Biochemical markers and FokI and TaqI vitamin D receptor genes polymorphism in rheumatoid arthritis.

BACKGROUND: Previous studies have reported the role of genes in different metabolic processes in the human body, and any variation in gene polymorphisms could lead to disturbances in these processes and different diseases. OBJECTIVE: This study aimed to compare vitamin D receptor (VDR) FokI and TaqI genotypes in terms of parathyroid hormone (PTH) and some biomarkers of inflammation and susceptibility to rheumatoid arthritis (RA) disease. METHODS: This study included 100 patients with rheumatoid arthritis (RA). Genotyping was performed by polymerase chain reaction (PCR) and examined by specific restriction enzymes using restriction fragment length polymorphism (RFLP). Serum intact PTH, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), rheumatoid factor (RF), and anti-cyclic citrullinated peptide antibodies (ACCPs) levels were measured. RESULTS: An increased PTH level (> 65 pg/ml) was found in 8% of patients. No significant differences among FokI and TaqI vitamin D receptor genes polymorphism regarding positive and negative RF or ACCPs were found. A significant difference was found among FokI (p = 0.009) and none in TaqI genotypes regarding intact parathyroid hormone level categories. No significant correlation was found between the serum intact PTH level and ESR or CRP levels (P = 0.13 and 0.28, respectively). The parathyroid hormone level was not a good predictor for RF or ACCPs (P = 0.5 and 0.06, respectively). CONCLUSION: The FokI gene may play a role in controlling PTH levels in patients with RA. There was no significant correlation found between the serum intact PTH level and RA severity according to ESR and CRP inflammatory biomarkers. There are no differences between VDR genes FokI and TaqI polymorphism in terms of RA susceptibility (for RF and ACCPs).

Incidence and risk factors of hypoparathyroidism and hypocalcemia after hemithyroidectomy.

PURPOSE: The incidence and risk factors for hypoparathyroidism after total thyroidectomy is well-known. However, the characteristics of hypoparathyroidism and hypocalcemia after hemithyroidectomy have not been investigated well. In this study, we aimed to evaluate the incidence, characteristics, and risk factors of hypoparathyroidism and hypocalcemia after hemithyroidectomy. METHOD: We retrospectively analyzed the medical data of 321 patients who underwent hemithyroidectomy, with or without central neck dissection, from January 2012 to April 2019. We analyzed the serum intact parathyroid hormone (iPTH), calcium, and ionized calcium (iCa) levels serially (preoperatively and postoperatively on the operation day; days 1 and 3; and months 1, 3, 6, and 12) and evaluated risk factors for postoperative hypoparathyroidism and hypocalcemia. RESULTS: The mean iPTH and calcium levels decreased significantly after hemithyroidectomy on the operation day and postoperative days 1 and 3, and returned to the preoperative level at the postoperative 1-month follow-up. The mean iCa level decreased significantly on the operation day and postoperative day 1. Transient hypoparathyroidism and transient hypocalcemia occurred in 16 (5%) and 250 (78%) participants, and they recovered to normal levels postoperatively by 1 month. Eight (2.5%) patients had mild symptoms of hypocalcemia necessitating oral calcium supplementation. No permanent hypoparathyroidism or hypocalcemia was observed. Preoperatively low serum iPTH and calcium levels were associated with transient hypoparathyroidism and hypocalcemia after hemithyroidectomy. CONCLUSION: Approximately 5% and 2.5% of participants showed transient hypoparathyroidism and mild symptomatic hypocalcemia after hemithyroidectomy. The risk factors for transient hypoparathyroidism and hypocalcemia include preoperative low serum iPTH and calcium levels.

LONG-TERM USE OF GLUCOCORTICOID MODULATED PARATHYROID HORMONE LEVELS IN OSTEOPOROSIS PATIENTS.

Glucocorticoids are drugs that are often used in both inpatient and outpatient settings. Their anti-inflammatory action is often utilized to treat a variety of diseases. A range of undesirable outcomes might occur with long-term glucocorticoid use, particularly long-term high-dose applications. This study designs as a case-control study, which was conducted in the Joint Enology Clinic/Al-Hilla Teaching Hospital, Al-Imam Al-Sadiq Hospital, and Merjan Teaching Hospital in Hilla City, Babylon Governorate of Iraq. This study was carried out between December 2022 to March 2023. In this study, the total number of subjects was 100; the patient group consisted of 50 with osteoporosis (19 males and 31 females). Patients and control group's ages were (41-50 years). They were selected as matched in terms of gender and age. The results referred to the increased levels, of parathyroid hormone in osteoporosis patients with highly significant differences (P≤0.0001) when compared with the control group, while there was a significant decrease in calcium in the patient group (P≤0.0001) when compared with the control group. In conclusion, the parathyroid hormone has a beneficial association to indicate bone mineralization status. Parathyroid hormone could be used as a prognostic marker in individuals with long-term use of glucocorticoid to predict the development of bone mineral disease.

Brown tumor of the cervical spine with primary hyperparathyroidism: A case report and literature review.

RATIONALE: Brown tumor (BT), an uncommon focal lytic bone tumor, is a non-neoplastic and reactive process caused by increased osteoclastic activity and fibroblastic proliferation in primary or secondary hyperparathyroidism. Vertebral tumor causing neural compression is relatively rare, especially in the cervical spine. PATIENT CONCERNS: A 29-year-old man developed neck pain and arm radicular pain 4 months ago, with the level of serum calcium significantly higher than normal. Computed tomography scan of the cervical spine revealed an expansile lytic lesion occupying the C6 body, left pedicle, and left lamina of C5-6. DIAGNOSES: Osteoclastoma according to imaging and histopathological results. INTERVENTIONS: A laminectomy of C5-6 was performed. OUTCOMES: One month later, he was re-hospitalized due to nausea and vomiting and the serum calcium, was still, kept at a high level. Additionally, the parathormone (PTH) was greatly higher than normal. BT with primary hyperparathyroidism due to the parathyroid tumor was considered. After the surgery of the right parathyroid gland was performed, serum calcium and PTH both decreased, and computed tomography showed good recovery. LESSONS: BTs might be misdiagnosed as other giant cell tumors, thus when giant cell tumors are considered, serum calcium and PTH examination may be needed to exclude BTs.

Changes in bone turnover markers in adolescents with gastroesophageal reflux disease treated with lansoprazole.

Background: Proton pump inhibitors (PPIs) have been suggested to lead to bone resorption, while the effects of PPIs on the bone mineral metabolism in children has received only limited attention in literature to date. The present study investigates whether lansoprazole alters bone turnover markers in adolescents with gastroesophageal reflux disease (GERD). Patients and methods: Included in the study were adolescents aged 16-18 with GERD and a healthy volunteers group. The GERD patient group was treated with lansoprazole 30 mg once daily for eight weeks. The serum calcium, phosphorus, magnesium, alkaline phosphatase (ALP), parathormone (PTH), 25 (OH) vitamin D, osteocalcin and urinary calcium, creatinine, deoxypyridinoline (DPD), collagen type-1 crosslinked C-telopeptide (CTX) and collagen type-1 crosslinked N-telopeptide (NTX) of both groups were studied before and after the end of the treatment. Results: A comparison of the 30 patients with GERD and the 30 volunteers revealed no significant difference in the serum calcium, phosphorus, magnesium, ALP, urinary calcium/creatinine ratio, 25 (OH) vitamin D and PTH levels measured before and after the lansoprazole treatment, while the osteocalcin, DPD, CTX and NTX values were found to be higher after treatment when compared to those at pre- treatment. Conclusions: The results of this study reveal that eight weeks of treatment with 30 mg lansoprazole daily increased the bone turnover markers of CTX, NTX, DPD and osteocalcin in adolescents aged 16-18.

Hypercalcemia: A Review.

Importance: Hypercalcemia affects approximately 1% of the worldwide population. Mild hypercalcemia, defined as total calcium of less than 12 mg/dL (<3 mmol/L) or ionized calcium of 5.6 to 8.0 mg/dL (1.4-2 mmol/L), is usually asymptomatic but may be associated with constitutional symptoms such as fatigue and constipation in approximately 20% of people. Hypercalcemia that is severe, defined as total calcium of 14 mg/dL or greater (>3.5 mmol/L) or ionized calcium of 10 mg/dL or greater (≥2.5 mmol/L) or that develops rapidly over days to weeks, can cause nausea, vomiting, dehydration, confusion, somnolence, and coma. Observations: Approximately 90% of people with hypercalcemia have primary hyperparathyroidism (PHPT) or malignancy. Additional causes of hypercalcemia include granulomatous disease such as sarcoidosis, endocrinopathies such as thyroid disease, immobilization, genetic disorders, and medications such as thiazide diuretics and supplements such as calcium, vitamin D, or vitamin A. Hypercalcemia has been associated with sodium-glucose cotransporter 2 protein inhibitors, immune checkpoint inhibitors, denosumab discontinuation, SARS-CoV-2, ketogenic diets, and extreme exercise, but these account for less than 1% of causes. Serum intact parathyroid hormone (PTH), the most important initial test to evaluate hypercalcemia, distinguishes PTH-dependent from PTH-independent causes. In a patient with hypercalcemia, an elevated or normal PTH concentration is consistent with PHPT, while a suppressed PTH level (<20 pg/mL depending on assay) indicates another cause. Mild hypercalcemia usually does not need acute intervention. If due to PHPT, parathyroidectomy may be considered depending on age, serum calcium level, and kidney or skeletal involvement. In patients older than 50 years with serum calcium levels less than 1 mg above the upper normal limit and no evidence of skeletal or kidney disease, observation may be appropriate. Initial therapy of symptomatic or severe hypercalcemia consists of hydration and intravenous bisphosphonates, such as zoledronic acid or pamidronate. In patients with kidney failure, denosumab and dialysis may be indicated. Glucocorticoids may be used as primary treatment when hypercalcemia is due to excessive intestinal calcium absorption (vitamin D intoxication, granulomatous disorders, some lymphomas). Treatment reduces serum calcium and improves symptoms, at least transiently. The underlying cause of hypercalcemia should be identified and treated. The prognosis for asymptomatic PHPT is excellent with either medical or surgical management. Hypercalcemia of malignancy is associated with poor survival. Conclusions and Relevance: Mild hypercalcemia is typically asymptomatic, while severe hypercalcemia is associated with nausea, vomiting, dehydration, confusion, somnolence, and coma. Asymptomatic hypercalcemia due to primary hyperparathyroidism is managed with parathyroidectomy or observation with monitoring, while severe hypercalcemia is typically treated with hydration and intravenous bisphosphonates.

Reconsidering vitamin D optimal values based on parathyroid hormone levels in a North Algerian cohort: stratification by gender and season.

"Health-based threshold value" is used to define the optimal cutoff of vitamin D. This approach is based on the hypothesis of a secondary hyperparathyroidism associated with hypovitaminosis D. We define the optimal values in a North Algerian population. The optimal value is 25.0 ng/ml in men and 30.0 ng/ml in women. PURPOSE/INTRODUCTION: There is no consensus defining the vitamin D optimal values. The aim of this study is to establish vitamin D optimal values in the Northern Algerian population, based on its skeletal effects as represented by the inverse relationship between 25-hydroxy vitamin D (25(OH) D) and parathyroid hormone (PTH). METHODS: 451 healthy volunteers of both genders, aged 19 to 79 years, were enrolled in a cross-sectional study conducted at the medical analysis laboratory of the University Hospital of Blida, Algeria. 25(OH) D was assessed by a sequential competitive immuno-fluoroassay technique. Determination of vitamin D optimal values was performed based on the kinetic relationship between 25(OH) D and PTH, as explored by inverse nonlinear regression on a spline plots curve. The optimal value represents the 25(OH) D level at which PTH ceases to increase and reaches a virtual plateau. RESULTS: In men and women, respectively, the 25 (OH) D thresholds are estimated at 25.0 ng/ml and 30 ng/ml, above this value, PTH stabilizes in a virtual plateau, estimated at 22.3 pg/ml and 26.8 pg/ml. In warm and cold seasons, respectively, the 25 (OH) D cut-offs are estimated at 30.0 ng/ml and 25.0 ng/ml, from these values, the PTH stabilizes in a virtual plateau, estimated at 21.5 pg/ml and 27.7 pg/ml. CONCLUSION: In this study, the optimal values of 25(OH) D were defined for the first time in a North Algerian adult population. The optimal value is 25.0 ng/ml in men and 30.0 ng/ml in women.

Secondary hyperparathyroidism (CKD-MBD) treatment and the risk of dementia.

BACKGROUND: Elevated parathyroid hormone (PTH) levels have been reported as a potential risk factor for cognitive impairment. Compared with the general population, older adults with end-stage renal disease (ESRD) who are frequently affected by secondary hyperparathyroidism (SHPT) are at increased risk of developing dementia. The main objective of our study was to evaluate if the risk of dementia in older (age ≥66 years) ESRD patients differed if they were treated for SHPT. METHODS: Using the United States Renal Data System and Medicare claims, we identified 189 433 older adults without a diagnosis of dementia, who initiated dialysis between 2006 and 2016. SHPT treatment was defined as the use of vitamin D analogs, phosphate binders, calcimimetics or parathyroidectomy. We quantified the association between treated SHPT and incident dementia during dialysis using a multivariable Cox proportional hazards model with inverse probability weighting, considering SHPT treatment as a time-varying exposure. RESULTS: Of 189 433 older ESRD adults, 92% had a claims diagnosis code of SHPT and 123 388 (65%) were treated for SHPT. The rate of incident dementia was 6 cases per 100 person-years among SHPT treated patients compared with 11 cases per 100 person-years among untreated patients. Compared with untreated SHPT patients, the risk of dementia was 42% lower [adjusted hazard ratio (aHR) = 0.58, 95% confidence interval (CI): 0.56-0.59] among SHPT treated patients. The magnitude of the beneficial effect of SHPT treatment differed by sex (Pinteraction = .02) and race (Pinteraction ≤ .01), with females (aHR = 0.56, 95% CI: 0.54-0.58) and those of Asian (aHR = 0.51, 95% CI: 0.46-0.57) or Black race (aHR = 0.51, 95% CI: 0.48-0.53) having a greatest reduction in dementia risk. CONCLUSION: Receiving treatment for SHPT was associated with a lower risk of incident dementia among older patients with ESRD. This work provides additional support for the treatment of SHPT in older ESRD patients.

Parathyroidectomy for Normocalcemic Tertiary Hyperparathyroidism: A 19-Year Experience.

INTRODUCTION: Parathyroidectomy is the standard management for patients with tertiary hyperparathyroidism (THPT) and hypercalcemia. However, a subset of patients with THPT have normal or mildly-elevated serum calcium levels in the setting of significantly elevated parathyroid hormone (PTH). The purpose of this study is to determine the effectiveness and safety of parathyroidectomy in normocalcemic THPT. MATERIALS AND METHODS: Retrospective review of 212 consecutive patients with THPT who subsequently underwent parathyroidectomy between 2001 and 2020 was performed. Patients were categorized as normocalcemic, "mild" (Ca ≤ 10.4 mg/dL) or hypercalcemic, "classic" THPT (Ca ≥ 10.5 mg/dL) and clinical data are compared. RESULTS: 71 of 212 (34%) were normocalcemic with median pre-operative Ca and PTH levels of 9.7 mg/dL and 225pg/mL, respectively and 141 of 212 (67%) were hypercalcemic with median preoperative Ca and PTH levels of 11 mg/dL and 211pg/mL, respectively. The mean length of stay was shorter in normocalcemic patients (0.33 versus 0.50 d; P = 0.03). 10 of 71 (14%) normocalcemic patients underwent reoperative parathyroidectomy, more than double that of hypercalcemic patients (5.6%; P = 0.06). Concomitant thymectomy was performed in 28.1% and 22.1% of normocalcemia and hypercalcemic patients, respectively (P = 0.44). No patient in either group required intravenous calcium or had undetectable PTH levels, but permanent hypocalcemia was more frequent in normocalcemic compared to hypercalcemic patients (11.2% versus 1.4%; P = 0.03). CONCLUSIONS: Parathyroidectomy for normocalcemic tertiary hyperthyroidism (HPT) can be performed safely. These data can help guide multidisciplinary discussions for earlier surgical referral and intervention. Future investigations are needed to evaluate the impact of parathyroidectomy on the renal allograft, bone health, and cardiovascular disease.

Vitamin D status and its association with parathyroid hormone in 23,134 outpatients.

In vitro studies indicate that 25-hydroxyvitamin D3 (25(OH)D3) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) inhibits the synthesis of parathyroid hormone (PTH). The degree of PTH inhibition in humans by circulating 25(OH)D and 1,25(OH)2D may be different. Moreover, age and sex as well as confounding factors like calcium and phosphate may likewise affect the relationship between vitamin D and PTH in humans. However, this was not done so far in adequately powered studies. We investigated the relationship between 25(OH)D as well as 1,25(OH)2D and intact parathyroid hormone (iPTH) in 23,134 outpatients (age mean: 59.81 years) from the Berlin-Brandenburg area of Germany with normal serum creatinine considering confounding factors like age, sex, calcium and phosphate. 25(OH)D and iPTH were inversely correlated (r = -0.17, p < 0.0001). The inverse linear correlation was observed over the entire spectrum of 25(OH)D concentrations - from low 25(OH)D concentrations to very high 25(OH)D concentrations. Multiple linear regression analysis revealed that this correlation was independent of age, sex, creatinine, calcium and phosphate (unstandardized coefficients B: -0.16, p < 0.0001). However, 1,25(OH)2D was only positively associated with iPTH in women (r = 0.05, p = 0.033) and in the subgroup of patients with lower 25(OH)D (25(OH)D< 40 ng/ml) (r = 0.09, p < 0.0001), which was also presented in multiple linear regression analysis (unstandardized coefficients B: 0.20, p = 0.001). Circulating 1,25(OH)2D does not contribute substantially to the regulation of PTH in middle aged and vitamin D sufficient outpatients from the Berlin-Brandenburg area of Germany with normal kidney function. Presumably, serum 25(OH)D that is converted to 1,25(OH)2D after uptake in the parathyroid chief cells plays the critical role.

Single bout of exercise triggers the increase of vitamin D blood concentration in adolescent trained boys: a pilot study.

Vitamin D is necessary for musculoskeletal health, however, the supplementation of vitamin D above the sufficiency level does not bring additional bone mass density (BMD), unlike physical exercise which enhances the bone formatting process. Regular physical activity has been shown to upregulate VDR expression in muscles and to increase circulating vitamin D. Here we investigate whether a single bout of exercise might change 25(OH)D3 blood concentration and how it affects metabolic response to exercise. Twenty-six boys, 13.8 years old (SD ± 0.7) soccer players, participated in the study. The participants performed one of two types of exercise: the first group performed the VO2max test until exhaustion, and the second performed three times the repeated 30 s Wingate Anaerobic Test (WAnT). Blood was collected before, 15 min and one hour after the exercise. The concentration of 25(OH)D3, parathyroid hormone (PTH), interleukin-6 (IL-6), lactate, non-esterified fatty acids (NEFA) and glycerol were determined. 25(OH)D3 concentration significantly increased after the exercise in all boys. The most prominent changes in 25(OH)D3, observed after WAnT, were associated with the rise of PTH. The dimensions of response to the exercises observed through the changes in the concentration of 25(OH)D3, PTH, NEFA and glycerol were associated with the significant increases of IL-6 level. A single bout of exercise may increase the serum's 25(OH)D3 concentration in young trained boys. The intensive interval exercise brings a more potent stimulus to vitamin D fluctuations in young organisms. Our results support the hypothesis that muscles may both store and release 25(OH)D3.

Association between blood lead levels and markers of calcium homeostasis: a systematic review and meta-analysis.

Chronic Pb exposure associated systemic illness are partly posited to involve calcium homeostasis. Present systematic review aims to comprehensively evaluate the association between chronic lead exposure and markers of calcium homeostasis. Observational studies documenting the changes in calcium homeostasis markers (i.e. serum calcium, parathyroid hormone, vitamin D & calcitonin) between occupationally Pb exposed group and control group were systematically searched from pubmed-Medline, Scopus, and Embase digital databases since inception to September 24, 2021. The protocol was earlier registered at PROSPERO (ID: CRD42020199503) and executed adhering to PRISMA 2020 guidelines. Mean differences of calcium homeostasis markers between the groups were analysed using random-effects model. Conventional I2 statistics was employed to assess heterogeneity, while the risk for various biases were assessed using Newcastle Ottawa Scale. Sub-group, sensitivity and meta-regression analyses were performed where data permitted. Eleven studies including 837 Pb exposed and 739 controls were part of the present study. Pb exposed group exhibited higher mean blood lead level [i.e. 36.13 (with 95% CI 25.88-46.38) µg/dl] significantly lower serum calcium (i.e. - 0.72 mg/dl with 95% CI - 0.36 to - 1.07) and trend of higher parathyroid levels and lower vitamin D levels than controls. Heterogeneity was high (I2 > 90%) among the studies. Considering the cardinal role of calcium in multiple biological functions, present observations emphasis the need for periodic evaluation of calcium levels and its markers among those with known cumulative Pb exposure.

Parathyroid hormone in situ measurement in patients with hyperparathyroidism: single-centre experience of 179 patients.

Context: The measurement of parathyroid hormone(PTH) in situ (PTHis) by fine-needle aspiration (FNA) has been proposed as a tool to preoperatively help localize parathyroid glands detected on ultrasound. However, the accuracy of PTHis is highly variable according to the few available studies. Aim: We aimed to develop and validate the PTHis procedure and assessed the performance of PTHis in a large series of patients with hyperparathyroidism and/or undetermined cervical lesions. Patients and methods: The technique set-up consisted of PTHis measurement in thyroid samples from patients with thyroid nodules and patients with high circulating PTH levels (tertiary hyperparathyroidism). Consecutive patients were recruited at one tertiary referral centre from 2017 to 2020 and submitted to ultrasound-guided FNA-PTHis determination. Results: During the method set-up, we obtained undetectable PTHis levels in all non-parathyroid tissues after sample dilutions. PTHis was higher in patients with hyperparathyroidism (n = 145; 1817 ± 3739 ng/L; range: <4.6-31 140) than in those with thyroid or undetermined cervical lesions (n= 34; <4.6 ng/mL; P < 0.0001). When evaluating PTHis performance in histologically proven samples (158 lesions from 121 patients), PTHis was detectable in 85/97 parathyroid lesions (87%; range: 22-31;140 ng/L) and undetectable in all non-parathyroid lesions (n = 61; P < 0.0001). The specificity and positive predictive value were 100%, and the sensitivity was 87.6%. False-negative lesions (n= 12) were smaller (9.4 ± 5.9 mm) and more often consisted of hyperplasias (75%) than true-positive lesions (16.1 ± 8.4 mm and 33%, P = 0.009 and P = 0.0089, respectively). The method was safe and well tolerated. Four educational cases are also provided. Conclusions: PTHis determination is a safe and well-tolerated procedure that enhances the specificity of ultrasound-detected lesions. If accurately set-up, it confirms the parathyroid origin of uncharacterized cervical lesions.

The value of clinical-ultrasonographic feature model to predict the severity of secondary hyperparathyroidism.

OBJECTIVES: To analyze conventional ultrasound (CUS) and contrast-enhanced ultrasound (CEUS) features in patients with secondary hyperparathyroidism (SHPT) and to evaluate the clinical-ultrasonographic feature based model for predicting the severity of SHPT. METHODS: From February 2016 to March 2021, a total of 59 patients (age 51.3 ± 11.7 years, seCr 797.8 ± 431.7 µmol/L, iPTH 1535.1 ± 1063.9 ng/L) with SHPT (including 181 parathyroid glands (PTGs)) without the history of intact parathyroid hormone (iPTH)-reducing drugs using were enrolled. The patients were divided into the mild SHPT group (mSHPT, iPTH <800 ng/L) and the severe SHPT group (sSHPT, iPTH ≥ 800 ng/L) according to the serum iPTH level. The clinical test data of patients were collected and CUS and CEUS examinations were performed for every patient. Multivariable logistic regression model according to clinical-ultrasonographic features was adopted to establish a nomogram. We performed K-fold cross-validation on this nomogram model and nomogram performance was determined by its discrimination, calibration, and clinical usefulness. RESULTS: There were 19 patients in the mSHPT group and 40 patients in the sSHPT group. Multivariable logistic regression indicated serum calcium, serum phosphorus and total volume of PTGs were independent predictors related with serum iPTH level. Even though CEUS score of wash-in and wash-out were showed related to severity of SHPT in univariate logistic regression analysis, they were not predictors of SHPT severity (p = 0.539, 0.474 respectively). The nomogram developed by clinical and ultrasonographic features showed good calibration and discrimination. The accuracy and the area under the curve (AUC), positive predictive value (PPV), negative predictive value (NPV) and accuracy of this model were 0.888, 92.5%, 63.2% and 83.1%, respectively. When applied to internal validation, the score revealed good discrimination with stratified fivefold cross-validation in the cohort (mean AUC = 0.833). CONCLUSIONS: The clinical-ultrasonographic features model has good performance for predicting the severity of SHPT.

Haplotypes in the GC, CYP2R1 and CYP24A1 Genes and Biomarkers of Bone Mineral Metabolism in Older Adults.

Candidate gene studies have analyzed the effect of specific vitamin D pathway genes on vitamin D availability; however, it is not clear whether genetic variants also affect overall bone metabolism. This study evaluated the association between genetic polymorphisms in GC, CYP2R1 and CYP24A1 and serum levels of total 25(OH)D, iPTH and other mineral metabolism biomarkers (albumin, total calcium and phosphorus) in a sample of 273 older Spanish adults. We observed a significant difference between CYP2R1 rs10741657 codominant model and total 25(OH)D levels after adjusting them by gender (p = 0.024). In addition, the two SNPs in the GC gene (rs4588 and rs2282679) were identified significantly associated with iPTH and creatinine serum levels. In the case of phosphorus, we observed an association with GC SNPs in dominant model. We found a relationship between haplotype 2 and 25(OH)D levels, haplotype 4 and iPTH serum levels and haplotype 7 and phosphorus levels. In conclusion, genetic variants in CYP2R1 and GC could be predictive of 25(OH)D and iPTH serum levels, respectively, in older Caucasian adults. The current study confirmed the role of iPTH as one of the most sensitive biomarkers of vitamin D activity in vivo.

Vitamin D Deficiency Is Associated with Glycometabolic Changes in Nondiabetic Patients with Arterial Hypertension.

Recent evidence indicates that mildly increased fasting and post-oral load blood glucose concentrations contribute to development of organ damage in nondiabetic patients with hypertension. In previous studies, vitamin D deficiency was associated with decreased glucose tolerance. The aim of this study was to examine the relationships between serum 25(OH)D levels and glucose tolerance and insulin sensitivity in hypertension. In 187 nondiabetic essential hypertensive patients free of cardiovascular or renal complications, we measured serum 25-hydroxyvitamin D (25(OH)D) and parathyroid hormone (PTH) and performed a standard oral glucose tolerance test (OGTT). Patients with 25(OH)D deficiency/insufficiency were older and had significantly higher blood pressure, fasting and post-OGTT (G-AUC) glucose levels, post-OGTT insulin (I-AUC), PTH levels, and prevalence of metabolic syndrome than patients with normal serum 25(OH)D. 25(OH)D levels were inversely correlated with age, blood pressure, fasting glucose, G-AUC, triglycerides, and serum calcium and PTH, while no significant relationships were found with body mass index (BMI), fasting insulin, I-AUC, HOMA index, and renal function. In a multivariate regression model, greater G-AUC was associated with lower 25(OH)D levels independently of BMI and seasonal vitamin D variations. Thus, in nondiabetic hypertensive patients, 25(OH)D deficiency/insufficiency could contribute to impaired glucose tolerance without directly affecting insulin sensitivity.

Novel Glial Cells Missing-2 (GCM2) variants in parathyroid disorders.

OBJECTIVE: The aim of this study was to analyze variants of the gene glial cells missing-2 (GCM2), encoding a parathyroid cell-specific transcription factor, in familial hypoparathyroidism and in familial isolated hyperparathyroidism (FIHP) without and with parathyroid carcinoma. DESIGN: We characterized 2 families with hypoparathyroidism and 19 with FIHP in which we examined the mechanism of action of GCM2 variants. METHODS: Leukocyte DNA of hypoparathyroid individuals was Sanger sequenced for CASR, PTH, GNA11 and GCM2 mutations. DNA of hyperparathyroid individuals underwent MEN1, CDKN1B, CDC73, CASR, RET and GCM2 sequencing. The actions of identified GCM2 variants were evaluated by in vitro functional analyses. RESULTS: A novel homozygous p.R67C GCM2 mutation which failed to stimulate transcriptional activity in a luciferase assay was identified in affected members of two hypoparathyroid families. Oligonucleotide pull-down assay and in silico structural modeling indicated that this mutant had lost the ability to bind the consensus GCM recognition sequence of DNA. Two novel (p.I383M and p.T386S) and one previously reported (p.Y394S) heterozygous GCM2 variants that lie within a C-terminal conserved inhibitory domain were identified in three affected individuals of the hyperparathyroid families. One family member, heterozygous for p.I138M, had parathyroid carcinoma (PC), and a heterozygous p.V382M variant was found in another patient affected by sporadic PC. These variants exerted significantly enhanced in vitrotranscriptional activity, including increased stimulation of the PTH promoter. CONCLUSIONS: We provide evidence that two novel GCM2 R67C inactivating mutations with an inability to bind DNA are causative of hypoparathyroidism. Additionally, we provide evidence that two novel GCM2 variants increased transactivation of the PTH promoter in vitro and are associated with FIHP. Furthermore, our studies suggest that activating GCM2 variants may contribute to facilitating more aggressive parathyroid disease.

Osteoprotegerin, Parathyroid Hormone and Vitamin D as Effective Factors on Serum-Urine Calcium Levels in Breast Cancer Patients.

Breast cancer represents one of the most popular kinds of cancer worldwide. During the early stages of the disease, the level of Osteoprotegerin remained within normal limits, showing that the bone was not being damaged to get calcium due to an increase in parathyroid hormone. The current study aimed to assess a number of biochemical variables in a group of women with malignant breast cancer who had reached menopause (less than 45 years old). One hundred thirty women were randomly divided into three groups as follows. The first group (G1) is made up of women who have never had breast cancer or any other disease, and their number (40) corresponds to the same age range (below menopause) as the control group. The second group (G2) comprises women diagnosed with breast cancer at an early stage whose numbers were relatively low (45). The third group (G3) included women of the same age who received one or two doses of chemotherapy and whose total number was (45) over the same period. The variables studied include Vitamin D, Parathyroid Hormone, Osteoprotegerin, blood calcium, and urine calcium, all of that are thought to play a role in the progress of the disease. Vitamin D levels were extremely low in the second group (G2), while they were slightly higher in the third group (G3) but remained extremely low. The first group (G1) maintained parameters within acceptable limits. There was a significant difference between the two breast cancer groups (9.38 1.43) and (4.98 1.67) when compared to the control group (20.04 2.80). (G1). The two breast cancer groups (G2) and (G3) had higher parathyroid hormone levels than the control group (G1), and there was a significant difference between the two breast cancer groups (136.52 58.56) (G3) and (G2) (167.79 35.21) compared to the control group (68.52 20.44) (G1). There was no significant difference in Osteoprotegerin levels between the two breast cancer groups (313.38 109.02) (G3) and (315.0 123.98) (G2) compared to the control group (G1) (324.11 104.73). The three groups' blood calcium levels were all within normal ranges, and there was no statistically significant difference between them (9.21 0.45), (9.23 0.38), and (9.23 0.38) (G3) (9.28 0.43). (G1), but urine-calcium levels were lower in both groups of breast cancer patients compared to the control group, and there was a significant difference between the two breast cancer groups (63.96 15.66) (G3) and (68.42 14.05) (G2) compared to the control group (213.77 63.94) (G1). In breast cancer patients, vitamin D deficiency and high parathyroid hormone levels were discovered, suggesting that vitamin D may play a role in cancer prevention. Osteoprotegerin levels were within normal ranges early in the illness, although this may alter as the patient matures and the disease advances.