study aimed to evaluate the diagnostic values of Tc-methoxyisobutylisonitrile (Tc-MIBI) single photon emission computed tomography/computed tomography (SPECT/CT) of parathyroid glands by analyzing the relationship between lesion weight and false-negative (FN) results, as well as to explain the possible reason.
METHODS
The data from 314 patients with suspected HPT who underwent Tc-MIBI SPECT/CT parathyroid imaging between 2011 and 2022 were retrospectively evaluated. The sensitivity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of parathyroid Tc-MIBI SPECT/CT were calculated, and the false-positive (FP) and FN findings were analyzed.
RESULTS
Accurate localization by Tc-MIBI SPECT/CT was significantly associated with the parathyroid hormone (PTH) level. The Tc-MIBI SPECT/CT for diagnosis/lesion location reached a sensitivity of 84.6%/56.8%, a PPV of 97.3%/98.4%, an NPV of only 23.7%/4.18%, and an accuracy of 83.4%/57.1%, respectively. The largest diameter, shortest diameter, and lesion volume were lower in the FN group than in the TP group. A total of 7 FP cases were found, including 2 cases of thyroid nodules, 4 cases of thyroid tissue, and 1 case of hibernoma. A total of 45 FN patients, including 321 FN lesions, were confirmed, of which parathyroid hyperplasia accounted for 97.8%. Lesion weights greater than 20 µg were able to be detected, but lightweight lesions less than 100 mg were the principal source of FN results, accounting for approximately 39.3%. With lesion weights 0-100, 101-300, 301-1,000, and >1,000 mg, the FN rate was 70.8% (126/178), 51.8% (103/199), 34.6% (81/234), and 8.33% (11/132), respectively.
CONCLUSIONS
Tc-MIBI SPECT/CT parathyroid imaging provides good sensitivity and high specificity in HPT location. Correct localization by Tc-MIBI SPECT/CT correlates positively with lesion weight and PTH levels. The smaller the lesion, the higher the FN rate in Tc-MIBI SPECT/CT parathyroid imaging, and lesions weighing less than 100 mg are the main source of FN results in Tc-MIBI SPECT/CT parathyroid imaging.
PubMed: 38106262
DOI: 10.21037/qims-23-1091 -
Telocytes/CD34+ Stromal Cells in the Normal, Hyperplastic, and Adenomatous Human Parathyroid Glands.International Journal of Molecular... Jul 2023Telocytes/CD34+ stromal cells (TCs/CD34+ SCs) have been studied in numerous organs and tissues, but their presence and characteristics in the parathyroid glands have not...
Telocytes/CD34+ stromal cells (TCs/CD34+ SCs) have been studied in numerous organs and tissues, but their presence and characteristics in the parathyroid glands have not been explored. Using immunological and ultrastructural procedures, we assess the location, arrangement, and behavior of TCs/CD34+ SCs in normal human parathyroids, during their development and in their most frequent pathologic conditions. In normal parathyroids, TCs/CD34+ SCs show a small somatic body and long thin processes with a moniliform aspect, form labyrinthine systems, connect other neighboring TCs/CD34+ SCs, vessels, adipocytes, and parenchymal cells directly or by extracellular vesicles, and associate with collagen I. TCs/CD34+ SCs and collagen I are absent around vessels and adipocytes within parenchymal clusters. In developing parathyroids, TCs/CD34+ SC surround small parenchymal nests and adipocytes. In hyperplastic parathyroids, TCs/CD34+ SCs are prominent in some thickened internodular septa and surround small extraglandular parenchymal cell nests. TCs/CD34+ SCs are present in delimiting regions with compressed parathyroids and their capsule in adenomas but absent in most adenomatous tissue. In conclusion, TCs/CD34+ SCs are an important cellular component in the human parathyroid stroma, except around vessels within parenchymal nests. They show typical characteristics, including those of connecting cells, are present in developing parathyroids, and participate in the most frequent parathyroid pathology, including hyperplastic and adenomatous parathyroids.
Topics: Humans; Parathyroid Glands; Stromal Cells; Telocytes; Antigens, CD34; Parathyroid Neoplasms; Hyperplasia; Cell Adhesion Molecules; Adenoma; Collagen
PubMed: 37569493
DOI: 10.3390/ijms241512118 -
Stem Cells and Development Nov 2023The parathyroid gland plays an essential role in mineral and bone metabolism. Cultivation of physiological human parathyroid cells has yet to be established and the...
The parathyroid gland plays an essential role in mineral and bone metabolism. Cultivation of physiological human parathyroid cells has yet to be established and the method by which parathyroid cells differentiate from pluripotent stem cells remains uncertain. Therefore, it has been hard to clarify the mechanisms underlying the onset of parathyroid disorders, such as hyperparathyroidism. In this study, we developed a new method of parathyroid cell differentiation from human induced pluripotent stem (iPS) cells. Parathyroid cell differentiation occurred in accordance with embryologic development. Differentiated cells, which expressed the parathyroid hormone, adopted unique cell aggregation similar to the parathyroid gland. In addition, these differentiated cells were identified as calcium-sensing receptor (CaSR)/epithelial cell adhesion molecule (EpCAM) double-positive cells. Interestingly, stimulation with transforming growth factor-α (TGF-α), which is considered a causative molecule of parathyroid hyperplasia, increased the CaSR/EpCAM double-positive cells, but this effect was suppressed by erlotinib, which is an epidermal growth factor receptor (EGFR) inhibitor. These results suggest that TGF-α/EGFR signaling promotes parathyroid cell differentiation from iPS cells in a similar manner to parathyroid hyperplasia.
Topics: Humans; Parathyroid Glands; Induced Pluripotent Stem Cells; Hyperplasia; Transforming Growth Factor alpha; Epithelial Cell Adhesion Molecule; ErbB Receptors; Cell Differentiation; Receptors, Calcium-Sensing
PubMed: 37639359
DOI: 10.1089/scd.2023.0130