Serum Parathyroid Hormone Concentrations Research Articles

Paradoxical Response of Parathyroid Hormone to Vitamin D–Calcium Supplementation in Indian Children

To investigate the effect of oral vitamin D-calcium supplementation on serum intact parathyroid hormone (PTH), calcium, phosphorous, and alkaline phosphatase (ALK-P) concentrations in children with habitually low calcium intakes. In this follow-up study to a randomized controlled trial that aimed to assess the effect of vitamin D-calcium supplementation on immunity, data related to dietary intake, anthropometry, and biochemistry [serum 25(OH)D and bone profile] were collected from 178 children-79 in the vitamin D group and 99 in the non-vitamin D group. Dietary calcium to phosphorus intake ratio was 0.4:1. Baseline serum 25(OH)D concentration was 58.2±10.9nmol/L; 66% children were vitamin D sufficient and none deficient. After supplementation, vitamin Dgroup, compared with the non-vitamin D group, had significantly (P<.05) greater 25(OH)D (83.9±30.1nmol/L vs 58.3±15.7nmol/L), significantly greater PTH (6.7±3.6 pmol/L vs 5.5±3.2 pmol/L), and positive correlation (rs=0.24) between serum 25(OH)D and PTH (vs negative correlation [rs=-0.1] in non-vitamin D group). Mean concentrations of serum bone measures in the vitamin D group were calcium (2.2±0.1mmol/L), phosphorus (1.7±0.2mmol/L), and ALK-P (178.7±40.7 IU/L). At follow-up, 1-year post-supplementation, in the vitamin D group, PTH concentrations continued to remain high (but not significantly different from levels at 6months), with low normal serum calcium, high normal phosphate, and ALK-P in reference range. In children who are vitamin D sufficient but with habitually low dietary calcium intake, vitamin D-calcium supplementation paradoxically and significantly increased serum PTH concentrations with no apparent effect on other bone biochemistry. Chronic low dietary calcium to phosphorus ratio is likely to have caused this paradoxical response.

Severe calcium deficiency increased visceral fat accumulation, down-regulating genes associated with fat oxidation, and increased insulin resistance while elevating serum parathyroid hormone in estrogen-deficient rats

Menopause impairs calcium(Ca) metabolism and reduces bone mineral density (BMD), but the interaction of menopause with Ca deficiency in energy, glucose, lipid, and bone metabolism has not been studied. Herein we hypothesized that Ca deficiency at levels for post-menopausal women would impair energy, glucose, lipid, and bone metabolism in estrogen-deficient rats. This hypothesis was examined in ovariectomized (OVX) rats fed high-fat diets with different Ca levels for 12 weeks. OVX rats were allocated into either very low Ca (0.02%, VLCA), low Ca (0.7%, LCA), adequate Ca (1.18%, ACA, control), or excessive Ca (2.1%, EXCA). Sham-operated rats had the same diet as ACA (Normal-control). Ca intake was 37, 107, 190, and 311 mg/kg bw/d in the VLCA, LCA, ACA, and EXCA groups. The ACA group had higher serum parathyroid hormone concentrations than the Normal-control but were highest in VLCA. VLCA decreased BMD and lean body mass compared to ACA. Fasting serum glucose concentrations, even with higher serum insulin concentrations, were higher in the VLCA than ACA, indicating increased insulin resistance in VLCA. VLCA deteriorated glucose tolerance after oral glucose administration and impaired lipid profiles. LCA and EXCA had similar effects on metabolism as ACA, but LCA did not improve insulin sensitivity and lipid profiles as much as ACA. Expressions of hepatic genes related to fatty acid and cholesterol synthesis (FAS and SREBP-1c and HMGCR) were much higher in the VLCA than ACA and expressions of genes related fatty acid degradation(CPT1 and CYP7A1) were much lower in VLCA than ACA. In conclusion, we accepted the hypothesis. Very low Ca intake (350–400 mg/d as a human equivalent) exacerbated estrogen-deficiency-induced impairments of energy, glucose, and lipid metabolism by elevating serum parathyroid hormone levels and inducing visceral fat accumulation and insulin resistance in estrogen-deficient rats, but there was no added benefit of excessive Ca.

Determining biological variation of serum parathyroid hormone in healthy adults.

IntroductionMeasurement of parathyroid hormone (PTH) is essential in the investigation and management of calcium metabolism disorders. To assess the significance of any assay result when clinical decision making biological variation (BV) of the measurand must be taken into consideration. The aim of the present study is determining the BV parameters for serum PTH.Materials and methodsBlood samples were taken at weekly intervals from 20 healthy subjects for ten weeks in this prospective BV study. Serum “intact PTH” concentrations were measured with electrochemiluminescence method. Biological variation parameters were estimated using the approach proposed by Fraser.ResultsThe values of within-subject biological variation (CVI), between-subject biological variation (CVG), analytical variation (CVA), reference change value (RCV) and individuality index (II) for serum PTH were 21.1%, 24.9%, 3.8%, 59.4% and 0.8%, respectively. Within-subject biological variation and CVG were also determined according to gender separately; 18.5% and 24.0%; 26.2% and 18.6% for male and female, respectively. Calculated desirable precision and bias goals were < 10.6% and < 6.3%, respectively.ConclusionThis study may contribute to BV data on serum PTH as it includes a sufficient number of volunteers from both genders over an acceptable period of time. We do not recommend the usage of population-based reference intervals for serum PTH concentrations. Reference change value may be helpful for the evaluation of serial serum PTH results. Nonetheless, evaluation of data according to gender is necessary when setting analytical performance specifications.

MANIFESTATIONS OF HYPERPARATHYROIDISM IN JUVENILE WHOOPING CRANES (GRUS AMERICANA).

Juvenile whooping cranes (Grus americana) raised for wild release were found to have an increased incidence of rib fractures at fledging in 2017 compared with the previous 16 years. Serum analysis showed 30-day-old juveniles in 2017 (n = 12) had significantly lower 25-hydroxyvitamin D3 and significantly higher parathyroid hormone concentrations than juveniles in 2010 (n = 6) with no history of rib fractures. Increased serum parathyroid hormone concentrations in the 2017 juveniles persisted to fledging age. Review of dietary and environmental management revealed that juveniles in 2017 were provided a commercial diet with a lower, and perhaps suboptimal, calcium:phosphorus ratio and experienced reduced time outdoors in the first month after hatch, presumably resulting in less ultraviolet B radiation exposure. Mild hyperparathyroidism in precocial whooping cranes may result when dietary constraints and/or outdoor access is compromised and manifest as rib fractures in the absence of traumatic injury.

High calcium intake from fat-free milk, body composition and glycaemic control in adults with type 2 diabetes: a randomised crossover clinical trial.

We evaluated the effects of high-Ca fat-free milk v. low-Ca control diet on adiposity and on glycaemic control. Fourteen subjects with type 2 diabetes (aged 49·5 (sd 8·6) years, BMI 29·4 (sd 4·5) kg/m2, low habitual Ca consumption (<600 mg/d)) were included in this randomised, crossover clinical trial. Subjects participated in two 12-week experimental sessions (high-Ca fat-free milk (HC) or low-Ca control (LC)) separated by 8-week washout. Subjects daily consumed in the laboratory a breakfast shake containing 700 mg (HC) or 6·4 mg (LC) of Ca. Energy-restricted diets containing 800 mg of dietary Ca/d were prescribed. Dietary records data indicated the consumption of 1200 mg of Ca/d during HC and of 525 mg of Ca/d during LC. There was a greater reduction in body weight, body fat mass, waist circumference and waist:hip ratio after HC. Serum 25-hydoxyvitamin D and homeostatic model assessment-2 β-cell function (HOMA2-%B) increased, and serum uric acid, parathormone (PTH) and glycated Hb (HbA1c) concentrations reduced after HC. In addition, changes from baseline in terms of serum uric acid, glucose, HbA1c and PTH concentrations were lower, and those of HOMA2-%B, serum Ca and 25-hydoxyvitamin D were higher after the HC than after LC. The consumption of approximately three servings of fat-free milk and 1200 mg of dietary Ca/d enhanced weight loss, improved body composition and promoted glycaemic control in subjects with type 2 diabetes and low habitual Ca consumption (<600 mg/d).

Serum Parathyroid Hormone and Risk of Coronary Artery Disease: Exploring Causality Using Mendelian Randomization.

Elevated circulating parathyroid hormone concentrations have been associated with increased risk of cardiovascular disease in observational studies, but whether the association is causal is unknown. We used the Mendelian randomization design to test whether genetically increased serum parathyroid hormone (S-PTH) concentrations are associated with coronary artery disease (CAD). Five single-nucleotide polymorphisms robustly associated with S-PTH concentrations were used as instrumental variables to estimate the association of genetically higher S-PTH concentrations with CAD. Summary statistics data for CAD were obtained from a genetic consortium with data from 184,305 individuals (60,801 CAD cases and 123,504 noncases). OR of CAD per genetically predicted one SD increase of S-PTH concentrations. Genetically higher S-PTH concentration was not associated with CAD as a whole or myocardial infarction specifically (∼70% of total cases). The ORs per genetically predicted one SD increase in S-PTH concentration were 1.01 (95% CI: 0.93 to 1.09; P = 0.88) for CAD and 1.02 (95% CI: 0.94 to 1.10; P = 0.64) for myocardial infarction. The lack of association remained in various sensitivity analyses. Genetic predisposition to higher S-PTH concentrations does not appear to be an independent risk factor for CAD.

Cinacalcet attenuated bone loss via inhibiting parathyroid hormone-induced endothelial-to-adipocyte transition in chronic kidney disease rats

Recently, cinacalcet (CINA) has been shown to be effective for attenuating bone loss in the treatment of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD), which might be associated with the reduction in serum parathyroid hormone (PTH) levels. However, the exact mechanism is largely unclear. Emerging studies have revealed that an increased number of bone marrow adipocytes (BMAs) are involved in bone loss and the endothelial-to-adipocyte transition via the endothelial-to-mesenchymal transition (EndMT) might play a key role in this pathological process. Here, we assessed whether CINA could attenuate bone loss via inhibiting endothelial-to-adipocyte transition in CKD rats. A rat model of CKD was induced by adenine and a high phosphorus diet. CINA was orally administrated to CKD animals (10 mg/kg once a day). Dual energy X-ray absorptiometry, micro-computed tomography, bone histomorphometry, and bone mechanical tests were used to determine the skeletal changes. The bone marrow expression of EndMT markers was also examined. The effect of elevated PTH levels on the endothelial-to-adipocyte transition was studied in endothelial cells (ECs). Elevation of serum PTH levels, remarkable bone loss and increased numbers of BMAs were observed in rats with CKD compared with the controls, and these changes were attenuated after treatment with CINA. Furthermore, the CINA treatment abolished the upregulation of mesenchymal markers (FSP1 and α-SMA) and the downregulation of an endothelial marker (CD31) in bone tissues from rats with CKD. The serum PTH concentrations were correlated with the bone marrow protein levels of these EndMT-related proteins. An in vitro treatment in ECs demonstrated that PTH induced the EndMT in a concentration- and time-dependent manner. Accordingly, ECs treated with PTH exhibited adipogenic potential following growth in adipogenic culture medium. Our study indicated CINA treatment attenuated bone loss in CKD rats, which might be associated with inhibiting PTH-induced endothelial-to-adipocyte transition in CKD rats.

Altered seric levels of albumin, sodium and parathyroid hormone may predict early mortality following hip fracture surgery in elderly.

To analyse a wide set of routine laboratory parameters at admission to predict mortality within 30 post-operative days in elderly patients with hip fracture, as well as calculate the critical values of those biomarkers. Data of 994 patients older than 65years with hip fracture were analysed of which 89 (8.2%) died within 30 post-operative days. Variables described in the literature with potential influence on early mortality were collected, including demographics, fracture type, American Society of Anesthesiologists score, Charlson's comorbidity index and pre-operative Hodkinson's mental test and the Katz index for activities of daily living. In addition, an exhaustive collection of biomarkers from routine blood testing at admission was performed. Critical levels of biomarkers were calculated by the method of area under ROC curve. At admission, early mortality group had significantly higher Charlson's index (p = 0.001) and lower the Katz index (p = 0.001). The surgical delay also was significantly longer in that group (p = 0.001). In univariate analyses, serum concentration at admission of total protein (p = 0.004), albumin (p = 0.001), sodium (p = 0.001), and parathyroid hormone (PTH) (p = 0.001) were significantly different between both groups. In multivariate analysis, serum albumin < 2.9g/dL (p = 0.013), sodium < 127mEq/L (p = 0.035) and PTH > 65pg/mL (p = 0.005) were predictors of early mortality. The three biomarkers together accounted for 67% of the variability in early mortality. The association of altered levels at admission of serum concentration of albumin, sodium and PTH was predictor of early mortality following hip fracture surgery in elderly patients.

Calcitropic Hormones and Metabolic Markers Differ in Young South Asian Indian Men and Caucasians (P04-119-19)

ObjectivesThe incidence rate of metabolic syndrome is higher in South Asian Indians (SAI) and is generally accompanied by changes in calcitropic hormones. Typically, these findings are reported in middle age or older adults and data in a younger population is scarce. The purpose of the study was to analyze the differences in calcitropic hormones and metabolic markers in younger South Asian Indian and Caucasian men MethodsCaucasian or South Asian Indian men between 21–41 years of age were recruited for this study. Anthropometric measurements such as weight (kg), height (cm) and waist circumference (cm) were obtained. An 8-hour fasting blood sample was collected for analysis of serum concentrations of 25 hydroxyvitamin D (25OHD), parathyroid hormone (PTH), C-reactive protein (CRP), osteocalcin (OC), high molecular weight (HMW) adiponectin, glycemic indices, and lipid profile. Independent sample t-tests were used to report the mean differences between groups. The significance level was set for P < 0.05. ResultsA total of 26 men (13 SAIs and 13 Caucasians) completed the study. The mean age for SAI men was 27.82 ± 5.64 y and 27.39 ± 5.29 y for Caucasian men. Body mass index (BMI) averaged at 25.93 ± 3.97 kg/m2 for SAIs and 26.44 ± 2.49 kg/m2 for Caucasians. Serum 25(OH)D concentrations were lower in the SAI men (21.58 ± 8.11 ng/mL) compared to Caucasian men (29.14 ± 7.17 ng/mL) (P = 0.019). Serum concentrations of PTH were higher (P = 0.007) in the SAI men (72.39 ± 24.32 pg/mL) compared to Caucasian Men (45.30 ± 21.95 pg/mL). Furthermore, HMW adiponectin was significantly lower (P = 0.008) in SAIs (2.00 ±1.29 mg/L) compared to Caucasians (3.95 ± 2.01 mg/L). Glycemic indices, inflammatory markers, serum osteocalcin, and lipid profiles were not different between groups. ConclusionsThese results show that differences in calcitropic hormones are observed in young South Asian Indian men compared to Caucasians although differences in metabolic parameters do not exist at this point. Changes in calcitropic hormones may provide early insight into the development of metabolic syndrome in this population. Intervention studies should address whether correction of vitamin D status will delay the development of metabolic syndrome in this population. Funding SourcesCNHP Seed Funding.

Role of routine frozen sections for parathyroid exploration in a resource poor setting

Removal of parathyroid is recommended for patients suffering from hypercalcemia due to excess parathyroid hormone levels. There are several causes for a hyperfunctioning parathyroid gland out of which parathyroid adenoma is the most common pathological entity. There is great variation in the number and location of parathyroid glands. Hence, intra-operative confirmation of parathyroid tissue makes it easier for the surgeon to be confident of the outcome of the procedure and assure the patient of a permanent cure. A descriptive cross sectional study was done in a cohort of 26 patients who presented with elevated total serum calcium and parathyroid hormone concentrations. Intra-operative frozen section diagnoses were correlated with routine histological studies and post-operative parathyroid hormone concentration. The majority of patients were diagnosed as having parathyroid adenoma (88.46%). Three out of 26 patients (11.53%) had parathyroid hyperplasia involving more than one gland. Sensitivity and specificity of intraoperative frozen section diagnosis was 100%. There was a statistically significant association (p In the light of the discussion on parathyroid surgery it is apparent that frozen sections play a pivotal role in resource poor settings, when facilities for novel intra-operative imaging studies such as sestamibi scan and single-photon emission computed tomography are limited. The participants of the study have been followed up during last 5 years with no evidence of residual disease or recurrence up to date.

Are certain factors involved in calcium metabolism associated with temporomandibular disorders?

ABSTRACT Objective: The aim of the present study was to investigate whether there is an association between serum concentrations of calcium, phosphate, alkaline phosphatase, parathyroid hormone (PTH), and vitamin D and temporomandibular disorders (TMDs). Methods: In this case-control study, 51 patients with TMDs (28 patients with TMJ clicking, 5 patients with muscular disorders, and 18 osteoarthritis patients) and 29 healthy subjects within the age range of 20–50 years as the control group, were referred to the laboratory for calcium, phosphate, alkaline phosphatase, PTH, and vitamin D (25 OHD) analysis tests. The TMJ status of all participants was examined according to RDC-TMD criteria by a prosthodontist who is an expert in TMDs. The results were analyzed with Fisher’s precise test. Results: No statistically significant difference was observed between TMD patients and healthy subjects. Conclusion: Serum concentrations of calcium, phosphate, alkaline phosphatase, PTH, and vitamin D are not associated with TMDs.

An integrated analysis of safety and tolerability of etelcalcetide in patients receiving hemodialysis with secondary hyperparathyroidism.

BackgroundCalcimimetics have been shown to be effective and safe therapies for the treatment of secondary hyperparathyroidism (sHPT), a serious complication of disordered mineral metabolism associated with dialysis-dependent chronic kidney disease. Etelcalcetide, a recently approved intravenous calcimimetic, reduces serum parathyroid hormone (PTH), calcium, phosphorus, and fibroblast growth factor-23 concentrations. Here we report the first integrated safety profile of etelcalcetide using pooled data from five pivotal clinical trials.MethodsThis analysis included data from patients receiving hemodialysis with moderate to severe sHPT enrolled in two randomized, placebo-controlled trials; a randomized active-controlled (with cinacalcet) trial; and two single-arm, open-label extension trials. Patients initially received etelcalcetide intravenously 5 mg three times weekly (TIW) after hemodialysis; with potential dose increases of 2.5 or 5 mg at 4-week intervals to a maximum dose of 15 mg TIW, depending on serum PTH and calcium levels. The nature, frequency, and severity of treatment-emergent adverse events (AEs) and changes in laboratory parameters were assessed.ResultsOverall, we evaluated 1023 patients from the placebo-controlled trials, 683 from the active-controlled trial, and 1299 from open-label extensions. The frequency and nature of common treatment-emergent AEs reported for the etelcalcetide arm were consistent among the placebo-controlled and active-controlled trials. The most common AEs were those related to mineral metabolism (decreased blood calcium, hypophosphatemia, muscle spasms) or gastrointestinal abnormalities (diarrhea, nausea, vomiting). Hypocalcemia leading to discontinuation of either calcimimetic was experienced in ≤ 1% of patients.ConclusionsThis integrated safety assessment of etelcalcetide across placebo- and active-controlled trials showed an overall favorable risk/benefit profile, with safety similar to that of cinacalcet. Consistent with its mechanism of action, the most important risks associated with etelcalcetide were serum calcium reductions and hypocalcemia-related AEs; no new safety findings were identified in the pooled long-term extension trials.

Parathyroidectomy versus cinacalcet for tertiary hyperparathyroidism; a retrospective analysis

IntroductionTertiary hyperparathyroidism (tHPT), i.e., persistent HPT after kidney transplantation, affects 17–50% of transplant recipients. Treatment of tHPT is mandatory since persistently elevated PTH concentrations after KTx increase the risk of renal allograft dysfunction and osteoporosis. The introduction of cinacalcet in 2004 seemed to offer a medical treatment alternative to parathyroidectomy (PTx). However, the optimal management of tHPT remains unclear.MethodsA retrospective analysis was performed on patients receiving a kidney transplantation (KT) in two academic centers in the Netherlands. Thirty patients undergoing PTx within 3 years of transplantation and 64 patients treated with cinacalcet 1 year after transplantation for tHPT were included. Primary outcomes were serum calcium and PTH concentrations 1 year after KT and after PTx.ResultsSerum calcium normalized in both the cinacalcet and the PTx patients. PTH concentrations remained above the upper limit of normal (median 22.0 pmol/L) 1 year after KT, but returned to within the normal range in the PTx group (median 3.7 pmol/L). Side effects of cinacalcet were difficult to assess; minor complications occurred in three patients. Re-exploration due to persistent tHPT was performed in three (10%) patients.ConclusionIn patients with tHPT, cinacalcet normalizes serum calcium, but does not lead to a normalization of serum PTH concentrations. In contrast, PTx leads to a normalization of both serum calcium and PTH concentrations. These findings suggest that PTx is the treatment of choice for tHPT.

Parathyroid autotransplantation at a novel site for better evaluation of the grafted gland function: study protocol for a prospective, randomized controlled trial

BackgroundHypoparathyroidism is one of the most common complications encountered in thyroidectomy. In addition to parathyroid in-situ preservation, parathyroid autotransplantation (PA) is another important remedial method for patients whose parathyroid glands have been removed. However, an accurate evaluation method for the function of a transplanted parathyroid is lacking. Our preliminary study indicated that patients with PA at novel sites near antecubital veins had higher serum concentrations of parathyroid hormone (PTH). Therefore, the main hypothesis is that a grafted site closer to the cephalic vein is more useful for better evaluation of transplanted parathyroid function. This study aims to confirm the more efficient and accurate evaluation system through a prospective, randomized controlled trial.MethodsIn total, 280 patients will be enrolled in this study and randomly divided into two groups: 140 patients with transplanted parathyroid glands in the traditional sites (group A) and the other 140 transplanted in the novel sites (group B), close to the antecubital veins. The serum concentration of PTH and calcium ion from both forearms will be measured and monitored regularly for 12 months. The primary outcome of this trial will be the survival of grafted glands, defined as the ratio of PTH between the grafted vs. the non-grafted forearms being no less than 1.5. The secondary outcome is hypoparathyroidism, defined as the PTH level from the non-grafted forearms being less than 15 pg/ml (normal range 15–65 pg/ml).DiscussionOur results from this study should provide a more accurate method to evaluate the function of transplanted parathyroid glands by comparing PTH concentrations in both the grafted and non-grafted forearms following PA at novel sites. A better PTH measurement is helpful not only for the management of postoperative patients, but also for further identification of factors affecting PA success.Trial registrationClinicalTrials.gov, ID: NCT02906748. Registered on 16 March 2016.

Parathyroid hormone and premature thymus ageing in patients with chronic kidney disease

Premature immune ageing, including thymic atrophy, is observed in patients with chronic kidney disease (CKD). Parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23), which are mineral and bone disorder (MBD)-related factors, affect immune cells and possibly cause thymic atrophy. We examined the cross-sectional association between thymic atrophy, evaluated as the number of CD3+CD4+CD45RA+CD31+ cells [recent thymic emigrants (RTE)/μL], and MBD-related factors [(serum PTH, FGF23, and alkaline phosphatase (ALP) level] in 125 patients with non-dialysis dependent CKD. Median estimated glomerular filtration rate (eGFR) was 17 mL/min/1.73 m2. Older age (r = −0.46), male sex (r = −0.34), lower eGFR (r = 0.27), lower serum-corrected calcium (r = 0.27), higher PTH (r = −0.36), and higher ALP level (r = −0.20) were identified as determinants of lower number of RTE. In contrast, serum concentrations of FGF23 and phosphorus were not correlated with RTE. Multivariate non-linear regression analysis indicated a negative association between serum PTH and log-transformed RTE (P = 0.030, P for non-linearity = 0.124). However, the serum levels of FGF23 and ALP were not associated with RTE. In patients with CKD, serum PTH concentrations were related to thymic atrophy which contributes to immune abnormality.

Effects of different training modalities on phosphate homeostasis and local vitamin D metabolism in rat bone.

ObjectivesMechanical loading may be an important factor in the regulation of bone derived hormones involved in phosphate homeostasis. This study investigated the effects of peak power and endurance training on expression levels of fibroblast growth factor 23 (FGF23) and 1α-hydroxylase (CYP27b1) in bone.MethodsThirty-eight rats were assigned to six weeks of training in four groups: peak power (PT), endurance (ET), PT followed by ET (PET) or no training (control). In cortical bone, FGF23 was quantified using immunohistochemistry. mRNA expression levels of proteins involved in phosphate and vitamin D homeostasis were quantified in cortical bone and kidney. C-terminal FGF23, 25-hydroxyvitamin D3, parathyroid hormone (PTH), calcium and phosphate concentrations were measured in plasma or serum.ResultsNeither FGF23 mRNA and protein expression levels in cortical bone nor FGF23 plasma concentrations differed between the groups. In cortical bone, mRNA expression levels of sclerostin (SOST), dental matrix protein 1 (DMP1), phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) and matrix extracellular phosphoglycoprotein (MEPE) were lower after PT compared to ET and PET. Expression levels of CYP27b1 and vitamin D receptor (VDR) in tibial bone were decreased after PT compared to ET. In kidney, no differences between groups were observed for mRNA expression levels of CYP27b1, 24-hydroxylase (CYP24), VDR, NaPi-IIa cotransporter (NPT2a) and NaPi-IIc cotransporter (NPT2c). Serum PTH concentrations were higher after PT compared to controls.ConclusionAfter six weeks, none of the training modalities induced changes in FGF23 expression levels. However, PT might have caused changes in local phosphate regulation within bone compared to ET and PET. CYP27b1 and VDR expression in bone was reduced after PT compared to ET, suggesting high intensity peak power training in this rat model is associated with decreased vitamin D signalling in bone.

Vitamin D deficiency in children: a challenging diagnosis!

The concern about the assessment of vitamin D status is growing. Numerous publications warn about the high prevalence of vitamin D deficiency, as well as the potential role of vitamin D in non-bone health outcomes. The status of vitamin D is usually assessed by measuring serum total 25-hydroxyvitamin D (25OHD) concentration. This is the major circulating form of vitamin D and keeps an inverse correlation with serum parathyroid hormone (PTH) concentration. A value of 25OHD of 20 ng/ml is generally assumed as threshold of vitamin D sufficiency in epidemiologic studies because serum PTH tends to increase when the 25OHD concentration stands below this value. In pediatric population, very few studies have analyzed this issue and the negative relationship between serum 25OHD and serum PTH is not clear, which is the suitable circulating concentration of 25OHD and the threshold of deficiency being matters of controversy. The majority of 25OHD circulates in serum tightly bound to a globulin (DBP). According to the free hormone hypothesis, protein-bound hormones are not biologically available and it is the free form that exerts or facilitates the physiologic actions. If this is true, factors that affect DBP may alter the interpretation of total serum 25OHD measurements.

The application of subcapsular saline injection during bilateral axillo-breast approach robotic thyroidectomy: a preliminary report.

Saving the parathyroid gland during robotic thyroidectomy is challenging. This study evaluated the application of a novel method, subcapsular saline injection (SCASI), to save the parathyroid gland during bilateral axillo-breast approach (BABA) robotic total thyroidectomy. Of the 81 included patients operated on from 2014 to 2016, 31 and 50 underwent BABA robotic total thyroidectomy with and without SCASI, respectively. Serum concentrations of parathyroid hormone (PTH), calcium, and ionized calcium were measured at 1day and 9 months postoperatively. Transient hypoparathyroidism was defined as PTH < 10.0pg/mL after 1day and permanent hypoparathyroidism as PTH < 15.0pg/mL at 9 months. There were no significant clinicopathologic differences between the two groups. The rate of transient hypoparathyroidism was significantly lower in the SCASI group than in the non-SCASI group [16.1% (5/31) vs. 44% (22/50), p < 0.01]. However, the rates of permanent hypoparathyroidism [0% (0/31) vs. 4% (2/50), p = 0.699] did not differ significantly. SCASI is a feasible and safe method of saving the parathyroid gland during BABA robotic total thyroidectomy.

High Rate of Occult Urolithiasis in Normocalcemic Primary Hyperparathyroidism

Introduction: Normocalcemic primary hyperparathyroidism (NPHPT) is characterized by elevations in serum parathyroid hormone levels in the presence of normal serum calcium concentrations after exclusion of secondary hyperparathyroidism. We have previously demonstrated no differences in the prevalence of clinically active urolithiasis between NPHPT and hypercalcemic asymptomatic PHPT, and that it is significantly higher in postmenopausal osteoporotic women with NPHPT in comparison to women with normal serum PTH and calcium concentrations. Few studies have addressed the occurrence of silent or occult kidney stones in asymptomatic hypercalcemic PHPT, but no data are available for NPHPT. Objective: To determine the presence of occult urolithiasis in NPHPT patients using routine abdominal ultrasonography. Methods and Results: We studied 35 patients with NPHPT (mean age 63.2 ± 10.7 years, 96% women; serum PTH 116.5 ± 39.2 pg/mL, 25OHD 38.5 ± 6.82 ng/mL, total calcium 9.1 ± 0.56 mg/dL; albumin 4.02 ± 0.37 g/dL; BUN 34.35 ±10.23 mg/dL; p = 3.51 ± 0.60 mg/dL; estimated glomerular filtration rate 88.44 ± 32.45 mL/min/1.73 m2, and 24-h urinary calcium excretion 140.6 ± 94.3 mg/24 h). The criteria for the diagnosis of NPHPT were as follows: serum PTH above the reference range (11–65 pg/mL), normal albumin-corrected serum calcium concentrations, normal 24-h urinary calcium excretion, serum 25OHD above 30 ng/mL, estimated GFR (MDRD) above 60 mL/min/1.73 m2 (with the exclusion of medications such as thiazide diuretics, lithium, bisphosphonates, and denosumab), a history of clinical symptoms of urolithiasis, and a family history of kidney stones. Thirty-five patients were evaluated and 25 of them met the inclusion criteria. Five patients presented nephrolithiasis corresponding to 20% of the study population. There were no statistically significant differences in any of the clinical or laboratory variables studied between patients with or without urolithiasis, although mean serum PTH levels were higher in patients with stones (180.06 ± 126.48 vs. 100.72 ± 25.28 pg/mL, p = 0.1). The size of the stones ranged from 0.6 to 0.9 cm and all of the stones were located in the renal pelvis. Conclusion: We found a high prevalence of occult kidney stones in NPHPT patients, similar to what is observed in clinically manifested urolithiasis, in hypercalcemic PHPT.

KLOTHO PROTEIN, FIBROBLAST GROWTH FACTOR 23 AND RENAL CALCIUM EXCRETION IN INITIAL STAGES OF EXPERIMENTAL CHRONIC KIDNEY DISEASE

INTRODUCTION.It is suggested that fibroblast growth factor 23 (FGF23) and its co-receptor Klotho are probably associatedwith changes in calcium metabolism in chronic kidney disease (CKD) due to ability to regulate intracellular Ca transport bymodulating the cationic channels TRPV5 and TRPV6.THE AIMis to investigate the association between Klotho, FGF23 and renal excretion of Ca in the initial stages of experimental CKD.MATERIAL AND METHODS.The experimental models of chronic kidney injury were resection of the renal tissue in spontaneously hypertensive rats (SHR). Serum concentrations of intact FGF23 and PTH were determined by ELISA, renal Klotho protein expression by IHC. The indices of Ca excretion were calculated.RESULTS.Serum creatinine concentration, creatinine clearance and the severity of interstitial fibrosis in experimental models corresponded to the initial stages of chronic kidney disease. UCa24 and FECa were higher, Klotho protein expression was lower in groups with more severe renal dysfunction, without significant differences in FGF23 and PTH levels. Multiple regression analysis showed that FECa and UCa24 were not associated with FGF23, Klotho, and PTH.CONCLUSION.Renal excretion of Ca in initial stages of experimental kidney damage is not associated with Klotho and FGF23 levels.