Serum Parathyroid Hormone Concentrations Research Articles

FAM111A is dispensable for electrolyte homeostasis in mice

Autosomal dominant mutations in FAM111A are causative for Kenny-Caffey syndrome type 2. Patients with Kenny-Caffey syndrome suffer from severe growth retardation, skeletal dysplasia, hypoparathyroidism, hypocalcaemia, hyperphosphataemia and hypomagnesaemia. While recent studies have reported FAM111A to function in antiviral response and DNA replication, its role in regulating electrolyte homeostasis remains unknown. In this study, we assessed the role of FAM111A in the regulation of serum electrolyte balance using a Fam111a knockout (Fam111a−/−) C57BL/6 N mouse model. Fam111a−/− mice displayed normal weight and serum parathyroid hormone (PTH) concentration and exhibited unaltered magnesium, calcium and phosphate levels in serum and 24-hour urine. Expression of calciotropic (including Cabp28k, Trpv5, Klotho and Cyp24a1), magnesiotropic (including Trpm6, Trpm7, Cnnm2 and Cnnm4) and phosphotropic (Slc20a1, Slc20a2, Slc34a1 and Slc34a3) genes in the kidneys, duodenum and colon were not affected by Fam111a depletion. Only Slc34a2 expression was significantly upregulated in the duodenum, but not in the colon. Analysis of femurs showed unaffected bone morphology and density in Fam111a−/− mice. Kidney and parathyroid histology were also normal in Fam111a−/− mice. In conclusion, our study is the first to characterise the function of FAM111A in vivo and we report that mice lacking FAM111A exhibit normal electrolyte homeostasis on a standard diet.

Chronic inflammation in hemodialysis patients with secondary hyperparathyroidism

Abstract. Our study aimed to establish a possible correlation between parathyroid hormone (PTH) levels and biomarkers of inflammation in hemodialysis patients with secondary hyperparathyroidism.
 Methods. This observational сross-sectional study involved 108 hemodialysis patients with secondary hyperparathyroidism. The levels of serum cytokines interleukin-1 (IL-1), IL-6 and tumor necrosis factor-alpha (TNF-alpha) were determined in all patients. The correlations between the levels of inflammatory mediators on the one hand and the level of PTH on the other were studied. The effects of diabetes, heart failure (HF), fractures, and smoking on the inflammatory status and PTH levels were assessed.
 Results. The level of IL-1 in patients with diabetes was more than 2 times higher than in patients without diabetes (p<0.05). The level of IL-6 in patients with diabetes was more than 3 times higher than in patients without diabetes (p<0.05). The level of TNF-alpha in patients with diabetes was more than 1.5 times higher than in patients without diabetes (p<0.05). The level of PTH was more than 2.4 times higher in patients with diabetes compared with patients without diabetes (p<0.05). The level of IL-1 in patients with HF was 1.7 times higher than that in patients without HF (p<0.05). The level of IL-6 in patients with HF was more than 3 times higher than in patients without HF (p<0.05). The level of TNF-alpha did not differ significantly in patients with and without HF. The level of PTH was more than 2.3 times higher in patients with HF compared with patients without HF (p<0.05). The level of IL-1 in patients with fractures was more than 2.8 times higher than in patients without fractures (p<0.05). The level of IL-6 in patients with fractures was more than 3.6 times higher than in patients without fractures (p <0.05). The level of TNF-alpha in patients with fractures was more than 1.5 times higher than in patients without fractures (p<0.05). The level of PTH was more than 2.4 times higher in patients with fractures compared to patients without fractures (p<0.05). Smoking status in our study did not affect the levels of both PTH and inflammatory mediators. A positive correlation between the concentration of IL-6 and serum PTH was found (r = 0.7; p <0.001).
 Conclusions. The presence of chronic inflammation is characteristic of hemodialysis patients with secondary hyperparathyroidism. Proinflammatory cytokine levels are significantly higher in patients with diabetes, HF, and a history of fractures. A positive correlation between the level of IL-6 and PTH may indicate a relationship between the development of secondary hyperparathyroidism and chronic inflammation.

Relationships Between 25-Hydroxyvitamin D, Parathyroid Hormone, and Bone Mass in 4-Year-Old Children in Dhaka, Bangladesh

ObjectivesElevated serum parathyroid hormone (PTH) concentration was incidentally observed in a high proportion of children in a study in Dhaka, Bangladesh. We explored potential correlates of elevated PTH by estimating the association of PTH with 25-hydroxyvitamin D (25(OH)D) and associations of 25(OH)D and PTH with bone outcomes.MethodsData were obtained from the BONe and mUScle health in Kids study (BONUSKids; NCT03537443). Total-body less head (TBLH) bone mineral content (BMC) and areal bone mineral density (aBMD) were measured by dual-energy X-ray absorptiometry (DXA). Serum PTH and 25(OH)D were analyzed by chemiluminescent immunoassay and liquid chromatography-tandem mass spectrometry, respectively. BONUSKids participants (n = 642) with DXA, PTH and 25(OH)D data at 4 years were included. Associations between 25(OH)D, PTH and bone outcomes were estimated using unadjusted linear and two-phase linear spline regression models. Model fit was compared using AIC.ResultsAmong the 534 children who met inclusion criteria, 43% were vitamin D deficient (< 30nmol/L) and 30% had PTH > 6.9pmol/L. A non-linear inverse relationship was observed between 25(OH)D and PTH. Model fit was optimized with an inflection point at 25nmol/L, above which the association attenuated (< 25nmol/L: −0.16pmol/L per 1nmol/L change in 25(OH)D [95%CI −0.23, −0.10]; ≥ 25nmol/L: –0.02pmol/L [95% CI −0.04, −0.008]. 25(OH)D was positively linearly associated with TBLH BMC (0.39g per 1nmol/L change in 25(OH)D [95%CI 0.10: 0.69]) and aBMD (0.0004g/cm2 per 1nmol/L change in 25(OH)D [95% CI 0.0002, 0.0006]). There was no significant association between PTH and TBLH BMC. The non-linear association between PTH and TBLH aBMD was negative at PTH > 4pmol/L (< 4pmol/L: 0.002g/cm2 per 1pmol/L change in PTH [95% CI –0.006, 0.01], ≥ 4pmol/L: −0.002g/cm2 [95% CI −0.0038, −0.0002]).ConclusionsThe non-linear inverse association of PTH with 25(OH)D supports the hypothesis that vitamin D deficiency contributed to elevated PTH in this population. Although 25(OH)D was associated with bone outcomes, the magnitude of the association was similar at 25(OH)D concentrations below and above 25nmol/L. PTH was inconsistently associated with bone outcomes, suggesting single measurements of PTH may not be a useful marker of bone health in this setting.Funding SourcesCanadian Institutes of Health Research.

MO541: Secondary Hyperparathyroidism Influence on Parathyroid Hormone Levels After Kidney Transplantation

Abstract BACKGROUND AND AIMS Optimal parathyroid hormone (PTH) control in patients before kidney transplantation (KT) might decrease the subsequent risk of parathyroid hyperplasia and hyperparathyroidism (HPT) after surgery. We evaluated the patient characteristics and HPT markers control before and over the first post-transplant year. METHOD We studied 210 patients (107 women, 103 men and age 45 ± 9 years) with end-stage renal failure (ESRF). All patients underwent primary KT. The duration of the pre-transplant period ranged from 0 to 158 months (median 19). The determination of HPT markers was carried out before 3 and 12 months after KT. The target PTH after KT was considered to be 130 pg/mL. Serum concentrations of PTH, calcium, phosphorus, total alkaline phosphatase activity, albumin and creatinine were determined using standard methods, estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI formula and stratification of chronic kidney disease stages was carried out according to the eGFR. RESULTS Patients were divided into two groups based on PTH before KT. In the first group were 63 patients with PTH &amp;gt; 585 pg/mL (median 866, Q1–Q3: 667; 1078), in the second group there were 147 patients with PTH 130–585 pg/mL (median 300, Q1–Q3: 225; 400). Patients with secondary HPT versus target PTH group had long duration of dialysis therapy (27 months versus 15 months; P = 0.005), frequency of hyperphosphatemia (87% versus 57%; P &amp;lt; 0.001) and increased activity of blood alkaline phosphatase (21% versus 4%; P &amp;lt; 0.001). Initial renal transplant function was the same in both groups: acute tubular necrosis amounted to 57% and 46% respectively (P = 0.07), duration of acute tubular necrosis 2 and 0 days respectively (P = 0.087). Three months after kidney transplantation in the first group median blood PTH decreased to 247 pg/mL (Q1–Q3: 163; 452), the prevalence of PTH &amp;gt; 130 pg/mL had 88% patients, in the second group median blood PTH decreased to 150 pg/mL (Q1–Q3: 120; 210), the prevalence of PTH &amp;gt; 130 pg/mL had 59% patients (P &amp;lt; 0.001). Hypercalcemia was in 13% patients of first group and 0 in second group (P &amp;lt; 0.001). Serum creatinine and eGFR did not differ and amounted respectively to 114 (Q1–Q3: 86; 150) and 110 (Q1–Q3: 80; 136) μmol/L (ns), 60 (Q1–Q3: 45; 80) and 60 (Q1–Q3: 49; 80) mL/min (ns). The ratio of stages of chronic kidney disease was the same (Figure 1). A total of 12 months after KT the blood level PTH was 180 (Q1–Q3: 95; 247) and 106 (Q1–Q3: 88; 125) pg/mL (P = 0.004), the prevalence of PTH &amp;gt; 130 pg/mL had 54% and 15% (P &amp;lt; 0.001) patients respectively. Kidney transplant function did not differ as well as after 3 months (median serum creatinine 120–121 μmol/L, eGFR 55 and 55 mL/min). In the post-transplant period, patients of the first group were more often prescribed vitamin D preparations and its analogues, five were treated with cinacalcet due to hypercalcemia and seven underwent parathyroidectomy after 1.5–2.5 years. CONCLUSION Secondary HPT before KT predicted a higher PTH level in the first year after surgery. Patients with ESRF who are on the waiting list for KT need careful monitoring of blood PTH and adequate treatment of secondary HPT.

MO808: Indoxyl-Sulphate and Cresyl Sulphate are Respectively Linked to Calcium-Phosphate Metabolism Variables and to Cardiovascular Morbidity in Hemodialysed Patients

Abstract BACKGROUND AND AIMS Indoxyl sulphate (IS) and Cresyl sulphate (CS) are uremic toxins generated by the intestinal amino acid catabolism. Blood levels of these toxins increase in patients with CKD and are linked to cardiovascular events. Therefore, we studied the relationship between serum levels of free IS and CS and divalent ion metabolism variables and cardiovascular morbidity (stroke, heart failure, angor and myocardial infarction) in 139 haemodialysis patients (age 68 + 13 years, weight 65 + 13 kg, dialysis vintage 69 + 71 months). METHOD We divided patients according to tertiles of free serum IS and CS. RESULTS Patients in the highest tertile of serum free IS showed shorter dialysis vintage and higher body weight gain between dialysis sessions than patients in the other two tertiles. Patients in the highest tertile of IS showed lower body weight and serum concentrations of alkaline phosphatase, 1,25(OH)2D and PTH compared with the lowest tertile. Serum PTH was also measured during 2 years after the baseline; it was higher in patients in the lowest than those in the highest tertile of serum free IS. No relationships of serum free CS concentrations with phosphate and calcium metabolism variables were observed. Kaplan–Meier survival analysis shows an increased cardiovascular morbidity in patients in the CS highest tertile (blue line in the figure) compared with those in the lowest and middle tertiles taken together (red line; P = 0.01). This association was not found considering IS tertiles. CONCLUSION Our findings suggest that serum free IS may be associated with PTH and 1,25(OH)2D secretion, whereas free PCS may predict cardiovascular risk in haemodialysis patients. A point for future investigation could be the relationship between IS and adynamic bone disease.

Metabolic Bone Disease of Prematurity.

Metabolic Bone Disease of Prematurity.

Vitamin D status and its relationship with obesity indicators in Moroccan adult women.

Background: Although vitamin D deficiency has been studied in various populations, there are few data on its prevalence and associated factors among Moroccan women. Aim: To determine the prevalence of vitamin D deficiency and investigate its association with body mass index (BMI), waist circumference, and serum concentrations of parathyroid hormone, calcium, and phosphorus in a sample of Moroccan adult women. Methods: This is a cross-sectional study conducted at Mohammed V Military Hospital of Instruction, Rabat. Anthropometric measurements and biochemical analyses were performed using standard procedures Results: A total of 714 women aged 18-65 years participated in this study. The overall prevalence of vitamin D deficiency was 74.4%. Approximately 24% and 51% of women had severe and moderate vitamin D deficiency, respectively. Serum 25-hydroxyvitamin D (25(OH)D) concentrations were inversely correlated with BMI in vitamin D-deficient subjects (P = 0.036) and with parathyroid hormone 1-84 (PTH1-84) levels in the study sample (P = 0.010). PTH1-84 concentrations were greater among overweight/obese individuals compared to their non-overweight peers (P = 0.001) and tended to be higher among vitamin D-deficient women than vitamin D-sufficient women (P = 0.053). Conclusion: This study showed a very high prevalence of vitamin D deficiency in this sample of Moroccan women. Lower serum 25(OH)D levels were associated with increased BMI in vitamin D-deficient women and with elevated PTH1-84 levels among the study sample. Although these findings come from a convenience sample of women that attended a nutrition clinic, they underscore the urgent need to develop public health interventions to improve women's vitamin D status.

The effect of combined magnesium and vitamin D supplementation on vitamin D status, systemic inflammation, and blood pressure: A randomized double-blinded controlled trial

ObjectivePoor vitamin D and magnesium status is observed in individuals who are overweight and obese (Owt/Ob) and is often associated with a heightened risk of cardiovascular disease. Magnesium is a cofactor that assists vitamin D metabolism. We aimed to determine the efficacy of a combined magnesium and vitamin D regimen compared with vitamin D only on increasing serum 25-hydroxyvitamin D (25OHD) concentrations and the effects of these supplements on cardiometabolic outcomes. MethodsThis 12-week double-blinded randomized controlled trial had three treatment arms: magnesium + vitamin D (MagD; 360 mg magnesium glycinate + 1000 IU vitamin D 3 × daily), vitamin D only (VitD; 1000 IU vitamin D 3 × daily), and placebo. A total of 95 Owt/Ob participants were randomized into one of these three study arms. Anthropometry, dietary intake, concentrations of serum 25OHD, serum parathyroid hormone (PTH), serum inflammatory markers, and blood pressure were obtained at baseline and week 12. ResultsThe MagD group experienced the greatest increase in serum 25OHD concentrations (6.3 ± 8.36 ng/mL; P < 0.05). There was a decrease in systolic blood pressure (7.5 ± 8.26 mmHg; P < 0.05) for individuals who had a baseline systolic blood pressure of >132 mmHg in the MagD group. There were no statistically significant treatment effects on serum PTH concentrations and markers of inflammation. ConclusionsA combined MagD treatment may be more effective in increasing serum 25OHD concentrations compared with VitD supplementation alone in Owt/Ob individuals.

The Predictive Role of Parathyroid Hormone for Nonalcoholic Fatty Liver Disease following Bariatric Surgery

Background Morbid obesity is frequently complicated by chronic liver diseases, including nonalcoholic fatty liver disease (NAFLD), nonalcoholic steatohepatitis (NASH), and fibrosis. Parathyroid hormone (PTH) is found to be elevated in morbid obesity due to the defective hepatic metabolism of vitamin D. Bariatric surgery is performed to help patients with BMI>40 kg/m2 to effectively lose weight, particularly in patients with obesity who are afflicted with complications such as NAFLD/NASH. Objective This study aimed to evaluate the PTH level as a predictor of hepatic function in individuals with morbid obesity who have undergone bariatric surgery. Methods Ninety subjects with morbid obesity referred for Roux en-Y gastric bypass surgery were recruited. After IRB approval, demographic profiles, anthropometric factors, liver biopsy, and laboratory tests were obtained. The two-dimensional shear wave elastography (2D-SWE) technique was applied to assess hepatic stiffness. Results A significant reduction occurred six months after bariatric surgery in the anthropometric indices (p < 0.001), hepatic elasticity (p=0.002), alanine aminotransferase (p < 0.001), serum alkaline phosphatase (p < 0.001), gamma-glutamyl transpeptidase (GGT) (p < 0.001), and nonalcoholic fatty liver disease fibrosis score (NFS) (p < 0.001). Serum PTH concentration was not predictive of postsurgical liver fibrosis and steatosis at six months but could predict weight loss success rate. No significant alteration in serum PTH levels was observed between presurgical vs. postsurgical time points. Conclusion A significant reduction was observed in the anthropometric parameters, liver enzymes, and hepatic elasticity after bariatric surgery. No significant effect was found on PTH levels.

Pleiotropic effects of atorvastatin in peritoneal dialysis patients: A retrospective-prospective observational cohort study

Abstract. Recent studies demonstrate a large number of non-lipid modifiable effects of statins in various diseases. However, although atherogenic dyslipidemia is a common feature in peritoneal dialysis (PD) patients, statins use is supported by limited data and there is a general lack of research on their pleiotropic effects in this patients’ cohort. The present study aimed to evaluate the possible pleiotropic effects of atorvastatin in PD patients.&#x0D; Methods. A total of 114 PD patients with an average age of 55 (48-65) years and a dialysis vintage of 31 (14-50) months were included in this combined retrospective and prospective multicentre cohort study. PD patients (n = 54) who had started receiving atorvastatin before or after dialysis initiation and been treated with atorvastatin no less than 12 months were included in the Atorvastatin Group. PD patients (n = 60) who have never taken statins consisted of Atorvastatin-free Group.&#x0D; In addition to routine clinical and PD adequacy tests, concentrations of interleukins -6, -10, tumor necrosis factor-alpha, and monocyte chemoattractant protein-1 in PD effluent (PDE) were evaluated in all study participants at the start of the follow-up period. The primary outcomes were the 3-year PD technique survival and the all-cause mortality of PD patients during the follow-up period.&#x0D; Results. Atorvastatin users had lower serum phosphate and parathyroid hormone concentrations, higher weekly creatinine clearance, peritoneal weekly Kt/V urea, and, accordingly, total weekly Kt/V compared to the Atorvastatin-free Group. PDE cytokines assessment demonstrated significantly lower concentrations of all studied cytokines in the Atorvastatin Group compared with the Atorvastatin-free Group. In the Cox regression models, atorvastatin use was significantly associated with better PD technique survival (HR = 0.28 (95% CI 0.15; 0.54), p = 0.003) and mortality reduction in the PD patients regardless of their age, diabetes, anuric status, albumin and C-reactive protein levels, and history of PD peritonitis (HR = 0.24 (95% CI 0.15; 0.44), p &lt; 0.0001).&#x0D; Conclusions. Atorvastatin treatment was associated with the normalization of phosphate-calcium metabolism, low intraperitoneal inflammation and incidence of PD-associated peritonitis, and better dialysis adequacy in our cohort of PD patients. These pleiotropic effects of atorvastatin may be one of the reasons for the lower all‐cause mortality in PD patients. Further studies are needed to determine the necessity of statins prescribing in PD patients.

Hypocalcemia in hospitalized patients with COVID-19: roles of hypovitaminosis D and functional hypoparathyroidism.

IntroductionDespite the high prevalence of hypocalcemia in patients with COVID-19, very limited studies have been designed to evaluate etiologies of this disorder. This study was designed to evaluate the status of serum parameters involved in calcium metabolism in patients with COVID-19 and hypocalcemia.Materials and methodsThis cross-sectional study was conducted on 123 hospitalized patients with COVID-19. Serum concentrations of PTH, 25 (OH) D, magnesium, phosphate, and albumin were assessed and compared across three groups of moderate/severe hypocalcemia (serum total calcium < 8 mg/dl), mild hypocalcemia (8 mg/dl ≤ serum total calcium < 8.5 mg/dl) and normocalcemia (serum total calcium ≥ 8.5 mg/dl). Multivariate analyses were performed to evaluate the independent roles of serum parameters in hypocalcemia.ResultsIn total, 65.9% of the patients had hypocalcemia. Vitamin D deficiency was found in 44.4% and 37.7% of moderate/severe and mild hypocalcemia cases, respectively, compared to 7.1% in the normal serum total calcium group (P = 0.003). In multivariate analysis, vitamin D deficiency was independently associated with 6.2 times higher risk of hypocalcemia (P = 0.001). Only a minority of patients with hypocalcemia had appropriately high PTH (15.1% and 14.3% in mild and moderate/severe hypocalcemia, respectively). Serum PTH was low/low-normal in 40.0% of patients with moderate/severe low-corrected calcium group. Magnesium deficiency was not associated with hypocalcemia in univariate and multivariate analysis.ConclusionVitamin D deficiency plays a major role in hypocalcemia among hospitalized patients with COVID-19. Inappropriately low/low-normal serum PTH may be a contributing factor in this disorder.

Correlation Between Serum 25-hydroxyvitamin D Level and Cognitive Function Among the Elderly in Enugu State, Nigeria

<i>Background</i>: Low serum vitamin D is now implicated in many disease conditions among the elderly including cognitive impairment. Cognitive impairment is a common disease among elderly people causing much financial and social burden to the elderly, their families and caregivers. Therefore, the study aimed to determine the relationship between serum 25-hydroxyvitamin D (25(OH)D) concentration and cognitive function among elderly people in Enugu State, South-eastern Nigeria. <i>Methods</i>: This was a cross-sectional survey of subjects aged ≥ 60 years with cognitive impairment in communities and old People’s home in Enugu State in Nigeria and age- and sex-matched controls. The subjects were further divided into those with severe cognitive impairment and those with mild cognitive impairment using the Mini-Mental State Examination (MMSE). Serum 25(OH)D and parathyroid hormone (PTH) were assayed by enzyme-linked immune-sorbent assay while serum calcium, inorganic phosphate, and albumin were determined using the spectrophotometric method. Student t-test was used to compare mean values obtained, while Pearson correlation was used to determine relationships between continuous data. A p-value<0.05 was considered to be statistically significant. <i>Result</i>: One hundred and four (104) patients comprising of 58 males and 46 females were recruited for the current study. Among the study subjects compared to those of the controls, there were significantly decreased levels of serum 25(OH)D (p=0.0001) and the adjusted calcium (p=0.0001) concentrations but significantly increased level of serum PTH (p=0.0001) and inorganic phosphate (p=0.005) concentrations. Also, the mean values of serum 25(OH)D and adjusted calcium were significantly lower, serum PTH values were significantly higher while serum inorganic phosphate concentrations showed no significant difference for those with severe cognitive impairment when compared to values of those with mild cognitive impairment and controls. Additionally, there was also significant positive correlations between serum 25(OH)D and cognitive function (r=0.504, ρ<0.05). <i>Conclusion</i>: The study findings suggest that decreased serum Vitamin D concentration is associated with diminished cognitive function among the elderly and vice versa. Hence, the determination of Vitamin D status among elderly patients presenting with impairment of cognitive function is highly recommended. However, further studies are needed to validate findings from the present study.

Influence of Single Experience with Intraoperative Near-Infrared Autofluorescence on Postoperative Parathyroid Insufficiency after Thyroidectomy - A Preliminary Clinical Study.

Introduction: Total thyroidectomy has become the most common thyroid procedure. This treatment method results in most postoperative hypocalcemia (PH) and hypoparathyroidism (HPT) cases due to the unwitting removal of the parathyroid glands (PTGs). Near-infrared autofluorescence (NIRAF) is a new method that helps identify PTGs. This study aimed to determine whether short-term experience with intraoperative NIRAF may influence postoperative complications after thyroidectomy.Materials and methods: Overall, 65 patients who underwent thyroidectomy by one high-volume surgeon were enrolled in the study between March 2018 and August 2021. In August 2020, the surgeon performed four operations using the NIRAF device. After that experience, the technique of operating and preserving PTGs has been totally changed. Postoperative serum calcium (Ca) and parathormone (PTH) concentrations were measured. Using retrospective study analysis, we assessed the rate of PH and HPT.Results: There was no statistically significant difference in Ca (p = 0.1612) and PTH (p = 0.3590) concentrations between groups operated on before and after the NIRAF experience. The serum concentrations of Ca and PTH of all patients were positively correlated (r = 0.4074; p = 0.0022) as well as the Ca concentration and age of patients (r = 0.3292; p = 0.0116), respectively.Conclusions: These findings suggest that short-term NIRAF experience, and changing attitude to preserving PTGs does not affect thyroidectomy outcomes, even when utilized by a highly experienced high-volume thyroid surgeon. However, continuous use of NIRAF might enhance treatment outcomes, particularly for surgeons with limited experience.

Filamin A and parafibromin expression in parathyroid carcinoma.

Parathyroid carcinoma (PC), atypical parathyroid tumours (APT) and parathyroid adenoma (PA), all present with hypercalcemia. Diminished calcium-sensing receptor (CaSR) expression is reported in PC but is rare in benign tumours. Filamin A (FLNA) binds to the CaSR and activates the mitogen-activated protein kinase (MAPK) signalling pathway. FLNA is related to tumour aggressiveness in several cancers, but its role in parathyroid neoplasia is unknown. We examined FLNA, CaSR and parafibromin expression in PCs (n = 32), APTs (n = 44) and PAs (n = 77) and investigated their potential as diagnostic and/or prognostic markers. Tissue microarray slides were immunohistochemically stained with antibodies for FLNA, CaSR and parafibromin. Staining results were correlated with detailed clinical data. All tumours stained positively for CaSR, with two tumours (one PC and one APT) showing diminished expression. Carcinomas were characterized by increased cytoplasmic FLNA expression compared to APTs and PAs (P = 0.004). FLNA expression was not correlated with Ki-67 proliferation index or loss of parafibromin expression. Cytoplasmic FLNA expression was also associated with higher serum calcium, PTH concentrations and male sex (P = 0.014, P = 0.017 and P = 0.049 respectively). Using a combined marker score, we found that parathyroid tumours with low FLNA expression and positive parafibromin staining were extremely likely to be benign (P < 0.001). Cytoplasmic and membranous FLNA expression is increased in parathyroid carcinomas compared to benign tumours. A combined FLNA and parafibromin expression score shows potential as a prognostic predictor of indolent behaviour in parathyroid neoplasms.

Simultaneous primary hyperparathyroidism and multiple myeloma in a dog with hypercalcaemia

AbstractA 14‐year‐old male castrated Pomeranian was found to be hypercalcaemic and hyperglobulinaemic during investigation of anorexia and haematochezia. Ionised hypercalcaemia, increased serum parathyroid hormone concentration, normophosphatemia and a parathyroid nodule found on cervical ultrasound examination were diagnostic for primary hyperparathyroidism (PHPT). Thoracic radiographs revealed ovoid lytic lesions in multiple bones. To investigate the hyperglobulinaemia, serum electrophoresis and immunoglobulin (Ig) quantification were performed, revealing an IgA biclonal gammopathy. Bone marrow cytopathology confirmed multiple myeloma (MM). Following bilateral parathyroidectomy, the dog's hypercalcaemia resolved, and pulse‐dose chemotherapy with prednisone and melphalan was initiated to treat MM. To the authors' knowledge, this is a unique case report of simultaneous PHPT and MM in the veterinary literature, diseases that are rarely reported concurrently in humans. This case highlights the need to thoroughly investigate multiple problems when they are not explained by a single diagnosis.

RESULTS OF CLINICAL STUDY OF COMPLEX TREATMENT OF GENERALIZED PERIODONTITIS WITH THE USE OF STRONTIUM DRUGS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS

The most significant periodontal disorders associated with diabetes mellitus are due to changes in bone tissue. It has become necessary for specific osteotropic therapy that can normalize metabolic processes in the alveolar bone. In turn, currently the most promising in terms of improving osteogenic activity are strontium ions. Strontium ranelate is used to treat osteoporosis due to its antiresorptive and osteoanabolic action. However, its effectiveness against alveolar bone has not been sufficiently studied.&#x0D; The purpose of the work is to conduct a clinical study of complex treatment of generalized periodontitis, supplemented with strontium ranelate, in patients with type 2 diabetes mellitus.&#x0D; Materials and methods of the research. The study included 60 patients with generalized periodontitis of I-II degree of severity, chronic course, aged 35-45 years. Type 2 diabetes mellitus was diagnosed and two groups were formed. The traditional treatment regimen was used in the group of comparison (main group) where Strontium Ranelate was prescribed additionally. The treatment was evaluated according to the dynamics of clinical observations, orthopantomography and computed tomography data, the results of biochemical studies. As markers of bone resorption, tartrate-resistant acid phosphatase (TRAP) activity was determined in blood serum and the content of β-CrossLaps fragments was determined in urine. As markers of osteogenesis, the concentration of C-terminal propeptide type I procollagen (CICP) was detected in blood plasma, bone alkaline phosphatase (BAP) and osteocalcin were detected in serum. Serum parathyroid hormone concentrations, total blood calcium and total inorganic phosphorus in the blood were studied as indicators of mineral metabolism.&#x0D; Results of the research. In the earliest possible timeframe the complex treatment of generalized periodontitis was conducted during the observation which led to clinical stabilization of the inflammatorydestructive process in the periodontal tissues without a significant difference between the experimental groups (p ˃ 0.05). However, the condition of periodontal tissues in patients of the experimental groups differed in a year after treatment. In 16.7% of patients from the comparison group, recurrence of the inflammatory-destructive process in periodontal tissues was diagnosed, while the cases the deterioration of the pathological process was not detected in the main group. A significant difference was found for complex periodontal indices (Ramfjord, PI and SPITN) (p &lt;0.05). Clinical and radiological stabilization was observed in 83.3% of patients of the comparison group and in 100% in the main group. According to the results of computed tomography of the alveolar bone, an increase in bone mineral density was established in both groups, but only in the main group the difference between indices before and after treatment was significant (p˂0.05).&#x0D; In patients of the main group a more pronounced decrease in the activity of tartrate-resistant acid phosphatase (TRAP) was found in the serum and the concentration of β-CrossLaps was found in the urine, indicating inhibition of bone resorption, as well as markers of bone formation the concentration of C-terminal propeptide (CICP) was found in blood plasma, bone alkaline phosphatase (BAP) was found in serum, osteocalcin (p &lt;0.05). Indicators of mineral metabolism in bone tissue, both during treatment and for experimental groups, almost did not differ (p&gt; 0.05).&#x0D; Thus, the use of strontium drugs in the complex treatment of generalized periodontitis in patients with type 2 diabetes mellitus provides a longer and more stable clinical and radiological stabilization of the pathological process in periodontal tissues, primarily by inhibiting bone resorption and enhancing osteogenesis. So, they can be recommended for the wide use in stomatological practice.

Effects of idiopathic hypoparathyroidism on tooth eruption of rats

Objective: To explore the effects of reduced parathyroid function in early growth and development on tooth eruption and enamel development by establishing an animal model of idiopathic hypoparathyroidism (IHP) and to explore the mechanism of IHP affecting tooth eruption with a view to provide experimental basis for early diagnosis and clinical treatment of IHP. Methods: Forty-eight SD rats at postnatal day 7 were randomly and equally divided into sham operation group and IHP group. The bilateral parathyroidectomy (PTX) was performed by using carbon nanoparticles technique to establish an IHP rat model, while no parathyroids were removed in the sham operation group using the same technique. Serum was extracted after surgery, serum calcium, serum phosphorus, and serum parathyroid hormone (PTH) concentrations were detected in order to verify the success of the modeling. At postnatal day 14, day 25 and day 38 (P14, P25 and P38) the rats were sacrificed to collect the mandible samples (six from each group) and to analyze the volume of enamel, the height of the tooth eruption and the bone microarchitecture parameters of the root-oriented alveolar bone of mandibular third molar quantitatively by micro-CT scanning. Histological sections were prepared. The distribution and expression levels of osteoblast differentiation markers runt-related transcription factor 2 (RUNX2) and osterix (OSX) in the alveolar bone around the third molar were detected by immunohistochemical staining and the osteoclast activity was detected by tartrate-resistant acid phosphatase (TRAP) staining. After each of the third molars was isolated, the microhardness of the enamel was measure by using a microhardness tester and the enamel microstructure was photographed by using scanning electron microscope. Primary dental follicle stem cells were isolated from other six mandibulars from each group at P14 and cultured in vitro. The cell proliferation activity was tested by cell colony forming units detection. After induction of dental follicle stem cells into osteogenic differentiation, the degree of mineralization was detected by using alkaline phosphatase staining and alizarin red staining. The mRNA of mandibular tissues and dental follicle cells were extracted, the expression of genes related to osteoblasts and osteoclast differentiations and parathyroid hormone receptor 1 (PTH1R) were detected by real-time quantitative PCR. Results: Bilateral parathyroidectomy was successfully performed on rats with the help of carbon nanoparticles under stereomicroscope. After surgery, the serum calcium concentration reduced, the serum phosphorus concentration increased and the serum PTH concentration distinctly reduced (P<0.01). The volume of enamel [(4.58±0.24) mm3] and the microhardness [(167.76±21.86) MPa] in IHP group were significantly lower than that in sham operation group [(5.22±0.46) mm3, P<0.05; (223.92±10.94) MPa, P<0.01, respectively]. The eruption height of the mandibular third molar in the IHP group was respectively lower than that in the sham operation group (P<0.05). The bone volume over total volume and trabecular number of the root-oriented alveolar bone of the mandibular third molars in the IHP group were respectively lower than that in sham operation group (P<0.05). The expression levels of RUNX2 and OSX proteins in the root-oriented alveolar bone of the mandibular third molars in the IHP group respectively reduced, compared to that in sham operation group (P<0.05). Furthermore, the number of osteoclasts (3.86±1.07) in crown-oriented alveolar bone in the IHP group was respectively lower than that in sham operation group (6.43±1.27) (P<0.01). The proliferative activity of dental follicle stem cells in the IHP group respectively decreased (P<0.01). After the induction of osteogenic differentiation, the mineralization ability of dental follicle stem cells in the IHP group was weakened. In the mandibular tissues of IHP group, the expression levels of osteogenesis related genes such as RUNX2 and OSX and the the expression of PTH1R significantly reduced (P<0.05). The receptor activator of nuclear factor-κB ligand/osteoprotegerin (RANKL/OPG) ratio reduced significantly (P<0.01) compared to those of sham operation group. Also in the dental follicle cells of IHP group, the expression levels of osteogenesis related genes such as RUNX2 and OSX, the RANKL/OPG ratio and the expression of PTH1R significantly decreased simultaneously compared to that in sham operation group (P<0.01). Conclusions: Under the condition of idiopathic hypoparathyroidism, the weakening of PTH/PTH1R signaling may reduce the proliferative activity of dental follicle stem cells, inhibit their regulation for osteoblast and osteoclast differentiations and functions, thereby interfere the bone remodeling of alveolar bone around the tooth germ during tooth eruption, which eventually leads to delayed tooth eruption.

Multidisciplinary team efforts to improve the pregnancy outcome of pregnancy complicated with primary hyperparathyroidism: case series from a single hospital

BackgroundThere is no consensus or management algorithm for primary hyperparathyroidism (PHPT) in pregnancy.MethodsThis study comprises a retrospective case series. From August 2014 to December 2020, 9 cases of PHPT in pregnancy were diagnosed by a multidisciplinary team (MDT) consultation center of obstetrics in our hospital. Their clinical manifestations, treatment strategies, and maternal and infant outcomes were analyzed.ResultsThe median onset age of the patients was 32 (25 ~ 38) years. PHPT was diagnosed in two cases before pregnancy, in six cases during pregnancy and in one case postpartum. The main clinical manifestations were nausea, vomiting, and other nonspecific symptoms, with anemia as the most common maternal complication. Hypercalcemia crisis was developed in one case. The median levels of preoperative serum calcium and parathyroid hormone (PTH) were 3.08 (2.77 ~ 4.21) mmol/L and 300.40 (108.80 ~ 2603.60) pg/ml, respectively. The parathyroid ultrasonography tests were positive in eight cases and negative in one patient who had an ectopic lesion localized by 99mTc-MIBI. Parathyroidectomy was conducted in 7 cases during the 2nd trimester, including 2 patients diagnosed before pregnancy who refused surgery, 1 patient during the 1st trimester, and 1 patient postpartum, with a significant reduction in serum concentrations of calcium and PTH. A management algorithm was developed.ConclusionThis case series suggests that pregnant women with PHPT should be managed by MDT according to the algorithm. If PHPT is confirmed in fertile women before pregnancy, parathyroidectomy should be strongly suggested and performed. If PHPT is diagnosed during pregnancy, even in its mild form, surgical treatment, optimally during the 2nd trimester, is effective and safe for pregnancy and neonatal outcome.

The Associations of Serum Osteocalcin and Cortisol Levels With the Psychological Performance in Primary Hyperparathyroidism Patients.

ObjectivesThe aim of this study was to investigate factors responsible for the psychological performance in primary hyperparathyroidism (PHPT) patients.MethodsA group of 38 PHPT patients receiving questionnaires, including Beck Depression Inventory (BDI), State–Trait Anxiety Inventory (STAI), and 36-Item Short Form Survey (SF-36), was evaluated. The relationships between scores of questionnaires and clinical biomarkers were examined. Collinearity and linear regression model were applied to examine variables determining the scores of the questionnaire. In 192 PHPT patients, bivariate and partial correlation were used to analyze the relationships between serum concentrations of parathyroid hormone (PTH), calcium, osteocalcin (OCN), and cortisol.ResultsAmong 38 patients receiving questionnaire tests, 50% (19/38) of the patients developed state anxiety, 60.5% (23/38) of the patients had the trait of developing anxiety. In addition, 18.4% (7/38) of the patients developed mild to severe depression. Serum cortisol at 8:00 was negatively and significantly correlated with social function (r = -0.389, p = 0.041) after controlling for age, sex, disease duration, serum PTH, calcium, phosphorus, and 25-hydroxyvitamin D [25(OH)D] concentration. OCN was significantly and negatively correlated with score of STAI-S (r = -0.426, p = 0.027). In the linear regression model for BDI score, variables with statistical significance were serum OCN (β = -0.422, p = 0.019) and cortisol at 0:00 (β = 0.371, p = 0.037). In 192 PHPT patients, the serum concentration of OCN (r = 0.373, p = 0.000) was positively correlated with PTH level. After controlling for age, sex, disease duration, serum 25(OH)D, phosphorus, and calcium concentration, the positive correlation between OCN and PTH was still statistically significant (r = 0.323, p = 0.000). The serum concentration of cortisol at 0:00 was significantly and positively correlated with serum calcium (r = 0.246, p = 0.001) in bivariate correlation analysis. After controlling for age, sex, disease duration, serum PTH, 25(OH)D, and phosphorus concentration, serum cortisol at 0:00 was still positively and significantly correlated with serum calcium (r = 0.245, p = 0.001).ConclusionSerum levels of OCN and cortisol, rather than PTH and calcium, are associated with the development of anxiety and depression symptoms in PHPT patients.

Parathyroid hormone serum concentration kinetic profile in critically ill patients undergoing continuous renal replacement therapies: a prospective observational study.

Elevated serum parathormone (PTH) levels have been observed in acute kidney injury and are related to calcium-phosphate metabolism disturbance, decreased renal production of 1,25 dihydroxyvitamin D3, impaired renal PTH excretion, and other renal-independent factors. There are no data regarding PTH concentration kinetics in critically ill patients undergoing continuous renal replacement therapies (CRRT) in an intensive care setting. The primary objective of this study was to investigate trends in PTH serum levels in critically ill patients with multiorgan failure undergoing CRRT, by performing periodic PTH measurements in the acute phase of critical illness. This was a single-centre, prospective, observational study conducted in an mixed, university-affiliated intensive care unit. Critically ill patients who fulfilled all of the following criteria were included: respiratory failure; circulatory failure; acute kidney injury treated by CRRT; and sequential organ failure assessment score (SOFA score) of 5 or more. Patients who met any of the following criteria were excluded: acute liver failure; hypercalcemia at admission (total calcium serum level > 10.6 mg/dL; total ionized calcium plasma level > 1.35 mmol/L); parathyroid gland disease; end-stage renal disease; patients undergoing therapeutic plasma exchange or extracorporeal membrane oxygenation procedures; aged under 18 years; pregnant; and life expectancy after admission to the intensive care unit anticipated to be less than 72 hours as assessed by the investigator. Thirty patients met the inclusion criteria. A statistically significant change in PTH over time was observed (Friedman ANOVA; p = 0.0001). The post-hoc test showed a statistically significant decrease in PTH: measurements 5-8 relative to measurement 1, and measurements 4-8 relative to measurement 2 (p < 0.05). No significant correlations between 25 hydroxyvitamin D3 deficiency, age, diagnosis, SOFA score, and PTH levels were observed. A statistical test indicated that serum concentrations of PTH were significantly higher in the de novo sepsis group (p < 0.05). The PTH serum concentration decreases during the course of CRRT in the majority of patients. When the course of the disease starts to be complicated by sepsis, PTH serum levels then remain high. A probable reason for this is the existence of the inflammatory state triggered by sepsis.