Density-Dependent Differentiation of Tonsil-Derived Mesenchymal Stem Cells into Parathyroid-Hormone-Releasing Cells

Mesenchymal stem cells (MSCs) can differentiate into endoderm lineages, especially parathyroid-hormone (PTH)-releasing cells. We have previously reported that tonsil-derived MSC (T-MSC) can differentiate into PTH-releasing cells (T-MSC-PTHCs), which restored the parathyroid functions in parathyroidectomy (PTX) rats. In this study, we demonstrate quality optimization by standardizing the differentiation rate for a better clinical application of T-MSC-PTHCs to overcome donor-dependent variation of T-MSCs. Quantitation results of PTH mRNA copy number in the differentiated cells and the PTH concentration in the conditioned medium confirmed that the differentiation efficiency largely varied depending on the cells from each donor. In addition, the differentiation rate of the cells from all the donors greatly improved when differentiation was started at a high cell density (100% confluence). The large-scale expression profiling of T-MSC-PTHCs by RNA sequencing indicated that those genes involved in exiting the differentiation and the cell cycle were the major pathways for the differentiation of T-MSC-PTHCs. Furthermore, the implantation of the T-MSC-PTHCs, which were differentiated at a high cell density embedded in hyaluronic acid, resulted in a higher serum PTH in the PTX model. This standardized efficiency of differentiation into PTHC was achieved by initiating differentiation at a high cell density. Our findings provide a potential solution to overcome the limitations due to donor-dependent variation by establishing a standardized differentiation protocol for the clinical application of T-MSC therapy in treating hypoparathyroidism.

The Study of the Association of Serum Parathyroid Hormone Level with Obesity in Patients Admitted to a Tertiary Care Center in Basrah

<b><i>Background:</i></b> Parathyroid hormone (PTH) has been reported to have a positive correlation with insulin resistance and the development of the metabolic syndrome. This study aims to evaluate if there is an association between obesity and serum PTH levels. <b><i>Methods:</i></b> This case-control study was conducted at the Faiha Specialized Diabetes Endocrine and Metabolism Center in Basrah (Southern Iraq) from September 2018 to July 2019. A total of 230 patients were recruited for this study (103 male and 127 female), divided into 2 groups according to the BMI: &#x3c;30 kg/m² were considered as the control group (83 persons) and ≥30 kg/m² were considered as obese persons (147 persons). The study groups were also subdivided into 3 groups according to the serum level of PTH: &#x3c;40 pg/mL, 40–65 pg/mL, and &#x3e;65 pg/mL. <b><i>Results:</i></b> The mean age of the obese and control groups was 44.39 ± 10.64 and 30.12 ± 8.95 years, respectively. About 46.25% of obese were men and 53.75% were women, while 42% of the control group were men and 58% were women. Serum PTH level was significantly higher (<i>p</i> &#x3c; 0.001) among obese persons with a mean level of 53.21 ± 19.58 pg/mL for obese and 37.63 ± 21.8 pg/mL for control. Vitamin D deficiency was seen in 84.4% of the obese group while in 71.1% of the control group (<i>p</i> value 0.04). Females turned to have higher PTH levels than males in both the obese and the control group (<i>p</i> value &#x3c;0.001). However, age and the presence of diabetes mellitus were not associated with higher PTH levels (<i>p</i> value 0.155 and 0.6, respectively). <b><i>Conclusion:</i></b> Obesity was associated with a higher serum PTH level related to the severity of vitamin D deficiency.

Prevalence of Vitamin D Deficiency and Its Association with Insulin Resistance in Obese Women with Normal Fasting Glucose

Background and Objective. Association of vitamin D (25-hydroxyvitamin-D; 25(OH)D), with glucose metabolism is ethnic dependent. We study the relation of vitamin D and its metabolites with the glycemic profile of obese women. Patients and Methods. Informed consent and demographic information was collected from obese ( BMI ≥ 30 kg / m 2 ) and nonobese women. A blood sample in fasting was obtained and analyzed for fasting glucose, fasting insulin, serum 25(OH)D, serum parathyroid hormone (PTH), and calcium levels. Insulin resistance (IR), detected by Matthews’ method (1985), was considered in women with HOMA − IR ≥ 2.5 . Vitamin D concentrations < 12 ng / ml were considered vitamin D deficiency. Results. A total of 264 obese and 133 normal BMI women (controls) of age range 20-50 years were selected. Obese women had significantly lower vitamin D compared to control women ( P < 0.05 ). Among euglycemic ( fasting glucose < 100 mg / dl ) obese women ( n = 221 ), 90 (40.7%) were vitamin D deficient. Serum PTH and calcium levels were negatively correlated, though nonsignificantly with vitamin D ( r = − 0.172 , P = 0.090 , and r = − 0.051 , P = 0.557 , respectively). The mean age, BMI, waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), fasting glucose, fasting insulin, PTH, and calcium were not significantly different in vitamin D-deficient as compared to nondeficient obese women. IR was detected in 109 (49.3%) obese women. Mean HOMA-IR in vitamin D-deficient women was significantly higher than that in the nondeficient obese women ( 3.03 ± 1.64 vs. 2.40 ± 1.02 ; P = 0.041 ), but the percentage of women with IR was comparable in both groups (51.1% vs. 45.8%; P = 0.745 ). Univariate analysis revealed that HOMA-IR was negatively correlated with vitamin D and positively with BMI and PTH. A multivariate regression analysis, stepwise method revealed that BMI and PTH were independent determinants of HOMA-IR instead of vitamin D. Conclusion. More than 40% of obese women were vitamin D deficient. Among euglycemic obese women, 49% were insulin resistant. Prevalence of insulin resistance, though negatively correlated with vitamin D, could be better explained by BMI and PTH levels.

Threshold for Relationship between Vitamin D and Parathyroid Hormone in Chinese Women of Childbearing Age

Background: The aim of this study was to assess the relationship between serum 25-hydroxyvitamin D [25(OH)D] and serum intact parathyroid hormone (PTH) in Chinese childbearing women, and to estimate the optimum threshold of 25(OH)D that maximally inhibits the PTH, which is considered to be the optimal status for vitamin D sufficiency. Methods: Serum samples were selected from the biological samples’ bank of the Chinese Chronic Diseases and Nutrition Survey (CCDNS) 2015. The serum 25(OH)D concentration was determined by liquid chromatography tandem mass spectrometry and the serum PTH was determined by electronic chemiluminescence. Simple linear and partial correlation analysis, locally weighted regression smooth scatterplot (LOESS), nonlinear least squares estimation (NLS), and segmented regression (SR) were utilized to estimate the relationship of 25(OH)D and PTH, and to determine the threshold of 25(OH)D. Results: A total of 1568 serum samples of 25(OH)D concentration and PTH concentration were analyzed. A significant inverse relationship between 25(OH)D and PTH concentration was observed below 15.25 (14.22–16.28) ng/mL, and PTH decreased slowly with the increase of 25(OH)D above 16.75 (15.43–18.06) ng/mL after adjusting by age, latitude, city type, season, corrected calcium, and phosphorus. A very short plateau of PTH was found at 15.25 ng/mL and 16.75 ng/mL in terms of 25(OH)D according to LOESS, NLS, and SR. Conclusions: The serum 25(OH)D was negatively correlated with the serum PTH. The threshold of VitD sufficiency was found in the range of 14.22–18.06 ng/mL in terms of serum 25(OH)D concentration for Chinese childbearing women aged 18–44 years old.

Bone Turnover Markers in Response to Ultrasound-Guided Microwave Ablation for Primary Hyperparathyroidism

ObjectiveTo assess the efficacy and safety of ultrasound-guided microwave ablation (MWA) in the treatment of primary hyperparathyroidism (PHPT), and to investigate whether MWA can improve the bone turnover and renal function.MethodsA total of 20 consecutive PHPT patients with 21 parathyroid lesions treated with MWA in our center from May 2019 to March 2021 were recruited in this study. Serum parathyroid hormone (PTH), calcium and phosphorus levels before MWA and at 20 minutes, 4 hours, 1 day, 3 months, 6 months and 12 months after MWA were measured. Bone turnover biomarkers, renal function and lesion volume with volume reduction rate (VRR) before MWA and at the last follow-up were compared. Any complication related with MWA was evaluated. The technical and clinical success rates of MWA in the treatment of PHPT were calculated. Clinical success was defined as normal serum PTH and calcium without PHPT-associated manifestations at more than 6 months after ablation. Technical success was defined as complete ablation indicated by immediate postoperative contrast-enhanced ultrasound.ResultsThe serum PTH, calcium and phosphorus levels at their respective follow-up time points dropped significantly after MWA (P &lt;0.05). The volume of parathyroid lesions at the final examination was significantly reduced, compared with pre-ablation volume (P &lt;0.001), with a median VRR reaching 89%. The technical and clinical success rates were 100% and 63.6%, respectively. Substantial changes of bone turnover biomarkers were observed before and after MWA (P &lt;0.05), but the differences in renal function were not statistically significant. No major complications were reported in all cases. Pre-MWA serum PTH, lesion volume, maximum diameter of lesion and ablation time were significantly different between patients with successful and failed MWA.ConclusionsPHPT can be effectively and safely treated by ultrasound-guided MWA, as proven by drop in serum PTH and reduction in the volume of parathyroid adenomas. Besides, MWA can impede bone remodeling to suppress hyperparathyroidism in the condition of PHPT.

Differential diagnosis of hypercalcemia in a patient with CKD G5D

Patients with chronic kidney disease are characterized by the development of mineral disorders due to a decrease in the number of functioning nephrons. These changes manifest by the development of secondary hyperparathyroidism (the overproduction of intact parathyroid hormone (PTH) associated with the serum hypocalcemia, hyperphosphatemia), dysfunctional vitamin D metabolism, bone mineralization and also extraosseous calcifications. Decreased serum PTH levels associated with hypercalcemia are suspicious for adynamic bone disease, but at the same time requires an extended differential diagnostic search (e.g. metastatic processes). One of the rare causes of hypercalcemia is a defect in 24-hydroxylase (CYP24A1). We present a case of a patient on hemodialysis with atypical secondary hyperparathyroidism and an established CYP24A1 defect.

Relationship Between Parathyroid Hormone Levels and Abdominal Aortic Calcification in Incident Hemodialysis Patients Not Treated with Calcium or Vitamin D

Vascular calcification (VC) and secondary hyperparathyroidism (SHPT) are important causes of high incidence of cardiovascular events in chronic kidney disease (CKD) patients. The relationship between parathyroid hormone (PTH) and VC is very complex. Different studies have inconsistent reports on the effect of PTH on VC. The present study investigated the correlation between PTH levels and abdominal aortic calcification (AAC) in incident hemodialysis patients who did not receive calcium, calcium-containing phosphorus binders, calcitriol or vitamin D analogs. Our data confirm that serum PTH levels is significantly negatively correlated with AAC within a certain concentration range in incident hemodialysis patients who not treated with calcium or vitamin D.

Effects of secondary hyperparathyroidism treatment on hemoglobin levels and erythropoietin doses in hemodialysis patients

Aim: Secondary hyperparathyroidism (SHPT) is an often underestimated cause of anemia in hemodialysis (HD) patients. The aim of this study was to assess the effect of pharmacological correction of SHPT on anemia and erythropoiesis-stimulating agents (ESAs) need. Methods: For the purpose of this retrospective pre-post observational study, we selected 55 HD patients, receiving HD at one single center, in the period from January 2005 to December 2020. The follow-up (F-U) lasted 12 months. The selection criteria were parathormone (PTH) levels > 300 pg/ mL, and hemoglobin (Hb) levels < 11 g/dL, despite treatment with ESAs. Parametric and non-parametric tests were used when appropriate. In the light of exploratory nature of the study, the limited sample size and in consideration of the pre-post-design, no further adjustment for potential confounders is performed. Results: The hemoglobin levels throughout the study were correlated to serum PTH (r = -.257, p < 0.01). At the end of the F-U, in the 40 patients whose PTH levels decreased ≥ 30% (responders group) Hb levels increased from 10.3 ± 0.5 g/dL to 12.2 ± 1.1 g/dL (p < 0.001), and ESAs doses decreased from 141 ± 101 IU/kg/b.w./week to 94 ± 76 IU/kg/b.w./week (p < 0.05). On the contrary, in the non-responders group Hb levels did not change 10.3 ± 0.5 gr/dL at baseline and 10.1 ± 1.1 gr/dL at F-U (P = NS), and the mean doses of ESAs increased from 144 ± 75 IU/kg/b.w./week to 218 ± 145 IU/kg/b.w./week (P = NS). Conclusion: Adequate control of SHPT is associated with concomitant improvement of anemia and decrease in ESAs need. Future endeavors are required to confirm these preliminary results.

Preventing calcium and vitamin D deficiencies following weight loss and metabolic surgery

Introduction Uncertain nutritional outcomes following common metabolic surgical techniques are concerning given the long-term potential for postoperative metabolic bone disease. This study aims to investigate the variations in serum calcium, vitamin D, and parathyroid hormone (PTH) levels following Roux-en-Y Gastric bypass (RYBP) and Sleeve Gastrectomy (SG). Methods A retrospective analysis of 370 patients who underwent metabolic surgery at a single-centre group practice in Melbourne, Australia, over 2 years. Results Patients underwent SG (n = 281) or RYGP (n = 89), with 75% and 87% of the cohort being female, respectively. Postoperative mean serum calcium levels and median serum vitamin D levels improved significantly by 24 months within both cohorts. Serum PTH levels within the RYBP group were significantly higher than the SG group across all time points. PTH levels significantly fell from 5.7 (IQR 4.2–7.4) to 5.00 (4.1–6.5) pmol/L by 24 months following SG. However, PTH levels following RYBP remained stable at 24 months, from 6.1 (IQR 4.7–8.7) to 6.4 (4.9–8.1) pmol/L. Furthermore, we failed to notice a significant improvement in PTH levels following RYBP among those with higher PTH levels preoperatively. Conclusion Higher PTH levels following RYBP, compared to SG, may imply we are undertreating patients who are inherently subjected to a greater degree of malabsorption and underlying nutritional deficiencies. This finding calls for a tailored supplementation protocol, particularly for those with high preoperative PTH levels undergoing RYBP, to prevent deficiencies.